Transjugular Liver Biopsy in Patients with Unexplained Liver Dysfunction and hemorrhage tendency: A Safety and Efficacy Analysis

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Aims To assess the diagnostic adequacy and safety of TJLB in combination with HVPG measurement in patients with unexplained Liver Dysfunction and hemorrhage tendency. Methods A total of 77 TJLB procedures were carried out in 58 patients with unexplained liver dysfunction using the COOK LABS kit. Biopsy specimens were evaluated for specimen length, number of complete portal tracts, diagnostic yield, and complications. Subgroup analyses were performed in different HVPG patients. Results Adequate histopathological samples were obtained in all procedures. The mean specimen length was 8 mm (range, 5–13 mm), with an average of 9 complete portal tracts (range, 4–20). 72.4% of patients have identified the causes after TJLB, which performed for 78.0% in patients with ascites and 72.7% with coagulopathy. For patients performed the pressure measure, higher HVPG values seemed to be correlated with shorter specimen length and fewer portal tracts. No procedure-related complications occurred. Conclusions TJLB is a safe and effective method for liver disease diagnosis and HVPG assessment in patients with unexplained Liver Dysfunction and hemorrhage tendency. Transjugular Liver Biopsy hepatic venous pressure gradient unexplained liver dysfunction Introduction Abnormal liver function has emerged as a leading reason for medical consultations in modern society, reflecting its growing prevalence among patients with liver disease. Common causes of abnormal liver function include hepatitis viruses, excessive alcohol consumption, non-alcoholic fatty liver disease, and drug- or toxin-induced injuries. Particularly in China, although the widespread hepatitis B vaccination has significantly reduced the incidence of hepatitis B and subsequent cirrhosis, there still have a substantial burden of hepatitis B–related liver disease. This is largely attributable to its large population base and the highly chronic, often asymptomatic nature of hepatitis B infection, which contributes to its persistence and underdiagnosis. [ 1 ] In addition, alcohol abuse, as well as the misuse of hepatotoxic chemical agents and herbal medicines, can cause significant liver injury. In European countries, excessive alcohol consumption is the most common cause of nonalcoholic fatty liver disease. In China, however, the inappropriate use of certain herbal remedies accounts for a considerably higher incidence of irreversible liver damage compared with western countries [ 2 ] . For example, exposure to pyrrolizidine alkaloids has been identified as one of the major causes of hepatic sinusoidal obstruction syndrome. [ 3 ] Severe sinusoidal obstruction syndrome often leads to multiorgan failure, with a mortality rate exceeding 80%. For example, liver dysfunction has been frequently reported in patients receiving long-term medications for chronic diseases, such as antirheumatic agents, targeted anticancer therapies, and immunosuppressive drugs [ 4 ] . However, the overlap with underlying conditions often hinders the early recognition of these drug-related causes [ 5 ] . In recent years, the incidence of autoimmune-related hepatitis has been steadily increasing, and it has emerged as a major disease with a global impact [ 6 ] . However, the clinical diagnosis of autoimmune liver disease remains highly challenging. Liver biopsy is therefore essential for autoimmune hepatitis (AIH), as approximately one-third of patients are already diagnosed with cirrhosis at presentation, even in the absence of symptoms. This significantly influences treatment decisions, follow-up strategies, and overall prognosis [ 7 ] . Notably, noninvasive tools such as transient elastography are often unreliable at the time of diagnosis, as liver stiffness measurements are influenced by both fibrosis and inflammation [ 7 ] . Various types of primary and secondary unrecognized abnormal liver functional may have different clinical manifestation and causes. And it is hard to make differential diagnosis by normal ways, like laboratory examination, echo and CT. Liver histology is still the golden standard for evaluating liver inflammation, necrosis and fibrosis. Although ultrasound and laboratory indicator with high sensitivity and specificity, liver biopsy is only a significant method to help doctor diagnose liver function damage, which can provide guide of treatment and prognosis. At most conditions, the way to obtain liver tissue is percutaneous liver biopsy (PLB) [ 8 ] . Unfortunately, patients who present with abnormal liver function often exhibit coexisting coagulopathy, which poses considerable challenges for obtaining liver tissue samples through percutaneous biopsy. transjugular liver biopsy (TJLB) is a relatively new performance in obtaining histopathological sample for diagnosis of unrecognized liver damage. When percutaneous liver biopsy is contraindicated, TJLB provides an effective, safe, and widely accepted alternative for obtaining liver tissue. TJLB can help doctor obtain liver tissue sample when patient have contraindications like preexisting coagulopathy, ascites, obesity, transplantation, and cirrhosis., which is not suitable to do PLB. Even in advanced liver disease, biopsy remains crucial for establishing etiology and uncovering potentially treatable causes [ 9 ] . TJLB can be combined with hepatic venous pressure gradient (HVPG) measurement to indirectly assess the severity of portal hypertension. The degree of portal hypertension is critical for guiding treatment and predicting prognosis in patients with cirrhosis. Therefore, this study aims to assess sample quality and safety of TJLB in patients with unexplained liver dysfunction and hemorrhage tendency [ 10 ] . These motivations prompted us to evaluate the use of TJLB combined with HVPG measurement in patients with unexplained liver dysfunction and a bleeding tendency, assessing technical success, complications, biopsy specimen quality, and resulting changes in patient management. Method Patients selection We retrospectively analyzed 58 patients with unrecognized liver function damage and hemorrhage tendency, performed TJLB to achieve pathological diagnosis between January 1st ,2018 and February 17th, 2020. All of the patients underwent TJLB and measured hepatic vein pressure. This research was admitted by ethic committee of Zhongshan hospital, Fudan University. All the patients enrolled in study was informed consent. Patients’ basic information and demographic information was collected from record (Name, age, gender, ID, clinical manifestation, previous treatment, laboratory examination and computed tomography). Number of hepatic lobes, vascular pressure was also extracted from record. Prognostic information and complications were also documented. Procedures All interventional operations are performed by experienced interventional doctors in accordance with the standard procedures recommended by the American Society of Interventional Radiology. Blood routine and coagulation-related laboratory indexes (PT, APTT, INR, TT and D-dimer) were measured in all patients three days before operation, and preoperative preparation was carried out strictly according to the indication of operation. The operation was performed under conscious sedation, continuous ECG monitoring and oxygen inhalation during the operation. All hepatic tissue samples obtained by TJLB were assessed by two independent pathologists and were confirmed to conform to the established criteria for adequate liver biopsy specimens. To minimize potential sources of bias, several measures were implemented in this retrospective study. All TJLB procedures were performed using the same COOK LABS kit and standardized protocol by experienced interventional radiologists to reduce operator-related variability. Clinical, laboratory, and hemodynamic data were collected from electronic medical records by two independent investigators, and discrepancies were resolved by consensus to ensure data accuracy. Diagnostic adequacy and histopathological interpretation were reviewed by two senior hepatopathologists who were blinded to clinical and HVPG data, minimizing interpretation bias. Inclusion criteria were predefined to avoid selection bias, and all consecutive eligible patients within the study period were included. Statistical analyses were performed using uniform thresholds and objective parameters to further reduce analytical bias. Complications Operation-related complications during and after TJLB were recorded. Minor complications refer to clinical symptoms that are self-limited