Clinicopathological Features of Hepatobiliary Cells in Primary Biliary Cholangitis Patients with Ursodeoxycholic acid respond incompletely

Clinicopathological Features of Hepatobiliary Cells in Primary Biliary Cholangitis Patients with Ursodeoxycholic acid respond incompletely | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinicopathological Features of Hepatobiliary Cells in Primary Biliary Cholangitis Patients with Ursodeoxycholic acid respond incompletely Kun Yang, Bingqing Yang, Jiamin Chen, Lili Gao, Xiaoyi Han, Junke Hu, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6763526/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 12 Feb, 2026 Read the published version in BMC Gastroenterology → Version 1 posted 13 You are reading this latest preprint version Abstract Background: The mechanisms underlying the incomplete response to ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) patients are not clear. This study investigated the Clinicopathological characteristics and mechanism of hepatobiliary (HB) cells among PBC patients who demonstrated an incomplete response to UDCA. Methods: This study involved 132 patients with PBC undergoing ultrasound-guided liver biopsies. The obtained samples were subjected to various staining techniques. Demographic data, clinical features, hematological factors, auto-antibody levels, and liver biochemistry of patients were retrospectively analyzed. The response to UDCA was determined per Paris criteria. We also performed high-performance liquid chromatography-mass spectrometry (LC-MS) to test bile acid metabolomics on paraffin-embedded tissue samples from 25 patients with PBC. Results: Among 132 patients, 52 (39.4%) had an inadequate UDCA response. The quantity of CK7 + HB cells, degree of copper deposition in hepatocytes, alkaline phosphatase (ALP), total bile acid (TBA) and GP210 showed the strong association with this inadequate UDCA response. These factors exhibited AUC values of 0.775, 0.699, 0.799, 0.758 and 0.623, respectively. The concentrations of TBA ( p =0.010) and glycoursodeoxycholic (GUDCA, p =0.037) in liver tissues revealed significantly increased in the group with incomplete response to UDCA than in the group with complete response to UDCA. Additionally, a notable positive correlation was observed between the quantity of CK7 + HB cells and the content of TBA ( r =0.544, p ＜0.01) and GUDCA ( r =0.480, p ＜0.05) in liver tissues. Conclusions: Hepatobiliary cells in PBC are correlated with bile acid metabolism and inadequate response to UDCA. cholestatic liver disease bile acid metabolism pathology treatment response bile salt Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Introduction Primary biliary cholangitis (PBC) is an autoimmune hepatopathy characterized by non-suppurative destructive cholangitis, where inflammatory cells, mainly plasma cells, and lymphocytes, selectively target and damage intrahepatic small bile ducts (septal and interlobular), resulting to progressive cholestasis and potential liver cirrhosis [ 1 ]. Currently, Ursodeoxycholic acid (UDCA) is the only safe and effective first-line treatment, yet 40% of patients still show an incomplete response in clinical practice which often have a poor prognosis[ 2 ]. Hence, investigating the reason behind the inadequate response to UDCA is highly important. Histological examinations have demonstrated that specific hepatocytes transform into Cytokeratin (CK)7 + hepatobiliary (HB) cells, which exhibit characteristics of both biliary and hepatocyte markers. This cellular conversion happens in various conditions, such as acute liver failure, cirrhosis, and cholestatic liver diseases [ 3 ]. CK7 + HB cells indicate cholestasis, particularly in conditions associated with ductopenia, such as PBC [ 4 ]. Presently, the potential relationship between CK7 + HB cells and incomplete response to UDCA remains unexplored. Also, the specific mechanisms involved in this association have yet to be elucidated. This study focuses on the correlation between CK7 + HB cells and incomplete UDCA response and its possible mechanisms. Materials and methods Patients Patients were recruited participants from Beijing Ditan Hospital between January 2019 and July 2021, which is in accordance with the diagnostic standards outlined in the 2018 Practice Guidelines of the American Association for the Study of Liver Diseases (AASLD) [5]. The research excluded individuals with other autoimmune liver diseases, systemic autoimmune diseases, metabolism-related fatty liver diseases, viral hepatitis, long-term excessive alcohol intake, use of suspected liver injury drugs within the past six months, primary liver cancer, and other liver tumors. Definition and discrimination criteria of UDCA response incompletely in PBC patients Patients received UDCA standard therapy of 13~15 mg/kg/day for 1 year. According to the Paris I and Paris II criteria and the examination results after this period, participants were divided into the UDCA incomplete response (n = 52) and the UDCA complete response groups (n = 80). The Paris I standard is as follows: 1 year after UDCA application, the patient’s alkaline phosphoridase (ALP) < 3x upper limit of normal (ULN), aspartate aminotransferase (AST) <2x ULN, and total bilirubin (TBiL) < 1 mg/dL [6]. The Paris II standard specifies: 1 year of UDCA administration, the patient has a basic ALP < 1.5xULN, AST< 1.5x ULN, and TBiL < 1 mg/dL [7]. Paris I is used to evaluate advanced PBC (stages III-IV), while Paris II assesses biochemical responses in patients with early PBC (stages I-II). Clinical data collection Clinical and laboratory data were carefully extracted from electronic medical records from Beijing Ditan Hospital from the month preceding UDCA therapy. Laboratory examinations included various blood components and biochemical markers, including the red blood cell (RBC) count, white blood cell (WBC) count, platelet count (PLT), as well as hemoglobin (HGB) levels. Additionally, other parameters assessed were alanine aminotransferase (ALT), AST, gamma-glutamyl transferase (GGT), ALP, total bile acid (TBA), TBiL, direct bilirubin (DBiL), globulin (GLO), albumin (ALB), total protein (TP), total cholesterol (TC), and triglycerides (TG). Liver biopsies and histopathological assessments A 16G needle was used to perform percutaneous liver biopsies on the right liver lobe following the local standard procedure. The present study included liver samples with 10 or more complete portal tracts. Following routine histological analysis, liver samples were fixed with 10% formalin, embedded in paraffin, and stained with hematoxylin and eosin (H&E), Masson’s trichrome (Nanjing Jiancheng Bioengineering Institute), reticular fiber, and rhodanine as described previously [8]. All the participants provided the informed consent. The research protocol received approval from the Ethics Committee of Beijing Ditan Hospital, Capital Medical University (NO. DTEC-KY2024-023-01). Furthermore, the human subject procedures in the present work followed ethical standards, the 1964 Helsinki Declaration, and its subsequent amendments or relevant ethical guidelines. Immunohistochemical analysis For immunohistochemical analysis, normal serum was first added to block liver sections and then stained using antibodies targeting cytokeratin 7 (CK7), CD10, and MUM-1, and left overnight at 4°C before incubation with horseradish peroxidase-labeled secondary antibody. Subsequently, protein bands were detected using diaminobenzidine, followed by counterstaining with hematoxylin. Images were captured using a Nikon Labophot 2 microscope. The tissue samples were categorized by using the Ludwig staging system. Thereafter, the Ishak score for liver tissue inflammation and fibrosis, bile duct loss degree in the portal tract, copper deposition level in hepatocytes [9], degree of bile duct rearrangement within the periportal area, degree of infiltration of lymphocytes, plasma cells, and eosinophils within the portal tract [10], CK7 immunostaining intensity in periportal hepatocytes [11], degree of CD10 + bile canaliculus, and MUM-1 positive cell number in the portal tract were evaluated and graded by two experienced pathologists (Table 1). Metabolome analysis Among the confirmed PBC patients, a subset of 11 with complete responses and 14 individuals with incomplete responses were selected for analysis. A 15 mg aliquot of each individual sample was precisely weighed and transferred to an Eppendorf tube. After the addition of 500 μL of extract solution (precooled at -40 ℃, acetonitrile-methanol-water, 2:2:1), the samples were vortexed for 30 s, homogenized at 35 Hz for 4 min, and sonicated for 5 min in ice-water bath. The homogenate and sonicate circle was repeated for three times, followed by incubation at -40 ℃ for 1 h and centrifugation at 12000 rpm (RCF=13800 (×g), R= 8.6 cm) and 4 ℃ for 15 min. The resulting supernatants of 100 μL were harvested and analyzed using an LC-MS system. A quality control sample was prepared by combining an equal amount of each sample. Statistical analysis SPSS 26.0 (SPSS Inc., Chicago, IL, USA) was used for the statistical analysis. Data normality was assessed employing the Shapiro-Wilk test. Normally distributed continuous data are represented as mean±standard deviation (x±SD), while the t-test was used for comparisons. Non-normally distributed variables are as median [M (P25~P75)], and comparisons were made using the Mann-Whitney U test. Categorical data were compared utilizing the χ² test. Further, to assess predictive performance, Receiver Operating Characteristic (ROC) curve was analyzed and the Area Under the Curve (AUC) was calculated. Additionally, forest plots to visualize risk values and correlation bubble plots were generated, and graphs and charts were created employing GraphPad Prism 8.4.0 and R 4.4.1. In all analyses, a p-value < 0.05 was considered statistically significant. Results Patients’ features First, liver biopsies were conducted on 140 patients with PBC. After excluding 8 individuals due to incomplete data, 132 patients with PBC were included in the study (Figure 1). The cohort included 115 women and 17 men with an average age of 50.37 ± 10.56 (29-77) years. Of the 132 patients, 98 (including 13 men and 85 women) were defined as having early-stage PBC, with ages ranging from 28 to 72 years (average, 49.14 ± 10.35) years. The advanced-stage PBC group comprised 34 cases, including 4 men and 30 women aged 31-77 (average, 53.91 ± 10.50) years. Patients received 1 year of UDCA standard therapy of 13~15 mg/kg/day. Subsequently, according to the Paris I and Paris II criteria and the examination results after 1 year, the patients were divided into two groups: the incomplete response to UDCA (n = 52) and the complete response to UDCA (n = 80). Certain baseline clinical characteristics are different in complete response to UDCA compared with incomplete response to UDCA groups The patients were classified as having a complete response to UDCA or incomplete response to the UDCA group according to Paris I and Paris II criteria. Incomplete response to UDCA group exhibited significantly elevated serum AST ( p <0.001), ALP ( p <0.001), GGT ( p <0.001), TBiL ( p <0.001), DBiL ( p <0.001), TBA ( p <0.001), TC ( p <0.001), TG ( p =0.044) and Gp210 ( p =0.006) levels compared to complete response to UDCA group. However, TP ( p =0.002), ALB ( p <0.001), RBC ( p <0.001), total lymphocytes ( p <0.001), T-lymphocytes ( p <0.001), CD4 Lymphocytes ( p =0.006), CD8 Lymphocytes ( p =0.001), and HGB ( p ＜0.001) levels were significantly decreased relative to the complete response to UDCA group (Table 2). Certain Liver pathological characteristics exhibit variations between complete response to UDCA and incomplete response to UDCA groups In the liver puncture tissue analysis, the incomplete response to UDCA group displayed remarkably increased levels of the Ishak grading of inflammation ( p =0.009), Ishak staging of fibrosis ( p <0.001), CK7 + HB cells ( p <0.001), and Copper deposition degree ( p <0.001) within one periportal area (zone 1) compared to the complete response to UDCA group (Figure 2). However, the CD10 + bile canaliculus ( p =0.005) was significantly decreased in incomplete response to the UDCA group (Table 3). Univariate analysis of clinicopathological indicators associated with UDCA responds incompletely . We further analyzed the clinicopathological risk factors associated with incomplete response to UDCA. The findings revealed that AST ( p ＜0.001), ALP ( p ＜0.001), GGT ( p ＜0.001), TBiL ( p ＜0.001), DBiL ( p ＜0.001), TBA ( p ＜0.001), TC ( p =0.001), TG ( p =0.022), TP ( p =0.003), ALB ( p ＜0.001), RBC ( p ＜0.001), HGB ( p =0.001), total lymphocytes ( p =0.018), T-lymphocytes ( p =0.029), GP210 ( p =0.015), Ishak grading of inflammation ( p =0.004), Ishak staging of fibrosis ( p =0.001), copper deposition ( p ＜0.001), CK7 ( p ＜0.001), and CD10 ( p =0.007) were found to be influential factors in determining an incomplete response to UDCA (Figure 3 and Table 4). Comparing diagnostic values of the serological indicators and pathological indicators with ROC curves ROC curves were plotted, and AUC were calculated to evaluate the effectiveness of serological and pathological indicators in predicting incomplete response to UDCA. Among serological indicators (Figure 4a and Table 5), the AUC of ALP and TBiL demonstrated the highest, at 0.799 (95%CI: 0.725-0.873) and 0.799 (95%CI: 0.718-0.881) respectively, followed by those of GGT, TBA, TC, and GP210. Further, GGT had a value of 0.788 (95%CI: 0.710-0.867), and TBA had a value of 0.758 (95%CI: 0.669-0.847), lower than that of ALP. AUC for TC and GP210 were decreased with values of 0.700 (95%CI: 0.606-0.795) and 0.623 (95%CI: 0.524-0.721) respectively. Regarding pathological indicators (Figure 4b and Table 5), CK7 exhibited the highest AUC of 0.775 (95%CI: 0.695-0.855), followed by copper deposition, Ishak staging of fibrosis, absence of CD10 + bile canaliculus, and Ishak