Introduction HIV cure remains one of the major unsolved global health challenges. The persistence of the HIV reservoir is the key barrier to achieving viral eradication. The acute HIV infection (AHI) is crucial for reservoir establishment, making early intervention essential for long-term viral remission. Pegylated interferon-α (Peg-IFN-α) exhibits potent antiviral and immunomodulatory properties that may enhance reservoir clearance when combined with antiretroviral therapy (ART). This study aims to evaluate the efficacy and safety of Peg-IFN-α combined with ART in promoting reservoir reduction and immune reconstitution in individuals with AHI.Methods and analysis This randomised, parallel-controlled, open-label clinical trial will enrol 68 participants with confirmed AHI. Eligible participants will be randomly assigned (1:1) to receive Peg-IFN-α plus ART or ART alone. All participants will continue ART for a total of 48 weeks. The primary outcome is the percentage reduction in total HIV-1 DNA at week 48. Secondary outcomes include HIV-1 DNA reduction at week 12, CD4+ T-cell recovery, cytokine profiles and safety endpoints. Statistical analysis will be performed using the intention-to-treat principle. Recruitment commenced in April 2025 and is expected to complete by December 2027.Ethics and dissemination This study has been approved by the Ethics Committee of Beijing You’an Hospital, Capital Medical University (approval no. LL-2024-150-K). Written informed consent will be obtained from all participants before enrolment. The results will be disseminated through peer-reviewed publications, academic conferences and communications with the clinical and scientific community. De-identified datasets will be available to qualified researchers on reasonable request following publication.Trial registration number ChiCTR2500100011.

Background and Aims:The current criterion of biochemical response to ursodeoxycholic acid in primary biliary cholangitis is an alkaline phosphatase (ALP) level of ≤1.67 × the upper limit of normal (ULN) after 12 months of treatment. However, a proportion of patients who meet this parameter may still progress to liver decompensation. This study aimed to optimize the clinical management of primary biliary cholangitis by (1) establishing ALP normalization as a core treatment target, (2) identifying early intervention windows, and (3) developing risk stratification criteria. Methods:This multicenter retrospective study included an internal cohort and an external validation cohort. We assessed the prognostic impact of ALP normalization with Kaplan-Meier and Cox regression. Sankey diagrams and segmented Poisson regression analysis mapped dynamic risk transitions to identify critical intervention windows. Predictive performance (sensitivity/specificity/positive predictive value/negative predictive value [NPV]) of Mayo, Paris II, and Toronto criteria for 12-month ALP normalization was compared. Results:Patients achieving ALP normalization showed significantly higher complication-free survival versus those with ALP 1.0-1.67 × ULN (89.8% vs. 79.8%; P = 0.016). Segmented Poisson regression identified significant change points at 3.73 and 5.5 months for high-to-medium and medium-to-low risk transitions, respectively. Failure to meet the Toronto criteria at month 3 predicted non-normalization with 95% NPV, whereas Paris II criteria at month 6 provided optimal specificity (73%) for identifying patients who failed to achieve ALP normalization. Conclusions:ALP normalization significantly improves clinical outcomes. Two subgroups demonstrate low normalization probability and warrant early intervention: (1) patients with ALP ≥ 1.67 × ULN after 3 months and (2) those not meeting Paris II criteria by month 6.

Background and Aims Anti-gp210 and antimitochondrial antibody (AMA) are important serological markers in primary biliary cholangitis (PBC). This study aimed to characterize the clinical features of anti-gp210-positive, AMA-negative patients with abnormal liver function and to explore factors associated with a final diagnosis of PBC in this retrospective cohort. Methods We retrospectively identified 93 anti-gp210-positive, AMA-negative patients. Clinical, biochemical, serological, pathological, and follow-up data were reviewed. Because the non-PBC group comprised multiple etiologies with different clinical and pathophysiological characteristics, comparisons between the PBC and non-PBC groups were considered exploratory and were interpreted with caution. Results Forty-eight patients were classified as PBC and 45 as non-PBC after clinical evaluation. Compared with the non-PBC group, patients with PBC had higher alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) levels, a higher anticentromere antibody (ACA) positivity rate, and higher anti-gp210 titers, whereas total bilirubin (TBIL) and aspartate aminotransferase (AST) levels were lower. During follow-up, anti-gp210 became negative in 1 of 23 followed PBC patients and in 6 of 20 followed non-PBC patients. Given the small follow-up subgroup, this observation is descriptive and should be interpreted cautiously. Conclusion Anti-gp210 positivity in AMA-negative patients supports consideration of PBC, but anti-gp210 positivity may also be detected in a subset of non-PBC liver diseases. In this retrospective cohort, higher anti-gp210 titers and a more cholestatic biochemical profile were more frequently observed in patients ultimately classified as PBC. These findings should be interpreted in light of the heterogeneity of the non-PBC group and the exploratory nature of the analyses.

