The possible impact of sortilin in reducing HBsAg expression in chronic hepatitis B

Abstract

Hepatitis B virus (HBV) infection is a major global health problem. Chronically infected people are at risk for progressive hepatic fibrosis and consequent cirrhosis. Hepatitis B surface antigen (HBsAg) level in serum is a complementary marker for intrahepatic HBV DNA and covalently closed circular DNA (cccDNA). Sortilin-1 (SORT1) has been reported to be involved in the post-Golgi vesicle trafficking of Apo lipoproteins degradation pathways. This study was designed to evaluate the hepatic and serum expression of HBsAg and its association with hepatic SORT1 gene expression in patients with chronic HBV. Thirty chronic hepatitis B patients with histological examination results were enrolled in this study. Liver biopsies were analyzed for hepatic HBsAg and SORT1 gene expression by immunohistochemistry and quantitative real time PCR (qRT-PCR), respectively. Twenty seven out of 30 (90%) liver biopsies had positive staining for HBsAg and showed a significant inverse association with hepatic SORT1 fold change gene expression (β = -0.5, P = 0.042). There was significant association between HBV DNA levels and HBsAg expression in hepatocyte or serum titer of HBsAg (r = 0.39, P = 0.029; r = 0.39, P = 0.032 respectively). Serum ALT was also correlated with hepatic activity index (HAI) score (β = 0.6, P = 0.001). Inverse association between hepatic SORT1 gene expression and hepatic HBsAg expression indicates the possible role of sortilin in HBsAg particle formation.

Higher Serum Levels of Type I Interferon Receptor in Adults with Chronic Hepatitis B Leading to Hepatitis B Surface Antigen Clearance

“…Our results revealed that the HBsAg titer was independently associated with HBsAg clearance that was significantly lower in subjects who cleared HBsAg during follow-up. Effects of HBV viral load have been examined in previous studies and indicated an association between HBsAg seroclearance and lower HBV DNA levels (4,5,21). Also, they showed that serum HBsAg and both serum and liver HBV DNA were more correlated in HBeAg-positive carriers.…”

On the potential role of intestinal microbial community in hepatocarcinogenesis in chronic hepatitis B

“…This toxin is like DNase, in structure and activity, which breaks the double‐strand DNA and induce cellular apoptosis . Colonization by colibactin‐producing B2 phylogroups at the early life of animal experiments associated with the reduction in regulatory T‐cell populations which is a susceptibility factor for the development of immune‐mediated diseases and the predisposition of cancer . The potential effect of intestinal E. coli on colorectal cancer development is extensively evaluated in animal and human models .…”

8-Hydroxy-2'-Deoxyguanosin in Peripheral Leukocyte Associated With HBsAg in Patients with Chronic Hepatitis B

“…Chronic infection is characterized by the persistence of hepatitis B surface antigen (HBsAg) synthesis. Higher production of HBsAg aggregates in the endoplasmic reticulum (ER) (main organelle in the synthesis, folding and trafficking of proteins) of hepatocytes that correlate with the cellular response known as ER stress (2,3). Recent work provided information on HBsAg quantitation that improves the understanding of treatment response and natural history of CHB (3,4).…”

“…Higher production of HBsAg aggregates in the endoplasmic reticulum (ER) (main organelle in the synthesis, folding and trafficking of proteins) of hepatocytes that correlate with the cellular response known as ER stress (2,3). Recent work provided information on HBsAg quantitation that improves the understanding of treatment response and natural history of CHB (3,4). Envelope proteins of hepatitis B virus (HBV) often appear in the form of "ground-glass" hepatocyte shown in pre-S mutants or HBV genome integration in the host genome (3,5,6).…”

“…Recent work provided information on HBsAg quantitation that improves the understanding of treatment response and natural history of CHB (3,4). Envelope proteins of hepatitis B virus (HBV) often appear in the form of "ground-glass" hepatocyte shown in pre-S mutants or HBV genome integration in the host genome (3,5,6). Quantitation of HBsAg is considered as a prognostic and therapeutic biomarker in numerous studies.…”