Association of the Hepatitis B Virus Large Surface Protein with Viral Infectivity and Endoplasmic Reticulum Stress-mediated Liver Carcinogenesis
CELLS
Authors: Lin, Wei-Ling; Hung, Jui-Hsiang; Huang, Wenya
Abstract
Hepatitis B is the most prevalent viral hepatitis worldwide, affecting approximately one-third of the world's population. Among HBV factors, the surface protein is the most sensitive biomarker for viral infection, given that it is expressed at high levels in all viral infection phases. The large HBV surface protein (LHBs) contains the integral pre-S1 domain, which binds to the HBV receptor sodium taurocholate co transporting polypeptide on the hepatocyte to facilitate viral entry. The accumulation of viral LHBs and its prevalent pre-S mutants in chronic HBV carriers triggers a sustained endoplasmic reticulum (ER) overload response, leading to ER stress-mediated cell proliferation, metabolic switching and genomic instability, which are associated with pro-oncogenic effects. Ground glass hepatocytes identified in HBV-related hepatocellular carcinoma (HCC) patients harbor pre-S deletion variants that largely accumulate in the ER lumen due to mutation-induced protein misfolding and are associated with increased risks of cancer recurrence and metastasis. Moreover, in contrast to the major HBs, which is decreased in tumors to a greater extent than it is in peritumorous regions, LHBs is continuously expressed during tumorigenesis, indicating that LHBs serves as a promising biomarker for HCC in people with CHB. Continuing efforts to delineate the molecular mechanisms by which LHBs regulates pathological changes in CHB patients are important for establishing a correlation between LHBs biomarkers and HCC development.
Clinical features of treatment-naive patients with hepatitis B virus infection A community-based survey from high- and intermediate-hepatitis B endemicity regions in Southeast China
MEDICINE
Authors: Wu, Wei; Zhu, Yu; Yu, Chenbo; Yang, Shigui; Ruan, Bing; Chen, Yu; Li, Lanjuan
Abstract
The aim of study was to investigate the clinical features of treatment-naive patients in 2 regions with high-and intermediate-hepatitis B endemicity level in Southeast China and provide the baseline data for monitoring health or planning therapy. This study included 8207 cases of treatment-naive patients with hepatitis B virus (HBV) infection from Yuhuan (YH, high-hepatitis B endemicity region) and Shaoxing (SX, intermediate-hepatitis B endemicity region) during 2014-2015. Clinical data were collected from the patients. Blood samples were kept for detecting hepatitis B surface antigen, hepatitis B envelope antigen (HBeAg), hepatitis B envelope antibody, hepatitis B surface antibody, hepatitis B core antibody, liver function, HBV DNA, and alpha-fetoprotein. All persons underwent B ultrasound to exclude liver cirrhosis or cancer. Of all 8207 HBsAg-positive patients, 52.9% patients were in the low-replication (LR) stage and 30.3% in the HBeAg-negative chronic hepatitis B (ENH) stage; 8.8% cases were in the ENH stage with elevated alanine aminotransferase (ALT). More male than female patients were in immune clearance (IC) or ENH stages with elevated ALT (10.4% vs 4.8%, 12.1% vs 5.3%, respectively, P<. 05). The percentage of patients in IC and immune tolerant (IT) stages declined with increasing age, whereas the percentages of ENH with elevated ALT stage were highest in 40 to 60 years. The percentage of patients in IT and IC stages was higher in YH than in SX (9.4% vs 3.8%, 9.9% vs 4.2%, respectively, P<. 05). More patients had HBVDNA >= 10(5)IU/mL in YH than in SX (24.6% vs 16.0%, P<. 05), and more male than female patients had HBVDNA >= 10(5)IU/mL(24.5% vs 17.9%, P<. 05). Clinical features varied in treatment-naive patients with HBV infection between different genders and regions. More attention should be paid to the surveillance and therapy of patients in YH especially male patients for the prevention and prognosis of hepatitis B.