grading of inflammation. The AUC values for copper deposition, the Ishak staging of fibrosis, the absence of CD10 + bile canaliculus, and the Ishak grading of inflammation were relatively lower, at 0.699 (95%CI: 0.606-0.791), 0.663 (95%CI: 0.566-0.760), 0.635 (95%CI: 0.539-0.731) and 0.633 (95%CI: 0.530-0.737). Bubble plot of correlation between serological indicators and pathological indicators. To investigate the effect of hepatobiliary cells on incomplete response to UDCA, this study analyzed the associations between CK7 + HB cells and risk factors for incomplete response to UDCA. From the correlation analysis of the bubble plot, we found that CK7 + HB cells were significantly associated with clinical indicators, including ALP, GGT, TBiL, DBiL, TBA, and TC, and pathological indicators, such as Ishak grading of inflammation, Ishak staging of fibrosis, and Copper deposition (Figure 5). Based on the bubble plot results, we further conducted a correlation analysis on the clinical and pathological indicators that are significantly associated with CK7 + HB cells. The results showed that serum TBA exhibited a significant correlation with CK7 + HB cells on the clinical indicators ( r =0.587, p ＜0.01), while copper deposition levels in hepatocytes demonstrated the highest correlation with CK7 + HB cells on the pathological indicators ( r =0.512, p ＜0.01) (Figure 6). These results indicate that CK7 + HB cells are closely related to an incomplete response to UDCA and potentially play a pivotal role in this response. CK7 + HB cells are likely involved in the incomplete response to UDCA by affecting bile acid metabolism. CK7 + hepatocytes and bile acid metabolism To investigate the relationship of CK7 + HB cells with bile acid metabolism and analyze how CK7 + HB cells participate in the process of poor UDCA response by affecting bile acid metabolism, liver biopsy tissues from 25 patients with PBC were selected for the detection of bile acid metabolites (including 11 complete response to UDCA and 14 incomplete response to UDCA). A total of 13 different bile acids were detected in all samples by LC-MS. The results indicate that Glycoursodeoxycholic acid (GUDCA) and TBA in the incomplete response to the UDCA group remarkably increased relative to the complete response (Figure 7a and Table 6). CK7 + HB cells showed a positive relationship with GUDCA ( r =0.544, p ＜0.01) and total bile acids ( r =0.480, p ＜0.05) in tissues (Figure 7b). Discussion UDCA is used as the current standard of treatment in PBC, and those who have a positive UDCA response, generally have a favorable prognosis, making it imperative to identify the causes for incomplete UDCA response [12]. The present work discussed the clinicopathological characteristics of incomplete response to UDCA and analyzed the clinical and pathological risk factors associated with it. Both ALP and GGT are the early biomarkers of cholestasis, whereas the elevated level of TBiL indicates advanced disease, and ALB levels are associated with cirrhosis. Further, ALP and TBiL levels predict prognosis (liver transplantation or death) in PBC patients and thus can be used to determine the alternative endpoint for clinical trials [13]. Some studies have reported that the patients with incomplete response to UDCA, have increased levels of ALP, GGT, TBiL, and TBA relative to the response group, whereas the ALB level in such patients is lower than the response group [14]. Our findings based on the biochemical markers analysis in patients with incomplete response to UDCA are consistent with those reported studies. And those whose biochemical indexes were obviously abnormal did not respond incompletely to UDCA. PBC cases with anti-GP210 expression exhibit a reduced response rate to UDCA compared to the cases without expression of anti-GP210. Haldar et al. found that among 499 PBC cases in the U.K., patients who expressed anti-GP210 demonstrated an inadequate response to UDCA treatment compared to those without anti-GP210 expression (39.3% vs. 16.7%). Meanwhile, anti-GP210 antibody can be used as an evaluation index of UDCA treatment response, and its sensitivity and specificity in predicting the non-response of PBC patients to UDCA were found to be 26.8% and 89.8%, respectively [15]. According to one retrospective cohort study involving 180 PBC Chinese patients receiving UDCA treatment, the importance of anti-GP210 in prognosis demonstrated the independent correlation of anti-GP210 positivity with increased liver-associated transplantation and mortality risks [16]. To sum up, PBC patients with anti-GP210 positivity show decreased UDCA response rates along with dismal prognostic outcomes. Our study also found that the anti-GP210 positive rate in the respond incompletely group is elevated, whereas ANA and AMA-M2 positive rates did not show any significant difference when compared with the response group, which is in agreement with earlier reported studies. Ludwig J et al. proposed a histological staging system for PBC, which is analogous to the chronic hepatitis system, by utilizing histological findings such as portal and periportal fibrosis and inflammation [17]. In one such study, liver fibrosis is analyzed among PBC patients with the Ishak staging system (a recognized method to assess liver histology in chronic viral hepatitis) [18]. Based on these two staging systems, we analyzed the risk factors associated with incomplete response to UDCA in liver biopsy specimens. We observed that in the Ishak inflammation score and fibrosis score, the number of both CK7 + HB cells and copper particles remarkably increased relative to the UDCA response group, while the CD10 + bile canaliculus number in zone 1 was found to be lower than that in the UDCA response group. Further, histological features like hepatic fibrosis, interface hepatitis, central cholestasis, and ductopenia are recognized to be important factors in predicting the dismal prognostic outcomes in PBC [19]. UDCA therapy improves histological conditions like ductular proliferation, portal inflammation, and cholestasis [20]. Assessment of twenty biopsy samples using the UDCA response scoring system revealed significant correlations between incomplete UDCA response and the presence of CK7 + intermediate hepatocyte and fibrosis [21]. Several studies have established that late histological features, such as interfacial hepatitis and bile duct deletion, have a strong correlation with an incomplete response to UDCA and are linked to prognosis [22]. Further, a cohort study has reported that patients with stage III and IV PBC experienced significantly higher liver-related mortality compared to those with stage I and II [23]. Moreover, a study published by Japanese scholars reported that patients with Scheuer stage >3 and Nakanuma fibrosis score (evaluation of bridging fibrosis in the confluent area) >2 scores might have incomplete response to UDCA [24]. Our results strongly corroborate the earlier findings. In this study, it was found that CK7 is not only expressed in the reactive hyperplasia of the fine bile duct but also in some liver cells of PBC patients. This abnormal expression of CK7 in the hepatocytes has been observed in a variety of cholestatic diseases as early as 1989, demonstrating that hepatocytes can express cholestatic cytokeratin and the expression of CK7 is more sensitive than CK19 during cholestasis, which supports the concept of hepatocyte to cholestatic cell transformation [25]. Hepatocyte-to-biliary reprogramming is characterized by the gradual acquisition of biliary features by hepatocytes while diminishing hepatocyte properties and functional abilities, resulting in the formation of HB cells [26]. Several histological studies have identified that HB cells express biliary and hepatocyte markers under conditions such as cirrhosis, cholestatic hepatopathy, and ALF [27-29]. The present study evaluated the presence and the effect of HB cells in a group of incomplete Ursodeoxycholic acid responders. We analyzed the correlation between CK7 + HB cell number and all clinical and pathological indicators and found that CK7 + HB cell number showed a remarkably positive relationship with risk factors for incomplete response to UDCA. Further, our research showed that HB cells were increased in patients with an inadequate UDCA response. Although liver fibrosis and cirrhosis may occur in patients with advanced PBC, the typical features of its clinical manifestations, pathological changes, and biochemical indices are intrahepatic cholestasis [30]. Therefore, we expect to further understand the mechanism of PBC pathogenesis from the effects of CK7+ HB cells on bile formation, secretion, and drainage obstruction. Previous studies have shown that oral UDCA enters the liver through the portal system after absorption in the ileum and then combines with glycine and taurine to form soluble GUDCA and taurodeoxycholic acid. Concurrently, it can reduce the high proportion of hydrophobic goosedeoxycholic acid in the bile acid pool, promote the excretion of endogenous bile acid, and thus inhibit its absorption in order to change the ratio of hydrophilic/hydrophobic bile acid in the bile acid pool, and reducing the toxicity of hydrophobic bile acid to hepatocytes. However, the patients with incomplete response to UDCA do not benefit from this process [31]. In the present study, the analysis of the metabolites of bile acids in tissues also revealed that GUDCA and TBA increase considerably in the respond incompletely group. Therefore, we speculate that in the respond incompletely group, the products of UDCA combined with glycine are not adequately excreted, and the TBA level also increases prominently in the respond incompletely group. Successively, CK7 + HB cell count shows a strong positive correlation with GUDCA and TBA levels. Therefore, we hypothesize that due to poor response to UDCA, GUDCA, and TBA are likely to deposit in HB cells, resulting in an apparent increase in the HB cell count. Overall, our study reveals the characteristics of HB cells and the possible relationship between HB cells and incomplete response to UDCA. However, the molecular mechanism depicting the functional role of HB cells in patients with incomplete response to UDCA needs to be investigated in the near future. Abbreviations AASLD, American Association for the Study of Liver Diseases ALB, albumin ALP, alkaline phosphatase AMA, anti-mitochondrial antibody AST, aspartate aminotransferase CK7, cytokeratin 7 DBiL, unconjugated bilirubin GGT, glutamine transpeptidase GLO, globulin GUDCA, glycoursodeoxycholic HB, hepatobiliary HGB, hemoglobin H&E, hematoxylin and eosin LC-MS, liquid chromatography-mass spectrometry PBC, primary biliary cholangitis PLT, platelet TBA, total bile acid TBiL, total bilirubin TC, total cholesterol TG, triglyceride TP, total Protein UDCA, ursodeoxycholic acid ULN, upper limit of normal Declarations Acknowledgements None. Author contributions statement Kun Yang participated in acquisition of data, analysis and interpretation of data and drafting of the manuscript. Bingqing Yang participated in acquisition of data, analysis and interpretation of data. Xiaoyi Han and Jiamin Chen conducted the drafting of the article or critical revision for important intellectual content. Lei Sun conceived of agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the article are appropriately investigated and resolved. All authors read and approved the final manuscript. Funding This work was supported by Capital‘s Funds for Health Improvement and Research (2024-2-2177) and Beijing Municipal Administration of Hospitals Incubating Program (PX2022072). Data Availability Statement The data that support the findings of this study are available from the corresponding author upon reasonable request. Ethical approval and consent to participate All procedures performed in studies involving patients were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study protocol was approved by the Ethics Committee of Beijing Ditan Hospital, capital medical University (NO. DTEC-KY2024-023-01). Informed consent was obtained from patients in the study. A written informed consent from participants were obtained by physicians. Competing interests The authors declare no competing interests. Conflict of interest The authors declare that they have no conflict of interest. References Tanaka A, Ma X, Takahashi A, Vierling JM. Primary biliary cholangitis. Lancet. 2024 Sep 14;404(10457):1053-1066. Yang C, Guo G, Li B, Zheng L, Sun R, Wang X, et al. Prediction and evaluation of high-risk patients with primary biliary cholangitis receiving ursodeoxycholic acid therapy: an early criterion. Hepatol Int. 2023 Feb;17(1):237-248. Sancho-Bru P, Altamirano J, Rodrigo-Torres D, Coll M, Millán C, José Lozano J, et al. Liver progenitor cell markers correlate with liver damage and predict short-term mortality in patients with alcoholic hepatitis. 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Aguilar-Bravo B, Ariño S, Blaya D, Pose E, Martinez García de la Torre RA, Latasa MU, et al. Hepatocyte dedifferentiation profiling in alcohol-related liver disease identifies CXCR4 as a driver of cell reprogramming. J Hepatol. 2023 Sep;79(3):728-740. Jung K, Kim M, So J, Lee SH, Ko S, Shin D. Farnesoid X Receptor Activation Impairs Liver Progenitor Cell-Mediated Liver Regeneration via the PTEN-PI3K-AKT-mTOR Axis in Zebrafish. Hepatology. 2021 Jul;74(1):397-410. Wang S, Link F, Munker S, Wang W, Feng R, Liebe R, et al. Retinoic acid generates a beneficial microenvironment for liver progenitor cell activation in acute liver failure. Hepatol Commun. 2024 Jul 18;8(8):e0483. Li T, Hasan MN, Gu L. Bile acids regulation of cellular stress responses in liver physiology and diseases. eGastroenterology. 2024 Apr;2(2):e100074. Hu H, Shao W, Liu Q, Liu N, Wang Q, Xu J, et al. Gut microbiota promotes cholesterol gallstone formation by modulating bile acid composition and biliary cholesterol secretion. Nat Commun. 