Diagnostic value of homocysteine combined with IgG in differentiating drug- induced liver injury and autoimmune hepatitis

Diagnostic value of homocysteine combined with IgG in differentiating drug- induced liver injury and autoimmune hepatitis | 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 Article Diagnostic value of homocysteine combined with IgG in differentiating drug- induced liver injury and autoimmune hepatitis Xue JiaoMD, Jing Liu, Yibing Zhou, Ze Chen, Yinglun Li, Qian WeiMD, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6720659/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract This study aims to investigate the diagnostic utility of homocysteine and IgG in distinguishing drug-induced liver injury from autoimmune hepatitis. A total of 181 patients with drug-induced liver damage and 143 patients with autoimmune hepatitis were included in this retrospective study. The clinical baseline data, homocysteine and IgG levels of the two groups were compared. The diagnostic sensitivity and specificity were determined using receiver operating characteristic (ROC) curves, and the diagnostic values were compared using the area under the receiver operating curve (AUROC). At a critical value of 10.05, the diagnostic sensitivity of homocysteine for autoimmune hepatitis was 88.1%, with a specificity of 92.3% and an AUROC of 0.881 (95% CI, [0.834 ~ 0.927]). When the critical value was 15.31, the AUROC for the diagnosis of autoimmune hepatitis by IgG was 0.732 (95% CI, 0.677 to 0.788). The combination of homocysteine and IgG resulted in an AUROC of 0.903 (95% CI, [0.864 ~ 0.942]), indicating a notable enhancement in diagnostic performance. Homocysteine has the potential to assist in the accurate differentiation between drug-induced liver injury and autoimmune hepatitis. Furthermore, the utilization of homocysteine in conjunction with IgG enhances its diagnostic efficacy. Biological sciences/Immunology Health sciences/Biomarkers Health sciences/Endocrinology Health sciences/Gastroenterology AIH DILI Homocysteine IgG differential diagnosis Figures Figure 1 Figure 2 1. Introduction Autoimmune hepatitis (AIH) is a progressive inflammatory response with an uncertain etiology, which belongs to the category of autoimmune liver diseases with a genetic predisposition 1 . The diagnosis of AIH is dependent upon the presence of elevated serum aminotransferase and IgG and/or γ levels, the existence of autoantibodies, and the histological presence of interfacial hepatitis in the liver 2 . AIH manifests in genetically susceptible individuals when a trigger, such as exposure to a virus, precipitates a T-cell-mediated autoimmune response against liver autoantigens. This immune response is the consequence of a loss of tolerance resulting from inadequate regulatory immune control 3 . The diagnosis of AIH is based on the presence of specific clinical, biochemical, serological, and histological patterns, which must be confirmed by the response to immunosuppressive therapy. The disease lacks clear diagnostic features, which makes it challenging to diagnose 4 . Drug-induced liver injury (DILI) represents one of the most prevalent adverse reactions observed in clinical drug use. It is typically induced by a diverse range of chemical drugs, traditional Chinese medicine, health products, biological agents and their metabolites 5 . The clinical manifestations of DILI are unspecific and may resemble other hepatic disorders with variable elevations in liver biochemistries 6 . At present, DILI is an exclusionary diagnosis. In the absence of reliable laboratory testing, diagnosing DILI can be challenging, particularly when features of AIH are present; if DILI and AIH cannot be reliably distinguished, rapidly reducing or stopping immunosuppressive therapy in cases where the underlying cause of liver damage is idiopathic AIH can result in a life-threatening risk of disease recurrence 7 . Therefore, it is crucial to exercise caution in order to ascertain the underlying etiology of the disease, in order to ensure the most appropriate treatment is selected. Liver biopsy remains the gold standard for the diagnosis of DILI and AIH. Although the accuracy is very high, the procedure is traumatic and not repeatable, rendering it unsuitable for routine monitoring as an invasive examination. Furthermore, it is challenging to gain acceptance from patients on a clinical level. The objective of this study was to retrospectively collect the basic information and clinical data of patients with DILI and AIH in order to identify a non-invasive, reliable and sensitive indicator that can distinguish between DILI and AIH. 2. Materials and Methods 2.1 Research object. Patient data was gathered from 2012 to 2022, finally resulting in the inclusion of 143 patients with AIH and 181 patients with DILI. The AIH is in accordance with the simplified diagnostic scoring system proposed by the International Autoimmune Hepatitis Working Group 8 ，and the DILI meets the diagnostic criteria for liver dysfunction as outlined in the RUCAM score 9 . Exclusion criteria: (1) In addition to other liver diseases that may result in liver dysfunction, including viral hepatitis, alcoholic hepatitis, hereditary metabolic liver disease, and non-alcoholic fatty liver disease; (2) A history of malignant tumors or other end-stage diseases; (3) The Patient data are incomplete. The study adhered to the principles outlined in the Declaration of Helsinki and was authorized by the Institutional Review Board of Tianjin Second People's Hospital (Approval No. [2024]68). 2.2 Research content. A collection of clinical data, serum biochemical indexes, thyroid function and immune function was made within one week of the liver biopsy. Clinical data encompasses age, gender, body mass index (BMI), Controlled Attenuation Parameter (CAP), Liver stiffness measurement (LSM), smoking, drinking, hypertension and diabetes. Serum biochemical markers include white blood cell (WBC), red blood cell (RBC), platelet (PLT), prothrombin time (PT), fibrinogen (FIB), thrombin time (TT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholinesterase (CHE), albumin (ALB), alkaline total cholesterol (TC), triglyceride (TG), , total bilirubin (TBIL), direct bilirubin (DBIL), homocysteine (HCY). Thyroid function include thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4)). Immunological markers (C3, C4, IgG, IgA, IgM). 2.3 Liver biopsy. Liver biopsy was performed on all patients under local anesthesia and ultrasound guidance. The specimens exhibited a length range of 1.0 to 2.0 cm. Liver tissue samples were obtained, fixed in 10% neutral buffered formalin, then subjected to a sequential process of paraffin embedding and staining with HE, Masson, and mesh fibers. Two experienced pathologists conducted an independent evaluation of liver tissue slices without access to the patient's clinical characteristics. 2.4 Statistical analysis Statistical analyses utilized SPSS version 26.0 and GraphPad Prism 9.5. Continuous variables with a normal distribution are expressed as mean±standard deviation, and an independent sample t-test is employed to compare the two groups. In the event that the continuous variables in question do not follow a normal distribution, they are expressed as the median (25th to 75th percentiles). In such instances, the Mann-Whitney U test is employed for the purpose of comparing the two groups. Percentages are employed to represent categorical variables and are compared between groups using Chi-square tests or Fisher's exact tests. The statistical significance was determined by a two-tailed P-value < 0.05. Binary logistic regression was utilized to analyze the effect of Hcy differentiation between AIH and DILI after the introduction of confounding factors. A receiver operating characteristic (ROC) curve was employed to measure the diagnostic effect of Hcy on AIH. 3. Result 3.1 Participant characteristics In the study, clinical symptoms observed in patients with drug-induced liver injury (DILI) included yellow urine in 109 cases (60.2%), gastrointestinal discomfort in 106 cases (58.6%), and fatigue in 96 cases (53.0%). In contrast, patients with autoimmune hepatitis (AIH) presented with yellow urine in 54 cases (37.8%), gastrointestinal discomfort in 60 cases (42.0%), and fatigue in 56 cases (39.2%). The incidence of yellow urine, gastrointestinal discomfort, and fatigue was significantly higher in the DILI group compared to the AIH group (P < 0.05). A summary of additional symptoms reported in both patient groups is provided in Table 1. Table 1 Comparison of clinical symptoms between DILI and AIH clinical manifestation DILI(n=181) AIH(n=143) c 2 p-value fatigue 96(53.0%) 56(39.2%) 6.178 0.013 Gastrointestinal symptoms 106(58.6%) 60(42.0%) 8.817 0.003 Upper abdominal discomfort, liver discomfort 11(6.1%) 15(10.5%) 2.107 0.147 fever 13(7.2%) 9(6.3%) 0.100 0.752 Yellow urine 109(60.2%) 54(37.8%) 16.118 ＜0.001 pruritus 6(3.3%) 7(4.9%) 0.5183 0.472 other 2(1.1%) 12(8.4%) 10.259 0.001 Note: Gastrointestinal symptoms encompass a range of issues such as loss of appetite, nausea, vomiting, bloating, diarrhea, acid reflux, and belching. Additionally, other symptoms may include a bitter taste in the mouth, dryness in the mouth and eyes, swelling or pain in the lower legs, and darkened skin. The baseline data of the two groups were compared, revealing that the women in the AIH group exhibited significantly higher values than those in the DILI group ( P < 0.05). The median age was 50 (38, 57) in the DILI group and 57 (50, 63) in the AIH group, with a statistically significant difference ( P < 0.05). A statistically significant difference was observed between the drinking habits of DILI patients (13.3%) and AIH patients (5.6%), with a higher prevalence of alcohol consumption among the former group ( P ＜0.05). The prevalence of hypertension was 18.8% in the DILI group and 28.7% in the AIH group ( P ＜0.05). No statistically significant correlations were identified between BMI, smoking, diabetes, WBC, PT, FIB, TC, DBIL, FT3, or C3. A comparison of the DILI group with the AIH group revealed statistically significant differences in the serum levels of RBC, PLT, TT, ALT, AST, CHE, ALB, TG, TBIL, HCY, TSH, FT4, C4, IgA and IgM in AIH group ( P ＜0.05). The full range of demographic, clinical and biochemical indicators for the study group is presented in Table 2. Table 2 Clinical features of patients Characteristic DILI(n=181) AIH(n=143) t/ u / c 2 p- value Sex c 2 =10.244 0.001 Male, n (%) 44(24.3%) 15(10.5%) Female, n (%) 137(75.7%) 128(89.5%) Age(years) 50 (38, 57) 57 (50, 63) u =8539.500 ＜0.001 BMI(Kg/m2) 23.01±3.45 23.40±3.33 t =-1.024 0.307 CAP (dB/m) 189(170,210) 197(178,218) u =11101 0.028 LSM (kPa) 11.2(8.5,15.1) 21.8(15.6,24.9) u =5116 ＜0.001 Smoking, n (%) 26(14.4%) 13(9.1%) c 2 =2.098 0.147 Drinking, n (%) 24(13.3%) 8(5.6%) c 2 =5.273 0.022 Hypertension, n (%) 34(18.9%) 41(28.7%) c 2 =4.278 0.039 Diabetes, n (%) 23(12.7%) 27(18.9%) c 2 =2.333 0.127 WBC(*^9/L) 4.83(3.82, 6.05) 4.77 (3.73, 5.61) u =12077 0.302 RBC(*^12/L) 4.33±0.52 4.06±0.50 t =4.676 ＜0.001 PLT(*^9/L) 207(165，257) 167(160，212) u =8284.5 ＜0.001 PT(s) 12.84(11.80, 13.50) 12.60(11.35, 13.50) u =12028.50 0.275 FIB(g/L) 2.21(1.88, 2.84) 2.24(1.80, 2.76) t =12497.50 0.596 TT(s) 19.8249±0.16709 20.4261±0.18676 u =5.747 0.017 ALT(U/L) 566(167, 919) 125(58, 358) u =6841.0 ＜0.001 AST(U/L) 389(130, 591) 172(70, 388) u =9608.5 ＜0.001 AST/ALT 0.6697(0.4735, 0.9333) 1.2196(0.8040, 2.2436) u =6467 ＜0.001 CHE(U/L) 6203±1562 5691±1916 t =2.651 0.008 ALB(g/L) 39.74(36.70,43.30) 37.70(34.25,42.25) u =10882.5 0.014 TC (mmol/L) 4.15(3.55,4.84) 4.35(3.52,5.08) u =11791 0.169 TG (mmol/L) 1.55(1.12,2.25) 1.30(1.03,1.87) u =10830 0.012 TBIL(μmol/L) 40.30(9.90,95.90) 12.10(5.70,48.40) u =9184.50 ＜0.001 DBIL(μmol/L) 12.60(8.50,20.30) 11.50(7.90,19.20) u =11760 0.158 Hcy(μmol/L) 9.20(8.70,9.60) 12.30(11.80,12.70) u =3093 ＜0.001 TSH(μIU/mL) 1.95(1.30,2.47) 2.12(1.47,3.16) u =10804.5 0.011 FT3(pmol/L) 4.51(3.89,5.12) 4.39(3.75,4.99) u =12321 0.459 FT4(pmol/L) 17.40(15.76,19.27) 16.06(14.67,18.45) u =9659.5 ＜0.001 C3(g/L) 1.23(0.98,1.45) 1.18(0.95,1.35) u =11530.5 0.092 C4(g/L) 0.24(0.18,0.29) 0.20(0.13,0.27) u =9972.5 ＜0.001 IgG(g/L) 14.10(11.55,16.30) 18.10(14.43, 23.52) u =6924 ＜0.001 IgA(g/L) 2.51(1.99,3.50) 3.14(2.26,3.95) u =10242 0.001 IgM(g/L) 1.12(0.82,1.56) 1.28(0.91,1.99) u =10804.5 0.011 Abbreviations: body mass index (BMI), Controlled Attenuation Parameter (CAP), Liver stiffness measurement (LSM), white blood cell (WBC), red blood cell (RBC), platelet (PLT), prothrombin time (PT), fibrinogen (FIB), thrombin time (TT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholinesterase (CHE), albumin (ALB), alkaline total cholesterol (TC), triglyceride (TG), total bilirubin (TBIL), direct bilirubin (DBIL), homocysteine (HCY). thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4)). 3.2 Correlation factors in logistic regression analysis between DLIL and AIH. Employing AIH as the dependent variable, the results of univariate regression analysis demonstrate that both Hcy（OR=2.020，95%CI=1.720~2.373)，P＜0.001) and IgG （OR=1.174，95%CI=1.117~1.234，P＜0.001）show statistical significance in differentiating between DILI and AIH (Table 3). Table 3 Univariate analysis of each index in DILI and AIH index OR 95%CI p-value Sex 2.741 1.454~5.164 0.002 Age(years) 1.047 1.027~1.067 ＜0.001 BMI(Kg/m2) 1.034 0.969~1.104 0.306 CAP (dB/m) 1.004 0.998~1.010 0.199 LSM (kPa) 1.102 1.066~1.139 ＜0.001 Smoking, n (%) 0.596 0.294~1.207 0.151 Drinking, n (%) 0.388 0.169~0.891 0.026 Hypertension, n (%) 1.726 1.026~2.904 0.040 Diabetes, n (%) 1.599 0.873~2.930 0.129 WBC(ⅹ10 9 /L) 0.890 0.777~1.020 0.095 RBC(ⅹ10 12 /L) 0.359 0.227~0.566 ＜0.001 PLT(ⅹ10 9 /L) 0.991 0.987~0.994 ＜0.001 PT(s) 0.938 0.347~0.822 1.071 FIB(g/L) 0.942 0.716~1.241 0.672 TT(s) 1.128 1.021~1.246 0.018 ALT(U/L) 0.998 0.997~0.999 ＜0.001 AST(U/L) 0.998 0.997~0.999 ＜0.001 AST/ALT 2.262 1.691~3.027 ＜0.001 CHE(U/L) 1.000 1.000~1.000 0.009 ALB(g/L) 1.001 0.998~1.004 0.503 TC (mmol/L) 1.057 0.913~1.223 0.456 TG (mmol/L) 0.715 0.552~0.925 0.011 DBIL(μmol/L) 0.994 0.990~0.998 0.002 IBIL(μmol/L) 0.993 0.978~1.008 0.332 Hcy(μmol/L) 2.020 1.720~2.373 ＜0.001 TSH(μIU/mL) 1.235 1.057~1.444 0.008 FT3(pmol/L) 0.978 0.841~1.137 0.772 FT4(pmol/L) 0.948 0.881~1.019 0.147 C3(g/L) 0.429 0.220~0.839 0.013 C4(g/L) 1.156 0.849~1.574 0.357 IgG(g/L) 1.174 1.117~1.234 ＜0.001 IgA(g/L) 1.346 1.131~1.601 0.001 IgM(g/L) 1.494 1.184~1.885 0.001 After adjusting for age, sex, BMI CAP, LSM, and medical history (Model 1), the OR value of Hcy was 1.776(1.502~2.099) ( P < 0.0001), the OR value of IgG was 1.130(1.072~1.190) ( P < 0.001), and the OR value of AST/ALT was 1.967(1.444~2.680) ( P < 0.001). The results demonstrated that Hcy and were statistically significant in all models ( P < 0.05). The highest OR value of Hcy is that 1.789 (95% CI = 1.371~2.002) in Model 2. AST/ALT exhibited a higher value than Hcy in the initial two models; however, it lost statistical significance upon the inclusion of immune and thyroid function variables (Hcy vs AST/ALT :1.694(1.404~2.043) P < 0.001 vs 1.321(0.889~1.963) P =0.168). All relevant data were shown in Table 4. Table 4 Logistic regression analysis of three serological indicators and two diseases Variables Model 1 Model 2 Model 3 OR (95%CI) P-value OR (95%CI) P-value OR (95%CI) P-value Hcy 1.776(1.502~2.099) ＜0.001 1.789(1.504~2.129) ＜0.001 1.694(1.404~2.043) ＜0.001 IgG 1.130(1.072~1.190) ＜0.001 1.136(1.074~1.203) ＜0.001 1.105(1.035~1.180) 0.003 AST/ALT 1.967(1.444~2.680) ＜0.001 1.882(1.372~2.581) ＜0.001 1.321(0.889~1.963) 0.168 Model 1: Sex, Age, body mass index, Controlled Attenuation Parameter, Liver stiffness measurement, Smoking, Drinking, Hypertension, Diabetes Model 2: adjusted by model 1 plus white blood cell, red blood cell, platelet, prothrombin time, fibrinogen, thrombin time Model 3: adjusted by model 2 plus alanine aminotransferase, aspartate aminotransferase, cholinesterase, albumin, alkaline total cholesterol, triglyceride, total bilirubin, direct bilirubin, homocysteine. thyroid stimulating hormone, free triiodothyronine, free thyroxine, C3, C4, IgA, IgM Abbreviations: OR, odds ratio; CI, confidence interval 3.3 Value of Hcy combined with IgG in diagnosis of AIH At a critical value of 10.05, the sensitivity of Hcy in diagnosing AIH was 88.1%, the specificity was 92.3%, and the AUROC was 0.881 (95% CI = 0.834 ~ 0.927). At a critical value of 15.31, the sensitivity of IgG for AIH was 67.8%, the specificity was 69.1%, and the AUROC was 0.732 (95% CI = 0.677 ~ 0.788). At a critical value of 0.8885, the sensitivity and specificity of AST/ALT for AH diagnosis were 69.2% and 72.9%, respectively, with an AUROC of 0.750 (95% CI = 0.697 ~ 0.803). The AUROC for Hcy diagnosed with AIH was significantly highest than that for IgG and AST/ALT [0.881 (95% CI = 0.834 ~ 0.927) vs 0.732 (95% CI = 0.677 ~ 0.788) vs 0.750 (95% CI = 0.697 ~ 0.803)]. Furthermore, the diagnostic performance of Hcy + IgG was significantly higher than that of Hcy 0.903 (95% CI = 0.864 ~ 0.942) vs. 0.881 (95% CI = 0.834 ~ 0.927)]. All relevant data were shown in Table 5. Table 5 Diagnostic performance of AST/ALT, Hcy, IgG, and HCY + IgG for diagnosis of AIH Variable Hcy IgG AST/ALT Hcy + IgG AUROC (95%CI) 0.881 (0.834~0.927) 0.732 (0.677~0.788) 0.750 (0.697~0.803) 0.903 (0.864~0.942) Cut-off 10.05 15.31 0.8885 0.4626871 Sensitivity, % 0.881 0.678 0.692 0.86 Specificity, % 0.923 0.691 0.729 0.917 PPV, % 90.51 63.39 66.89 90.22 NPV, % 89.83 73.09 75.00 87.95 PLR 12.07 2.19 2.55 11.68 NLR 0.14 0.46 0.42 0.17 Abbreviations: AUROC, area under the receiver operating characteristic curve; CI, confidence interval; PPV, positive predictive value; NPV, negative predictive value; PLR, positive likelihood ratio; NLR, negative likelihood ratio. The Figure 1 clearly demonstrated the excellent value of Hcy combined with IgG in the diagnosis of AIH. Based on the estimated cut-off point, Hcy＞10.05 in patients with AIH group accounted for 88.112%, whereas the DILI group accounted for only 7.735% (Figure 2). 4. Discussion There are discrepancies in the therapeutic regimens employed for DILI and AIH. A misdiagnosis or failure to diagnose can result in a suboptimal therapeutic outcome. Should the disease progress, this may also impact the prognosis for patients. The absence of specific markers for DILI contributes to the complexity of establishing a clinical diagnosis 10 . It is therefore imperative to identify a non-invasive, reliable and sensitive indicator that can effectively distinguish between DILI and AIH. The findings of the study indicated that Hcy demonstrated superior efficacy in distinguishing between DILI and AIH diagnoses. Furthermore, the diagnostic accuracy was enhanced when Hcy was combined with IgG. Since the 1960s, it has been demonstrated that immunoglobulin subtypes secreted by plasma cells in liver tissue may have a diagnostic significance in the context of AIH 11, 12 . At present, the selective elevation of serum IgG levels is regarded as a characteristic of AIH, occurring in up to 85% of patients. Consequently, this has been incorporated into the diagnostic score 13 . Indeed, in addition to the presence of characteristic autoantibodies, the identification of specific histological features within the liver, and the exclusion of viral hepatitis, the elevated levels of IgG are the fundamental diagnostic pillars of the simplified diagnostic scoring system proposed by the IAIHG 14 in 2008. Furthermore, elevated IgG levels have been demonstrated to indicate the persistence of inflammatory activity in patients with AIH who have undergone treatment 13 . Consequently, the most recent practice guidelines have defined complete biochemical remission as the repeated normalization of serum transaminase and IgG levels, which is now accepted as the primary therapeutic goal for AIH 15 . Consistent with the preceding studies, our investigation demonstrated that elevated IgG levels were associated with an increased likelihood of AIH ( P <0.0001). Besides, IgG demonstrated efficacy in the diagnosis of AIH, exhibiting a sensitivity of 67.8% and a specificity of 69.1%. The aminotransferase enzymes, specifically aspartate aminotransferase (AST) and alanine aminotransferase (ALT), are the most sensitive indices of liver cell injury. The AAR (AST to ALT ratio) is an independent risk factor for the development of cirrhosis in patients with AIH, and AST/ALT ratio >1 is a predictor of severe fibrosis in patients with AIH 16 . In this study, the mean AST/ALT of patients with AIH was much higher than that of patients with DILI [1.2196(0.8040, 2.2436) vs 0.6697(0.4735, 0.9333), P <0.0001]. However, the liver fibrosis score was not performed in this study, so we were not able to examine the relationship between AST/ALT and fibrosis in patients with AIH. Hcy is a sulfur-containing amino acid that is produced by the demethylation of methionine. The clearance of Hcy relies on the remethylating and transsulfuration pathways 17 .Furthermore, the metabolism of Hcy is dependent on the presence of sufficient levels of vitamins B9 and B12; a deficiency of these vitamins interferes with the remethylated pathway of Hcy, resulting in elevated Hcy levels 18 . Additionally, research indicates that administering a therapeutic dose of vitamin D3 for a minimum of two months may assist in reducing Hcy levels and may enhance liver function tests, thereby reducing the likelihood of developing liver disease 19 . Elevations in Hcy are also linked to physical