Accurate staging of liver fibrosis in autoimmune hepatitis (AIH) remains challenging due to the invasive nature and sampling limitations of liver biopsy. This study aimed to identify readily available predictors of severe fibrosis and to develop an AIH-specific noninvasive machine-learning model. This two-stage study retrospectively enrolled 208 patients with biopsy-confirmed AIH, with prospective validation in 26 additional patients. Transient elastography (TE) was performed in 110 retrospective and 12 prospective patients. Severe fibrosis was defined as Scheuer stages S3 to S4. Candidate variables underwent univariable and multivariable logistic regression with collinearity control. A random forest (RF) model was trained on the independent predictors and evaluated by the area under the receiver operating characteristic curve (AUROC), calibration, and decision curve analysis. Shapley Additive exPlanations were used for interpretability. Inflammatory activity was graded by Scheuer and prespecified for subgroup analyses (G0-G2 vs G3-G4). A TE-inclusive RF model was also developed in the TE subgroup. The globulin-to-platelet index, international normalized ratio, and blood urea nitrogen were identified as independent predictors of severe fibrosis in AIH. The RF model based on these variables yielded AUROCs of 0.863 (95% confidence interval [CI], 0.802-0.917) in the training set, 0.747 (95% CI, 0.602-0.863) in the test set, and 0.784 (95% CI, 0.556-0.959) in the prospective cohort. Stratified by inflammatory grade, AUROCs were 0.842 (95% CI, 0.757-0.914) in G0-G2 and 0.814 (95% CI, 0.726-0.886) in G3-G4. In contrast, the aspartate aminotransferase-to-platelet ratio index and fibrosis-4 index performed poorly overall and deteriorated further under moderate-to-severe inflammation. In the TE subgroup, the RF model outperformed TE alone (AUROC, 0.786 vs 0.682), and performance improved further when TE was integrated (AUROC, 0.898 [95% CI, 0.841-0.949]). Globulin-to-platelet index, international normalized ratio, and blood urea nitrogen were independent predictors of severe fibrosis in AIH. An RF model constructed from these markers provided a robust, noninvasive tool whose performance was preserved across inflammatory grades and was further enhanced by incorporating TE.

Background:Despite the global success of antiretroviral therapy (ART) in reducing human immunodeficiency virus (HIV) related morbidity and mortality, late presentation of HIV infection remains a major challenge. This study aims to explore whether the immune dysregulation of pathological proliferation exists in late presenters (LP). Methods:People living with HIV (PLWH) were recruited and divided into LP group (n=55, defined as the presence of an AIDS-defining event and/or CD4 count <350 cells/μL) and non-late-presenters (n-LP) group (n=54). We evaluated the phenotype and function of CD4+ T cells in PLWH, and their correlation with clinical parameters. Mass cytometry was used to detect and analyze the phenotypic and functional characteristics of CD4+ T cells following ART. Results:The LP exhibited significantly lower CD4+ T cell counts compared to n-LP. A higher proportion of CD4+ T cell subpopulations with characteristics of proliferation (Ki67), activation (HLA-DR), exhaustion (PD-1) and senescence (CD57) was observed in LP. Besides, the proportion of CD4+ T cells with "pathological proliferation" properties (such as Ki67+CD57+, Ki67+HLA-DR+, Ki67+CD38+) in LP was much higher than that in n-LP. We found that the immune dysregulation characterized by pathological proliferation is related to multiple clinical parameters in LP. Conclusion:LP have persistent immune dysfunction post-ART, characterized by excessive and pathological T cell proliferation accompanied by activation or senescence. Future studies focusing on this pathological proliferation phenomenon will be essential to improve immune recovery, long-term prognosis, and health outcomes in advanced patients.