and can be cured without too much medical intervention, such as pain, bleeding at the puncture point. Major complications were recorded according to the complication grading system of the Interventional Radiology Association. What is more, patients with major complications who needed for minor( 48h) hospitalization or with permanent adverse complications and death was specially recorded. Live tissue specimen The pathological specimens of the liver obtained by puncture were fixed in 4% formalin solution and sent to the pathology department for preparation. The histological sections of the liver were embedded, sliced and stained by pathological technicians, and then read by a pathologist specializing in liver tissue. The content of the evaluation was the tissue length of the biopsy, the number and extent of hepatic lobules, the condition of hepatocytes, and the quantity and quality of portal ducts. Statistics STATA/SE 15.1 software was used for statistical analysis. Continuous variables are expressed in the form of mean ± standard deviation (SD) or median and quartile spacing. Categorical variables were expressed as numbers and proportions. Results Patient characteristics 58 patients with 77 TJLB were retrospectively included in this study. There are 36 males (62.7%) and 22 females (37.93%) in this study, the mean age is 51.95 ± 15.16. All the patients were presented unknown liver function damage or with cogulation disorder. The most majority of symptoms is abdominal distention (n = 22, 39.28%). 16 of 58 patients (27.12%) is with poor appetite and varicosity was shown in 11 patients (18.64%). Besides, fifteen patients have melena symptoms and only one patient had jaundice. In these patients, most of them were first diagnosed with unrecognized portal vein hypertension (n = 13, 22.03%) and unrecognized liver function injury (n = 14, 23.72%). Fourteen patients (23.72%) suffered liver cirrhosis. Besides, 12 patients have rt-PA history and only 1 patient had chemotherapy before TJLB. For the examination of the coagulation system, 46 patients (77.07%) are in normal prothrombin time (PT), but 11 patients (18.94%) show long PT. Besides, in the cohort, forty-two patients (71.19%) appeared as ascites. Specific information weas shown in Table 1 . Table 1 Patients baseline characteristic Characteristic Variable Percentage Gender Male 36 62.07% Female 22 37.93% Age, years 51.95 ± 15.16 Main compliants, n(%) Abdominal distention 22 39.28 Poor appetite 16 27.12 Varicosity 11 18.64 Melena 15 25.42 Jaundice 1 1.69 History, n (%) Suspicious Portal hypertension 13 22.03 Liver function damage 14 23.72 Liver cirrhosis 14 23.72 rt-PA 12 20.33 Chemotherapy 1 1.69 PT, n(%) 16s 11 18.64 Ascites, n(%) Yes 42 71.19 No 17 28.81 Diagnostic performance of TJLB Diagnostic performance of TJLB in patients was listed in Table 2 . The mean sample length of TJLB is 8mm (Maximum-Minimum, 5-13mm). Around 9 hepatic lobules (Maximum-Minimum, 4–20) were obtained in each sample of TJLB. In special cohort, mean number hepatic lobule is 9 (Maximum-Minimum, 7–10) in liver cirrhosis biopsy specimen. Besides, in patients with ascites, the length of the puncture specimen is 9 (Maximum-Minimum, 5–20). For patients with coagulation disorders, intravascular biopsy specimens can still obtain 8 liver lobes (Maximum-Minimum, 4–12). Also, about 10 hepatic lobules (Maximum-Minimum, 7–12) in melena patients were found. For all the patients, all the patients (100%) have successfully reached histological diagnosis. 16 patients (72.14%) were successfully diagnosed by TJLB in etiology level. For special patients, 13 of 41 patients (78.04%) with ascites were performed and have a final diagnosis. Besides, histological diagnosis possible in coagulopathy patients was 72.72%. Table 2 Sample quality and TJLB performance of TJLB. Performance Sample Length, mm 8(5–13) Number of hepatic lobule 9 (4–20) Number of hepatic lobule in cirrhosis patients 9(7–10) Number of hepatic lobule in HVOD patients 5(4–6) Number of hepatic lobule in hepatitis patients 9(8–13) Number of hepatic lobule in ki67 + > 10% patients 10(8–13) Number of hepatic lobule in ascites patients 9(5–20) Number of hepatic lobule in coagulopathy patients 8(4–12) Number of hepatic lobule in melena patients 10(7–12) Histological diagnosis possible, n 100% Etiology successfully determined by TJLB 16 (72.41%) Unclear etiology before TJLB 100% Histological diagnosis possible in ascites, n 31/41(78.04%) Histological diagnosis possible in coagulopathy, n 8/11(72.72%) Diagnostic performance in patients for different HVPG HVPG is divided into five subgroups, and in each subgroup, we describe its number of sample lengths, the number of liver lobule, the number of etiology successfully determined by TJLB and complications (Table 3 ). In patients with HVPG < 5mmHg, the sample of 8 patients was obtained, average length of the samples was 7 mm (Maximum-Minimum, 3-11mm). The mean number of liver lobule was 9 (from 7 to 14) under the microscope. Three of eight patients received the ultimate histopathological diagnosis through TJLB. For the patient subgroup with an HVPG between 5 and 10 mmHg (n = 8), the mean biopsy sample length was 8 mm (range: 6–11 mm), with an average of 13 hepatic lobules obtained per sample (range: 8–16). Table 3 Sample quality in different HVPG subgroups. HVPG 20mmHg (N = 7) p Sample Length, mm 7(3–11) 8(6–11) 10(8–12) 8(7–10) NS Number of hepatic lobule, N(min-max) 9(7–14) 13(8–16) 9(6–12) 7(6–13) P < 0.05 Etiology successfully determined by TJLB, n(min-max) 3/8(37.5%) 7/8(87.5%) 12/20(60%) 5/7(71.42%) NS Complications, n 0 0 0 0 NS Safety of TJLB in liver biopsy of unknown liver damage In total, no complications were observed during or after the procedures. Specifically, there were no minor complications such as subclinical capsule perforation, bleeding at the puncture site, abdominal pain, hypotension, or tachycardia. Likewise, no major complications—including pneumothorax, ventricular arrhythmias, or accidental injury to adjacent organs—were reported. Importantly, there were no deaths related to the TJLB procedure in our cohort . Discussion Liver biopsy is a crucial clinical tool for the diagnosis of liver diseases, providing comprehensive histological information and guiding subsequent treatment strategies. However, due to impaired hepatic function, many patients with liver disease present with complications such as significant ascites and coagulopathy, rendering conventional percutaneous liver biopsy risky, with potential for life-threatening complications including hemorrhage and infection [ 11 ] . Our study demonstrates that TJLB is a safe and effective alternative for diagnosis in cases of unexplained liver disease or with bleeding tendency. Moreover, it enables the assessment of hepatic hemodynamic parameters, such as HVPG [ 12 ] , thereby providing both histological and hemodynamic parameter to help doctor have an accurate diagnosis and do a clinical decision-making of liver disease. The Liver Access and Biopsy Set (LABS) from COOK Medical was used to perform TJLB in our studies. Liver tissue samples were obtained using an 18G Quick-Core Tru-Cut needle. Evidence suggests that, compared to the Menghini needle, the Tru-Cut needle yields longer and diagnostically superior specimens, potentially due to a lower fragmentation rate [ 10 ] . Comparative studies of Tru-Cut and Menghini needles used in TJLB have reported similar findings [ 13 ] . For those aiming to obtain longer specimens with reduced fragmentation, the use of a finer Tru-Cut needle may be considered [ 14 ] . The quality of samples, to be considered optimal for diagnosis of diffuse liver disease, the specimens should be at least 15 mm long and contain at least 6 CPTs [ 15 ] . Reliable grading and staging of liver disease require a biopsy of at least 20 mm in length and at least 11 portal tracts [ 16 ] . A biopsy shorter than 2 cm but containing at least 11 CPTs may still be considered acceptable for grading and staging [ 17 ] . In a systematic review of 64 studies with more than 7500 biopsies, TJLB offered adequate quality samples in 96% of the cases and the specimens obtained were considered adequate for histologic diagnosis in the most of them [ 18 ] . Although it is generally accepted that obtaining more tissue is advantageous, our findings demonstrate that even with an average specimen length of 8 mm, distinct liver disease diagnosis can be identified by experienced pathologists. Therefore, TJLB can provide more useful information for doctors than empirical treatment without biopsy. Our center think additional sampling beyond the standard requirements is unnecessary once tissue quality is confirmed, as this