exercise, poor skeletal muscle mass, fatty diets and obesity 20 . A potential mechanism for the elevated hcy levels observed in AIH relative to DILI is as follows: (1) Patients with AIH might be more susceptible to deficiencies of vitamins B6 and B12, leading to a reduction in HCY clearance and subsequent elevation. (2) It has been shown that vitamin D activates the cystathionine β -synthase gene, which potentially aids in the metabolism of Hcy 21 . Vitamin D deficiency is a prevalent phenomenon among patients with immune-mediated liver and non-liver diseases, and has been linked to the histological severity of AIH 22 . (3) Previous studies had shown that Hcy may cause local/systemic pro-inflammatory or anti-inflammatory responses by affecting the activation, differentiation, proliferation and secretion of a variety of immune cells, leading to immune dysregulation and dysfunction of the autoimmune response 23 . In patients with AIH, HCY may also play these roles. Although our study demonstrated that Hcy can be employed as an indicator to distinguish DILI from AIH, the precise mechanism by which Hcy exerts its effects on AIH remains unclear. Further investigation into the mechanism by which Hcy exerts its influence on AIH may be conducted by means of gene knockout in mice. However, it should be noted that the study is not without limitations. Firstly, the cross-sectional design of this study precludes the drawing of definitive conclusions regarding potential cause and effect. Further prospective studies are required to determine this. Secondly, the study was conducted in a single hospital, and it would have been beneficial to collect more data from multiple hospitals at different levels in multiple regions to further confirm the veracity of the study. Declarations Ethics approval and consent to participate The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board of Tianjin Second People's Hospital (Approval No. [2024]68). Written informed consent was obtained from each patient prior to the study related procedures. Consent for publication The authors agree to publish. Author Contributions Conceptualization,Methodology, X.J., J.L., and Y.Z. ; Formal Analysis, Y.L.; Investigation, Z.C. Y.L.and Q.W.; Resources, P.L.; Writing --Original Draft Preparation, X.J., J.L., and Y.Z.; Writing-- Review & Editing,X.J., J.L., and Y.Z.; Supervision, Ping Li. Funding This study funded by Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-059B). Competing interests The authors declare no conflict of interest. Availability of data and material The data that support the study findings are available from the corresponding author on reasonable request. 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Serum vitamins and homocysteine levels in autoimmune liver disease: A systematic review and meta-analysis. Immun. Inflamm. Dis. 12 (4), e1258 (2024). Al-Bayyari, N. et al. Vitamin D(3) reduces risk of cardiovascular and liver diseases by lowering homocysteine levels: double-blinded, randomised, placebo-controlled trial. Br. J. Nutr. 125 (2), 139–146 (2021). Tehlivets, O. et al. Homocysteine contributes to atherogenic transformation of the aorta in rabbits in the absence of hypercholesterolemia. Biomed. Pharmacother . 178 , 117244 (2024). Amer, M. & Qayyum, R. The relationship between 25-hydroxyvitamin D and homocysteine in asymptomatic adults. J. Clin. Endocrinol. Metab. 99 (2), 633–638 (2014). Czaja, A. J. & Montano-Loza, A. J. Evolving Role of Vitamin D in Immune-Mediated Disease and Its Implications in Autoimmune Hepatitis. Dig. Dis. Sci. 64 (2), 324–344 (2019). Hu, X. et al. Homocysteine as a trigger and potential therapeutic target for autoimmune diseases. Autoimmun. Rev. 22 (9), 103389 (2023). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 19 Aug, 2025 Reviews received at journal 13 Aug, 2025 Reviews received at journal 11 Aug, 2025 Reviewers agreed at journal 24 Jul, 2025 Reviewers agreed at journal 23 Jul, 2025 Reviewers agreed at journal 23 Jul, 2025 Reviewers invited by journal 22 Jul, 2025 Editor invited by journal 06 Jun, 2025 Editor assigned by journal 23 May, 2025 Submission checks completed at journal 22 May, 2025 First submitted to journal 21 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. 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-6720659","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":490457527,"identity":"f7b0444f-7fc3-44a2-9ff0-52911c13868f","order_by":0,"name":"Xue JiaoMD","email":"","orcid":"","institution":"Tianjin University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Xue","middleName":"","lastName":"JiaoMD","suffix":""},{"id":490457528,"identity":"c7ccda03-c904-4035-a701-9ccfddad5f18","order_by":1,"name":"Jing Liu","email":"","orcid":"","institution":"Tianjin Second People’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jing","middleName":"","lastName":"Liu","suffix":""},{"id":490457529,"identity":"594d4e48-c3d2-45d0-94de-54467c3842b2","order_by":2,"name":"Yibing Zhou","email":"","orcid":"","institution":"Central Laboratory, Department of Scientific Research, Changshu Hospital Affiliated to Soochow University, Changshu No.1 People's Hospital, Jiangsu","correspondingAuthor":false,"prefix":"","firstName":"Yibing","middleName":"","lastName":"Zhou","suffix":""},{"id":490457530,"identity":"4ebf79e0-44fc-4f08-9fb8-9c061910e3f8","order_by":3,"name":"Ze Chen","email":"","orcid":"","institution":"天津医科大学第二人民医院临床学院","correspondingAuthor":false,"prefix":"","firstName":"Ze","middleName":"","lastName":"Chen","suffix":""},{"id":490457531,"identity":"e73498ea-f0e5-416d-add4-03ce5742a387","order_by":4,"name":"Yinglun Li","email":"","orcid":"","institution":"天津医科大学第二人民医院临床学院","correspondingAuthor":false,"prefix":"","firstName":"Yinglun","middleName":"","lastName":"Li","suffix":""},{"id":490457532,"identity":"8ea07d6a-cd4e-4504-93c2-2fbe860d9e27","order_by":5,"name":"Qian WeiMD","email":"","orcid":"","institution":"天津医科大学第二人民医院临床学院","correspondingAuthor":false,"prefix":"","firstName":"Qian","middleName":"","lastName":"WeiMD","suffix":""},{"id":490457533,"identity":"32ba1500-93c8-4442-a2f1-626748c84afa","order_by":6,"name":"Ping Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAtklEQVRIiWNgGAWjYFCCww0MDxgY5NjY2w8Qp4GH4WADQwIDgzEfz5kEYrUwgrUkzpNwMCBOiz3jwbYHiW216W0SQJ0/KrYR5bB2g4Qzx3PbpBsPMPacuU2UljaJhIpjuW0yBxKYGduI1mJwLJ0NSJKipaImgQQtB8B+OWDYBgzkg0T5hX3G4WMPPrbVycu3tx988KOCCC0MEgfYgORhMPsAEeqBgL8BpKWOOMWjYBSMglEwMgEAAzNARrDaoGQAAAAASUVORK5CYII=","orcid":"","institution":"Tianjin Second People’s Hospital","correspondingAuthor":true,"prefix":"","firstName":"Ping","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2025-05-22 03:23:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6720659/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6720659/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":87724579,"identity":"bccca63e-f0a6-4621-8ebb-4f837a36a77b","added_by":"auto","created_at":"2025-07-28 10:24:40","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":53415,"visible":true,"origin":"","legend":"\u003cp\u003eThe performance of AST/ALT, Hcy, IgG, and HCY + IgG for distinguishing AIH.\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6720659/v1/5fcb4e34938e844e5087862b.jpg"},{"id":87724580,"identity":"610b04b5-7963-4198-a2c9-78caec5016a1","added_by":"auto","created_at":"2025-07-28 10:24:40","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":14827,"visible":true,"origin":"","legend":"\u003cp\u003eThe distribution of AIH and DILI patients, when the cut-off of Hcy toke 10.05.\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6720659/v1/9e38afca4d38808c21d34f04.jpg"},{"id":87725898,"identity":"01827f84-d4f2-4e94-b3b8-22166929755e","added_by":"auto","created_at":"2025-07-28 10:40:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":698147,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6720659/v1/f6dc6708-f0c4-43cd-8463-9b69c7d7e040.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Diagnostic value of homocysteine combined with IgG in differentiating drug- induced liver injury and autoimmune hepatitis","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eAutoimmune hepatitis (AIH) is a progressive inflammatory response with an uncertain etiology, which belongs to the category of autoimmune liver diseases with a genetic predisposition\u003csup\u003e1\u003c/sup\u003e. The diagnosis of AIH is dependent upon the presence of elevated serum aminotransferase and IgG and/or γ levels, the existence of autoantibodies, and the histological presence of interfacial hepatitis in the liver\u003csup\u003e2\u003c/sup\u003e. AIH manifests in genetically susceptible individuals when a trigger, such as exposure to a virus, precipitates a T-cell-mediated autoimmune response against liver autoantigens. This immune response is the consequence of a loss of tolerance resulting from inadequate regulatory immune control\u003csup\u003e3\u003c/sup\u003e. The diagnosis of AIH is based on the presence of specific clinical, biochemical, serological, and histological patterns, which must be confirmed by the response to immunosuppressive therapy. The disease lacks clear diagnostic features, which makes it challenging to diagnose\u003csup\u003e4\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eDrug-induced liver injury (DILI) represents one of the most prevalent adverse reactions observed in clinical drug use. It is typically induced by a diverse range of chemical drugs, traditional Chinese medicine, health products, biological agents and their metabolites\u003csup\u003e5\u003c/sup\u003e. The clinical manifestations of DILI are unspecific and may resemble other hepatic disorders with variable elevations in liver biochemistries\u003csup\u003e6\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eAt present, DILI is an exclusionary diagnosis. In the absence of reliable laboratory testing, diagnosing DILI can be challenging, particularly when features of AIH are present; if DILI and AIH cannot be reliably distinguished, rapidly reducing or stopping immunosuppressive therapy in cases where the underlying cause of liver damage is idiopathic AIH can result in a life-threatening risk of disease recurrence\u003csup\u003e7\u003c/sup\u003e. Therefore, it is crucial to exercise caution in order to ascertain the underlying etiology of the disease, in order to ensure the most appropriate treatment is selected.\u003c/p\u003e\n\u003cp\u003eLiver biopsy remains the gold standard for the diagnosis of DILI and AIH. Although the accuracy is very high, the procedure is traumatic and not repeatable, rendering it unsuitable for routine monitoring as an invasive examination. Furthermore, it is challenging to gain acceptance from patients on a clinical level. The objective of this study was to retrospectively collect the basic information and clinical data of patients with DILI and AIH in order to identify a non-invasive, reliable and sensitive indicator that can distinguish between DILI and AIH.