Diagnostic Value of Serum Golgi Protein 73 for Liver Inflammation in Patients with Autoimmune Hepatitis and Primary Biliary Cholangitis

Background. There is lack of reliable serum biomarkers to reflect the severity of liver necroinflammation for those who suffer autoimmune liver diseases (AILDs). In this study, a previously established patient cohort was used to explore the potential of serum Golgi protein 73 (GP73) as a noninvasive marker of AILD-related liver necroinflammation. Methods. Serum GP73 concentration was measured in a retrospective cohort of 168 AILD patients, which included 74 patients with autoimmune hepatitis (AIH) and 94 with primary biliary cholangitis (PBC) who had undergone liver biopsy. Spearman’s correlation and multivariate analysis were used to evaluate the relationship between serum GP73 and liver necroinflammation. A receiver operating characteristic curve was constructed to evaluate the value of GP73 for the prediction of moderate or severe liver necroinflammation. The diagnostic value of serum GP73 was also compared with that of alkaline phosphatase (ALP) in patients with PBC. Histologically, immunohistochemical analysis was performed to assess hepatic GP73 expression. Results. Both the serum level and hepatic tissue expression of GP73 protein were aberrantly elevated and correlated well with the severity of necroinflammation in both AIH ( rho = 0.655 , P < 0.001 ) and PBC ( rho = 0.547 , P < 0.001 ) patients. The results here suggested that serum GP73 could be an independent biomarker to reflect the severity of liver necroinflammation. The AUROCs for GP73 to predict moderate necroinflammation (≥G2) and severe necroinflammation (≥G3) in patients with AIH were 0.828 and 0.832, respectively. Moreover, the AUROCs of serum GP73 for the identification of moderate necroinflammation (≥G2) ( AUROC = 0.820 , P < 0.001 ) and severe necroinflammation (≥G3) ( AUROC = 0.803 , P < 0.001 ) were superior to those of ALP (≥G2: AUROC = 0.607 , P = 0.028 and ≥G3: AUROC = 0.559 , P = 0.357 ) in patients with PBC. Mechanically, interlukin-6 (IL-6), the proinflammatory and prohepatic regenerating cytokine, could transcriptionally upregulate GP73 gene expression. Conclusion. Serum GP73 is a potential noninvasive biomarker to evaluate the severity of liver necroinflammation in patients with AILDs.

Clinical and Genetic Characteristics of Thymoma Patients With Autoimmune Hepatitis and Myocarditis

BackgroundOur study investigated a special series of thymoma with autoimmune hepatitis and myocarditis and tried to reveal the gene expression profiles of this series of thymoma.MethodsFrom 2011 to 2019, a total of 13 special thymoma patients presented with autoimmune hepatitis and myocarditis, accounting for about 1.26% of thymoma patients undergoing surgery in Beijing TongRen Hospital. Clinical data were retrospectively collected. All samples were harvested during surgical procedures, and analyzed to identify changes in gene expression using the CapitalBio mRNA microarray analysis, the Whole exome sequencing analysis (WES), qPCR and immunohistochemistry (IHC) tools.ResultsAfter surgery, patient symptoms were relieved gradually. Levels of lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), aspartate transaminase (AST), and alanine amiotransferase (ALT) increased to some extent within 1 to 3 months after surgery, and fluctuated, and then, gradually decreased close to normal within 6 months after surgery. Enrichment analysis of Kyoto Genome and Genome Encyclopedia (KEGG) pathway was performed and enrichment results were visualized. It indicated that gene expression of 5 signaling pathways, including cell cycle and p53 signaling pathway, were generally abnormal. P53 expression was up-regulated in all tumor tissues. However, IHC and qPCR analysis showed that there was no significant difference in p21 expression between normal and tumor tissue. Results of WES showed that only one driver gene-MDM4 amplified 4 fold in 53.2% thymoma cells. Further qPCR and IHC analysis confirmed the up-regulation of the expression of p53 and mdm4 in 13 thymoma patients with autoimmune hepatitis and myocarditis.ConclusionOur study reveals the clinical and genetic characteristics of thymoma patients with autoimmune hepatitis and myocarditis. For this special category of thymoma, the up-regulation of p53 and mdm4 plays an important role in the occurrence of thymoma and autoimmune hepatitis/myocarditis.

Cyclosporine Ameliorates Silica-Induced Autoimmune Hepatitis in Rat Model by Altering the Expression of Toll-Like Receptor-4, Interleukin-2 and Tumor Necrosis Factor-α

Background: Autoimmune hepatitis (AIH) is an inflammatory liver disease which is characterized histologically by interface hepatitis, biochemically by elevated transaminase levels, and serologically by the presence of autoantibodies. Toll-like receptor (TLR)-4 is a TLR family member that, upon activation in hepatocytes, initiates a cascade of events. Interleukin-2 (IL-2) and tumour necrosis factor-α (TNF-α) are potent inflammatory cytokines secreted in AIH playing an important role in the early development of inflammation, and hepatocyte damage. Objective: This study examined cyclosporine role in AIH and tried to illustrate its actions on altered hepatic function in silica-induced AIH model. Methods: AIH was induced in Wester rats using Sodium Silicate. The rats were divided into four groups: control group, Silica-AIH group, cyclosporine-treated group, and prevention group. TLR-4, and IL-2 mRNA expression in liver tissues was tested by RT-PCR. Results: AIH was associated with up-regulation of liver enzymes, IL-2, and TLR-4 gene expression while cyclosporine significantly down-regulated the expression of both. The relative quantity of TLR-4 mRNA was 1±0, 13.57±1.91, 4±0.38, and 2±0 in the control, AIH, cyclosporine, and prevention groups, respectively (p<0.001). Also, the relative quantity of IL-2 mRNA was 1±0, 14.79±1.42, 7.07±0.96, and 3.4±0.55 in the same groups, respectively (p<0.001). Additionally, immuno-histochemical staining for TNF-α in liver sections was increased in the silica-AIH group but it was decreased in the cyclosporine-treated and prevention groups. Conclusion: This study advocates a therapeutic role of cyclosporine in treating immune-mediated hepatic diseases. Cyclosporine improves histological alterations in the liver and inhibits the production of proinflammatory cytokines.

Autoimmune Hepatitis and Primary Biliary Cholangitis Overlap in a Patient with Systemic Lupus Erythematosus and Rheumatoid Arthritis Overlap (Rhupus) - An Unusual Association

The diagnosis of overlap syndrome involving systemic lupus erythematosus (SLE) and autoimmune hepatitis (AIH) isn’t easily established due to its similar clinical presentations and biochemical features to those of lupus hepatitis. The term overlap syndrome is typically utilized in the context of overlap of autoimmune hepatitis with PSC (primary sclerosing cholangitis) or PBC (primary biliary cholangitis). Few rare cases of AIH complicated by SLE are reported within the literature. Overlapping of SLE and AIH should be suspected when patients with SLE have abnormal liver function tests or AIH patients present with a rash. Liver biopsy plays a really important role in establishing the medical diagnosis of SLE with liver impairment or overlap with AIH. The prompt diagnosis and adequate treatment plan can improve the disease outcome. Key words: autoimmune hepatitis, primary biliary cholangitis, systemic lupus erythematosus, overlap syndrome.