may increase the risk of unforeseen complications. Among patients later confirmed to have cirrhosis, biopsy specimens still contained an average of 9 hepatic lobules, fully meeting the diagnostic criteria for cirrhotic liver biopsy based on our experience. The Tru-Cut needle not only yields larger tissue samples but also allows for angular adjustments of the biopsy set within the vessel, enabling multiple passes to achieve an adequate number of CPTs while reduces the bleeding risks, which commonly occurred in percutaneous biopsy [ 19 ] . Previous studies have shown that TJLB, with a median of 2.3 passes, achieves a similar number of CPTs compared to PLB [ 20 ] . However, CPT counts in TJLB may still be underestimated relative to PLB [ 21 ] . In this study, doctors were highly experienced and performed the procedures according to established indications. No minor or major complications required medication or surgery were observed, with an incidence lower than previously published [ 15 , 22 , 23 ] . Even in patients receiving oral anticoagulants, our experience suggests that TJLB can still be. performed safely. Biopsy-related complications like mortality, pneumothorax, biliary bleeding, pseudoaneurysm or intra-abdominal hemorrhage were also not observed after TJLB. Make sure that, although TJLB is generally considered a safe liver biopsy technique, this does not preclude the occurrence of complications, which may even be life-threatening in certain cases [ 22 ] . Previous studies have reported that the incidence of complications associated with TJLB ranges from 1.3% to 20%. These include minor incidental adverse events, such as fever, tachycardia, and hematoma, as well as severe events, including pneumothorax, cervical pseudoaneurysm, biliary bleeding, and intraperitoneal hemorrhage [ 22 ] . A large-scale study by Kalambokis et al. systematically reviewed 64 articles involving 7,649 patients undergoing TJLB, and reported incidences of minor and major complications of 6.5% and 0.56%, respectively [ 24 ] . It has been reported that hemoperitoneum occurs in approximately 0.2% of all procedures, usually resulting from perforation of Glisson’s capsule [ 25 ] . Fatal intraperitoneal hemorrhage secondary to hepatic subcapsular hematoma has also been documented [ 26 ] . Notably, such fatal complications may occur even when the procedure is performed by well-trained operators [ 25 ] . Among patients undergoing TJLB, nearly all procedure-related deaths have been attributed to hemoperitoneum (0.06%) and ventricular arrhythmia (0.04%). [ 25 ] even supraventricular arrhythmia—the most frequently reported minor complication in previous studies—was not encountered in our TJLB. The association between the number of needle passes and the incidence of complications remains controversial. In our study, adequate specimens were obtained with a single pass in all cases. In one study, many patients underwent multiple biopsies, with a complication rate of 10.4%, which was very similar to their overall complication rate [ 27 ] ; therefore, the authors concluded that multiple biopsies do not increase the risk of complications. In contrast, Lebrec et al. reported that complications were associated with an increased number of passes required to obtain sufficient liver tissue, whereas other studies found no relationship between the occurrence of major complications and the number of specimens collected [ 25 ] . In view of this, TJLB should be considered as the first option when repeated liver biopsies are required in patients with liver disease [ 28 ] . Furthermore, TJLB with coagulopathies showed no statistically significant differences in complication rates in subgroups stratified by platelet count or INR. The authors concluded that TJLB can be safely performed in patients with abnormal platelet counts or INR, which is consistent with our observations [ 29 ] . However, TJLB should be performed with caution to minimize the risk of iatrogenic, potentially fatal hemorrhage. Moreover, during the puncture, ultrasound guidance of the internal jugular vein should be used whenever possible to avoid life-threatening complications such as pneumothorax or inadvertent arterial puncture. Notably, we observed a trend toward shorter specimen lengths and fewer hepatic lobules as HVPG increased. However, this did not correlate with the final histological diagnostic yield, suggesting that the degree of cirrhosis seems not significantly affect the adequacy of samples obtained through TJLB. Based on this observation, we strongly recommend performing TJLB in conjunction with HVPG measurement to obtain histological confirmation, which can guide subsequent therapeutic decisions—particularly in tailoring anti-cirrhotic strategies. This aligns with the current hepatological practice of using TJLB for both primary and secondary prevention in patients with portal hypertension [ 12 , 30 ] . Furthermore, recent evidence indicates that HVPG may outperform histology in assessing the response to antiviral therapy in chronic hepatitis C [ 31 ] . Therefore, the transjugular biopsy approach may represent the preferred method for liver biopsy in this context, offering both diagnostic and prognostic advantages while partially offsetting the additional costs associated with TJLB compared to percutaneous liver biopsy. This study has several limitations. First, TJLB has been considered to be less satisfactory compared with PLB because the samples obtained are more fragmented, smaller and the cylinders thinner owing to the limited size of the sheath. But doctors can do multiple samplings to obtain adequate specimens. [ 32 ] The sample size was relatively small in our study, and further validation with larger cohorts is warranted. Second, although adequate sampling and recently proposed minimum standards (≥ 11CPTs) continue to constrain the accuracy of staging and grading in chronic hepatitis, TJLB has been shown to be comparable to percutaneous liver biopsy in this regard [ 32 ] . Third, this study is retrospective, we need more prospective data to support. Conclusions In summary, TJLB is a safe procedure with high diagnostic value, providing adequate histopathological samples as well as HVPG data, which makes it particularly useful in patients with unexplained liver dysfunction and hemorrhage tendency for diagnosis and therapy. Declarations Ethics approval and consent to participate The study was approved by the Ethics Committee of Zhongshan Hospital Fudan University under the Declaration of Helsinki. (No.2025-114) All patients provided written informed consent. Authors’ Contributions Z.Zheng. was responsible for study design, methodology, statistical analysis, and drafting of the manuscript; M.Y. was responsible for data acquisition and compilation and methodology; J.Y., J.M. and Z.Zhang. were responsible for data acquisition, statistical analysis, and methodology; L.M., S.C. and J.W. was responsible for study design and conceptualization; Y.J. offered assistance for pathological diagnosis; X.W., Z.Y. and J.L. was responsible for study design, drafting and supervision; W.Z. was responsible for study design and methodology, drafting and revision of the manuscript, and supervision. All authors have read and approved the final version of the manuscript. Consent for publication This study does not contain any individual person’s data; therefore, consent for publication is not applicable. Conflicts of Interest The authors declare that there are no conflicts of interest in this study. Data availability No datasets were generated or analysed during the current study. Funding information This study was supported by funding from the National Key Research and Development Program of China (Grant No. 24YFC2417505). References Shan S, Zhao X, Jia J. Comprehensive approach to controlling chronic hepatitis B in China[J]. Clin Mol Hepatol. 2024;30(2):135–43. Zhu L, Zhang CY, Li DP, et al. Tu-San-Qi (Gynura japonica): the culprit behind pyrrolizidine alkaloid-induced liver injury in China[J]. Acta Pharmacol Sin. 2021;42(8):1212–22. Wang JY, Gao H. Tusanqi and hepatic sinusoidal obstruction syndrome[J]. J Dig Dis. 2014;15(3):105–7. Zheng Z, Yang H, Shi Y, et al. 