The early diagnosis and treatment of atypical autoimmune liver disease should be taken seriously / 临床肝胆病杂志

Autoimmune liver disease is a group of diseases mainly caused by autoimmune abnormalities, including autoimmune hepatitis dominated by hepatocellular injury, primary biliary cholangitis and primary sclerosing cholangitis dominated by bile duct injury, and overlap syndrome with the main features of the above two diseases. Recently, IgG4-related hepatobiliary diseases have also been included in this category, and without timely diagnosis and treatment, it can progress to liver cirrhosis and even liver failure. Different autoimmune liver diseases have their own features, and with the popularization of the knowledge on autoimmune liver diseases, physicians have gradually increased their understanding of such diseases and can achieve the early diagnosis and timely treatment of most typical autoimmune liver diseases. However, some patients may have atypical manifestations or laboratory markers, which may easily delay the diagnosis, and therefore, it is of great importance to identify atypical autoimmune liver disease and give timely diagnosis and treatment as soon as possible.

Role of intestinal flora in the development/progression and treatment of autoimmune liver diseases / 临床肝胆病杂志

Overgrowth of intestinal bacteria, change in intestinal flora, translocation between bacteria and their products, and bile acid metabolism are the important pathways for the development and progression of liver diseases. Hepatocytes are persistently exposed to intestinal metabolites and various antigens and antibodies via the portal vein system, and the constituents or metabolites of some intestinal bacteria can activate the autoimmune mechanism targeting hepatocytes through several mechanisms, including molecular mimicry. Therefore, intestinal flora plays an important role in the development/progression and treatment of autoimmune liver diseases, including autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. This article reviews the related research advances in recent years.

Role of autoimmune ecological factors in the pathogenesis of autoimmune hepatitis / 临床肝胆病杂志

Autoimmune hepatitis (AIH) is a chronic liver inflammatory disease with unknown etiology, and at present, both genetic and environmental factors are thought to be involved in the pathogenesis of AIH. Environmental exposure has an important impact on the development of AIH. Autoimmune ecology is the study of the interactions between individuals and their environment, the development of imbalance between individuals and environment, and the mechanism of such imbalance in promoting the development of autoimmune disease. This article reviews the research advances in the role of autoimmune ecology in the pathogenesis of AIH.

Clinical features of autoimmune hepatitis in children: An analysis of 10 cases / 临床肝胆病杂志

ObjectiveTo investigate the clinical features and treatment outcome of children with autoimmune hepatitis (AIH). MethodsA retrospective analysis was performed for the clinical data, liver pathology, treatment outcome, and follow-up data of 10 children with AIH who were treated in Beijing YouAn Hospital, Capital Medical University, from December 2008 to December 2017. ResultsThe children were aged 3-16 years (median 10 years), and girls accounted for 70%. Of all patients, 5 had type 1 AIH, and 5 had type 2 AIH; 3 (30%) had an acute onset, 2 (20%) had a subacute onset, and 5 (50%) had a chronic onset. Elevation of aminotransferases was found in 8 children (80%), and elevations of bilirubin, gamma-glutamyl transpeptidase, and immunoglobulin G were found in 7 children (70%), 7 children (70%), and 6 children (60%), respectively. Among the 7 children who underwent liver biopsy, 3 had grade ≥3 liver inflammation, 4 had stage ≥3 liver fibrosis, 5 had interface hepatitis, 5 had plasma cell infiltration, 4 had rosette-like annulation of hepatocytes, and 7 had lymphocyte infiltration. One child died, and one was lost to follow-up; among the other 8 children, 6 had good response, 1 experienced recurrence, and one had poor response. 4 patients with type 2 AIH were treated with glucocorticoids combined with azathioprine, the disease was effectively controlled. ConclusionChildren with AIH have diverse clinical manifestations, and some children have serious conditions. Most patients with type 2 AIH need the treatment of glucocorticoids combined with azathioprine.