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cp\u003e2.1 Research object.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatient data was gathered from 2012 to 2022, finally resulting in the inclusion of 143 patients with AIH and 181 patients with DILI. The AIH is in accordance with the simplified diagnostic scoring system proposed by the International Autoimmune Hepatitis Working Group\u003csup\u003e8\u003c/sup\u003e，and the DILI meets the diagnostic criteria for liver dysfunction as outlined in the RUCAM score\u003csup\u003e9\u003c/sup\u003e. Exclusion criteria: (1) In addition to other liver diseases that may result in liver dysfunction, including viral hepatitis, alcoholic hepatitis, hereditary metabolic liver disease, and non-alcoholic fatty liver disease; (2) A history of malignant tumors or other end-stage diseases; (3) The Patient data are incomplete.\u0026nbsp;The study adhered to the principles outlined in the Declaration of Helsinki and\u0026nbsp;was authorized by the Institutional Review Board of Tianjin Second People's Hospital (Approval No. [2024]68).\u003c/p\u003e\n\u003cp\u003e2.2 Research content.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA collection of clinical data, serum biochemical indexes, thyroid function and immune function was made within one week of the liver biopsy. Clinical data encompasses\u0026nbsp;age, gender, body mass index (BMI), Controlled Attenuation Parameter (CAP), Liver stiffness measurement (LSM), smoking, drinking, hypertension and diabetes. Serum biochemical markers include white blood cell (WBC), red blood cell (RBC),\u0026nbsp;platelet (PLT), prothrombin time (PT), fibrinogen (FIB), thrombin time (TT),\u0026nbsp;alanine aminotransferase (ALT), aspartate aminotransferase (AST),\u0026nbsp;cholinesterase (CHE), albumin (ALB), alkaline total cholesterol (TC), triglyceride (TG), , total bilirubin (TBIL), direct bilirubin (DBIL), homocysteine (HCY). Thyroid function\u0026nbsp;include\u0026nbsp;thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4)).\u0026nbsp;Immunological markers (C3, C4, IgG, IgA, IgM).\u003c/p\u003e\n\u003cp\u003e2.3 Liver biopsy.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLiver biopsy was performed on all patients under local anesthesia and ultrasound guidance. The specimens exhibited a length range of 1.0 to 2.0 cm. Liver tissue samples were obtained, fixed in 10% neutral buffered formalin, then subjected to a sequential process of paraffin embedding and staining with HE, Masson, and mesh fibers. Two experienced pathologists conducted an independent evaluation of liver tissue slices without access to the patient's clinical characteristics.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2.4 Statistical analysis\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eStatistical analyses utilized SPSS version 26.0 and GraphPad Prism 9.5. Continuous variables with a normal distribution are expressed as mean±standard deviation, and an independent sample t-test is employed to compare the two groups. In the event that the continuous variables in question do not follow a normal distribution, they are expressed as the median (25th to 75th percentiles). In such instances, the Mann-Whitney U test is employed for the purpose of comparing the two groups. Percentages are employed to represent categorical variables and are compared between groups using Chi-square tests or Fisher's exact tests. The statistical significance was determined by a two-tailed P-value \u0026lt; 0.05. Binary logistic regression was utilized to analyze the effect of Hcy differentiation between AIH and DILI after the introduction of confounding factors. A receiver operating characteristic (ROC) curve was employed to measure the diagnostic effect of Hcy on AIH.\u003c/p\u003e"},{"header":"3. Result","content":"\u003cp\u003e3.1 Participant characteristics\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn the study, clinical symptoms observed in patients with drug-induced liver injury (DILI) included yellow urine in 109 cases (60.2%), gastrointestinal discomfort in 106 cases (58.6%), and fatigue in 96 cases (53.0%). In contrast, patients with autoimmune hepatitis (AIH) presented with yellow urine in 54 cases (37.8%), gastrointestinal discomfort in 60 cases (42.0%), and fatigue in 56 cases (39.2%). The incidence of yellow urine, gastrointestinal discomfort, and fatigue was significantly higher in the DILI group compared to the AIH group (P \u0026lt; 0.05). A summary of additional symptoms reported in both patient groups is provided in Table 1.\u003c/p\u003e\n\u003cp\u003eTable 1 Comparison of clinical symptoms between DILI and AIH\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"576\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003eclinical manifestation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eDILI(n=181)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eAIH(n=143)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003ec\u003c/em\u003e\u003cem\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003efatigue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e96(53.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e56(39.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e6.178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.013\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003eGastrointestinal symptoms\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e106(58.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e60(42.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e8.817\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\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: 170px;\"\u003e\n \u003cp\u003eUpper abdominal discomfort, liver discomfort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e11(6.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e15(10.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e2.107\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.147\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003efever\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e13(7.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e9(6.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.752\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003eYellow urine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e109(60.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e54(37.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e16.118\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\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: 170px;\"\u003e\n \u003cp\u003epruritus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e6(3.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e7(4.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.5183\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.472\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003eother\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e2(1.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e12(8.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e10.259\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.001\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\u003eNote: Gastrointestinal symptoms encompass a range of issues such as loss of appetite, nausea, vomiting, bloating, diarrhea, acid reflux, and belching. Additionally, other symptoms may include a bitter taste in the mouth, dryness in the mouth and eyes, swelling or pain in the lower legs, and darkened skin.\u003c/p\u003e\n\u003cp\u003eThe baseline data of the two groups were compared, revealing that the women in the AIH group exhibited significantly higher values than those in the DILI group (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05). The median age was 50 (38, 57) in the DILI group and 57 (50, 63) in the AIH group, with a statistically significant difference (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05). A statistically significant difference was observed between the drinking habits of DILI patients (13.3%) and AIH patients (5.6%), with a higher prevalence of alcohol consumption among the former group (\u003cem\u003eP\u003c/em\u003e＜0.05). The prevalence of hypertension was 18.8% in the DILI group and 28.7% in the AIH group (\u003cem\u003eP\u003c/em\u003e＜0.05). No statistically significant correlations were identified between BMI, smoking, diabetes, WBC, PT, FIB, TC, DBIL, FT3, or C3. A comparison of the DILI group with the AIH group revealed statistically significant differences in the serum levels of RBC, PLT, TT, ALT, AST, CHE, ALB, TG, TBIL, HCY, TSH, FT4, C4, IgA and IgM in AIH group (\u003cem\u003eP\u003c/em\u003e＜0.05). The full range of demographic, clinical and biochemical indicators for the study group is presented in Table 2.\u003c/p\u003e\n\u003cp\u003eTable 2 Clinical features of patients\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"576\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eDILI(n=181)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eAIH(n=143)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003et/\u003c/em\u003e \u003cem\u003eu /\u003c/em\u003e\u003cem\u003ec\u003c/em\u003e\u003cem\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\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 valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003ec\u003c/em\u003e\u003cem\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e=10.244\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\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: 123px;\"\u003e\n \u003cp\u003eMale, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e44(24.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e15(10.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eFemale, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e137(75.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e128(89.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eAge(years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e50 (38, 57)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e57 (50, 63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003eu\u003c/em\u003e=8539.500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\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: 123px;\"\u003e\n \u003cp\u003eBMI(Kg/m2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e23.01\u0026plusmn;3.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e23.40\u0026plusmn;3.