Background:Differentiating among liver disease entities such as autoimmune liver disease (AILD), drug-induced liver injury (DILI), and chronic hepatitis B (CHB) remains clinically challenging due to overlapping clinical manifestations and nonspecific laboratory findings. Conventional machine learning (ML) approaches rely mainly on structured laboratory data, whereas free-text clinical reports and other heterogeneous electronic medical record data are often underused. Large language models (LLMs) may provide a strategy for encoding heterogeneous clinical information, yet their usefulness for liver disease classification remains insufficiently evaluated. Objective:This study aimed to evaluate the usefulness of LLM-derived embeddings for clinical data mining in liver disease and to determine whether integrating these embeddings with laboratory variables improves classification across broad disease categories and closely related subtypes. Methods:We retrospectively analyzed electronic medical record data from 7543 patients with nonoverlapping liver disease etiologies treated at Beijing Youan Hospital, Capital Medical University, between 2010 and 2025. Three LLMs (Qwen3, Huatuo-o1, and II-Medical) generated semantic embeddings from standardized clinical text, combining free-text examination reports, and structured clinical observations. Performance was assessed in a 3-class etiological task (AILD, DILI, and CHB) and a 4-class task further subclassifying AILD into autoimmune hepatitis and primary biliary cholangitis. We compared embedding-only models, LLM-integrated ML models, and an ML-only baseline using the same structured variable set and preprocessing pipeline, with lightweight natural language processing encoders and zero-shot LLM reasoning as additional comparators. Models were developed using 5-fold cross-validation and evaluated on an internal holdout set using accuracy, macroaveraged precision, recall, and F1-score. Results:In the 3-class task, the LLM-integrated ML models achieved macro F1-scores of 0.835-0.837, compared with 0.791 for the ML-only baseline, with corresponding accuracies of 0.925-0.929 versus 0.893. In the 4-class task, the LLM-integrated ML models achieved macro F1-scores of 0.717-0.734, compared with 0.665 for the ML-only baseline, with corresponding accuracies of 0.920-0.922 versus 0.874. A temporal split sensitivity analysis using cases from 2010 to 2019 for training and cases from 2020 to 2025 for testing showed that the relative advantage of LLM-integrated ML models over the ML-only baseline was preserved. Direct zero-shot LLM reasoning and lightweight natural language processing encoders performed below the embedding-based integrated models. Conclusions:In this single-center retrospective cohort of patients with clear-cut, nonoverlapping liver disease etiologies, LLM-derived embeddings provided complementary information to structured laboratory variables for multiclass liver disease classification. The integrated framework showed improved internal validation performance compared with the ML-only model, particularly for non-CHB categories and fine-grained subtype discrimination. Because patients with overlapping liver disease etiologies were excluded, the reported performance may overestimate diagnostic accuracy in broader real-world clinical settings where overlapping syndromes are common. Multicenter external validation and prospective evaluation in more heterogeneous patient populations are needed before clinical implementation.

BACKGROUND:Autoimmune liver diseases, including primary biliary cholangitis (PBC), autoimmune hepatitis (AIH), and their overlap syndrome (OS), involve immune-mediated liver injury, with OS occurring in 1.2%-25% of PBC patients. OS carries a higher risk of cirrhosis, hepatocellular carcinoma, and reduced survival. While its pathogenesis remains unclear, gut microbiota dysbiosis and serum metabolite alterations may play key roles. This study uses 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC-MS) metabolomics to compare gut microbiota and serum metabolites among PBC, AIH, and OS patients, and explores their associations with liver function. AIM:To differentiate OS from PBC and AIH based on gut microbiota, serum metabolites, and liver function. METHODS:Gut microbiota profiles were analyzed using 16S rRNA sequencing, while untargeted serum metabolomics was conducted via LC-MS. Comparative analyses were performed to identify differences in microbial composition and serum metabolite levels among PBC, AIH, and OS groups. Correlation analyses and network visualization techniques were applied to elucidate the interactions among liver function parameters, gut microbiota, and serum metabolites in OS patients. RESULTS:Compared to patients with PBC or AIH, OS patients demonstrated significantly reduced microbial diversity and richness. Notable taxonomic shifts included decreased abundances of Firmicutes, Bacteroidetes, and Actinobacteria, alongside increased levels of Proteobacteria and Verrucomicrobia. Distinct serum metabolites, such as pentadecanoic acid and aminoimidazole carboxamide ribonucleotide, were identified in OS patients. Correlation analysis revealed that aspartate aminotransferase (AST) levels were negatively associated with the bacterial genus Fusicatenibacter and the metabolite L-Tyrosine. A microbial-metabolite network diagram further confirmed a strong association between Fusicatenibacter and L-Tyrosine in OS patients. CONCLUSION:OS patients show decreased gut microbiota diversity and unique serum metabolites. Multi-omics linked AST, Fusicatenibacter, and L-Tyrosine, revealing OS mechanisms and diagnostic potential.