Clinical value of anti-liver/kidney microsomal-1 antibody in patients with liver disease / 中华肝脏病杂志

Objective@#To investigate the clinical and laboratory features of patients with liver disease and positive anti-liver/kidney microsomal-1 (anti-LKM-1) antibody, and to provide a reference for clinical diagnosis and differential diagnosis.@*Methods@#The clinical data of patients with positive anti-LKM-1 antibody who were treated in our hospital from 2006 to 2016 were collected, and clinical and laboratory features were analyzed and compared. An analysis was also performed for special cases.@*Results@#The measurement of related autoantibodies was performed for about 100 thousand case-times, and 15 patients were found to have positive anti-LKM-1 antibody. Among the 15 patients, 7 were diagnosed with type 2 autoimmune hepatitis (AIH) with an age of 11.0 ± 9.0 years and were all adolescents with acute onset; 8 were diagnosed with hepatitis C with an age of 51.5 ± 9.0 years, among whom 7 were middle-aged patients and 1 was a child aged 12 years, and all of them had an insidious onset. Compared with the patients with hepatitis C, the AIH patients had significantly higher levels of alanine aminotransferase (1 003.9 ± 904.3 U/L vs 57.0 ± 84.1 U/L, P < 0.05), aspartate aminotransferase (410.7 ± 660.3 U/L vs 34.9 ± 42.9 U/L, P < 0.05), and total bilirubin (98.0 ± 191.0 μmol/L vs 15.4 ± 6.0 μmol/L, P < 0.05). There was a reduction in immunoglobulin G after the treatment with immunosuppressant, compared with the baseline. Of all 8 patients with hepatitis C, 6 received antiviral therapy with interferon and ribavirin, and 5 out of them achieved complete response, among whom 4 had a reduction in the level of anti-LKM-1 antibody after treatment; however, a 12-year-old child developed liver failure after interferon treatment and died eventually.@*Conclusion@#Positive anti-LKM-1 antibody is commonly seen in patients with type 2 AIH or hepatitis C, but there are differences between these two groups of patients in terms of age, disease onset, liver function, and the level of anti-LKM-1 antibody. The hepatitis C patients with a confirmed diagnosis and exclusion of autoimmune hepatitis can achieve good response to interferon under close monitoring, even if anti-LKM-1 antibody is positive. As for adolescent patients with hepatitis C and positive anti-LKM-1 antibody, the possibility of AIH should be excluded.

Characteristics of IgH-CDR3 repertoire of peripheral B cells in a patient with primary biliary cholangitis: a preliminary study using high-throughput sequencing / 中华肝脏病杂志

Objective@#To analyze the characteristics of immunoglobulin heavy chain complementarity-determining region (IgH-CDR3) repertoire of peripheral B cells in a patient with primary biliary cholangitis (PBC) and to investigate the diversity of the immune system.@*Methods@#Arm-PCR was used to amplify the IgH-CDR3 region of circulating B cells isolated from a PBC patient, and high-throughput sequencing was used to analyze the amplified product. The characteristics of immune repertoire were analyzed by bioinformatics.@*Results@#In total, 329219 sequence reads were generated from the sample, with 325540 total CDR3 sequences and 72774 distinct CDR3 sequences, and the D50 of IGH-CDR3 was 7.7. The dominant CDR3 length of the sample was 45 nt (9.6%); the N addition with the highest frequency ranged from 13 to 14 nt (5.25%); the J trimming with the highest frequency was 0 nt (12.7%); the three most frequent V alleles were V4-59 (9.5%), V3-23 (8.1%), and V1-69 (6.4%).@*Conclusion@#The diversity of IgH-CDR3 repertoire is relatively low in this patient with PBC, with several B-cell clonal expansions. The specificity needs to be further verified after increasing the sample size.

Prognostic evaluation of primary biliary cirrhosis and its value in guiding therapeutic regimens / 临床肝胆病杂志

Prognostic evaluation of patients with primary biliary cirrhosis (PBC) and how to improve the prognosis have attracted much attention. Further therapeutic regimens for PBC patients with poor prognosis has become the direction of clinical and scientific studies. This article summarizes the association between baseline indices and prognosis and prognostic evaluation of patients undergoing ursodeoxycholic acid (UDCA) treatment, introduces the current status of UDCA combined with budesonide, fibrates, and obeticholic acid for patients with poor response to UDCA and the drugs being developed, and analyzes the influencing factors for prognosis and efficacy of UDCA. It is pointed out that prognosis and efficacy should be evaluated before and during UDCA treatment, and that therapeutic regimens should be adjusted in time to improve prognosis.