2022 Jan 11;13(1):252. Murillo Perez CF, Goet JC, Lammers WJ, Gulamhusein A, van Buuren HR, Ponsioen CY, et al. GLOBAL PBC Study Group. Milder disease stage in patients with primary biliary cholangitis over a 44-year period: A changing natural history. Hepatology. 2018 May;67(5):1920-1930. Tables Table 1 Grading of histological Characteristics of PBC Project 0 1+ 2+ 3+ CK7 + HB cells in periportal areas No CK7+ HB cells CK7+ HB cells in at least ten hepatocytes in one periportal area (zone 1) CK7+ HB cells in at least ten hepatocytes in 1/3–2/3 of periportal areas CK7+ HB cells in at least ten hepatocytes in more than 2/3 of periportal areas CD10 + bile canaliculus loss in periportal areas No CD10 + bile canaliculus loss CD10 + bile canaliculus loss in 2/3 of periportal areas Copper deposition in periportal areas No deposition of granules Deposition of granules in several periportal hepatocytes in 2/3 of periportal areas Table 2. Baseline Clinical Characteristics in 132 patients with PBC Variables Total (n=132) UDCA respond completely (n=80) UDCA respond incompletely (n=52) p Value Male(n,%) 17 (12.88) 10 (12.50) 7 (13.46) 0.872 Age(years) 50.37±10.56 50.44±11.28 50.27±9.43 0.929 ALT (U/ L) 44.65 (27.55,76.93) 41.70 (26.83,74.20) 48.90 (31.93,93.00) 0.215 AST (U/ L) 50.60 (34.90,74.95) 39.95 (31.60,61.53) 64.00 (45.50,102.68) ＜0.001** ALP (U/ L) 188.15 (116.13,198.28) 142.10 (94.53,205.25) 265.60 (189.45,364.33) ＜0.001** GGT (U/ L) 198.50 (83.48,365.80) 127.30 (63.43,221.85) 309.00 (204.10,566.83) ＜0.001** TBiL (μmol/ L) 16.45 (12.43,27.45) 14.05 (11.50,18.50) 27.65 (16.20,61.78) ＜0.001** DBiL (μmol/ L) 6.60 (4.50,15.88) 5.10 (3.90,7.48) 15.90 (8.10,51.23) ＜0.001** TBA (μmol/ L) 21.80 (7.93,55.33) 14.10 (6.30,27.53) 56.40 (13.95,55.33) ＜0.001** TC (mmol/ L) 5.12 (4.51,6.09) 4.90 (4.38,5.53) 5.84 (4.84,7.08) ＜0.001** TG (mmol/ L) 1.28 (1.06,1.78) 1.28 (0.96,1.70) 1.43 (1.10,2.37) 0.044* TP (g/ L) 74.18±6.44 75.54±6.18 72.08±6.30 0.002** ALB (g/ L) 40.01±4.50 41.35±4.01 37.96±4.46 ＜0.001** GLO (g/ L) 34.23±5.44 34.26±5.27 34.18±5.74 0.939 WBC ( ×10 12 L -1 ) 4.94±1.71 4.96±1.54 4.90±1.96 0.832 RBC ( ×10 12 L -1 ) 4.06±0.54 4.22±0.50 3.80±0.50 ＜0.001** HGB (g/ L) 123.95 (113.00,133.00) 126.00 (120.00,134.00) 117.00 (106.35,128.75) ＜0.001** PLT ( ×10 12 -1 ) 201.25 (137.50,253.00) 205.25 (147.00,256.75) 157.35 (125.50,241.75) 0.151 Total lymphocytes (cells/ul) 1653.50 (1373.50,1737.75) 1671.00 (1543.25,1762.25) 1373.50 (1234.50,1572.75) ＜0.001** T-lymphocytes (cells/ul) 1175.00 (997.50,1219.75) 1175.00 (1096.75,1242.75) 997.50 (919.25,1183.50) ＜0.001** CD4 Lymphocytes (cells/ul) 739.00 (625.50,793.25) 739.00 (637.50,830.00) 672.50 (570.50,734.50) 0.006** CD8 Lymphocytes (cells/ul) 380.00 (302.25,411.00) 380.00 (349.00,427.75) 314.00 (288.75,363.00) 0.001** AMA [M(P25～P75)] 1.00 (0.00, 2.00) 1.00 (0.00, 2.00) 1.00 (0.00, 2.00) 0.819 AMA-M2 [M(P25～P75)] 2.00 (0.00, 3.00) 2.00 (0.00, 3.00) 2.00 (0.00, 3.00) 0.733 GP210 [M(P25～P75)] 0.00 (0.00, 3.00) 0.00 (0.00, 3.00) 0.00 (1.00, 3.00) 0.006** RO-52 [M(P25～P75)] 0.00 (0.00, 2.00) 0.00 (0.00, 2.75) 0.00 (0.00, 2.00) 0.800 ANA [M(P25～P75)] 1.00 (0.00, 2.00) 1.00 (0.00, 2.00) 1.00 (0.25, 2.00) 0.565 BPO [M(P25～P75)] 3.00 (1.00, 3.00) 3.00 (1.00, 3.00) 3.00 (0.00, 3.00) 0.742 IgG (g/ L) 16.03 (13.00,18.00) 16.05 (13.40,18.45) 15.60 (12.88,17.55) 0.293 IgM (g/ L) 3.20 (2.16,4.27) 3.20 (2.07,4.75) 3.03 (2.31,3.76) 0.315 Data is presented as mean (SD) or median (P25–P75). * p < 0.05, ** p ＜0.01. Abbreviation: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; GGT, glutamine transpeptidase; TBiL, total bilirubin; DBiL, unconjugated bilirubin; TBA, total bile acid; TC,total cholesterol; TG, triglyceride; TP, total Protein; ALB, albumin; GLO, globulin; HGB, hemoglobin; globulin; PLT, platelet; AMA: anti-mitochondrial antibody. Table 3. Analysis of liver pathological characteristics in 132 patients with PBC Variables total UDCA respond completely UDCA respond incompletely p Value Ishak grading of inflammation [M(P25～P75)] 6.00 (5.00, 9.00) 6.00 (5.00, 7.00) 7.00 (5.00, 11.00) 0.009** Ishak staging of fiber[M(P25～P75)] 1.00 (1.00,2.00) 1.00 (1.00, 2.00) 2.00 (1.00, 3.00) ＜0.001** Proportion of portal with bile duct loss [M(P25～P75)] 0.82 (0.67, 0.92) 0.80 (0.67, 0.91) 0.84 (0.71, 0.93) 0.312 Degree of bile duct rearranged [M(P25～P75)] 1.00 (0.50, 1.00) 1.00 (0.50, 1.00) 1.00 (0.50, 1.00) 0.098 Copper deposition [M(P25～P75)] 0.50 (0.00, 1.00) 0.00 (0.00, 1.00) 1.00 (0.13, 1.88) <0.001** CK7+ HB cells [M(P25～P75)] 1.00 (0.00, 2.00) 0.50 (0.00, 1.00) 2.00 (1.00, 2.00) <0.001** MUM1 [M(P25～P75)] 1.00 (1.00, 1.00) 1.00 (1.00, 1.00) 1.00 (1.00, 1.00) 0.448 CD38 [M(P25～P75)] 1.00 (0.50, 1.00) 1.00 (0.50, 1.00) 1.00 (1.00, 1.00) 0.849 absence of CD10+ bile canaliculus [M(P25～P75)] 0.50 (0.00, 0.50) 0.50 (0.13, 1.00) 0.50 (0.00, 0.50) 0.005** Lymphocyte infiltration in the portal tract [M(P25～P75)] 2.00 (1.00, 2.00) 2.00 (1.00, 2.00) 2.00 (1.00, 2.00) 0.674 Eosinophils infiltration in portal tract [M(P25～P75)] 1.00 (0.00, 1.00) 1.00 (0.00, 1.00) 1.00 (0.00, 1.00) 0.489 Plasma cell infiltration in the portal tract [M(P25～P75)] 0.00 (0.00, 0.38) 0.00 (0.00, 0.00) 0.00 (0.00, 1.00) 0.185 Data is presented as median (P25–P75). * p < 0.05, ** p ＜0.01. Abbreviation: CK7, cytokeratin 7; HB: hepatobiliary. Table 4. Univariate analysis of indicators associated with UDCA responds incompletely Variables Univariate analysis OR (95% CI) p Value sex 1.089 (0.386-3.068) 0.872 age＜45 0.892 (0.416-1.914) 0.769 AST(U/ L) 1.025 (1.012-1.037) ＜0.001** ALP(U/ L) 1.007 (1.004-1.011) ＜0.001** GGT(U/ L) 1.005 (1.003-1.007) ＜0.001** TBiL(μmol/ L) 1.108 (1.059-1.161) ＜0.001** DBiL(μmol/ L) 1.165 (1.085-1.250) ＜0.001** TBA(μmol/ L) 1.029 (1.016-1.042) ＜0.001** TC(mmol/ L) 1703 (1.256-2.311) 0.001** TG(mmol/ L) 1.741 (1.084-2.796) 0.022* TP(g/ L) 0.913 (0.859-0.970) 0.003** ALB(g/ L) 0.820 (0.743-0.905) ＜0.001** RBC( ×10 12 L -1 ) 0.178 (0.079-0.404) ＜0.001** HGB(g/ L) 0.958 (0.933-0.983) 0.001** Total lymphocytes (cells/ul) 0.999 (0.998-1.000) 0.018* T-lymphocytes (cells/ul) 0.999 (0.998-1.000) 0.029* CD4-Lymphocytes (cells/ul) 0.998 (0.997-1.000) 0.072 CD8-Lymphocytes (cells/ul) 0.998 (0.995-1.000) 0.064 GP210 1.313 (1.062-1.750) 0.015* Ishak grading of inflammation 1.220 (1.065-1.399) 0.004** Ishak staging of fiber 1.898 (1.306-2.759) 0.001** Copper deposition 2.652 (1.580-4.451) ＜0.001** CK7+ HB cells 3.954 (2.325-6.723) ＜0.001** absence of CD10+ bile canaliculus 0.345 (0.159-0.749) 0.007** Results were obtained with logistic regression models and given as OR with 95% CI for UDCA responds incompletely. * p < 0.05, ** p ＜0.01. AST, aspartate aminotransferase; ALP, alkaline phosphatase; GGT, glutamine transpeptidase; TBiL, total bilirubin; DBiL, unconjugated bilirubin; TBA, total bile acid; TC, total cholesterol; TG, triglyceride; TP, total Protein; ALB, albumin; GLO, globulin; HGB, hemoglobin; globulin; PLT, platelet; CK7, cytokeratin 7; HB: hepatobiliary. Table 5. Comparison of the efficacy of clinical indicators in predicting the risk of UDCA responds incompletely Variables AUC 95% CI p Value AST(U/ L) 0.564 0.461-0.666 0.215 ALP(U/ L) 0.799 0.725-0.873 ＜0.001** GGT(U/ L) 0.788 0.710-0.867 ＜0.001** TBiL(μmol/ L) 0.799 0.718-0.881 ＜0.001** TBA(μmol/ L) 0.758 0.669-0.847 ＜0.001** TC(mmol/ L) 0.700 0.606-0.795 ＜0.001** GP210 0.623 0.524-0.721 0.017* Ishak grading of inflammation 0.633 0.530-0.737 0.010* Ishak staging of fiber 0.663 0.566-0.760 0.002** Copper deposition 0.699 0.606-0.791 ＜0.001** CK7+ HB cells 0.775 0.695-0.855 ＜0.001** absence of CD10+ bile canaliculus 0.635 0.539-0.731 0.009** Results were obtained with ROC Curve and AUC with 95% CI for UDCA responds incompletely. * p < 0.05, ** p ＜0.01. AST, aspartate aminotransferase; ALP, alkaline phosphatase; GGT, glutamine transpeptidase; TBiL, total bilirubin; TBA, total bile acid; TC, total cholesterol; CK7, cytokeratin 7; HB: hepatobiliary. Table 6. Analysis of different types of bile acids in liver tissue in 25 patients with PBC Variables Total (n=25) UDCA respond completely (n=11) UDCA respond incompletely (n=14) p Value Dehydrolithocholic acid (nmol/l) 0.00 (0.00, 0.00) 0.00 (0.00, 0.00) 0.00 (0.00, 0.00) 0.698 Deoxycholic acid (nmol/l) 115.13 (106.76, 125.17) 110.69 (101.67, 125.34) 116.25 (106.98, 125.86) 0.584 Glycolithocholic acid (nmol/l) 19.00(17.47, 21.62) 19.00 (17.50, 23.36) 19.05 (16.87, 20.56) 0.443 Glycoursodeoxycholic acid (nmol/l) 80.34 (41.41, 142.87) 43.09 (0.00, 110.27) 102.53 (70.32, 243.11) 0.010* Glycochenodeoxycholic acid (nmol/l) 0.00 (0.00, 31.38) 0.00 (0.00, 30.82) 0.00 (0.00, 32.70) 0.757 Lithocholic Acid-3-Sulfate (nmol/l) 0.00 (0.00, 0.00) 0.00 (0.00, 0.00) 0.00 (0.00, 0.00) 0.907 Glycocholic acid (nmol/l) 22.50 (0.00, 33.23) 21.67 (0.00, 23.75) 28.48 (0.00, 42.17) 0.133 Taurolithocholic acid (nmol/l) 0.00 (0.00, 10.89) 9.52 (0.00, 12.19) 0.00 (0.00, 10.29) 0.157 Taurochenodeoxycholic acid (nmol/l) 0.00 (0.00, 45.26) 38.82 (0.00, 45.39) 0.00 (0.00, 45.70) 0.768 Glycoursodeoxycholic Acid-3-Sulfate (nmol/l) 0.00 (0.00, 17.44) 0.00 (0.00, 14.38) 13.69 (0.00, 40.73) 0.117 Glycocholic Acid-3-Sulfate (nmol/l) 0.00 (0.00, 10.11) 0.00 (0.00, 0.00) 0.00 (0.00, 22.55) 0.609 Taurodeoxycholic Acid-3-Sulfate (nmol/l) 0.00 (0.00, 0.00) 0.00 (0.00, 0.00) 0.00 (0.00, 0.00) 0.375 Taurocholic Acid-3-Sulfate (nmol/l) 0.00 (0.00, 0.00) 0.00 (0.00, 0.00) 0.00 (0.00, 0.00) 0.259 Total tissue TBA (nmol/l) 303.03(222.23, 423.61) 237.83 (204.07, 315.14) 394.32 (239.41, 506.47) 0.037* Data is presented as median (P25–P75). * p < 0.05. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 12 Feb, 2026 Read the published version in BMC Gastroenterology → Version 1 posted Editorial decision: Revision requested 02 Nov, 2025 Reviews received at journal 01 Nov, 2025 Reviews received at journal 30 Oct, 2025 Reviews received at journal 30 Oct, 2025 Reviewers agreed at journal 24 Oct, 2025 Reviewers agreed at journal 23 Oct, 2025 Reviewers agreed at journal 22 Oct, 2025 Reviewers agreed at journal 22 Oct, 2025 Reviewers invited by journal 25 Jun, 2025 Editor invited by journal 30 May, 2025 Editor assigned by journal 28 May, 2025 Submission checks completed at journal 28 May, 2025 First submitted to journal 27 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Patients were divided into two subgroups: UDCA complete response group (n= 80) and UDCA incomplete responsegroup (n=52).\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-6763526/v1/d50988b28903c26a0ee11216.png"},{"id":85741915,"identity":"29b1d932-f577-4a6d-a31c-1fdcdd0b186f","added_by":"auto","created_at":"2025-07-01 09:01:27","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1122374,"visible":true,"origin":"","legend":"\u003cp\u003eHistological analysis of primary biliary cholangitis patients after ursodeoxycholic acid treatment including hematoxylin and eosin staining x100, Cytokeratin7 staining x100 and Copper staining x400. A. ursodeoxycholic acid incomplete response group; B. ursodeoxycholic acid complete response group. CK7, Cytokeratin7\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-6763526/v1/717928656aaa761a050d458f.png"},{"id":85743381,"identity":"54bacbcc-4be3-4337-88f5-2e7690c29896","added_by":"auto","created_at":"2025-07-01 09:09:27","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":135134,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of factors influencing UDCA incomplete response. AST, aspartate aminotransferase; ALP, alkaline phosphatase; GGT, glutamine transpeptidase; TBiL, total bilirubin; DBiL, unconjugated bilirubin; TBA, total bile acid; TC, total cholesterol; TG, triglyceride; TP, Total Protein; ALB, albumin; GLO, globulin; HGB, Hemoglobin; globulin; PLT, platelet; CK7, Cytokeratin 7.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-6763526/v1/da17ebf574617b091e1784c5.png"},{"id":85743384,"identity":"127a8e71-f440-4206-bbad-3d270acb6d27","added_by":"auto","created_at":"2025-07-01 09:09:27","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":318540,"visible":true,"origin":"","legend":"\u003cp\u003eA. The receiver operating characteristic curves of the hematological factors and auto-antibody levels;. B. The receiver operating characteristic curves of the pathological indicators. ALP, alkaline phosphatase; GGT, glutamine transpeptidase; TBiL, total bilirubin; TBA, total bile acid; CK7, Cytokeratin 7.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-6763526/v1/254caf35efcef30af257a278.png"},{"id":85743386,"identity":"075b256c-6010-4921-ac1f-c9e6c7b38cef","added_by":"auto","created_at":"2025-07-01 09:09:27","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":447354,"visible":true,"origin":"","legend":"\u003cp\u003eBubble plot of association analysis of risk factors for incomplete ursodeoxycholic acid response. ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; GGT, glutamine transpeptidase; TBiL, total bilirubin; DBiL, unconjugated bilirubin; TBA, total bile acid; TC,total cholesterol; TG, triglyceride; TP, total Protein; ALB, albumin; GLO, globulin; HGB, hemoglobin; globulin; PLT, platelet; AMA: anti-mitochondrial antibody. CK7, Cytokeratin 7\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-6763526/v1/9dd1b3e112d7898d0b8e4efb.png"},{"id":85741924,"identity":"b46549ac-69ec-466c-aed7-1fa6ad6c7cef","added_by":"auto","created_at":"2025-07-01 09:01:27","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":350075,"visible":true,"origin":"","legend":"\u003cp\u003eA. Correlation analysis of Cytokeratin7 with some clinical indicators. B. Correlation analysis of Cytokeratin7 with some pathological indicators including Ishak grading of inflammation, Ishak staging of fiber and Copper deposition. ALP, alkaline phosphatase; GGT, glutamine transpeptidase; TBiL, total bilirubin; DBiL, unconjugated bilirubin; TBA, total bile acid; TC,total cholesterol; CK7, Cytokeratin 7.