BACKGROUND:About 1/3 of primary biliary cholangitis (PBC) patients suffered from poor response worldwide. And these patients present intestinal disturbances. We aimed to identify signatures of microbiota and metabolites in PBC patients with poor response, comparing to patients with response.METHODS:This study enrolled 25 subjects (14 PBC patients with response and 11 PBC patients with poor response). Metatranscriptomics and metabolomics analysis were carried out on their fecal.RESULTS:PBC patients with poor response had significant differences in the composition of bacteria, characterized by decreased Gemmiger etc. and increased Ruminococcus etc. The differential microbiota functions characterized by decreased abundance of elongation factor Tu and elongation factor G base on the KO database, as well as decreased abundance of Replicase large subunit etc. based on the SWISS-PROT database. PBC with poor response also had significant differences in 17 kinds of bacterial metabolites, characterized by decreased level of metabolites vital in bile acids metabolism pathway (L-Cysteine etc.) and the all-trans-Retinoic acid, a kind of immune related metabolite. The altered microbiota was associated with the differential expressed metabolites and clinical liver function indicators. 1 bacterial genera, 2 bacterial species and 9 metabolites simultaneously discriminated PBC with poor response from PBC with response with high accuracy.CONCLUSION:PBC patients with poor response exhibit unique changes in microbiota and metabolite. Gut microbiota and metabolite-based algorithms could be used as additional tools for differential prediction of PBC with poor prognosis.

BACKGROUND:Primary biliary cholangitis (PBC) is associated closely with the gut microbiota. This study aimed to explore the characteristics of the gut microbiota after the progress of PBC to cirrhosis. METHOD:This study focuses on utilizing the 16S rRNA gene sequencing method to screen for differences in gut microbiota in PBC patients who progress to cirrhosis. Then, we divided the data into training and verification sets and used seven different machine learning (ML) models to validate them respectively, calculating and comparing the accuracy, F1 score, precision, and recall, and screening the dominant intestinal flora affecting PBC cirrhosis. RESULT:PBC cirrhosis patients showed decreased diversity and richness of gut microbiota. Additionally, there are alterations in the composition of gut microbiota in PBC cirrhosis patients. The abundance of Faecalibacterium and Gemmiger bacteria significantly decreases, while the abundance of Veillonella and Streptococcus significantly increases. Furthermore, machine learning methods identify Streptococcus and Gemmiger as the predominant gut microbiota in PBC patients with cirrhosis, serving as non-invasive biomarkers (AUC = 0.902). CONCLUSION:Our study revealed that PBC cirrhosis patients gut microbiota composition and function have significantly changed. Streptococcus and Gemmiger may become a non-invasive biomarker for predicting the progression of PBC progress to cirrhosis.

Primary biliary cholangitis (PBC) is an autoimmune liver disease. During the diagnostic process, the patient's autoimmune antibodies are routinely examined. Approximately 20% of PBC patients have positive anti-centromere antibody (ACA). We evaluated the clinical characteristics of ACA-positive and ACA-negative PBC patients to explain the differences in disease progression between these two groups. Retrospective data from 961 PBC patients at Beijing Youan Hospital from 2010 to 2019 were gathered and separated into two groups based on ACA positivity. We collected and evaluated clinical laboratory indices, gastroscopy findings, and liver function assessments. In addition, 60 liver biopsies were available for comparison between the 2 groups. Pathologists staged the histological findings using the Ludwig staging criteria and Nakanuma staging and grading. Immunohistochemical staining was also performed on liver biopsies to examine the expression of cytokeratin 7 (CK7) in the tissue. A synthesis of clinical indicators in the large cohort showed that alanine transaminase, aspartate aminotransferase, total bilirubin, IgG, white blood cell, and platelet were significantly lower in the ACA-positive group, indicating that the overall status of liver injury was more moderate in the ACA-positive group. Additionally, ACA-positive patients in the non-cirrhotic group were more likely to present with gastroesophageal varices related to portal hypertension. Finally, analysis of pathologic findings showed that parameters were mostly comparable in the two groups, but CK7 differed and was more significantly lower in the ACA-positive group in albumin-bilirubin grade 2 and 3 patients. In summary, we characterized and compared the clinical features of ACA-positive and ACA-negative PBC patients, corroborating previous studies on the relationship between ACA positivity and portal hypertension cross-sectionally. It suggested that gastroesophageal varices might happen in the earlier course of PBC natural progression in the ACA-positive group.

