This article has an accompanying continuing medical education activity, also eligible for MOC credit, on page e18 (https://www. gastrojournal.org/cme/home). Learning Objective: Upon completion of this CME activity, successful learners will be able to explain the prevalence, predictors, and significance of hepatitis B surface antigen (HBsAg) seroclearance in adults with chronic hepatitis B virus (HBV) infection.

Serum HBsAg concentration might serve as a surrogate marker of HBV DNA level in CHB patients.

Signal transducer and activator of transcription 3 (STAT3) had been involved in liver fibrogenesis. We aimed to explore the antifibrotic activities of sorafenib and its derivative SC-1 (devoid of Raf kinase inhibition activity) both in vivo and in vitro with special focus on the STAT3 pathway in hepatic stellate cells (HSCs). The clinical role of STAT3 in chronic hepatitis B (CHB) was also investigated. Experimental fibrosis mouse models were established by thioacetamide injection and bile duct ligation in Balb/C mice and treated with sorafenib and SC-1. Rat and human HSCs were used for mechanistic investigations. Forty CHB patients were enrolled to quantify the hepatic phospho-STAT3 (p-STAT3) levels and correlated with liver fibrosis. Both sorafenib and SC-1 ameliorated liver fibrosis in vivo and promoted HSC apoptosis in vitro. p-STAT3 and downstream signals were down-regulated after sorafenib and SC-1 treatment in HSC. STAT3 overexpression in HSC enhanced cell proliferation and undermined the apoptotic effects of sorafenib and SC-1, whereas STAT3-specific inhibition promoted HSC apoptosis. Sorafenib and SC-1 activated Src-homology protein tyrosine phosphatase-1 (SHP-1) and STAT3 inhibition followed. Of particular interest, in CHB patients with advanced liver fibrosis, p-STAT3 in HSC was significantly overexpressed and positively correlated with the severity of liver fibrosis and plasma IL-6 levels. In conclusion, sorafenib and SC-1 ameliorate liver fibrosis through STAT3 inhibition in HSC and STAT3 may potentially serve as a promising fibrotic biomarker and target in liver fibrosis. SHP-1 phosphatase-directed STAT3 inhibition may represent a previously unidentified strategy for antifibrotic drug discovery.hepatic stellate cell | STAT3 | SHP-1 | hepatitis B | liver fibrosis

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Spontaneous clearance of hepatitis B surface antigen (HBsAg) in chronic hepatitis B (CHB) patients usually indicates a remission of hepatitis activity and a favorable outcome. Two single nucleotide polymorphisms (SNP), rs3077 near HLA-DPA1 region and rs9277535 near HLA-DPB1 region, have been shown to be associated with HBV persistence after acute HBV infection. However, little is known about the impact of these 2 SNPs on spontaneous HBsAg clearance in CHB patients. In this case-control study, a total of 100 male HBeAg-negative chronic HBV carriers who cleared HBsAg spontaneously (case group) and 100 age-matched HBeAg-negative male patients with persistent HBsAg positivity (control group) were enrolled. We investigated the relationship between these 2 SNPs and HBsAg clearance. There was a higher frequency of rs9277535 non-GG genotype in the case group (57% vs. 42%). Patients with rs9277535 non-GG genotype had a higher chance to clear HBsAg [Odds ratio (OR): 1.83, 95% confidence interval (CI): 1.04∼3.21, P = 0.034]. Compared to GG haplotype of rs3077 and rs9277535, GA haplotype had a higher chance of achieving spontaneous HBsAg loss (OR: 2.17, 95% CI: 1.14∼4.16, P = 0.030). In conclusion, rs9277535 non-GG genotype is associated with a higher likelihood of spontaneous HBsAg seroclearance in CHB patients.