\u003c/p\u003e","description":"","filename":"Figure6.png","url":"https://assets-eu.researchsquare.com/files/rs-6763526/v1/0c2d2f2ac3fd36d6f3ec4822.png"},{"id":85741926,"identity":"66811719-f655-45dd-82b5-11923cb80f60","added_by":"auto","created_at":"2025-07-01 09:01:27","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":153667,"visible":true,"origin":"","legend":"\u003cp\u003eA. Tissues from 25 patients were selected for analysis of bile acid differences. B. Graph of correlation analysis between glycoursodeoxycholic acid, total bile acid and Cytokeratin 7.\u003c/p\u003e","description":"","filename":"Figure7.png","url":"https://assets-eu.researchsquare.com/files/rs-6763526/v1/df93f1d81831cdbf4c689dba.png"},{"id":102785276,"identity":"4f99aac9-b943-43c8-bc56-1be9400d38de","added_by":"auto","created_at":"2026-02-16 16:04:02","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":6326779,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6763526/v1/1ac6f719-51c6-43ed-b7b5-40d4ecd89d39.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinicopathological Features of Hepatobiliary Cells in Primary Biliary Cholangitis Patients with Ursodeoxycholic acid respond incompletely","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePrimary biliary cholangitis (PBC) is an autoimmune hepatopathy characterized by non-suppurative destructive cholangitis, where inflammatory cells, mainly plasma cells, and lymphocytes, selectively target and damage intrahepatic small bile ducts (septal and interlobular), resulting to progressive cholestasis and potential liver cirrhosis [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Currently, Ursodeoxycholic acid (UDCA) is the only safe and effective first-line treatment, yet 40% of patients still show an incomplete response in clinical practice which often have a poor prognosis[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Hence, investigating the reason behind the inadequate response to UDCA is highly important.\u003c/p\u003e \u003cp\u003eHistological examinations have demonstrated that specific hepatocytes transform into Cytokeratin (CK)7\u003csup\u003e+\u003c/sup\u003e hepatobiliary (HB) cells, which exhibit characteristics of both biliary and hepatocyte markers. This cellular conversion happens in various conditions, such as acute liver failure, cirrhosis, and cholestatic liver diseases [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. CK7\u003csup\u003e+\u003c/sup\u003e HB cells indicate cholestasis, particularly in conditions associated with ductopenia, such as PBC [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePresently, the potential relationship between CK7\u003csup\u003e+\u003c/sup\u003e HB cells and incomplete response to UDCA remains unexplored. Also, the specific mechanisms involved in this association have yet to be elucidated. This study focuses on the correlation between CK7\u003csup\u003e+\u003c/sup\u003e HB cells and incomplete UDCA response and its possible mechanisms.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003e\u003cstrong\u003ePatients\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients were recruited participants from Beijing Ditan Hospital between January 2019 and July 2021, which is in accordance with the diagnostic standards outlined in the 2018 Practice Guidelines of the American Association for the Study of Liver Diseases (AASLD) [5]. The research excluded individuals with other autoimmune liver diseases, systemic autoimmune diseases, metabolism-related fatty liver diseases, viral hepatitis, long-term excessive alcohol intake, use of suspected liver injury drugs within the past six months, primary liver cancer, and other liver tumors.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDefinition and discrimination criteria of\u003c/strong\u003e \u003cstrong\u003eUDCA response incompletely in PBC patients\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients received UDCA standard therapy of 13~15 mg/kg/day for 1 year. According to the Paris I and Paris II criteria and the examination results after this period, participants were divided into the UDCA incomplete response (n = 52) and the UDCA complete response groups (n = 80). The Paris I standard is as follows: 1 year after UDCA application, the patient\u0026rsquo;s alkaline phosphoridase (ALP) \u0026lt; 3x upper limit of normal (ULN), aspartate aminotransferase (AST) \u0026lt;2x ULN, and total bilirubin (TBiL) \u0026lt; 1 mg/dL [6]. The Paris II standard specifies: 1 year of UDCA administration, the patient has a basic ALP \u0026lt; 1.5xULN, AST\u0026lt; 1.5x ULN, and TBiL \u0026lt; 1 mg/dL [7]. Paris I is used to evaluate advanced PBC (stages III-IV), while Paris II assesses biochemical responses in patients with early PBC (stages I-II).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical data collection\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinical and laboratory data were carefully extracted from electronic medical records from Beijing Ditan Hospital from the month preceding UDCA therapy. Laboratory examinations included various blood components and biochemical markers, including the red blood cell (RBC) count, white blood cell (WBC) count, platelet count (PLT), as well as hemoglobin (HGB) levels. Additionally, other parameters assessed were alanine aminotransferase (ALT), AST, gamma-glutamyl transferase (GGT), ALP, total bile acid (TBA), TBiL, direct bilirubin (DBiL), globulin (GLO), albumin (ALB), total protein (TP), total cholesterol (TC), and triglycerides (TG).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLiver biopsies and histopathological assessments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA 16G needle was used to perform percutaneous liver biopsies on the right liver lobe following the local standard procedure. The present study included liver samples with 10 or more complete portal tracts. Following routine histological analysis, liver samples were fixed with 10% formalin, embedded in paraffin, and stained with hematoxylin and eosin (H\u0026amp;E), Masson\u0026rsquo;s trichrome (Nanjing Jiancheng Bioengineering Institute), reticular fiber, and rhodanine as described previously [8]. All the participants provided the informed consent. The research protocol received approval from the Ethics Committee of Beijing Ditan Hospital, Capital Medical University (NO. DTEC-KY2024-023-01). Furthermore, the human subject procedures in the present work followed ethical standards, the 1964 Helsinki Declaration, and its subsequent amendments or relevant ethical guidelines.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eImmunohistochemical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFor immunohistochemical analysis, normal serum was first added to block liver sections and then stained using antibodies targeting cytokeratin 7 (CK7), CD10, and MUM-1, and left overnight at 4\u0026deg;C before incubation with horseradish peroxidase-labeled secondary antibody. Subsequently, protein bands were detected using diaminobenzidine, followed by counterstaining with hematoxylin. Images were captured using a Nikon Labophot 2 microscope.\u003c/p\u003e\n\u003cp\u003eThe tissue samples were categorized by using the Ludwig staging system. Thereafter, the Ishak score for liver tissue inflammation and fibrosis, bile duct loss degree in the portal tract, copper deposition level in hepatocytes [9], degree of bile duct rearrangement within the periportal area, degree of infiltration of lymphocytes, plasma cells, and eosinophils within the portal tract [10], CK7 immunostaining intensity in periportal hepatocytes [11], degree of CD10\u003csup\u003e+\u003c/sup\u003e bile canaliculus, and MUM-1 positive cell number in the portal tract were evaluated and graded by two experienced pathologists (Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMetabolome analysis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong the confirmed PBC patients, a subset of 11 with complete responses and 14 individuals with incomplete responses were selected for analysis. A 15 mg aliquot of each individual sample was precisely weighed and transferred to an Eppendorf tube. After the addition of 500 \u0026mu;L of extract solution (precooled at -40 ℃, acetonitrile-methanol-water, 2:2:1), the samples were vortexed for 30 s, homogenized at 35 Hz for 4 min, and sonicated for 5 min in ice-water bath. The homogenate and sonicate circle was repeated for three times, followed by incubation at -40 ℃ for 1 h and centrifugation at 12000 rpm (RCF=13800 (\u0026times;g), R= 8.6 cm) and 4 ℃ for 15 min. The resulting supernatants of 100 \u0026mu;L were harvested and analyzed using an LC-MS system. A quality control sample was prepared by combining an equal amount of each sample.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSPSS 26.0 (SPSS Inc., Chicago, IL, USA) was used for the statistical analysis. Data normality was assessed employing the Shapiro-Wilk test. Normally distributed continuous data are represented as mean\u0026plusmn;standard deviation (x\u0026plusmn;SD), while the t-test was used for comparisons. Non-normally distributed variables are as median [M (P25~P75)], and comparisons were made using the Mann-Whitney U test. Categorical data were compared utilizing the \u0026chi;\u0026sup2; test. Further, to assess predictive performance, Receiver Operating Characteristic (ROC) curve was analyzed and the Area Under the Curve (AUC) was calculated. Additionally, forest plots to visualize risk values and correlation bubble plots were generated, and graphs and charts were created employing GraphPad Prism 8.4.0 and R 4.4.1. In all analyses, a p-value \u0026lt; 0.05 was considered statistically significant.\u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003ePatients\u0026rsquo; features\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFirst, liver biopsies were conducted on 140 patients with PBC. After excluding 8 individuals due to incomplete data, 132 patients with PBC were included in the study (Figure 1). The cohort included 115 women and 17 men with an average age of 50.37 \u0026plusmn; 10.56 (29-77) years. Of the 132 patients, 98 (including 13 men and 85 women) were defined as having early-stage PBC, with ages ranging from 28 to 72 years (average, 49.14 \u0026plusmn; 10.35) years. The advanced-stage PBC group comprised 34 cases, including 4 men and 30 women aged 31-77 (average, 53.91 \u0026plusmn; 10.50) years. Patients received 1 year of UDCA standard therapy of 13~15 mg/kg/day. Subsequently, according to the Paris I and Paris II criteria and the examination results after 1 year, the patients were divided into two groups: the incomplete response to UDCA (n = 52) and the complete response to UDCA (n = 80).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCertain baseline clinical characteristics\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;are different in complete response to UDCA compared with incomplete response to UDCA groups\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patients were classified as having a complete response to UDCA or incomplete response to the UDCA group according to Paris I and Paris II criteria.\u003cem\u003e\u0026nbsp;\u003c/em\u003eIncomplete response to UDCA group exhibited significantly elevated serum AST (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001), ALP (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001), GGT (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001), TBiL (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001), DBiL (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001), TBA (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001), TC (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001), TG (\u003cem\u003ep\u003c/em\u003e=0.044) and Gp210 (\u003cem\u003ep\u003c/em\u003e=0.006) levels compared to complete response to UDCA group. However, TP (\u003cem\u003ep\u003c/em\u003e=0.002), ALB (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001), RBC (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001), total lymphocytes (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001), T-lymphocytes (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001), CD4 Lymphocytes (\u003cem\u003ep\u003c/em\u003e=0.006), CD8 Lymphocytes (\u003cem\u003ep\u003c/em\u003e=0.001), and HGB (\u003cem\u003ep\u003c/em\u003e＜0.001) levels were significantly decreased relative to the complete response to UDCA group (Table 2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCertain Liver pathological characteristics exhibit variations between complete response to\u003c/strong\u003e \u003cstrong\u003eUDCA\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eand incomplete response to UDCA groups\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn the liver puncture tissue analysis, the incomplete response to UDCA group displayed remarkably increased levels of the Ishak grading of inflammation (\u003cem\u003ep\u003c/em\u003e=0.009), Ishak staging of fibrosis (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001), CK7\u003csup\u003e+\u003c/sup\u003e HB cells (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001), and Copper deposition degree (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001)\u0026nbsp;within one periportal area (zone 1) compared to the complete response to UDCA group (Figure 2). However, the CD10\u003csup\u003e+\u003c/sup\u003e bile canaliculus (\u003cem\u003ep\u003c/em\u003e=0.005) was significantly decreased in incomplete response to the UDCA group (Table 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eUnivariate analysis of clinicopathological indicators associated with\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eUDCA responds incompletely\u003c/strong\u003e\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe further analyzed the clinicopathological risk factors associated with\u0026nbsp;incomplete response to UDCA. The findings revealed that AST\u0026nbsp;(\u003cem\u003ep\u003c/em\u003e＜0.001), ALP (\u003cem\u003ep\u003c/em\u003e＜0.001), GGT (\u003cem\u003ep\u003c/em\u003e＜0.001), TBiL (\u003cem\u003ep\u003c/em\u003e＜0.001), DBiL (\u003cem\u003ep\u003c/em\u003e＜0.001), TBA (\u003cem\u003ep\u003c/em\u003e＜0.001), TC (\u003cem\u003ep\u003c/em\u003e=0.001), TG (\u003cem\u003ep\u003c/em\u003e=0.022), TP (\u003cem\u003ep\u003c/em\u003e=0.003), ALB (\u003cem\u003ep\u003c/em\u003e＜0.001), RBC (\u003cem\u003ep\u003c/em\u003e＜0.001), HGB (\u003cem\u003ep\u003c/em\u003e=0.001), total lymphocytes (\u003cem\u003ep\u003c/em\u003e=0.018), T-lymphocytes (\u003cem\u003ep\u003c/em\u003e=0.029), GP210 (\u003cem\u003ep\u003c/em\u003e=0.015), Ishak grading of inflammation (\u003cem\u003ep\u003c/em\u003e=0.004), Ishak staging of fibrosis (\u003cem\u003ep\u003c/em\u003e=0.001), copper deposition (\u003cem\u003ep\u003c/em\u003e＜0.001), CK7 (\u003cem\u003ep\u003c/em\u003e＜0.001), and CD10 (\u003cem\u003ep\u003c/em\u003e=0.007) were found to be influential factors in determining an incomplete response to UDCA (Figure 3 and Table 4).