Background The Albumin-Bilirubin (ALBI) score and grade are widely used to stratify patients with primary biliary cholangitis (PBC) into different disease statuses and risk levels. Recent studies have increasingly highlighted the role of gut microbiota in autoimmune liver diseases. This study aimed to investigate the differences in gut microbiota among PBC patients with varying ALBI grades.Methods Clinical data and stool samples were collected from outpatient and inpatient PBC patients between 2019 and 2022. Gut microbiota profiles were obtained using 16S rDNA sequencing of stool samples. We analyzed alpha diversity, beta diversity, LEfSe analysis and pathway function prediction. Additionally, various machine learning methods-including random forest (RF), lasso, gradient boosting machine (GBM) and support vector machine (SVM)-were employed to identify key features and to build and validate predictive models using bootstrap techniques.Results Clinical characteristics of ALBI grade 1 patients were comparatively better than those of ALBI grade 2 and 3 patients, including multiple laboratory indices. Gut microbiota analysis revealed that species richness and balance were higher in ALBI grade 1 patients. Both the comparison of the most abundant genera and the linear discriminant analysis (LDA) in LEfSe demonstrated that Lachnospira had a higher abundance and better discriminative ability in ALBI grade 1. Pathway function prediction indicated that sulfur metabolism was upregulated in higher ALBI grades. Furthermore, RF identified 10 specific genera, which were then used to build and validate models for discriminating PBC patients according to their ALBI grades. All three models, developed using different machine learning methods, demonstrated good discrimination ability (mean AUC 0.75-0.80).Conclusion This study highlights significant differences in gut microbiota profiles among PBC patients with different ALBI grades. The increased abundance of Lachnospira and upregulation of sulfur metabolism pathways are notable in patients with lower ALBI grades. The machine learning models developed based on gut microbiota features offer promising tools for discriminating between PBC patients with varying disease severities, which could enhance the precision of treatment strategies.

Background & aims: Association studies have greatly refined the important role of the major histocompatibility complex (MHC) region in autoimmune hepatitis (AIH). However, the effects of human leucocyte antigen (HLA) polymorphisms on AIH are not well established. The aim of this study is to systematically characterise the association of MHC variants with AIH in our well-defined cohort of patients.Methods: We performed an imputation-based analysis on the extensive association observed within the MHC region using the Han-MHC reference panel, and tested the comprehensive associations of HLA polymorphisms with AIH in 1622 Chinese AIH type 1 patients and 10,466 population controls.Results: A total of 588 HLA variants were significantly associated with AIH, with HLA-B & lowast;35:01 (p = 8.17 x 10(-304); odds ratio [OR] = 7.32) contributing the strongest signal. Stepwise conditional analysis revealed additional independent signals at HLA-B & lowast;08:01 (p = 1.35 x 10(-33); OR = 4.26) and rs7765379 (p = 5.08 x 10(-18); OR = 1.66). A strong link between the lead HLA variant and clinical phenotypes of AIH was observed: patients with HLA-B & lowast;35:01 were less frequently positive for ANA and tended to have higher serum AST and ALT levels at diagnosis, but lower serum IgG levels.Conclusions: Our study reveals three novel and independent variants at HLA-B & lowast;35:01, HLA-B & lowast;08:01, and rs7765379 associated with AIH across the whole MHC region in the Han Chinese population. The findings illustrate the value of the MHC region in AIH and provide a new perspective for the immunogenetics of AIH.Impact and implications: This study revealed three novel and independent variants associated with autoimmune hepatitis across the whole major histocompatibility complex region in the Han Chinese population. These findings are significant in identifying autoantigens, providing insights into the activation of the autoimmune processes, and further advancing our understanding of the immunogenetic basis underlying autoimmune hepatitis.(c) 2023 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

BackgroundA variety of autoantibodies have been detected in primary biliary cholangitis (PBC), while the presence of autoantibody clusters and their clinical significance have not been fully understood. We aimed at defining autoantibody clusters and to better understand the clinical features and prognosis of PBC patients based on autoantibody clusters under real-world conditions.MethodsWe retrospectively analyzed 788 inpatients with PBC evaluated between October 2008 and July 2019, and included 537 patients. Nineteen autoantibodies which were measured routinely were investigated for cluster analysis. Two-step clustering, Kaplan-Meier survival, and Cox regression analyses were used.ResultsFive clusters were defined. A cluster of antinuclear antibodies (ANA) and anti-gp210 positive patients were identified with a high rate of cirrhosis at baseline and low survival rate; a cluster of ANA, anti-centromere antibodies (ACA) and/or anti-CENP-B female dominant patients with older disease onset, low level of platelet count at baseline, high rate of hepatic decompensation, and low survival rate was also characterized; and another cluster of anti-mitochondrial antibodies (AMA) and/or AMA-M2, anti-Ro52 and a high rate of anti-gp210 positive patients were identified with a high proportion of male patients and low survival rate. A subgroup of patients with anti-SSA and/or anti-SSB coexists with SjS was also identified; patients with only AMA and/or AMA-M2-positive with a benign clinical outcome and relatively high complication of non-alcoholic fatty liver disease (NAFLD) were also identified. Only anti-gp210 was considered as a significant predictor for poor outcomes especially in patients with cirrhosis.ConclusionClustering methods allow the identification of distinct autoantibody profiles of PBC that form clinical subsets and can be useful for personalized approaches to diagnosis, clinical management, and the prediction of clinical outcomes. Anti-gp210 was the strongest predictive factor for poor outcomes especially in PBC patients with cirrhosis under real-world conditions.