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Cite Share Download PDF Status: Published Journal Publication published 30 Jan, 2026 Read the published version in BMC Gastroenterology → Version 1 posted Editorial decision: Revision requested 26 Dec, 2025 Reviews received at journal 23 Dec, 2025 Reviews received at journal 10 Dec, 2025 Reviewers agreed at journal 04 Dec, 2025 Reviewers agreed at journal 02 Dec, 2025 Reviewers invited by journal 02 Dec, 2025 Editor assigned by journal 01 Dec, 2025 Editor invited by journal 13 Nov, 2025 Submission checks completed at journal 12 Nov, 2025 First submitted to journal 12 Nov, 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8033515","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":554338508,"identity":"8229e383-6e96-4555-9667-10c39a05bb3a","order_by":0,"name":"Zhiyuan Zheng","email":"","orcid":"","institution":"Zhongshan Hospital Fudan University, Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Zhiyuan","middleName":"","lastName":"Zheng","suffix":""},{"id":554338509,"identity":"9e1e1a89-9942-4fb4-aa93-805fbb7c73a6","order_by":1,"name":"Minjie Yang","email":"","orcid":"","institution":"Zhongshan Hospital Fudan University, 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University","correspondingAuthor":false,"prefix":"","firstName":"Zihan","middleName":"","lastName":"Zhang","suffix":""},{"id":554338513,"identity":"6cf82726-9eb7-4338-b97c-3e7a25a75745","order_by":5,"name":"Jian Wang","email":"","orcid":"","institution":"Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Jian","middleName":"","lastName":"Wang","suffix":""},{"id":554338514,"identity":"32cf1d6d-1732-4f67-a879-38547cd6b5cc","order_by":6,"name":"Yuan Ji","email":"","orcid":"","institution":"Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Yuan","middleName":"","lastName":"Ji","suffix":""},{"id":554338515,"identity":"b6b013b1-1a64-4fcb-840d-d4bb23e609b1","order_by":7,"name":"Shiyao Chen","email":"","orcid":"","institution":"Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Shiyao","middleName":"","lastName":"Chen","suffix":""},{"id":554338516,"identity":"e4cdb1f1-2c65-438a-8f7e-c4035b4d0006","order_by":8,"name":"Xiaolin Wang","email":"","orcid":"","institution":"Zhongshan Hospital Fudan University, Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Xiaolin","middleName":"","lastName":"Wang","suffix":""},{"id":554338517,"identity":"935bf812-9385-409c-8474-9dcf95580198","order_by":9,"name":"Zhiping Yan","email":"","orcid":"","institution":"Zhongshan Hospital Fudan University, Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Zhiping","middleName":"","lastName":"Yan","suffix":""},{"id":554338518,"identity":"af5d4175-8c54-4c81-91ee-850760cf5256","order_by":10,"name":"Jianjun Luo","email":"","orcid":"","institution":"Zhongshan Hospital Fudan University, Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Jianjun","middleName":"","lastName":"Luo","suffix":""},{"id":554338519,"identity":"bffa65c2-025d-4621-b810-d6d46abcb864","order_by":11,"name":"Wen Zhang","email":"data:image/png;base64,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","orcid":"","institution":"Zhongshan Hospital Fudan University, Fudan University","correspondingAuthor":true,"prefix":"","firstName":"Wen","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2025-11-05 03:08:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8033515/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8033515/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12876-026-04642-7","type":"published","date":"2026-01-30T15:59:33+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":97471831,"identity":"f4eb4624-c0bb-426d-a18c-210153b406ce","added_by":"auto","created_at":"2025-12-04 17:45:56","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":46384,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.docx","url":"https://assets-eu.researchsquare.com/files/rs-8033515/v1/88cd8ae7b5a0e92f0879dd8e.docx"},{"id":97471832,"identity":"a89d675a-b929-481e-977c-ae8963fd8ca0","added_by":"auto","created_at":"2025-12-04 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16:09:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":713582,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8033515/v1/d1db1312-a7b3-492a-a057-ef09046a32ef.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Transjugular Liver Biopsy in Patients with Unexplained Liver Dysfunction and hemorrhage tendency: A Safety and Efficacy Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAbnormal liver function has emerged as a leading reason for medical consultations in modern society, reflecting its growing prevalence among patients with liver disease. Common causes of abnormal liver function include hepatitis viruses, excessive alcohol consumption, non-alcoholic fatty liver disease, and drug- or toxin-induced injuries. Particularly in China, although the widespread hepatitis B vaccination has significantly reduced the incidence of hepatitis B and subsequent cirrhosis, there still have a substantial burden of hepatitis B\u0026ndash;related liver disease. This is largely attributable to its large population base and the highly chronic, often asymptomatic nature of hepatitis B infection, which contributes to its persistence and underdiagnosis.\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e In addition, alcohol abuse, as well as the misuse of hepatotoxic chemical agents and herbal medicines, can cause significant liver injury. In European countries, excessive alcohol consumption is the most common cause of nonalcoholic fatty liver disease. In China, however, the inappropriate use of certain herbal remedies accounts for a considerably higher incidence of irreversible liver damage compared with western countries\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. For example, exposure to pyrrolizidine alkaloids has been identified as one of the major causes of hepatic sinusoidal obstruction syndrome.\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003eSevere sinusoidal obstruction syndrome often leads to multiorgan failure, with a mortality rate exceeding 80%. For example, liver dysfunction has been frequently reported in patients receiving long-term medications for chronic diseases, such as antirheumatic agents, targeted anticancer therapies, and immunosuppressive drugs\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. However, the overlap with underlying conditions often hinders the early recognition of these drug-related causes\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. In recent years, the incidence of autoimmune-related hepatitis has been steadily increasing, and it has emerged as a major disease with a global impact\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. However, the clinical diagnosis of autoimmune liver disease remains highly challenging. Liver biopsy is therefore essential for autoimmune hepatitis (AIH), as approximately one-third of patients are already diagnosed with cirrhosis at presentation, even in the absence of symptoms. This significantly influences treatment decisions, follow-up strategies, and overall prognosis\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. Notably, noninvasive tools such as transient elastography are often unreliable at the time of diagnosis, as liver stiffness measurements are influenced by both fibrosis and inflammation\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eVarious types of primary and secondary unrecognized abnormal liver functional may have different clinical manifestation and causes. And it is hard to make differential diagnosis by normal ways, like laboratory examination, echo and CT. Liver histology is still the golden standard for evaluating liver inflammation, necrosis and fibrosis. Although ultrasound and laboratory indicator with high sensitivity and specificity, liver biopsy is only a significant method to help doctor diagnose liver function damage, which can provide guide of treatment and prognosis. At most conditions, the way to obtain liver tissue is percutaneous liver biopsy (PLB)\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. Unfortunately, patients who present with abnormal liver function often exhibit coexisting coagulopathy, which poses considerable challenges for obtaining liver tissue samples through percutaneous biopsy.\u003c/p\u003e\u003cp\u003etransjugular liver biopsy (TJLB) is a relatively new performance in obtaining histopathological sample for diagnosis of unrecognized liver damage. When percutaneous liver biopsy is contraindicated, TJLB provides an effective, safe, and widely accepted alternative for obtaining liver tissue. TJLB can help doctor obtain liver tissue sample when patient have contraindications like preexisting coagulopathy, ascites, obesity, transplantation, and cirrhosis., which is not suitable to do PLB. Even in advanced liver disease, biopsy remains crucial for establishing etiology and uncovering potentially treatable causes\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. TJLB can be combined with hepatic venous pressure gradient (HVPG) measurement to indirectly assess the severity of portal hypertension. The degree of portal hypertension is critical for guiding treatment and predicting prognosis in patients with cirrhosis. Therefore, this study aims to assess sample quality and safety of TJLB in patients with unexplained liver dysfunction and hemorrhage tendency\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. These motivations prompted us to evaluate the use of TJLB combined with HVPG measurement in patients with unexplained liver dysfunction and a bleeding tendency, assessing technical success, complications, biopsy specimen quality, and resulting changes in patient management.