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e =-1.024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.307\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eCAP (dB/m)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e189(170,210)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e197(178,218)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003eu\u003c/em\u003e=11101\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.028\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eLSM (kPa)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e11.2(8.5,15.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e21.8(15.6,24.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003eu\u003c/em\u003e=5116\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\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: 123px;\"\u003e\n \u003cp\u003eSmoking, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e26(14.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e13(9.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003ec\u003c/em\u003e\u003cem\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e=2.098\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.147\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eDrinking, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e24(13.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e8(5.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003ec\u003c/em\u003e\u003cem\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e=5.273\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\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: 123px;\"\u003e\n \u003cp\u003eHypertension, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e34(18.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e41(28.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003ec\u003c/em\u003e\u003cem\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e=4.278\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.039\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eDiabetes, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e23(12.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e27(18.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003ec\u003c/em\u003e\u003cem\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e=2.333\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.127\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eWBC(*^9/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e4.83(3.82, 6.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e4.77 (3.73, 5.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003eu\u003c/em\u003e=12077\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.302\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003eRBC(*^12/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e4.33\u0026plusmn;0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e4.06\u0026plusmn;0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e =4.676\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003ePLT(*^9/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e207(165，257)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e167(160，212)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003eu\u003c/em\u003e=8284.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003ePT(s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e12.84(11.80, 13.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e12.60(11.35, 13.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003eu\u003c/em\u003e=12028.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.275\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003eFIB(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e2.21(1.88, 2.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e2.24(1.80, 2.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e=12497.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.596\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003eTT(s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e19.8249\u0026plusmn;0.16709\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e20.4261\u0026plusmn;0.18676\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003eu\u003c/em\u003e=5.747\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.017\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003eALT(U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e566(167, 919)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e125(58, 358)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003eu\u003c/em\u003e=6841.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003eAST(U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e389(130, 591)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e172(70, 388)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003eu\u003c/em\u003e=9608.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003eAST/ALT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e0.6697(0.4735, 0.9333)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e1.2196(0.8040, 2.2436)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003eu\u003c/em\u003e=6467\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003eCHE(U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e6203\u0026plusmn;1562\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e5691\u0026plusmn;1916\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e=2.651\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003eALB(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e39.74(36.70,43.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e37.70(34.25,42.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003eu\u003c/em\u003e=10882.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.014\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003eTC (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e4.15(3.55,4.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e4.35(3.52,5.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003eu\u003c/em\u003e=11791\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.169\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003eTG (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e1.55(1.12,2.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e1.30(1.03,1.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003eu\u003c/em\u003e=10830\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003eTBIL(\u0026mu;mol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e40.30(9.90,95.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e12.10(5.70,48.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003eu\u003c/em\u003e=9184.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003eDBIL(\u0026mu;mol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e12.60(8.50,20.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e11.50(7.90,19.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003eu\u003c/em\u003e=11760\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.158\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003eHcy(\u0026mu;mol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e9.20(8.70,9.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e12.30(11.80,12.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003eu\u003c/em\u003e=3093\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003eTSH(\u0026mu;IU/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e1.95(1.30,2.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e2.12(1.47,3.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003eu\u003c/em\u003e=10804.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.011\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003eFT3(pmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e4.51(3.89,5.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e4.39(3.75,4.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003eu\u003c/em\u003e=12321\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.459\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003eFT4(pmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e17.40(15.76,19.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e16.06(14.67,18.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003eu\u003c/em\u003e=9659.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003eC3(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e1.23(0.98,1.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e1.18(0.95,1.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003eu\u003c/em\u003e=11530.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.092\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003eC4(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e0.24(0.18,0.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e0.20(0.13,0.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003eu\u003c/em\u003e=9972.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\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: 123px;\"\u003e\n \u003cp\u003eIgG(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e14.10(11.55,16.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e18.10(14.43, 23.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003eu\u003c/em\u003e=6924\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\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: 123px;\"\u003e\n \u003cp\u003eIgA(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e2.51(1.99,3.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e3.14(2.26,3.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003eu\u003c/em\u003e=10242\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\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: 123px;\"\u003e\n \u003cp\u003eIgM(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e1.12(0.82,1.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e1.28(0.91,1.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003eu\u003c/em\u003e=10804.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.011\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\u003eAbbreviations: body mass index (BMI), Controlled Attenuation Parameter (CAP), Liver stiffness measurement (LSM), white blood cell (WBC), red blood cell (RBC), platelet (PLT), prothrombin time (PT), fibrinogen (FIB), thrombin time (TT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholinesterase (CHE), albumin (ALB), alkaline total cholesterol (TC), triglyceride (TG), total bilirubin (TBIL), direct bilirubin (DBIL), homocysteine (HCY). thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4)).\u003c/p\u003e\n\u003cp\u003e3.2 Correlation factors in logistic regression analysis between DLIL and AIH.\u003c/p\u003e\n\u003cp\u003eEmploying AIH as the dependent variable, the results of univariate regression analysis demonstrate that both Hcy（OR=2.020，95%CI=1.720~2.373)，P＜0.001) and IgG\u0026nbsp;（OR=1.174，95%CI=1.117~1.234，P＜0.001）show statistical significance in differentiating between DILI and AIH (Table 3).