OBJECTIVE:To investigate the clinical characteristics of systemic lupus erythematosus accompanied by autoimmune liver cirrhosis (SLE-ALC) patients and differences from the non-cirrhosis group.METHODS:Forty-three patients with SLE-ALC were enrolled in this study from 2653 patients with SLE in Peking University People's Hospital. A descriptive case-control study was performed between SLE-ALC patients and the entry time-matched non-cirrhosis group.RESULTS:Among the 43 SLE-ALC patients, 41 (95.3%) were female. Eight patients (18.6%) were first found to have cirrhosis and then diagnosed with SLE. Eighteen patients (41.9%) had jaundice and 27 (62.8%) had esophageal and gastric varices. The age of SLE-ALC patients was 51.1 ± 17.2 years, which was significantly older than the non-cirrhosis group (P < 0.001). Lung involvement was more common as initial manifestations in SLE-ALC patients during the SLE course (P=0.027). Compared with the non-cirrhosis group, SLE-ALC patients had worse liver function. A significantly higher rate of hematological system involvement (anemia, leucopenia, and thrombocytopenia) and a higher level of immunoglobulins were observed in SLE-ALC patients (P<0.05). Moreover, SLE-ALC patients displayed a lower positive rate of anti-double-stranded DNA and anti-ribosomal P protein (P<0.05). The most common radiologic manifestations are ascitic fluid (72.1%) and splenomegaly (71.4%) in SLE-ALC patients. Six SLE-ALC patients underwent liver biopsy, and interface hepatitis was present in all patients.CONCLUSIONS:Cirrhosis is rare in SLE patients but is manifested as a unique pattern of clinical features characterized by late-onset age, lung involvement, high immunoglobulins, and impaired liver function.

Objective: This study aimed to investigate the prognostic significance of combined serum IL-2 and total bilirubin (TBIL) on liver failure in patients with primary biliary cirrhosis (PBC). Methods: A total of 160 PBC patients who were treated with UDCA therapy was retrospectively analyzed. The demographic data and laboratory parameters at admission were collected, and the COX regression model was used to predict independent risk factors related to the progression of PBC disease. The optimal cut-off values and prognosis effects of serum IL-2 and TBIL were identified based on the time-dependent receiver operating characteristic (ROC) curve. The incidence of liver failure was also analyzed with Kaplan-Meier survival analysis. In addition, a cytokine detection was performed to observe the changes of cytokines (mainly IL-2) with liver tissue and blood samples from 11 patients with end stage PBC liver failure and 5 healthy control patients. Results: Age, IL-2, ALB,γ-GT, ALP, TBIL, Hb, TBA, WBC, and PLT, as well as anti-Sp100, were found to be independent risk factors in PBC patients with liver failure. Patients with decreased serum IL-2 levels and increased TBIL levels have a significant higher incidence of liver failure, a lower survival rate, and a worse prognosis. Patients with advanced liver transplantation with PBC liver failure exhibited a significant decrease in the level of serum IL-2and a relatively immunosuppressed status. Conclusions: The combination of serum IL-2 and TBIL can be a predictor of progression of liver failure in patients with primary biliary cholangitis, and it is likely to be related to the expression of GM-CSF and G-CSF.

Background In primary biliary cholangitis (PBC), the levels of serum IL-2 were involved in liver inflammation and immune changes. This study aimed to investigate the prognostic significance of serum IL-2 combined with total bilirubin (TBIL) in liver failure and cytokine changes during the disease. Methods A total of 160 PBC patients treated with UDCA were included. Parameters at admission were collected, and the COX regression model was used to predict independent risk factors associated with PBC disease progression. We identified the optimal cut-off values and prognosis effects of serum IL-2 and TBIL based on the time-dependent receiver operating characteristic (ROC) curve. We also analyzed the incidence of liver failure with Kaplan-Meier survival analysis. In addition, the changes of cytokines (mainly IL-2) in liver tissues and blood samples from 11 patients with end-stage PBC liver failure and five healthy controls were examined. Results Age, IL-2, ALB, γ-GT, ALP, TBIL, Hb, TBA, WBC, and PLT, as well as anti-Sp100, were found to be independent risk factors in PBC patients with liver failure. Patients with decreased serum IL-2 levels and increased TBIL levels have a significantly higher incidence of liver failure and a worse prognosis. Patients with advanced PBC liver failure after liver transplantation exhibited a significant decrease in levels of serum IL-2 and a relatively immunosuppressed status. Conclusions The combination of serum IL-2 and TBIL can be a predictor of the progression of liver failure in patients with primary biliary cholangitis, and it is likely to be related to the expression of GM-CSF and G-CSF.