\u003c/p\u003e"},{"header":"Method","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003ePatients selection\u003c/h2\u003e\u003cp\u003eWe retrospectively analyzed 58 patients with unrecognized liver function damage and hemorrhage tendency, performed TJLB to achieve pathological diagnosis between January 1st ,2018 and February 17th, 2020. All of the patients underwent TJLB and measured hepatic vein pressure. This research was admitted by ethic committee of Zhongshan hospital, Fudan University. All the patients enrolled in study was informed consent. Patients\u0026rsquo; basic information and demographic information was collected from record (Name, age, gender, ID, clinical manifestation, previous treatment, laboratory examination and computed tomography). Number of hepatic lobes, vascular pressure was also extracted from record. Prognostic information and complications were also documented.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eProcedures\u003c/h3\u003e\n\u003cp\u003eAll interventional operations are performed by experienced interventional doctors in accordance with the standard procedures recommended by the American Society of Interventional Radiology. Blood routine and coagulation-related laboratory indexes (PT, APTT, INR, TT and D-dimer) were measured in all patients three days before operation, and preoperative preparation was carried out strictly according to the indication of operation. The operation was performed under conscious sedation, continuous ECG monitoring and oxygen inhalation during the operation. All hepatic tissue samples obtained by TJLB were assessed by two independent pathologists and were confirmed to conform to the established criteria for adequate liver biopsy specimens. To minimize potential sources of bias, several measures were implemented in this retrospective study. All TJLB procedures were performed using the same COOK LABS kit and standardized protocol by experienced interventional radiologists to reduce operator-related variability. Clinical, laboratory, and hemodynamic data were collected from electronic medical records by two independent investigators, and discrepancies were resolved by consensus to ensure data accuracy. Diagnostic adequacy and histopathological interpretation were reviewed by two senior hepatopathologists who were blinded to clinical and HVPG data, minimizing interpretation bias. Inclusion criteria were predefined to avoid selection bias, and all consecutive eligible patients within the study period were included. Statistical analyses were performed using uniform thresholds and objective parameters to further reduce analytical bias.\u003c/p\u003e\n\u003ch3\u003eComplications\u003c/h3\u003e\n\u003cp\u003eOperation-related complications during and after TJLB were recorded. Minor complications refer to clinical symptoms that are self-limited and can be cured without too much medical intervention, such as pain, bleeding at the puncture point. Major complications were recorded according to the complication grading system of the Interventional Radiology Association. What is more, patients with major complications who needed for minor(\u0026lt;\u0026thinsp;48h) and major(\u0026gt;\u0026thinsp;48h) hospitalization or with permanent adverse complications and death was specially recorded.\u003c/p\u003e\n\u003ch3\u003eLive tissue specimen\u003c/h3\u003e\n\u003cp\u003eThe pathological specimens of the liver obtained by puncture were fixed in 4% formalin solution and sent to the pathology department for preparation. The histological sections of the liver were embedded, sliced and stained by pathological technicians, and then read by a pathologist specializing in liver tissue. The content of the evaluation was the tissue length of the biopsy, the number and extent of hepatic lobules, the condition of hepatocytes, and the quantity and quality of portal ducts.\u003c/p\u003e\n\u003ch3\u003eStatistics\u003c/h3\u003e\n\u003cp\u003eSTATA/SE 15.1 software was used for statistical analysis. Continuous variables are expressed in the form of mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) or median and quartile spacing. Categorical variables were expressed as numbers and proportions.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003ePatient characteristics\u003c/h2\u003e\u003cp\u003e58 patients with 77 TJLB were retrospectively included in this study. There are 36 males (62.7%) and 22 females (37.93%) in this study, the mean age is 51.95\u0026thinsp;\u0026plusmn;\u0026thinsp;15.16. All the patients were presented unknown liver function damage or with cogulation disorder. The most majority of symptoms is abdominal distention (n\u0026thinsp;=\u0026thinsp;22, 39.28%). 16 of 58 patients (27.12%) is with poor appetite and varicosity was shown in 11 patients (18.64%). Besides, fifteen patients have melena symptoms and only one patient had jaundice. In these patients, most of them were first diagnosed with unrecognized portal vein hypertension (n\u0026thinsp;=\u0026thinsp;13, 22.03%) and unrecognized liver function injury (n\u0026thinsp;=\u0026thinsp;14, 23.72%). Fourteen patients (23.72%) suffered liver cirrhosis. Besides, 12 patients have rt-PA history and only 1 patient had chemotherapy before TJLB. For the examination of the coagulation system, 46 patients (77.07%) are in normal prothrombin time (PT), but 11 patients (18.94%) show long PT. Besides, in the cohort, forty-two patients (71.19%) appeared as ascites. Specific information weas shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePatients baseline characteristic\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePercentage\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e62.07%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e37.93%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge, years\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e51.95\u0026thinsp;\u0026plusmn;\u0026thinsp;15.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMain compliants, n(%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbdominal distention\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e39.28\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePoor appetite\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e27.12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVaricosity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e18.64\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMelena\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e25.42\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eJaundice\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.69\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHistory, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSuspicious Portal\u0026nbsp;hypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e22.03\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLiver function damage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e23.72\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLiver cirrhosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e23.72\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ert-PA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e20.33\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChemotherapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.69\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePT, n(%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;13s\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e13-16s\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e77.97\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;16s\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e18.64\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAscites, n(%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e71.19\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e28.81\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eDiagnostic performance of TJLB\u003c/h3\u003e\n\u003cp\u003eDiagnostic performance of TJLB in patients was listed in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The mean sample length of TJLB is 8mm (Maximum-Minimum, 5-13mm). Around 9 hepatic lobules (Maximum-Minimum, 4\u0026ndash;20) were obtained in each sample of TJLB. In special cohort, mean number hepatic lobule is 9 (Maximum-Minimum, 7\u0026ndash;10) in liver cirrhosis biopsy specimen. Besides, in patients with ascites, the length of the puncture specimen is 9 (Maximum-Minimum, 5\u0026ndash;20). For patients with coagulation disorders, intravascular biopsy specimens can still obtain 8 liver lobes (Maximum-Minimum, 4\u0026ndash;12). Also, about 10 hepatic lobules (Maximum-Minimum, 7\u0026ndash;12) in melena patients were found. For all the patients, all the patients (100%) have successfully reached histological diagnosis. 