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eComparing diagnostic values of the\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eserological indicators\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;and pathological indicators\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;with ROC curves\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eROC curves were plotted, and AUC were calculated to evaluate the effectiveness of serological and pathological indicators in predicting incomplete response to UDCA.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAmong serological indicators (Figure 4a and Table 5), the AUC of ALP and TBiL demonstrated the highest, at 0.799 (95%CI: 0.725-0.873) and 0.799 (95%CI: 0.718-0.881) respectively, followed by those of GGT, TBA, TC, and GP210. Further, GGT had a value of 0.788 (95%CI: 0.710-0.867), and TBA had a value of 0.758 (95%CI: 0.669-0.847), lower than that of ALP. AUC for TC and GP210 were decreased with values of 0.700 (95%CI: 0.606-0.795) and 0.623 (95%CI: 0.524-0.721) respectively.\u003c/p\u003e\n\u003cp\u003eRegarding pathological indicators (Figure 4b and Table 5), CK7 exhibited the highest AUC of 0.775 (95%CI: 0.695-0.855), followed by copper deposition, Ishak staging of fibrosis,\u0026nbsp;absence of CD10\u003csup\u003e+\u003c/sup\u003e bile canaliculus, and Ishak grading of inflammation. The AUC values for copper deposition, the Ishak staging of fibrosis, the absence of CD10\u003csup\u003e+\u003c/sup\u003e bile canaliculus, and the Ishak grading of inflammation were relatively lower, at 0.699 (95%CI: 0.606-0.791), 0.663 (95%CI: 0.566-0.760), 0.635 (95%CI: 0.539-0.731) and 0.633 (95%CI: 0.530-0.737).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBubble plot of correlation between serological indicators and pathological indicators.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo investigate the effect of hepatobiliary cells on incomplete response to UDCA, this study analyzed the associations between CK7\u003csup\u003e+\u0026nbsp;\u003c/sup\u003eHB cells and risk factors for incomplete response to UDCA. From the correlation analysis of the bubble plot, we found that CK7\u003csup\u003e+\u0026nbsp;\u003c/sup\u003eHB cells were significantly associated with clinical indicators, including ALP, GGT, TBiL, DBiL, TBA, and TC, and pathological indicators, such as Ishak grading of inflammation, Ishak staging of fibrosis, and Copper deposition\u0026nbsp;(Figure 5). Based on the bubble plot results, we further conducted a correlation analysis on the clinical and pathological indicators that are significantly associated with\u0026nbsp;CK7\u003csup\u003e+\u0026nbsp;\u003c/sup\u003eHB cells. The results showed that serum TBA exhibited a significant correlation with\u0026nbsp;CK7\u003csup\u003e+\u0026nbsp;\u003c/sup\u003eHB cells\u0026nbsp;on the clinical indicators\u0026nbsp;(\u003cem\u003er\u003c/em\u003e=0.587, \u003cem\u003ep\u003c/em\u003e＜0.01),\u0026nbsp;while copper deposition\u0026nbsp;levels in hepatocytes\u0026nbsp;demonstrated the highest correlation with\u0026nbsp;CK7\u003csup\u003e+\u0026nbsp;\u003c/sup\u003eHB cells\u0026nbsp;on the pathological indicators (\u003cem\u003er\u003c/em\u003e=0.512, \u003cem\u003ep\u003c/em\u003e＜0.01)\u0026nbsp;(Figure 6). These results indicate that CK7\u003csup\u003e+\u0026nbsp;\u003c/sup\u003eHB cells are closely related to an incomplete response to UDCA and potentially play a pivotal role in this response. CK7\u003csup\u003e+\u003c/sup\u003e HB cells are likely involved in the incomplete response to UDCA by affecting bile acid metabolism.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCK7\u003csup\u003e+\u003c/sup\u003e hepatocytes and bile acid metabolism\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo investigate the relationship of CK7\u003csup\u003e+\u0026nbsp;\u003c/sup\u003eHB cells with bile acid metabolism and analyze how CK7\u003csup\u003e+\u0026nbsp;\u003c/sup\u003eHB cells participate in the process of poor UDCA response by affecting bile acid metabolism, liver biopsy tissues from 25 patients with PBC were selected for the detection of bile acid metabolites (including 11 complete response to UDCA and 14 incomplete response to UDCA). A total of 13 different bile acids were detected in all samples by LC-MS. The results indicate that Glycoursodeoxycholic acid (GUDCA) and TBA in the incomplete response to the UDCA group remarkably increased relative to the complete response (Figure 7a and Table 6). CK7\u003csup\u003e+\u003c/sup\u003e HB cells showed a positive relationship with GUDCA (\u003cem\u003er\u003c/em\u003e=0.544,\u0026nbsp;\u003cem\u003ep\u003c/em\u003e＜0.01)\u0026nbsp;and total bile acids (\u003cem\u003er\u003c/em\u003e=0.480, \u003cem\u003ep\u003c/em\u003e＜0.05) in tissues (Figure 7b).\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eUDCA is used as the current standard of treatment in PBC, and those who have a positive UDCA response, generally have a favorable prognosis, making it imperative to identify the causes for incomplete UDCA response [12]. The present work discussed the clinicopathological characteristics of incomplete response to UDCA and analyzed the clinical and pathological risk factors associated with it.\u003c/p\u003e\n\u003cp\u003eBoth ALP and GGT are the early biomarkers of cholestasis, whereas the elevated level of TBiL indicates advanced disease, and ALB levels are associated with cirrhosis. Further, ALP and TBiL levels predict prognosis (liver transplantation or death) in PBC patients and thus can be used to determine the alternative endpoint for clinical trials [13]. Some studies have reported that the patients with incomplete response to UDCA, have increased levels of ALP, GGT, TBiL, and TBA relative to the response group, whereas the ALB level in such patients is lower than the response group [14]. Our findings based on the biochemical markers analysis in patients with incomplete response to UDCA are consistent with those reported studies. And\u0026nbsp;those whose biochemical indexes were obviously abnormal did not respond incompletely to UDCA.\u003c/p\u003e\n\u003cp\u003ePBC cases with anti-GP210 expression exhibit a reduced response rate to UDCA compared to the cases without expression of anti-GP210. Haldar et al. found that among 499 PBC cases in the U.K., patients who expressed anti-GP210 demonstrated an inadequate response to UDCA treatment compared to those without anti-GP210 expression (39.3% vs. 16.7%). Meanwhile, anti-GP210 antibody can be used as an evaluation index of UDCA treatment response, and its sensitivity and specificity in predicting the non-response of PBC patients to UDCA were found to be 26.8% and 89.8%, respectively [15]. According to one retrospective cohort study involving 180 PBC Chinese patients receiving UDCA treatment, the importance of anti-GP210 in prognosis demonstrated the independent correlation of anti-GP210 positivity with increased liver-associated transplantation and mortality risks [16]. To sum up, PBC patients with anti-GP210 positivity show decreased UDCA response rates along with dismal prognostic outcomes. Our study also found that the anti-GP210 positive rate in the respond incompletely group is elevated, whereas ANA and AMA-M2 positive rates did not show any significant difference when compared with the response group, which is in agreement with earlier reported studies.\u003c/p\u003e\n\u003cp\u003eLudwig J et al. proposed a histological staging system for PBC, which is analogous to the chronic hepatitis system, by utilizing histological findings such as portal and periportal fibrosis and inflammation [17]. In one such study, liver fibrosis is analyzed among PBC patients with the Ishak staging system (a recognized method to assess liver histology in chronic viral hepatitis) [18]. Based on these two staging systems, we analyzed the risk factors associated with incomplete response to UDCA in liver biopsy specimens. We observed that in the Ishak inflammation score and fibrosis score, the number of both CK7\u003csup\u003e+\u0026nbsp;\u003c/sup\u003eHB cells and copper particles remarkably increased relative to the UDCA response group, while the CD10\u003csup\u003e+\u0026nbsp;\u003c/sup\u003ebile canaliculus number in zone 1 was found to be lower than that in the UDCA response group. Further, histological features like hepatic fibrosis, interface hepatitis, central cholestasis, and ductopenia are recognized to be important factors in predicting the dismal prognostic outcomes in PBC [19]. UDCA therapy improves histological conditions like ductular proliferation, portal inflammation, and cholestasis [20]. Assessment of twenty biopsy samples using the UDCA response scoring system revealed significant correlations between incomplete UDCA response and the presence of CK7\u003csup\u003e+\u003c/sup\u003e intermediate hepatocyte and fibrosis [21]. Several studies have established that late histological features, such as interfacial hepatitis and bile duct deletion, have a strong correlation with an incomplete response to UDCA and are linked to prognosis [22]. Further, a cohort study has reported that patients with stage III and IV PBC experienced significantly higher liver-related mortality compared to those with stage I and II [23]. Moreover, a study published by Japanese scholars reported that patients with Scheuer stage \u0026gt;3 and Nakanuma fibrosis score (evaluation of bridging fibrosis in the confluent area) \u0026gt;2 scores might have incomplete response to UDCA [24]. Our results strongly corroborate the earlier findings.\u003c/p\u003e\n\u003cp\u003eIn this study, it was found that CK7 is not only expressed in the reactive hyperplasia of the fine bile duct but also in some liver cells of PBC patients. This abnormal expression of CK7 in the hepatocytes has been observed in a variety of cholestatic diseases as early as 1989, demonstrating that hepatocytes can express cholestatic cytokeratin and the expression of CK7 is more sensitive than CK19 during cholestasis, which supports the concept of hepatocyte to cholestatic cell transformation [25]. Hepatocyte-to-biliary reprogramming is characterized by the gradual acquisition of biliary features by hepatocytes while diminishing hepatocyte properties and functional abilities, resulting in the formation of HB cells [26]. Several histological studies have identified that HB cells express biliary and hepatocyte markers under conditions such as cirrhosis, cholestatic hepatopathy, and ALF [27-29]. The present study evaluated the presence and the effect of HB cells in a group of incomplete Ursodeoxycholic acid responders. We analyzed the correlation between CK7\u003csup\u003e+\u0026nbsp;\u003c/sup\u003eHB cell number and all clinical and pathological indicators and found that CK7\u003csup\u003e+\u0026nbsp;\u003c/sup\u003eHB cell number showed a remarkably positive relationship with risk factors for incomplete response to UDCA. Further, our research showed that HB cells were increased in patients with an inadequate UDCA response.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAlthough liver fibrosis and cirrhosis may occur in patients with advanced PBC, the typical features of its clinical manifestations, pathological changes, and biochemical indices are intrahepatic cholestasis [30].\u0026nbsp;Therefore, we expect to further understand the mechanism of PBC pathogenesis from the effects of CK7+ HB cells on bile formation, secretion, and drainage obstruction. Previous studies have shown that oral UDCA enters the liver through the portal system after absorption in the ileum and then combines with glycine and taurine to form soluble GUDCA and taurodeoxycholic acid. Concurrently, it can reduce the high proportion of hydrophobic goosedeoxycholic acid in the bile acid pool, promote the excretion of endogenous bile acid, and thus inhibit its absorption in order to change the ratio of hydrophilic/hydrophobic bile acid in the bile acid pool, and reducing the toxicity of hydrophobic bile acid to hepatocytes. However, the patients with incomplete response to UDCA do not benefit from this process [31]. In the present study, the analysis of the metabolites of bile acids in tissues also revealed that GUDCA and TBA increase considerably in the respond incompletely group. Therefore, we speculate that in the respond incompletely group, the products of UDCA combined with glycine are not adequately excreted, and the TBA level also increases prominently in the respond incompletely group. Successively, CK7\u003csup\u003e+\u0026nbsp;\u003c/sup\u003eHB cell count shows a strong positive correlation with GUDCA and TBA levels. Therefore, we hypothesize that due to poor response to UDCA, GUDCA, and TBA are likely to deposit in HB cells, resulting in an apparent increase in the HB cell count.\u003c/p\u003e\n\u003cp\u003eOverall, our study reveals the characteristics of HB cells and the possible relationship between HB cells and incomplete response to UDCA. However, the molecular mechanism depicting the functional role of HB cells in patients with incomplete response to UDCA needs to be investigated in the near future.