\u003c/p\u003e\n\u003cp\u003eTable 3 Univariate analysis of each index in DILI and AIH\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"453\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eindex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cem\u003eOR\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cem\u003e95%CI\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e2.741\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.454~5.164\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\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: 151px;\"\u003e\n \u003cp\u003eAge(years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1.047\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.027~1.067\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\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: 151px;\"\u003e\n \u003cp\u003eBMI(Kg/m2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1.034\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.969~1.104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.306\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCAP (dB/m)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.998~1.010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.199\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eLSM (kPa)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1.102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.066~1.139\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\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: 151px;\"\u003e\n \u003cp\u003eSmoking, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0.596\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.294~1.207\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.151\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eDrinking, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0.388\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.169~0.891\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eHypertension, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1.726\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.026~2.904\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.040\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eDiabetes, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1.599\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.873~2.930\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.129\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eWBC(ⅹ10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0.890\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.777~1.020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.095\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eRBC(ⅹ10\u003csup\u003e12\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0.359\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.227~0.566\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003ePLT(ⅹ10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0.991\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.987~0.994\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003ePT(s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0.938\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.347~0.822\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e1.071\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eFIB(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0.942\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.716~1.241\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.672\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eTT(s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1.128\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.021~1.246\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.018\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eALT(U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0.998\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.997~0.999\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eAST(U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0.998\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.997~0.999\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eAST/ALT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e2.262\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.691~3.027\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eCHE(U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.000~1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eALB(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.998~1.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.503\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eTC (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1.057\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.913~1.223\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.456\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eTG (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0.715\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.552~0.925\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.011\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 151px;\"\u003e\n \u003cp\u003eDBIL(\u0026mu;mol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0.994\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.990~0.998\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 151px;\"\u003e\n \u003cp\u003eIBIL(\u0026mu;mol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0.993\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.978~1.008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.332\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eHcy(\u0026mu;mol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e2.020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.720~2.373\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eTSH(\u0026mu;IU/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1.235\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.057~1.444\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eFT3(pmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0.978\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.841~1.137\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.772\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eFT4(pmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0.948\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.881~1.019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.147\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eC3(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0.429\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.220~0.839\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.013\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eC4(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1.156\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.849~1.574\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.357\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eIgG(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1.174\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.117~1.234\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\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: 151px;\"\u003e\n \u003cp\u003eIgA(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1.346\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.131~1.601\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\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: 151px;\"\u003e\n \u003cp\u003eIgM(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1.494\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.184~1.885\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.001\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\u003eAfter adjusting for age, sex, BMI CAP, LSM, and medical history (Model\u0026nbsp;1), the\u0026nbsp;OR value of Hcy was\u0026nbsp;1.776(1.502~2.099) (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.0001), the OR value of IgG was 1.130(1.072~1.190) (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001), and the OR value of AST/ALT was 1.967(1.444~2.680) (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001). The results demonstrated that Hcy and were statistically significant in all models (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05). The highest OR value of Hcy is that 1.789 (95% CI = 1.371~2.002) in Model 2. AST/ALT exhibited a higher value than Hcy in the initial two models; however, it lost statistical significance upon the inclusion of immune and thyroid function variables (Hcy vs AST/ALT :1.694(1.404~2.043) \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001 vs 1.321(0.889~1.963) \u003cem\u003eP\u003c/em\u003e =0.168). All relevant data were shown in Table 4.\u003c/p\u003e\n\u003cp\u003eTable 4 Logistic regression analysis of three serological indicators and two diseases\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"666\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eModel 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eModel 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eModel 3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e\u003cem\u003eOR (95%CI)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u003cem\u003eP-value\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e\u003cem\u003eOR (95%CI)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u003cem\u003eP-value\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e\u003cem\u003eOR (95%CI)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e\u003cem\u003eP-value\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eHcy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e1.776(1.502~2.099)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e1.789(1.504~2.129)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e1.694(1.404~2.043)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\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: 72px;\"\u003e\n \u003cp\u003eIgG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e1.130(1.072~1.190)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e1.136(1.074~1.203)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e1.105(1.035~1.180)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\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: 72px;\"\u003e\n \u003cp\u003eAST/ALT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e1.967(1.444~2.680)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e1.882(1.372~2.581)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e1.321(0.889~1.963)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e0.168\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eModel 1: Sex, Age, body mass index, Controlled Attenuation Parameter, Liver stiffness measurement, Smoking, Drinking, Hypertension, Diabetes\u003c/p\u003e\n\u003cp\u003eModel 2: adjusted by model 1 plus white blood cell, red blood cell, platelet, prothrombin time, fibrinogen, thrombin time\u003c/p\u003e\n\u003cp\u003eModel 3: adjusted by model 2 plus alanine aminotransferase, aspartate aminotransferase, cholinesterase, albumin, alkaline total cholesterol, triglyceride, total bilirubin, direct bilirubin, homocysteine. thyroid stimulating hormone, free triiodothyronine, free thyroxine, C3, C4, IgA, IgM\u003c/p\u003e\n\u003cp\u003eAbbreviations: OR, odds ratio; CI, confidence interval\u003c/p\u003e\n\u003cp\u003e3.3 Value of Hcy combined with IgG in diagnosis of AIH\u003c/p\u003e\n\u003cp\u003eAt a critical value of 10.05, the sensitivity of Hcy in diagnosing AIH was 88.1%, the specificity was 92.3%, and the AUROC was 0.881 (95% CI = 0.834 ~ 0.927). At a critical value of 15.31, the sensitivity of IgG for AIH was 67.8%, the specificity was 69.1%, and the AUROC was 0.732 (95% CI = 0.677 ~ 0.788). At a critical value of 0.8885, the sensitivity and specificity of AST/ALT for AH diagnosis were 69.2% and 72.9%, respectively, with an AUROC of 0.750 (95% CI = 0.697 ~ 0.803).