The relationship between mutations in reverse transcriptase region of hepatitis B virus and progression of liver disease.

The specific objective of this study was to investigate mutations of Hepatitis B virus (HBV) reverse transcriptase (RT) region in Chinese HBV-infected patients at different stages and their association with the progression of liver disease. HBV RT regions in serum samples were amplified and sequenced from 384 patients with chronic HBV infection, including 100 asymptomatic carriers (ASC), 101 chronic hepatitis B, 96 liver cirrhosis, and 87 hepatocellular carcinoma (HCC). Further analysis of genotyping and AA substitution within RT was performed by the online HBV genotyping tool and MEGA7.0 software. A logistic regression model was used to explore the relationship between RT mutations and advanced liver disease (ALD). The mutation rate gradually increased from ASC to HCC (P for trend < 0.05). Logistic regression analysis showed that one RT site mutation, rtS106A/C, was significantly associated with the ALD. Multivariate regression analysis confirmed that two RT mutations, rtH55R/Q/K and rtS137T/Q/E, were independent risk factors for HBV-related HCC. The current study reveals that mutations within the RT region might be associated with the progression of HBV-related liver diseases and might serve as predictive biomarkers for patients with HBV infection at high risk of developing HCC.