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAASLD, American Association for the Study of Liver Diseases\u003c/p\u003e\n\u003cp\u003eALB, albumin\u003c/p\u003e\n\u003cp\u003eALP, alkaline phosphatase\u003c/p\u003e\n\u003cp\u003eAMA, anti-mitochondrial antibody\u003c/p\u003e\n\u003cp\u003eAST, aspartate aminotransferase\u003c/p\u003e\n\u003cp\u003eCK7, cytokeratin 7\u003c/p\u003e\n\u003cp\u003eDBiL, unconjugated bilirubin\u003c/p\u003e\n\u003cp\u003eGGT, glutamine transpeptidase\u003c/p\u003e\n\u003cp\u003eGLO, globulin\u003c/p\u003e\n\u003cp\u003eGUDCA, glycoursodeoxycholic\u003c/p\u003e\n\u003cp\u003eHB, hepatobiliary\u003c/p\u003e\n\u003cp\u003eHGB, hemoglobin\u003c/p\u003e\n\u003cp\u003eH\u0026amp;E, hematoxylin and eosin\u003c/p\u003e\n\u003cp\u003eLC-MS, liquid chromatography-mass spectrometry\u003c/p\u003e\n\u003cp\u003ePBC, primary biliary cholangitis\u003c/p\u003e\n\u003cp\u003ePLT, platelet\u003c/p\u003e\n\u003cp\u003eTBA, total bile acid\u003c/p\u003e\n\u003cp\u003eTBiL, total bilirubin\u003c/p\u003e\n\u003cp\u003eTC, total cholesterol\u003c/p\u003e\n\u003cp\u003eTG, triglyceride\u003c/p\u003e\n\u003cp\u003eTP, total Protein\u003c/p\u003e\n\u003cp\u003eUDCA, ursodeoxycholic acid\u003c/p\u003e\n\u003cp\u003eULN, upper limit of normal\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKun Yang participated in acquisition of data, analysis and interpretation of data and drafting of the manuscript. Bingqing Yang participated in acquisition of data, analysis and interpretation of data. Xiaoyi Han and Jiamin Chen conducted the drafting of the article or critical revision for important intellectual content. Lei Sun conceived of agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the article are appropriately investigated and resolved. All authors read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by Capital\u0026lsquo;s Funds for Health Improvement and Research (2024-2-2177) and Beijing Municipal Administration of Hospitals Incubating Program (PX2022072).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures performed in studies involving patients were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study protocol was approved by the Ethics Committee of Beijing Ditan Hospital, capital medical University (NO. DTEC-KY2024-023-01). Informed consent was obtained from patients in the study. A written informed consent from participants were obtained by physicians.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eTanaka A, Ma X, Takahashi A, Vierling JM. Primary biliary cholangitis. Lancet. 2024 Sep 14;404(10457):1053-1066.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eYang C, Guo G, Li B, Zheng L, Sun R, Wang X, et al. 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J Hepatol. 2023 Sep;79(3):728-740. \u0026nbsp;\u003c/li\u003e\n \u003cli\u003eJung K, Kim M, So J, Lee SH, Ko S, Shin D. Farnesoid X Receptor Activation Impairs Liver Progenitor Cell-Mediated Liver Regeneration via the PTEN-PI3K-AKT-mTOR Axis in Zebrafish. Hepatology. 2021 Jul;74(1):397-410. \u0026nbsp;\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eWang S, Link F, Munker S, Wang W, Feng R, Liebe R, et al. Retinoic acid generates a beneficial microenvironment for liver progenitor cell activation in acute liver failure. Hepatol Commun. 2024 Jul 18;8(8):e0483. \u0026nbsp;\u003c/li\u003e\n \u003cli\u003eLi T, Hasan MN, Gu L. Bile acids regulation of cellular stress responses in liver physiology and diseases. eGastroenterology. 2024 Apr;2(2):e100074.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eHu H, Shao W, Liu Q, Liu N, Wang Q, Xu J, et al. Gut microbiota promotes cholesterol gallstone formation by modulating bile acid composition and biliary cholesterol secretion. Nat Commun. 2022 Jan 11;13(1):252.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMurillo Perez CF, Goet JC, Lammers WJ, Gulamhusein A, van Buuren HR, Ponsioen CY, et al. GLOBAL PBC Study Group. Milder disease stage in patients with primary biliary cholangitis over a 44-year period: A changing natural history. Hepatology. 2018 May;67(5):1920-1930.\u0026nbsp;\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1 \u0026nbsp;Grading of histological Characteristics of PBC\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"552\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eProject\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e2+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e3+\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eCK7\u003csup\u003e+\u0026nbsp;\u003c/sup\u003eHB cells in periportal areas\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eNo CK7+ HB cells\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eCK7+ HB cells in at least ten hepatocytes in one periportal area\u0026nbsp;(zone 1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eCK7+ HB cells in at least ten hepatocytes in 1/3\u0026ndash;2/3 of periportal areas\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003eCK7+ HB cells in at least ten hepatocytes in more than 2/3 of periportal areas\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eCD10\u003csup\u003e+\u003c/sup\u003e bile canaliculus loss in periportal areas\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eNo CD10\u003csup\u003e+\u003c/sup\u003e bile canaliculus loss\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eCD10\u003csup\u003e+\u003c/sup\u003e bile canaliculus loss in \u0026lt;1/3 of periportal areas (zone 1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eCD10\u003csup\u003e+\u003c/sup\u003e bile canaliculus loss in 1/3\u0026ndash;2/3 of periportal areas\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003eCD10\u003csup\u003e+\u003c/sup\u003e bile canaliculus loss in \u0026gt;2/3 of periportal areas\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eCopper deposition in periportal areas\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eNo deposition of granules\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eDeposition of granules in several periportal hepatocytes in \u0026lt;1/3 of periportal areas (zone 1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eDeposition of granules in variable periportal hepatocytes in 1/3\u0026ndash;2/3 of periportal areas\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003eDeposition of granules in many hepatocytes in \u0026gt;2/3 of periportal areas\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Baseline Clinical Characteristics in 132 patients with PBC\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"97%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003eTotal (n=132)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003eUDCA respond completely (n=80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003eUDCA respond incompletely (n=52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003eValue\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eMale(n,%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e17 (12.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e10 (12.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e7 (13.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.872\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eAge(years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e50.37\u0026plusmn;10.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e50.44\u0026plusmn;11.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e50.27\u0026plusmn;9.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.929\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eALT (U/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e44.65 (27.55,76.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e41.70 (26.83,74.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e48.90 (31.93,93.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.215\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eAST (U/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e50.60 (34.90,74.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e39.95 (31.60,61.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e64.00 (45.50,102.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eALP (U/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e188.15 (116.13,198.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e142.10 (94.53,205.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e265.60 (189.45,364.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eGGT (U/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e198.50 (83.48,365.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e127.30 (63.43,221.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e309.00 (204.10,566.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eTBiL (\u0026mu;mol/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e16.45 (12.43,27.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e14.05 (11.50,18.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e27.65 (16.20,61.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eDBiL (\u0026mu;mol/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e6.60 (4.50,15.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e5.10 (3.90,7.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e15.90 (8.10,51.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eTBA\u003c/p\u003e\n \u003cp\u003e(\u0026mu;mol/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e21.80 (7.93,55.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e14.10 (6.30,27.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e56.40 (13.95,55.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eTC\u003c/p\u003e\n \u003cp\u003e(mmol/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e5.12 (4.51,6.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e4.90 (4.38,5.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e5.84 (4.84,7.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eTG\u003c/p\u003e\n \u003cp\u003e(mmol/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e1.28 (1.06,1.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e1.28 (0.96,1.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e1.43 (1.10,2.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.044*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eTP\u003c/p\u003e\n \u003cp\u003e(g/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e74.18\u0026plusmn;6.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e75.54\u0026plusmn;6.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e72.08\u0026plusmn;6.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.002**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eALB\u003c/p\u003e\n \u003cp\u003e(g/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e40.01\u0026plusmn;4.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e41.35\u0026plusmn;4.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e37.96\u0026plusmn;4.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eGLO\u003c/p\u003e\n \u003cp\u003e(g/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e34.23\u0026plusmn;5.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e34.26\u0026plusmn;5.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e34.18\u0026plusmn;5.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.939\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eWBC\u003c/p\u003e\n \u003cp\u003e( \u0026times;10\u003csup\u003e12\u003c/sup\u003eL\u003csup\u003e-1\u003c/sup\u003e )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e4.94\u0026plusmn;1.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e4.96\u0026plusmn;1.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e4.90\u0026plusmn;1.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.832\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eRBC\u003c/p\u003e\n \u003cp\u003e( \u0026times;10\u003csup\u003e12\u003c/sup\u003eL\u003csup\u003e-1\u003c/sup\u003e )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e4.06\u0026plusmn;0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e4.22\u0026plusmn;0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e3.80\u0026plusmn;0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eHGB\u003c/p\u003e\n \u003cp\u003e(g/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e123.95 (113.00,133.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e126.00 (120.00,134.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e117.00 (106.35,128.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003ePLT\u003c/p\u003e\n \u003cp\u003e( \u0026times;10\u003csup\u003e12\u003c/sup\u003e \u003csup\u003e-1\u003c/sup\u003e )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e201.25 (137.50,253.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e205.25 (147.00,256.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e157.35 (125.50,241.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.151\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eTotal lymphocytes\u003c/p\u003e\n \u003cp\u003e(cells/ul)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e1653.50 (1373.50,1737.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e1671.00 (1543.25,1762.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e1373.50 (1234.50,1572.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eT-lymphocytes\u003c/p\u003e\n \u003cp\u003e(cells/ul)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e1175.00 (997.50,1219.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e1175.00 (1096.75,1242.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e997.50 (919.25,1183.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eCD4\u003c/p\u003e\n \u003cp\u003eLymphocytes\u003c/p\u003e\n \u003cp\u003e(cells/ul)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e739.00 (625.50,793.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e739.00 (637.50,830.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e672.50 (570.50,734.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.006**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eCD8\u003c/p\u003e\n \u003cp\u003eLymphocytes\u003c/p\u003e\n \u003cp\u003e(cells/ul)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e380.00 (302.25,411.