目的 分析自身免疫性肝炎患者服用硫唑嘌呤治疗后发生骨髓抑制病例的特点及治疗方法.方法 选取2017-2021年首都医科大学附属北京佑安医院收治的3例接受硫唑嘌呤治疗后发生骨髓抑制的自身免疫性肝炎患者,对其临床资料、实验室检查、诊断及治疗情况进行回顾性分析,并进行文献复习.结果 3例患者检测巯基嘌呤甲基转移酶(thiopurine S-methyltransferase enzyme,TPMT)基因型均正常,但在用药后1个月内(19～28 d)出现骨髓抑制,主要表现为严重粒细胞缺乏(中性粒细胞绝对值最低降至检测不到)和(或)PLT进行性降低(最低降至7 x 109/L),贫血情况通常晚于粒细胞缺乏;其中2例患者发现骨髓抑制时粒细胞已降至低谷,PLT降低发生较晚,甚至在中性粒细胞开始恢复后仍呈下降趋势.3例患者经治疗后均预后良好,全血细胞完全恢复正常需19～60 d.文献研究显示,硫唑嘌呤引起的骨髓抑制大多数可逆,多数患者预后良好.结论 自身免疫性肝炎患者尽管TPMT基因型正常,亦可能会在应用硫唑嘌呤过程中发生严重的骨髓抑制,临床应予以充分重视.

To the Editor: Autoimmune hepatitis (AIH) is a type of liver parenchymal inflammation mediated by the autoimmune response of liver cells. AIH was previously considered to be a chronic liver disease, but recent observers have confirmed that AIH patients can have acute onset or even liver failure (AIH-LF).[1] The incidence of AIH-LF has also increased. Once LF occurs, the mortality rate within 90 days could reach >40%.[2] Therefore, the occurrence of LF has a major impact on the prognosis of AIH. Although AIH-LF has a low incidence and a high mortality rate, some cases can still be cured by treatment. The clinical characteristics that may affect the prognosis of patients with AIH-LF are still unclear. To clarify the factors affecting the prognosis of AIH-LF, we compared the clinical characteristics of two groups of AIH-LF patients with different prognosis. This study was approved by the Ethics Committee of the Beijing You An Hospital, Capital Medical University. Written informed consent was obtained from all participants. We enrolled 53 patients with AIH-LF, who were treated at our center from October 2009 to October 2019. Of the 53 patients, there were four males and 49 females with a mean age of 48.7 ± 14.7 years (range: 11–84 years). All patients were scored according to the scoring system of the International Autoimmune Hepatitis Group in 1999 or simplified AIH score.[3] Diagnosis of LF was according to the Chinese guidelines for diagnosis and treatment of LF.[4] Patients were divided into improvement (I) group (n = 26) and deterioration (D) group (n = 27). Improvement was defined as clinical cure or amelioration without liver transplantation within 6 months. Deterioration was defined as worse condition than that at admission or death from LF. Routine serological indices, such as liver function, blood cell analysis, circulating autoantibodies, serum immuno-globulin, serum a-fetoprotein (AFP), and hepatotropic virus, were performed in all patients and detected at the first visit before therapy. Histological specimens were available in 23 patients and were reviewed retrospectively and blindly by two pathologists in our facility. The first-line treatment was defined as the standardized treatment with corticosteroids and/or azathioprine drugs. Data on mortality, improvement periods, and outcomes were available from stored medical records and consultations with the patients' physicians or follow-up of the patients and their family members, which ended on the date of death, liver transplantation, or the end of the study. In all patients who underwent transplantation, their organs were available from voluntary donations. We found that gender and age structure in the two groups were similar and the peak age of onset was 41 to 60 years. Twenty (76.9%) patients were cured and six (23.1%) patients were improved in the I group, while 11 (40.7%) patients survived because of liver transplantation and 16 (59.3%) patients died (one after liver transplantation) in the D group. About 59.2% (16/27) of patients who had been diagnosed with AIH for >6 months in the D group were higher than 34.6% (9/26) in the I group (P = 0.039), and the average interval from diagnosis of AIH to occurrence of liver failure in the D group was 26.5 months, which was longer than 13.0 months in the I group (P = 0.009). Patients in the I group were more likely to have subacute liver failure (SALF) (46.2% vs. 14.8%, P = 0.004) and early-stage LF on admission (73.1% vs. 40.7%, P = 0.018), but less acute-on-chronic liver failure or subacute acute-on-chronic liver failure (ACLF/SACLF) (50.0% vs. 74.1%, P = 0.035), end-stage LF (3.8% vs. 25.9%, P = 0.018), or cirrhosis (30.8% vs. 43.7%, P = 0.033) than in the D group. More patients in the I group received steroids or immunosuppressive drugs (80.8% vs. 44.4%, P = 0.018). Patients in the D group had more symptoms and complications, such as anorexia, bacterial infection, renal insufficiency (P < 0.050). The laboratory tests of the two groups were similar, but the AFP level and the former infection of hepatitis B virus and parvovirus B19 in the I group were significantly higher (P = 0.016 and 0.024, respectively). In addition, the detection of autoantibodies in the two groups was similar. Severe interface hepatitis was more common in the I group (P = 0.033), but the stage of liver fibrosis and bile duct injury were more severe in the D group (P = 0.033 and 0.002, respectively) [Table 1]. Table 1 - Comparison of clinical characteristics between improvement and deterioration LF-AIH patients. Characteristics I group (n = 26) D group (n = 27) P Sex (M/F) 2/24 2/25 NS Age at onset (years) 49.5 (24.0–84.0) 47.9 (19.0–71.0) NS AIH diagnosed >6 months 9 (34.6) 16 (59.2) 0.039 Interval from diagnosis of AIH to LF (months) 13.0 (0.5–72.0) 26.5 (0.5–120.0) 0.009 Classification of LF (Sub) Acute 13 (50.0) 6 (26.9) 0.035 Acute 1 (3.8) 3 (11.1) NS Subacute 12 (46.2) 3 (14.8) 0.004 (Sub) Acute-on-chronic 13 (50.0) 21 (74.1) 0.035 Acute-on-chronic 2 (7.7) 6 (22.2) NS Subacute-on-chronic 11 (42.3) 15 (51.9) NS Stage of LF on admission Early (30%