Drug-induced liver injury accompanied by autoimmune phenomena: an analysis of clinical characteristics / 临床肝胆病杂志

ObjectiveTo analyze the clinical characteristics of drug-induced liver injury (DILI) accompanied by autoimmune phenomena and to provide evidence for clinical practice. MethodsAn analysis was performed on the clinical data of 51 patients who were admitted to Beijing You′an Hospital from 2011 to 2013 and diagnosed with DILI. The participants were divided into anti-nuclear antibody (ANA)-positive group and ANA-negative group and, according to the simple scoring system for autoimmune hepatitis (AIH), divided into low-score (sore: 1-4) group and high-score (score≥5) group, respectively. Comparison was made for laboratory parameters ［alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), albumin (Alb), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), prothrombin time (PT), immunoglobulin M(IgM), immunoglobulin A(IgA), immunoglobulin G(IgG)］, length of hospital stay, and recurrence. Comparison of normally distributed continuous data between groups was performed by t test, comparison of non-normally distributed continuous data between groups was made by rank-sum test, and comparison of categorical data between groups was conducted by chi-square test. Results Among the 51 patients, 34 cases were positive for ANA, and 17 cases were negative for ANA; 17 cases were in the high-score group, and 34 cases were in the low-score group. There were no significant differences in ALT, TBil, Alb, ALP, GGT, PT, and IgM between the two groups for both grouping criteria (all P＞0.05). AST and IgG differed significantly between the two groups for both grouping criteria (all P＜0.05). The IgG level and recurrence rate in the high-score group (3.87±1.73 g/L and 10/17) were significantly higher than those in the low-score group (2.75±1.38 g/L and 8/34) (both P＜0.05). ConclusionThe clinical manifestations are similar between patients with DILI alone and those with DILI accompanied by autoimmune phenomena. The simple scoring system for AIH is worthy of clinical application in DILI accompanied by autoimmune phenomena.

Correlation between clinical data and pathological stage in patients with primary biliary cirrhosis: a study of 54 cases / 临床肝胆病杂志

ObjectiveTo investigate the correlation between clinical data and pathological stage in patients with primary biliary cirrhosis (PBC) and to provide guidance for clinical diagnosis and treatment. MethodsThe clinical data of 54 PBC patients were collected for analyzing the correlation between the clinical data and pathological stage. The clinical data included biochemical parameters, immunological markers, and autoantibodies. Biopsy of the liver was used for the pathological staging of PBC. For the continuous data of normal distribution, analysis of variance was applied for comparisons between groups; for continuous data of skewed distribution, Wilcoxon rank sum test was used. For categorical data, chi-square test was used. Correlation analysis was performed by Pearson correlation and logistic regression. ResultsAmong the 54 patients, the male-to-female ratio was 1∶5; the mean age was 48.9±9.3 years; pathological stage Ⅰ was identified in 15 cases, stage Ⅱ in 18 cases, stage Ⅲ in 12 cases, and stage Ⅳ in 9 cases, and patients with stage Ⅳ disease were significantly older than the other patients (P＜0.05). Total bilirubin (TBil), alkaline phosphatase, prothrombin time, IgA, IgG, and SP200 were positively correlated with pathological stage (r=0.592, 0.343, 0.281, 0.388, 0.274, and 0.320, respectively, P＜0.05), while a negative correlation was found between albumin and pathological stage (r=-0.569, P=0.000). Multivariate analysis revealed an independent correlation between TBil level and pathological stage (P=0.039). Patients with the same pathological stage might have different clinical stages, while those with the same clinical stage might have different pathological stages. ConclusionsThe same pathological stage may appear in different clinical stages. TBil level is an independent predictive factor for pathological stage in PBC patients.

HLA class I alleles and haplotypes in Chinese patients with primary biliary cirrhosis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To analyze the HLA class I alleles and haplotypes in Chinese patients with primary biliary cirrhosis (PBC).</p><p><b>METHODS</b>Sequencing based typing-polymerase chain reaction (SBT-PCR) was used to investigate the HLA class I alleles of 146 PBC patients and 500 normal controls in northern China. The frequencies of alleles and haplotypes were calculated and compared for the two groups. The chi-square test and Fisher's exact test were used for statistical analyses.</p><p><b>RESULTS</b>There were 26, 51 and 21 alleles identified at the HLA-A, B and C loci respectively, and the frequencies of these alleles were not significantly different between the PBC and normal control groups.However, the frequencies of A *11:01-B*40:06 and A*02:01-B*l5:01 haplotypes were significantly higher in the PBC group than in the normal control group (7.53% vs. 1.40%, P<0.01, OR=5.38; 6.85% vs. 2.00%, P=0.003, OR=3.425).</p><p><b>CONCLUSION</b>This study established the role of HLA class I haplotypes in determining PBC susceptibility in a Chinese population.</p>