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e380.00 (349.00,427.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e314.00 (288.75,363.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eAMA\u003c/p\u003e\n \u003cp\u003e[M(P25～P75)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e1.00 (0.00, 2.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e1.00 (0.00, 2.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e1.00 (0.00, 2.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.819\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eAMA-M2\u003c/p\u003e\n \u003cp\u003e[M(P25～P75)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e2.00 (0.00, 3.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e2.00 (0.00, 3.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e2.00 (0.00, 3.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.733\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eGP210\u003c/p\u003e\n \u003cp\u003e[M(P25～P75)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e0.00 (0.00, 3.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e0.00 (0.00, 3.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e0.00 (1.00, 3.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.006**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eRO-52\u003c/p\u003e\n \u003cp\u003e[M(P25～P75)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e0.00 (0.00, 2.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e0.00 (0.00, 2.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e0.00 (0.00, 2.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.800\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eANA\u003c/p\u003e\n \u003cp\u003e[M(P25～P75)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e1.00 (0.00, 2.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e1.00 (0.00, 2.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e1.00 (0.25, 2.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.565\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eBPO\u003c/p\u003e\n \u003cp\u003e[M(P25～P75)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e3.00 (1.00, 3.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e3.00 (1.00, 3.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e3.00 (0.00, 3.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.742\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eIgG\u003c/p\u003e\n \u003cp\u003e(g/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e16.03 (13.00,18.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e16.05 (13.40,18.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e15.60 (12.88,17.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.293\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eIgM\u003c/p\u003e\n \u003cp\u003e(g/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e3.20 (2.16,4.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e3.20 (2.07,4.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e3.03 (2.31,3.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.315\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData is presented as mean (SD) or median (P25\u0026ndash;P75). *\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05, **\u003cem\u003ep\u003c/em\u003e＜0.01.\u003c/p\u003e\n\u003cp\u003eAbbreviation: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; GGT, glutamine transpeptidase; TBiL, total bilirubin; DBiL, unconjugated bilirubin; TBA, total bile acid; TC,total cholesterol; TG, triglyceride; TP, total Protein; ALB, albumin; GLO, globulin; HGB, hemoglobin; globulin; PLT, platelet; AMA: anti-mitochondrial antibody.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. Analysis of liver pathological characteristics in 132 patients with PBC\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"97%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003etotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eUDCA respond completely\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003eUDCA respond incompletely\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e Value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003eIshak grading of inflammation\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e[M(P25～P75)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e6.00 (5.00, 9.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e6.00 (5.00, 7.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e7.00 (5.00, 11.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.009**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003eIshak staging of fiber[M(P25～P75)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e1.00 (1.00,2.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e1.00 (1.00, 2.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e2.00 (1.00, 3.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003eProportion of portal with bile duct loss\u003c/p\u003e\n \u003cp\u003e[M(P25～P75)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e0.82 (0.67, 0.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e0.80 (0.67, 0.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e0.84 (0.71, 0.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.312\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003eDegree of bile duct rearranged\u003c/p\u003e\n \u003cp\u003e[M(P25～P75)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e1.00 (0.50, 1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e1.00 (0.50, 1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e1.00 (0.50, 1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.098\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003eCopper deposition\u003c/p\u003e\n \u003cp\u003e[M(P25～P75)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e0.50 (0.00, 1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e0.00 (0.00, 1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e1.00 (0.13, 1.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026lt;0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003eCK7+ HB cells\u003c/p\u003e\n \u003cp\u003e[M(P25～P75)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e1.00 (0.00, 2.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e0.50 (0.00, 1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e2.00 (1.00, 2.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026lt;0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003eMUM1\u003c/p\u003e\n \u003cp\u003e[M(P25～P75)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e1.00 (1.00, 1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e1.00 (1.00, 1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e1.00 (1.00, 1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.448\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003eCD38\u003c/p\u003e\n \u003cp\u003e[M(P25～P75)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e1.00 (0.50, 1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e1.00 (0.50, 1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e1.00 (1.00, 1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.849\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003eabsence of CD10+ bile canaliculus\u003c/p\u003e\n \u003cp\u003e[M(P25～P75)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e0.50 (0.00, 0.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e0.50 (0.13, 1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e0.50 (0.00, 0.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.005**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003eLymphocyte infiltration in the portal tract\u003c/p\u003e\n \u003cp\u003e[M(P25～P75)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e2.00 (1.00, 2.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e2.00 (1.00, 2.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e2.00 (1.00, 2.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.674\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003eEosinophils \u0026nbsp;infiltration in portal tract\u003c/p\u003e\n \u003cp\u003e[M(P25～P75)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e1.00 (0.00, 1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e1.00 (0.00, 1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e1.00 (0.00, 1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.489\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003ePlasma cell infiltration in the portal tract\u003c/p\u003e\n \u003cp\u003e[M(P25～P75)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e0.00 (0.00, 0.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e0.00 (0.00, 0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e0.00 (0.00, 1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.185\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData is presented as median (P25\u0026ndash;P75). *\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05, **\u003cem\u003ep\u003c/em\u003e＜0.01.\u003c/p\u003e\n\u003cp\u003eAbbreviation: CK7, cytokeratin 7; HB: hepatobiliary.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4. Univariate analysis of indicators associated with UDCA responds incompletely\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"97%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eUnivariate analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003eOR (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e Value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003esex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e1.089 (0.386-3.068)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e0.872\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eage＜45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e0.892 (0.416-1.914)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e0.769\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eAST(U/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e1.025 (1.012-1.037)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eALP(U/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e1.007 (1.004-1.011)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eGGT(U/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e1.005 (1.003-1.007)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eTBiL(\u0026mu;mol/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e1.108 (1.059-1.161)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eDBiL(\u0026mu;mol/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e1.165 (1.085-1.250)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eTBA(\u0026mu;mol/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e1.029 (1.016-1.042)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eTC(mmol/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e1703 (1.256-2.311)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eTG(mmol/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e1.741 (1.084-2.796)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e0.022*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eTP(g/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e0.913 (0.859-0.970)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e0.003**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eALB(g/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e0.820 (0.743-0.905)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eRBC( \u0026times;10\u003csup\u003e12\u003c/sup\u003eL\u003csup\u003e-1\u003c/sup\u003e )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e0.178 (0.079-0.404)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eHGB(g/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e0.958 (0.933-0.983)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eTotal lymphocytes (cells/ul)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e0.999 (0.998-1.000)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e0.018*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eT-lymphocytes (cells/ul)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e0.999 (0.998-1.000)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e0.029*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eCD4-Lymphocytes (cells/ul)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e0.998 (0.997-1.000)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e0.072\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eCD8-Lymphocytes (cells/ul)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e0.998 (0.995-1.000)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e0.064\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eGP210\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e1.313 (1.062-1.750)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e0.015*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eIshak grading of inflammation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e1.220 (1.065-1.399)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e0.004**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eIshak staging of fiber\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e1.898 (1.306-2.759)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eCopper deposition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e2.652 (1.580-4.451)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eCK7+ HB cells\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e3.954 (2.325-6.723)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eabsence of CD10+ bile canaliculus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e0.345 (0.159-0.749)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e0.007**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eResults were obtained with logistic regression models and given as OR with 95% CI for UDCA responds incompletely. *\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05, **\u003cem\u003ep\u003c/em\u003e＜0.01. AST, aspartate aminotransferase; ALP, alkaline phosphatase; GGT, glutamine transpeptidase; TBiL, total bilirubin; DBiL, unconjugated bilirubin; TBA, total bile acid; TC, total cholesterol; TG, triglyceride; TP, total Protein; ALB, albumin; GLO, globulin; HGB, hemoglobin; globulin; PLT, platelet; CK7, cytokeratin 7; HB: hepatobiliary.