16 patients (72.14%) were successfully diagnosed by TJLB in etiology level. For special patients, 13 of 41 patients (78.04%) with ascites were performed and have a final diagnosis. Besides, histological diagnosis possible in coagulopathy patients was 72.72%.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSample quality and TJLB performance of TJLB.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePerformance\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSample Length, mm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8(5\u0026ndash;13)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of hepatic lobule\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (4\u0026ndash;20)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of hepatic lobule in cirrhosis patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9(7\u0026ndash;10)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of hepatic lobule in HVOD patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5(4\u0026ndash;6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of hepatic lobule in hepatitis patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9(8\u0026ndash;13)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of hepatic lobule in ki67\u0026thinsp;+\u0026thinsp;\u0026gt;\u0026thinsp;10% patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10(8\u0026ndash;13)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of hepatic lobule in ascites patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9(5\u0026ndash;20)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of hepatic lobule in coagulopathy patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8(4\u0026ndash;12)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of hepatic lobule in melena patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10(7\u0026ndash;12)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHistological diagnosis possible, n\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e100%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEtiology successfully determined by TJLB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16 (72.41%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnclear etiology before TJLB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e100%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHistological diagnosis possible in ascites, n\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e31/41(78.04%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHistological diagnosis possible in coagulopathy, n\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8/11(72.72%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eDiagnostic performance in patients for different HVPG\u003c/h2\u003e\u003cp\u003eHVPG is divided into five subgroups, and in each subgroup, we describe its number of sample lengths, the number of liver lobule, the number of etiology successfully determined by TJLB and complications (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). In patients with HVPG\u0026thinsp;\u0026lt;\u0026thinsp;5mmHg, the sample of 8 patients was obtained, average length of the samples was 7 mm (Maximum-Minimum, 3-11mm). The mean number of liver lobule was 9 (from 7 to 14) under the microscope. Three of eight patients received the ultimate histopathological diagnosis through TJLB. For the patient subgroup with an HVPG between 5 and 10 mmHg (n\u0026thinsp;=\u0026thinsp;8), the mean biopsy sample length was 8 mm (range: 6\u0026ndash;11 mm), with an average of 13 hepatic lobules obtained per sample (range: 8\u0026ndash;16).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSample quality in different HVPG subgroups.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHVPG\u0026thinsp;\u0026lt;\u0026thinsp;5mmHg\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHVPG5-10mmHg\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eHVPG10-20mmHg\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eHVPG\u0026thinsp;\u0026gt;\u0026thinsp;20mmHg\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSample Length, mm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7(3\u0026ndash;11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8(6\u0026ndash;11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10(8\u0026ndash;12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8(7\u0026ndash;10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of hepatic lobule,\u003c/p\u003e\u003cp\u003eN(min-max)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9(7\u0026ndash;14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13(8\u0026ndash;16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9(6\u0026ndash;12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7(6\u0026ndash;13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEtiology successfully determined by TJLB, n(min-max)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3/8(37.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7/8(87.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12/20(60%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5/7(71.42%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eComplications, n\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eSafety of TJLB in liver biopsy of unknown liver damage\u003c/h2\u003e\u003cp\u003eIn total, no complications were observed during or after the procedures. Specifically, there were no minor complications such as subclinical capsule perforation, bleeding at the puncture site, abdominal pain, hypotension, or tachycardia. Likewise, no major complications\u0026mdash;including pneumothorax, ventricular arrhythmias, or accidental injury to adjacent organs\u0026mdash;were reported. Importantly, there were no deaths related to the TJLB procedure in our cohort .\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eLiver biopsy is a crucial clinical tool for the diagnosis of liver diseases, providing comprehensive histological information and guiding subsequent treatment strategies. However, due to impaired hepatic function, many patients with liver disease present with complications such as significant ascites and coagulopathy, rendering conventional percutaneous liver biopsy risky, with potential for life-threatening complications including hemorrhage and infection\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. Our study demonstrates that TJLB is a safe and effective alternative for diagnosis in cases of unexplained liver disease or with bleeding tendency. Moreover, it enables the assessment of hepatic hemodynamic parameters, such as HVPG\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e, thereby providing both histological and hemodynamic parameter to help doctor have an accurate diagnosis and do a clinical decision-making of liver disease.\u003c/p\u003e\u003cp\u003eThe Liver Access and Biopsy Set (LABS) from COOK Medical was used to perform TJLB in our studies. Liver tissue samples were obtained using an 18G Quick-Core Tru-Cut needle. Evidence suggests that, compared to the Menghini needle, the Tru-Cut needle yields longer and diagnostically superior specimens, potentially due to a lower fragmentation rate\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. Comparative studies of Tru-Cut and Menghini needles used in TJLB have reported similar findings\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. For those aiming to obtain longer specimens with reduced fragmentation, the use of a finer Tru-Cut needle may be considered\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe quality of samples, to be considered optimal for diagnosis of diffuse liver disease, the specimens should be at least 15 mm long and contain at least 6 CPTs\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. Reliable grading and staging of liver disease require a biopsy of at least 20 mm in length and at least 11 portal tracts\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. A biopsy shorter than 2 cm but containing at least 11 CPTs may still be considered acceptable for grading and staging\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. In a systematic review of 64 studies with more than 7500 biopsies, TJLB offered adequate quality samples in 96% of the cases and the specimens obtained were considered adequate for histologic diagnosis in the most of them\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. Although it is generally accepted that obtaining more tissue is advantageous, our findings demonstrate that even with an average specimen length of 8 mm, distinct liver disease diagnosis can be identified by experienced pathologists. Therefore, TJLB can provide more useful information for doctors than empirical treatment without biopsy. Our center think additional sampling beyond the standard requirements is unnecessary once tissue quality is confirmed, as this may increase the risk of unforeseen complications. Among patients later confirmed to have cirrhosis, biopsy specimens still contained an average of 9 hepatic lobules, fully meeting the diagnostic criteria for cirrhotic liver biopsy based on our experience.