\u0026nbsp;The AUROC for Hcy diagnosed with AIH was significantly highest than that for IgG and AST/ALT [0.881 (95% CI = 0.834 ~ 0.927) vs\u0026nbsp;0.732 (95% CI = 0.677 ~ 0.788) vs 0.750 (95% CI = 0.697 ~ 0.803)]. Furthermore, the diagnostic performance of\u0026nbsp;Hcy + IgG\u0026nbsp;was significantly higher than that of\u0026nbsp;Hcy\u0026nbsp;0.903 (95% CI = 0.864 ~ 0.942) vs. 0.881 (95% CI = 0.834 ~ 0.927)].\u0026nbsp;All relevant data were shown in Table 5.\u003c/p\u003e\n\u003cp\u003eTable 5 Diagnostic performance of AST/ALT, Hcy, IgG, and HCY + IgG for diagnosis of AIH\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eHcy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eIgG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eAST/ALT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eHcy + IgG\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eAUROC (95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.881\u003c/p\u003e\n \u003cp\u003e(0.834~0.927)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.732\u003c/p\u003e\n \u003cp\u003e(0.677~0.788)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.750\u003c/p\u003e\n \u003cp\u003e(0.697~0.803)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.903\u003c/p\u003e\n \u003cp\u003e(0.864~0.942)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eCut-off\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e10.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e15.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.8885\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.4626871\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eSensitivity, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.881\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.678\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.692\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.86\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eSpecificity, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.923\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.691\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.729\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.917\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003ePPV, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e90.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e63.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e66.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e90.22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eNPV, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e89.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e73.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e75.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e87.95\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003ePLR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e12.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e2.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e2.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e11.68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eNLR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: AUROC, area under the receiver operating characteristic curve; CI, confidence interval; PPV, positive predictive value; NPV, negative predictive value; PLR, positive likelihood ratio; NLR, negative likelihood ratio.\u003c/p\u003e\n\u003cp\u003eThe Figure 1 clearly demonstrated the excellent value of Hcy combined with IgG in the diagnosis of AIH. Based on the estimated cut-off point, Hcy＞10.05 in patients with AIH group accounted for 88.112%, whereas the DILI group accounted for only 7.735% (Figure 2).\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThere are discrepancies in the therapeutic regimens employed for DILI and AIH. A misdiagnosis or failure to diagnose can result in a suboptimal therapeutic outcome. Should the disease progress, this may also impact the prognosis for patients.\u0026nbsp;The absence of specific markers for DILI contributes to the complexity of establishing a clinical diagnosis\u003csup\u003e10\u003c/sup\u003e. It is therefore imperative to identify a non-invasive, reliable and sensitive indicator that can effectively distinguish between DILI and AIH.\u0026nbsp;The findings of the study indicated that Hcy demonstrated superior efficacy in distinguishing between DILI and AIH diagnoses. Furthermore, the diagnostic accuracy was enhanced when Hcy was combined with IgG.\u003c/p\u003e\n\u003cp\u003eSince the 1960s, it has been demonstrated that immunoglobulin subtypes secreted by plasma cells in liver tissue may have a diagnostic significance in the context of AIH\u003csup\u003e11, 12\u003c/sup\u003e. At present, the selective elevation of serum IgG levels is regarded as a characteristic of AIH, occurring in up to 85% of patients. Consequently, this has been incorporated into the diagnostic score\u003csup\u003e13\u003c/sup\u003e. Indeed, in addition to the presence of characteristic autoantibodies, the identification of specific histological features within the liver, and the exclusion of viral hepatitis, the elevated levels of IgG are the fundamental diagnostic pillars of the simplified diagnostic scoring system proposed by the IAIHG\u003csup\u003e14\u003c/sup\u003e in 2008. Furthermore, elevated IgG levels have been demonstrated to indicate the persistence of inflammatory activity in patients with AIH who have undergone treatment\u003csup\u003e13\u003c/sup\u003e. Consequently, the most recent practice guidelines have defined complete biochemical remission as the repeated normalization of serum transaminase and IgG levels, which is now accepted as the primary therapeutic goal for AIH\u003csup\u003e15\u003c/sup\u003e. Consistent with the preceding studies, our investigation demonstrated that elevated IgG levels were associated with an increased likelihood of AIH (\u003cem\u003eP\u003c/em\u003e \u0026lt;0.0001). Besides, IgG demonstrated efficacy in the diagnosis of AIH, exhibiting a sensitivity of 67.8% and a specificity of 69.1%.\u003c/p\u003e\n\u003cp\u003eThe aminotransferase enzymes, specifically aspartate aminotransferase (AST) and alanine aminotransferase (ALT), are the most sensitive indices of liver cell injury.\u0026nbsp;The AAR (AST to ALT ratio) is an independent risk factor for the development of cirrhosis in patients with AIH, and AST/ALT ratio \u0026gt;1 is a predictor of severe fibrosis in patients with AIH\u003csup\u003e16\u003c/sup\u003e.\u0026nbsp;In this study, the mean AST/ALT of patients with AIH was much higher than that of patients with DILI [1.2196(0.8040, 2.2436) vs 0.6697(0.4735, 0.9333), \u003cem\u003eP\u003c/em\u003e\u0026lt;0.0001]. However, the liver fibrosis score was not performed in this study, so we were not able to examine the relationship between AST/ALT and fibrosis in patients with AIH.\u003c/p\u003e\n\u003cp\u003eHcy is a sulfur-containing amino acid that is produced by the demethylation of methionine. The clearance of Hcy relies on the remethylating and transsulfuration pathways\u003csup\u003e17\u003c/sup\u003e.Furthermore, the metabolism of Hcy is dependent on the presence of sufficient levels of vitamins B9 and B12; a deficiency of these vitamins interferes with the remethylated pathway of Hcy, resulting in elevated Hcy levels\u003csup\u003e18\u003c/sup\u003e. Additionally, research indicates that administering a therapeutic dose of vitamin D3 for a minimum of two months may assist in reducing Hcy levels and may enhance liver function tests, thereby reducing the likelihood of developing liver disease\u003csup\u003e19\u003c/sup\u003e. Elevations in Hcy are also linked to physical exercise, poor skeletal muscle mass, fatty diets and obesity\u003csup\u003e20\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eA potential mechanism for the elevated hcy levels observed in AIH relative to DILI is as follows: (1) Patients with AIH might be more susceptible to deficiencies of vitamins B6 and B12, leading to a reduction in HCY clearance and subsequent elevation. (2) It has been shown that vitamin D activates the cystathionine\u003cem\u003eβ\u003c/em\u003e-synthase gene, which potentially aids in the metabolism of Hcy\u003csup\u003e21\u003c/sup\u003e\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003eVitamin D deficiency is a prevalent phenomenon among patients with immune-mediated liver and non-liver diseases, and has been linked to the histological severity of AIH\u003csup\u003e22\u003c/sup\u003e. (3)\u0026nbsp;Previous studies had shown that Hcy may cause local/systemic pro-inflammatory or anti-inflammatory responses by affecting the activation, differentiation, proliferation and secretion of a variety of immune cells, leading to immune dysregulation and dysfunction of the autoimmune response\u003csup\u003e23\u003c/sup\u003e.\u0026nbsp;In patients with AIH, HCY may also play these roles.\u003c/p\u003e\n\u003cp\u003eAlthough our study demonstrated that Hcy can be employed as an indicator to distinguish DILI from AIH, the precise mechanism by which Hcy exerts its effects on AIH remains unclear. Further investigation into the mechanism by which Hcy exerts its influence on AIH may be conducted by means of gene knockout in mice. However, it should be noted that the study is not without limitations. Firstly, the cross-sectional design of this study precludes the drawing of definitive conclusions regarding potential cause and effect. Further prospective studies are required to determine this. Secondly, the study was conducted in a single hospital, and it would have been beneficial to collect more data from multiple hospitals at different levels in multiple regions to further confirm the veracity of the study.