BACKGROUND Vitamin D deficiency is universal among patients with chronic liver disease. Vitamin D may be involved in the regulation of immune function of chronic hepatitis B and related to disease progression. METHODS The study was a cross-sectional study. The level of vitamin 25(OH)D was detected in patients with chronic hepatitis B, hepatitis B cirrhosis, hepatitis B cancer, and healthy groups by isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS). At the same time, the clinical data, biochemical indexes, and T lymphocyte subsets were collected to study the relationship between vitamin 25(OH)D deficiency and clinical indexes of hepatitis B patients. RESULTS The prevalence of vitamin D deficiency (< 20 ng/mL) was higher in patients with liver cancer group (96.97%, 10.59 ± 3.06 ng/mL) and cirrhosis group (93.18%, 11.85 ± 2.66 ng/mL) than in the healthy group (76.92%, 16.38 ± 5.53 ng/mL) and chronic hepatitis B group (77.83%, 15.06 ± 4.91 ng/mL). There were significant differences in vitamin 25(OH)D levels between the cirrhosis groups and the healthy groups, the liver cancer groups and the healthy groups, the hepatitis B cirrhosis groups and the chronic hepatitis B groups, the liver cancer groups and the chronic hepatitis B groups (p < 0.05). There was no significant difference in vitamin 25 (OH)D level between liver cancer group and hepatitis B cirrhosis group, healthy group and chronic hepatitis B group (p > 0.05). Vitamin 25(OH)D level was correlated with age (r = -0.24, p = 0.015), lymphocyte (r = 0.24, p = 0.015), hemoglobin (r = 0.28, p = 0.005), platelet (r = 0.27, p = 0.006), PTA (r = 0.33, p = 0.001), albumin (r = 0.30, p = 0.002), prealbumin (r = 0.39, p = 0.001), cholinesterase (r = 0.29, p = 0.003), CD3+ (r = 0.20, p = 0.04), CD3+ CD8+ (r = 0.20, p = 0.04), CD45+ (r = 0.24, p = 0.017), but none correlated with liver function and HBV-DNA. CONCLUSIONS Vitamin D deficiency existed in patients with hepatitis B, which was related to the clinical progress of hepatitis B and may be involved in the regulation of immune function in patients with chronic HBV infection.

Through big data, this paper reviews the national research projects and the academic papers published in China and globally in the field of autoimmune liver diseases in China from 2001 to 2020, revealing the development trend in the past two decades. This paper also introduces the updates of the newly issued guidelines for the diagnosis and treatment of autoimmune liver diseases, and reviews the development of autoantibody detection technology and analyzes its progress.