\u003c/p\u003e\u003cp\u003eThe Tru-Cut needle not only yields larger tissue samples but also allows for angular adjustments of the biopsy set within the vessel, enabling multiple passes to achieve an adequate number of CPTs while reduces the bleeding risks, which commonly occurred in percutaneous biopsy\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e. Previous studies have shown that TJLB, with a median of 2.3 passes, achieves a similar number of CPTs compared to PLB\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. However, CPT counts in TJLB may still be underestimated relative to PLB\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eIn this study, doctors were highly experienced and performed the procedures according to established indications. No minor or major complications required medication or surgery were observed, with an incidence lower than previously published\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. Even in patients receiving oral anticoagulants, our experience suggests that TJLB can still be. performed safely. Biopsy-related complications like mortality, pneumothorax, biliary bleeding, pseudoaneurysm or intra-abdominal hemorrhage were also not observed after TJLB. Make sure that, although TJLB is generally considered a safe liver biopsy technique, this does not preclude the occurrence of complications, which may even be life-threatening in certain cases\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. Previous studies have reported that the incidence of complications associated with TJLB ranges from 1.3% to 20%. These include minor incidental adverse events, such as fever, tachycardia, and hematoma, as well as severe events, including pneumothorax, cervical pseudoaneurysm, biliary bleeding, and intraperitoneal hemorrhage\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. A large-scale study by Kalambokis et al. systematically reviewed 64 articles involving 7,649 patients undergoing TJLB, and reported incidences of minor and major complications of 6.5% and 0.56%, respectively\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. It has been reported that hemoperitoneum occurs in approximately 0.2% of all procedures, usually resulting from perforation of Glisson\u0026rsquo;s capsule\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e. Fatal intraperitoneal hemorrhage secondary to hepatic subcapsular hematoma has also been documented\u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e. Notably, such fatal complications may occur even when the procedure is performed by well-trained operators\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e. Among patients undergoing TJLB, nearly all procedure-related deaths have been attributed to hemoperitoneum (0.06%) and ventricular arrhythmia (0.04%).\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e even supraventricular arrhythmia\u0026mdash;the most frequently reported minor complication in previous studies\u0026mdash;was not encountered in our TJLB.\u003c/p\u003e\u003cp\u003eThe association between the number of needle passes and the incidence of complications remains controversial. In our study, adequate specimens were obtained with a single pass in all cases. In one study, many patients underwent multiple biopsies, with a complication rate of 10.4%, which was very similar to their overall complication rate\u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e; therefore, the authors concluded that multiple biopsies do not increase the risk of complications. In contrast, Lebrec et al. reported that complications were associated with an increased number of passes required to obtain sufficient liver tissue, whereas other studies found no relationship between the occurrence of major complications and the number of specimens collected\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e. In view of this, TJLB should be considered as the first option when repeated liver biopsies are required in patients with liver disease\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e. Furthermore, TJLB with coagulopathies showed no statistically significant differences in complication rates in subgroups stratified by platelet count or INR. The authors concluded that TJLB can be safely performed in patients with abnormal platelet counts or INR, which is consistent with our observations\u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e. However, TJLB should be performed with caution to minimize the risk of iatrogenic, potentially fatal hemorrhage. Moreover, during the puncture, ultrasound guidance of the internal jugular vein should be used whenever possible to avoid life-threatening complications such as pneumothorax or inadvertent arterial puncture. Notably, we observed a trend toward shorter specimen lengths and fewer hepatic lobules as HVPG increased. However, this did not correlate with the final histological diagnostic yield, suggesting that the degree of cirrhosis seems not significantly affect the adequacy of samples obtained through TJLB. Based on this observation, we strongly recommend performing TJLB in conjunction with HVPG measurement to obtain histological confirmation, which can guide subsequent therapeutic decisions\u0026mdash;particularly in tailoring anti-cirrhotic strategies. This aligns with the current hepatological practice of using TJLB for both primary and secondary prevention in patients with portal hypertension\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e. Furthermore, recent evidence indicates that HVPG may outperform histology in assessing the response to antiviral therapy in chronic hepatitis C\u003csup\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e. Therefore, the transjugular biopsy approach may represent the preferred method for liver biopsy in this context, offering both diagnostic and prognostic advantages while partially offsetting the additional costs associated with TJLB compared to percutaneous liver biopsy.\u003c/p\u003e\u003cp\u003eThis study has several limitations. First, TJLB has been considered to be less satisfactory compared with PLB because the samples obtained are more fragmented, smaller and the cylinders thinner owing to the limited size of the sheath. But doctors can do multiple samplings to obtain adequate specimens.\u003csup\u003e[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/sup\u003e The sample size was relatively small in our study, and further validation with larger cohorts is warranted. Second, although adequate sampling and recently proposed minimum standards (\u0026ge;\u0026thinsp;11CPTs) continue to constrain the accuracy of staging and grading in chronic hepatitis, TJLB has been shown to be comparable to percutaneous liver biopsy in this regard\u003csup\u003e[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/sup\u003e. Third, this study is retrospective, we need more prospective data to support.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn summary, TJLB is a safe procedure with high diagnostic value, providing adequate histopathological samples as well as HVPG data, which makes it particularly useful in patients with unexplained liver dysfunction and hemorrhage tendency for diagnosis and therapy.