\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board of Tianjin Second People's Hospital (Approval No.\u0026nbsp;[2024]68). Written informed consent was obtained from each patient prior to the study related procedures.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eThe authors agree to publish.\u003c/p\u003e\n\u003cp\u003eAuthor Contributions\u003c/p\u003e\n\u003cp\u003eConceptualization,Methodology, X.J., J.L., and Y.Z. ; Formal Analysis, Y.L.; Investigation, Z.C. Y.L.and Q.W.; Resources, P.L.; Writing --Original Draft Preparation, X.J., J.L., and Y.Z.; Writing-- Review \u0026amp; Editing,X.J., J.L., and Y.Z.; Supervision, \u0026nbsp;Ping Li.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThis study funded by Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-059B).\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003eAvailability of data and material\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe data that support the study findings are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHiguchi, T. et al. Genetic risk factors for autoimmune hepatitis: implications for phenotypic heterogeneity and biomarkers for drug response. \u003cem\u003eHum. Genomics\u003c/em\u003e. \u003cb\u003e15\u003c/b\u003e (1), 6 (2021).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEASL Clinical Practice Guidelines. Autoimmune hepatitis. \u003cem\u003eJ. Hepatol.\u003c/em\u003e \u003cb\u003e63\u003c/b\u003e (4), 971\u0026ndash;1004 (2015).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePandey, S. P. et al. Tet2 deficiency drives liver microbiome dysbiosis triggering Tc1 cell autoimmune hepatitis. \u003cem\u003eCell. host microbe\u003c/em\u003e. \u003cb\u003e30\u003c/b\u003e (7), 1003\u0026ndash;1019e1010 (2022).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eManns, M. P. et al. Diagnosis and management of autoimmune hepatitis. \u003cem\u003eHepatol. (Baltimore Md)\u003c/em\u003e. \u003cb\u003e51\u003c/b\u003e (6), 2193\u0026ndash;2213 (2010).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhu, L. et al. Hepatotoxicity of epidermal growth factor receptor - tyrosine kinase inhibitors (EGFR-TKIs). \u003cem\u003eDrug Metab. Rev.\u003c/em\u003e \u003cb\u003e2024\u003c/b\u003e:1\u0026ndash;16 .\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDevarbhavi, H. et al. Drug-induced liver injury: Asia Pacific Association of Study of Liver consensus guidelines. \u003cem\u003eHepatol. Int.\u003c/em\u003e \u003cb\u003e15\u003c/b\u003e (2), 258\u0026ndash;282 (2021).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWeber, S. et al. Early ALT response to corticosteroid treatment distinguishes idiosyncratic drug-induced liver injury from autoimmune hepatitis. \u003cem\u003eLiver Int.\u003c/em\u003e \u003cb\u003e39\u003c/b\u003e (10), 1906\u0026ndash;1917 (2019).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAlvarez, F. et al. International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. \u003cem\u003eJ. Hepatol.\u003c/em\u003e \u003cb\u003e31\u003c/b\u003e (5), 929\u0026ndash;938 (1999).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDanan, G. \u0026amp; Benichou, C. Causality assessment of adverse reactions to drugs\u0026ndash;I. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries. \u003cem\u003eJ. Clin. Epidemiol.\u003c/em\u003e \u003cb\u003e46\u003c/b\u003e (11), 1323\u0026ndash;1330 (1993).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBrennan, P. N. et al. Guideline review: EASL clinical practice guidelines: drug-induced liver injury (DILI). \u003cem\u003eFrontline Gastroenterol.\u003c/em\u003e \u003cb\u003e13\u003c/b\u003e (4), 332\u0026ndash;336 (2022).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCohen, S. et al. Immunocytochemical study of gamma globulin in liver in hepatitis and postnecrotic cirrhosis. \u003cem\u003eJ. Exp. Med.\u003c/em\u003e \u003cb\u003e111\u003c/b\u003e (2), 285\u0026ndash;294 (1960).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVan Spreeuwel, J. P. et al. Immunoglobulin-containing cells in liver biopsies of patients with chronic hepatitis and primary biliary cirrhosis. \u003cem\u003eHistopathology\u003c/em\u003e \u003cb\u003e8\u003c/b\u003e (4), 559\u0026ndash;566 (1984).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHartl, J. et al. Features and outcome of AIH patients without elevation of IgG. \u003cem\u003eJHEP reports: Innov. Hepatol.\u003c/em\u003e \u003cb\u003e2\u003c/b\u003e (3), 100094 (2020).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHennes, E. M. et al. Simplified criteria for the diagnosis of autoimmune hepatitis. \u003cem\u003eHepatol. (Baltimore Md)\u003c/em\u003e. \u003cb\u003e48\u003c/b\u003e (1), 169\u0026ndash;176 (2008).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHartl, J. et al. Usefulness of biochemical remission and transient elastography in monitoring disease course in autoimmune hepatitis. \u003cem\u003eJ. Hepatol.\u003c/em\u003e \u003cb\u003e68\u003c/b\u003e (4), 754\u0026ndash;763 (2018).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZeng, T. et al. Noninvasive indices for monitoring disease course in Chinese patients with autoimmune hepatitis. \u003cem\u003eClin. Chim. Acta\u003c/em\u003e. \u003cb\u003e486\u003c/b\u003e, 135\u0026ndash;141 (2018).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYan, H. et al. Ribosomal modification protein rimK-like family member A activates betaine-homocysteine S-methyltransferase 1 to ameliorate hepatic steatosis. \u003cem\u003eSignal. Transduct. Target. Ther.\u003c/em\u003e \u003cb\u003e9\u003c/b\u003e (1), 214 (2024).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLi, J. et al. Serum vitamins and homocysteine levels in autoimmune liver disease: A systematic review and meta-analysis. \u003cem\u003eImmun. Inflamm. Dis.\u003c/em\u003e \u003cb\u003e12\u003c/b\u003e (4), e1258 (2024).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAl-Bayyari, N. et al. Vitamin D(3) reduces risk of cardiovascular and liver diseases by lowering homocysteine levels: double-blinded, randomised, placebo-controlled trial. \u003cem\u003eBr. J. Nutr.\u003c/em\u003e \u003cb\u003e125\u003c/b\u003e (2), 139\u0026ndash;146 (2021).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTehlivets, O. et al. Homocysteine contributes to atherogenic transformation of the aorta in rabbits in the absence of hypercholesterolemia. \u003cem\u003eBiomed. Pharmacother\u003c/em\u003e. \u003cb\u003e178\u003c/b\u003e, 117244 (2024).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAmer, M. \u0026amp; Qayyum, R. The relationship between 25-hydroxyvitamin D and homocysteine in asymptomatic adults. \u003cem\u003eJ. Clin. Endocrinol. Metab.\u003c/em\u003e \u003cb\u003e99\u003c/b\u003e (2), 633\u0026ndash;638 (2014).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCzaja, A. J. \u0026amp; Montano-Loza, A. J. Evolving Role of Vitamin D in Immune-Mediated Disease and Its Implications in Autoimmune Hepatitis. \u003cem\u003eDig. Dis. Sci.\u003c/em\u003e \u003cb\u003e64\u003c/b\u003e (2), 324\u0026ndash;344 (2019).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHu, X. et al. Homocysteine as a trigger and potential therapeutic target for autoimmune diseases. \u003cem\u003eAutoimmun. Rev.\u003c/em\u003e \u003cb\u003e22\u003c/b\u003e (9), 103389 (2023).\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":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"AIH, DILI, Homocysteine, IgG, differential diagnosis","lastPublishedDoi":"10.21203/rs.3.rs-6720659/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6720659/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThis study aims to investigate the diagnostic utility of homocysteine and IgG in distinguishing drug-induced liver injury from autoimmune hepatitis. A total of 181 patients with drug-induced liver damage and 143 patients with autoimmune hepatitis were included in this retrospective study. The clinical baseline data, homocysteine and IgG levels of the two groups were compared. The diagnostic sensitivity and specificity were determined using receiver operating characteristic (ROC) curves, and the diagnostic values were compared using the area under the receiver operating curve (AUROC). At a critical value of 10.05, the diagnostic sensitivity of homocysteine for autoimmune hepatitis was 88.1%, with a specificity of 92.3% and an AUROC of 0.881 (95% CI, [0.834\u0026thinsp;~\u0026thinsp;0.927]). When the critical value was 15.31, the AUROC for the diagnosis of autoimmune hepatitis by IgG was 0.732 (95% CI, 0.677 to 0.788). The combination of homocysteine and IgG resulted in an AUROC of 0.903 (95% CI, [0.864\u0026thinsp;~\u0026thinsp;0.942]), indicating a notable enhancement in diagnostic performance. Homocysteine has the potential to assist in the accurate differentiation between drug-induced liver injury and autoimmune hepatitis. Furthermore, the utilization of homocysteine in conjunction with IgG enhances its diagnostic efficacy.\u003c/p\u003e","manuscriptTitle":"Diagnostic value of homocysteine combined with IgG in differentiating drug- induced liver injury and autoimmune hepatitis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-28 10:24:35","doi":"10.21203/rs.3.rs-6720659/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-08-19T13:00:13+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-13T08:18:21+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-11T11:15:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"136448115420948658507771948046778870643","date":"2025-07-24T16:45:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"102322038869237548406887296714747687533","date":"2025-07-24T00:53:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"244858750004568448220330788875501678294","date":"2025-07-23T12:22:30+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-23T02:10:54+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-06-06T10:53:08+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-23T06:23:18+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-22T12:14:54+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-05-22T03:11:59+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"725673ce-0eec-4275-a023-d9b7345d4e34","owner":[],"postedDate":"July 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":52077979,"name":"Biological sciences/Immunology"},{"id":52077980,"name":"Health sciences/Biomarkers"},{"id":52077981,"name":"Health sciences/Endocrinology"},{"id":52077982,"name":"Health sciences/Gastroenterology"}],"tags":[],"updatedAt":"2026-03-11T08:38:15+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-28 10:24:35","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6720659","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6720659","identity":"rs-6720659","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}