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5. Comparison of the efficacy of clinical indicators in predicting the risk of UDCA responds incompletely\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"97%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003eAUC\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp; 95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e Value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003eAST(U/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.564\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.461-0.666\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e0.215\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003eALP(U/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.799\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.725-0.873\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003eGGT(U/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.788\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.710-0.867\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003eTBiL(\u0026mu;mol/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.799\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.718-0.881\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003eTBA(\u0026mu;mol/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.758\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.669-0.847\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003eTC(mmol/ L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.700\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.606-0.795\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003eGP210\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.623\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.524-0.721\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e0.017*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003eIshak grading of inflammation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.633\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.530-0.737\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e0.010*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003eIshak staging of fiber\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.663\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.566-0.760\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e0.002**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003eCopper deposition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.699\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.606-0.791\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003eCK7+ HB cells\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.775\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.695-0.855\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e＜0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003eabsence of CD10+ bile canaliculus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e0.635\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.539-0.731\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e0.009**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eResults were obtained with ROC Curve and AUC with 95% CI for UDCA responds incompletely. *\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05, **\u003cem\u003ep\u003c/em\u003e＜0.01. AST, aspartate aminotransferase; ALP, alkaline phosphatase; GGT, glutamine transpeptidase; TBiL, total bilirubin; TBA, total bile acid; TC, total cholesterol; CK7, cytokeratin 7; HB: hepatobiliary.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 6. Analysis of different types of bile acids in liver tissue in 25 patients with PBC\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"97%\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eVariables\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003eTotal (n=25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003eUDCA respond completely (n=11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003eUDCA respond incompletely (n=14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e Value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 28px;\"\u003e\n \u003cp\u003eDehydrolithocholic acid (nmol/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e0.00 (0.00, 0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e0.00 (0.00, 0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e0.00 (0.00, 0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.698\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 28px;\"\u003e\n \u003cp\u003eDeoxycholic acid (nmol/l)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e115.13 (106.76, 125.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e110.69 (101.67, 125.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e116.25 (106.98, 125.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.584\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 28px;\"\u003e\n \u003cp\u003eGlycolithocholic acid (nmol/l)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e19.00(17.47, 21.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e19.00 (17.50, 23.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e19.05 (16.87, 20.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.443\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 28px;\"\u003e\n \u003cp\u003eGlycoursodeoxycholic acid (nmol/l)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e80.34 (41.41, 142.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e43.09 (0.00, 110.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e102.53 (70.32, 243.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.010*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 28px;\"\u003e\n \u003cp\u003eGlycochenodeoxycholic acid (nmol/l)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e0.00 (0.00, 31.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e0.00 (0.00, 30.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e0.00 (0.00, 32.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.757\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 28px;\"\u003e\n \u003cp\u003eLithocholic Acid-3-Sulfate (nmol/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e0.00 (0.00, 0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e0.00 (0.00, 0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e0.00 (0.00, 0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.907\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 28px;\"\u003e\n \u003cp\u003eGlycocholic acid (nmol/l)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e22.50 (0.00, 33.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e21.67 (0.00, 23.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e28.48 (0.00, 42.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.133\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 28px;\"\u003e\n \u003cp\u003eTaurolithocholic acid (nmol/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e0.00 (0.00, 10.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e9.52 (0.00, 12.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e0.00 (0.00, 10.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.157\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 28px;\"\u003e\n \u003cp\u003eTaurochenodeoxycholic acid (nmol/l)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e0.00 (0.00, 45.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e38.82 (0.00, 45.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e0.00 (0.00, 45.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.768\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 28px;\"\u003e\n \u003cp\u003eGlycoursodeoxycholic Acid-3-Sulfate (nmol/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e0.00 (0.00, 17.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e0.00 (0.00, 14.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e13.69 (0.00, 40.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.117\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 28px;\"\u003e\n \u003cp\u003eGlycocholic Acid-3-Sulfate (nmol/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e0.00 (0.00, 10.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e0.00 (0.00, 0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e0.00 (0.00, 22.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.609\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 28px;\"\u003e\n \u003cp\u003eTaurodeoxycholic Acid-3-Sulfate (nmol/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e0.00 (0.00, 0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e0.00 (0.00, 0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e0.00 (0.00, 0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.375\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 28px;\"\u003e\n \u003cp\u003eTaurocholic Acid-3-Sulfate (nmol/l)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e0.00 (0.00, 0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e0.00 (0.00, 0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e0.00 (0.00, 0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.259\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 28px;\"\u003e\n \u003cp\u003eTotal tissue TBA (nmol/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e303.03(222.23, 423.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e237.83 (204.07, 315.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e394.32 (239.41, 506.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.037*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eData is presented as median (P25\u0026ndash;P75). *\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"cholestatic liver disease, bile acid metabolism, pathology, treatment response, bile salt","lastPublishedDoi":"10.21203/rs.3.rs-6763526/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6763526/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eThe mechanisms underlying the incomplete response to ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) patients are not clear. This study investigated the Clinicopathological characteristics and mechanism of hepatobiliary (HB) cells among PBC patients who demonstrated an incomplete response to UDCA.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eThis study involved 132 patients with PBC undergoing ultrasound-guided liver biopsies. The obtained samples were subjected to various staining techniques. Demographic data, clinical features, hematological factors, auto-antibody levels, and liver biochemistry of patients were retrospectively analyzed. The response to UDCA was determined per Paris criteria. We also performed high-performance liquid chromatography-mass spectrometry (LC-MS) to test bile acid metabolomics on paraffin-embedded tissue samples from 25 patients with PBC.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eAmong 132 patients, 52 (39.4%) had an inadequate UDCA response. The quantity of CK7\u003csup\u003e+ \u003c/sup\u003eHB cells, degree of copper deposition in hepatocytes, alkaline phosphatase (ALP), total bile acid (TBA) and GP210 showed the strong association with this inadequate UDCA response. These factors exhibited AUC values of 0.775, 0.699, 0.799, 0.758 and 0.623, respectively. The concentrations of TBA (\u003cem\u003ep\u003c/em\u003e=0.010) and glycoursodeoxycholic (GUDCA, \u003cem\u003ep\u003c/em\u003e=0.037) in liver tissues revealed significantly increased in the group with incomplete response to UDCA than in the group with complete response to UDCA. Additionally, a notable positive correlation was observed between the quantity of CK7\u003csup\u003e+\u003c/sup\u003e HB cells and the content of TBA (\u003cem\u003er\u003c/em\u003e=0.544, \u003cem\u003ep\u003c/em\u003e＜0.01) and GUDCA (\u003cem\u003er\u003c/em\u003e=0.480, \u003cem\u003ep\u003c/em\u003e＜0.05) in liver tissues.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eHepatobiliary cells in PBC are correlated with bile acid metabolism and inadequate response to UDCA.\u003c/p\u003e","manuscriptTitle":"Clinicopathological Features of Hepatobiliary Cells in Primary Biliary Cholangitis Patients with Ursodeoxycholic acid respond incompletely","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-01 09:01:22","doi":"10.21203/rs.3.rs-6763526/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-11-02T06:55:18+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-01T15:27:33+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-30T17:36:39+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-30T13:37:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"181985690328862591420766840570980640234","date":"2025-10-24T10:00:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"85867943055827313960097475245168072905","date":"2025-10-23T06:06:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"100993840503342746848800690537715145176","date":"2025-10-22T12:22:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"27301514822617277155044539128682026276","date":"2025-10-22T11:26:56+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-06-25T08:28:29+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-05-30T08:28:28+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-28T15:11:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-28T15:09:48+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Gastroenterology","date":"2025-05-28T02:41:46+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"beb96dd3-f4b1-4c83-8487-131bb840192c","owner":[],"postedDate":"July 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-16T16:01:18+00:00","versionOfRecord":{"articleIdentity":"rs-6763526","link":"https://doi.org/10.1186/s12876-026-04686-9","journal":{"identity":"bmc-gastroenterology","isVorOnly":false,"title":"BMC Gastroenterology"},"publishedOn":"2026-02-12 15:58:23","publishedOnDateReadable":"February 12th, 2026"},"versionCreatedAt":"2025-07-01 09:01:22","video":"","vorDoi":"10.1186/s12876-026-04686-9","vorDoiUrl":"https://doi.org/10.1186/s12876-026-04686-9","workflowStages":[]},"version":"v1","identity":"rs-6763526","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6763526","identity":"rs-6763526","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}