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethics Committee of Zhongshan Hospital Fudan University under the Declaration of Helsinki. (No.2025-114) All patients provided written informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZ.Zheng. was responsible for study design, methodology, statistical analysis, and drafting of the manuscript; M.Y. was responsible for data acquisition and compilation and methodology; J.Y., J.M. and Z.Zhang. were responsible for data acquisition, statistical analysis, and methodology; L.M., S.C. and J.W. was responsible for study design and conceptualization; Y.J. offered assistance for pathological diagnosis; X.W., Z.Y. and J.L. was responsible for study design, drafting and supervision; W.Z. was responsible for study design and methodology, drafting and revision of the manuscript, and supervision. All authors have read and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study does not contain any individual person’s data; therefore, consent for publication is not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there are no conflicts of interest in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo datasets were generated or analysed during the current study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by funding from the National Key Research and Development Program of China (Grant No. 24YFC2417505).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eShan S, Zhao X, Jia J. Comprehensive approach to controlling chronic hepatitis B in China[J]. Clin Mol Hepatol. 2024;30(2):135\u0026ndash;43.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhu L, Zhang CY, Li DP, et al. Tu-San-Qi (Gynura japonica): the culprit behind pyrrolizidine alkaloid-induced liver injury in China[J]. Acta Pharmacol Sin. 2021;42(8):1212\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang JY, Gao H. Tusanqi and hepatic sinusoidal obstruction syndrome[J]. J Dig Dis. 2014;15(3):105\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZheng Z, Yang H, Shi Y, et al. Identification of tumor antigens and anoikis-based molecular subtypes in the hepatocellular carcinoma immune microenvironment: implications for mRNA vaccine development and precision treatment[J]. J Big Data. 2023;10(1):129.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBj\u0026ouml;rnsson ES. 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Eur J Gastroenterol Hepatol, 2021, 33(12).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKalambokis G, Manousou P, Vibhakorn S, et al. Transjugular liver biopsy\u0026ndash;indications, adequacy, quality of specimens, and complications\u0026ndash;a systematic review[J]. J Hepatol. 2007;47(2):284\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSawyerr AM, Mccormick PA, Tennyson GS, et al. A comparison of transjugular and plugged-percutaneous liver biopsy in patients with impaired coagulation[J]. J Hepatol. 1993;17(1):81\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEichholz JC, Kirstein MM, Book T, et al. Transjugular liver biopsy and hepatic venous pressure gradient measurement in patients with and without liver cirrhosis[J]. Eur J Gastroenterol Hepatol. 2021;33(12):1582\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStift J, Semmler G, W\u0026ouml;ran K, et al. Comparison of the diagnostic quality of aspiration and core-biopsy needles for transjugular liver biopsy[J]. Dig Liver Dis. 2020;52(12):1473\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLari\u0026ntilde;o-Noia J, Fern\u0026aacute;ndez-Castroagud\u0026iacute;n J, De La Iglesia-Garc\u0026iacute;a D, et al. Quality of Tissue Samples Obtained by Endoscopic Ultrasound-Guided Liver Biopsy: A Randomized, Controlled Clinical Trial[J]. Am J Gastroenterol. 2023;118(10):1821\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBravo AA, Sheth SG, Chopra S. Liver biopsy[J]. N Engl J Med. 2001;344(7):495\u0026ndash;500.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang Q, Fiel MI, Blank S, et al. Impact of liver fibrosis on prognosis following liver resection for hepatitis B-associated hepatocellular carcinoma[J]. Br J Cancer. 2013;109(3):573\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMagahis PT, Hissong E, Hanscom M, et al. Outcomes of EUS-guided liver biopsy using 22-gauge versus 19-gauge needles with a novel hydrostatic sampling technique[J]. Gastrointest Endosc; 2025.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJeor JDS, Reisenauer CJ, Andrews JC, et al. Transjugular renal biopsy bleeding risk and diagnostic yield: a systematic review[J]. J Vasc Interv Radiol. 2020;31(12):2106\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eClark TWI, Mccann JW, Salsamendi J, et al. Optimizing Needle Direction During Transjugular Liver Biopsy Provides Superior Biopsy Specimens[J]. Cardiovasc Interv Radiol. 2014;37(6):1540\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKalambokis G, Manousou P, Vibhakorn S, et al. 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Assessment of therapeutic benefit of antiviral therapy in chronic hepatitis C: is hepatic venous pressure gradient a better end point?[J]. Gut. 2002;50(3):425\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBa\u0026ntilde;ares R, Alonso S, Catalina M-V, et al. Randomized Controlled Trial of Aspiration Needle versus Automated Biopsy Device for Transjugular Liver Biopsy[J]. J Vasc Interv Radiol. 2001;12(5):583\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003c/ol\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":"Transjugular Liver Biopsy, hepatic venous pressure gradient, unexplained liver dysfunction","lastPublishedDoi":"10.21203/rs.3.rs-8033515/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8033515/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e\u003cp\u003eTransjugular liver biopsy (TJLB) enables histopathological diagnosis of liver disease and simultaneous assessment of the hepatic venous pressure gradient (HVPG).\u003c/p\u003e\u003cp\u003e\u003cb\u003eAims\u003c/b\u003e\u003c/p\u003e\u003cp\u003eTo assess the diagnostic adequacy and safety of TJLB in combination with HVPG measurement in patients with unexplained Liver Dysfunction and hemorrhage tendency.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e\u003cp\u003eA total of 77 TJLB procedures were carried out in 58 patients with unexplained liver dysfunction using the COOK LABS kit. Biopsy specimens were evaluated for specimen length, number of complete portal tracts, diagnostic yield, and complications. Subgroup analyses were performed in different HVPG patients.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAdequate histopathological samples were obtained in all procedures. The mean specimen length was 8 mm (range, 5\u0026ndash;13 mm), with an average of 9 complete portal tracts (range, 4\u0026ndash;20). 72.4% of patients have identified the causes after TJLB, which performed for 78.0% in patients with ascites and 72.7% with coagulopathy. For patients performed the pressure measure, higher HVPG values seemed to be correlated with shorter specimen length and fewer portal tracts. No procedure-related complications occurred.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e\u003cp\u003eTJLB is a safe and effective method for liver disease diagnosis and HVPG assessment in patients with unexplained Liver Dysfunction and hemorrhage tendency.\u003c/p\u003e","manuscriptTitle":"Transjugular Liver Biopsy in Patients with Unexplained Liver Dysfunction and hemorrhage tendency: A Safety and Efficacy Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-04 17:45:51","doi":"10.21203/rs.3.rs-8033515/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-26T07:27:23+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-23T08:18:48+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-10T14:07:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"327803014389044638543779342289632479971","date":"2025-12-04T17:19:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"338820945237705217259592494962317722442","date":"2025-12-03T00:30:28+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-02T13:00:10+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-01T18:09:17+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-11-13T06:56:25+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-12T12:45:06+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Gastroenterology","date":"2025-11-12T12:41:56+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":"0c8d5bef-f634-44b9-80a3-292284803203","owner":[],"postedDate":"December 4th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-02T16:06:31+00:00","versionOfRecord":{"articleIdentity":"rs-8033515","link":"https://doi.org/10.1186/s12876-026-04642-7","journal":{"identity":"bmc-gastroenterology","isVorOnly":false,"title":"BMC Gastroenterology"},"publishedOn":"2026-01-30 15:59:33","publishedOnDateReadable":"January 30th, 2026"},"versionCreatedAt":"2025-12-04 17:45:51","video":"","vorDoi":"10.1186/s12876-026-04642-7","vorDoiUrl":"https://doi.org/10.1186/s12876-026-04642-7","workflowStages":[]},"version":"v1","identity":"rs-8033515","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8033515","identity":"rs-8033515","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}