Accumulation of mutations in reverse transcriptase of hepatitis B virus is associated with liver disease severity in treatment-native Chinese patients with chronic hepatitis B

Abstract

Background. Mutations in reverse transcriptase (RT) of the hepatitis B virus (HBV) are demonstrated to be strongly associated with nucleos(t)ide analog resistance, which is supposed to be the biggest obstacle during the long-term anti-viral treatment of chronic hepatitis B. However, the presence of RT mutations in treatment-native chronic hepatitis B patients and its clinical significance are not well known. Objectives. To investigate the significance of mutations in reverse transcriptase of the hepatitis B virus in treatment-native Chinese patients with chronic hepatitis B. Material and methods. In this study, 288 treatment-native chronic HBV patients were recruited and the RT region was sequenced. The results showed that 71 patients (24.65%) were found with RT mutations, within which there were no well-defined primary nucleotide analog-resistant mutations. Results. There were a total of 28 mutant sites, which formed three dominant mutant clusters: rt124-139, rt191-212 and rt225-229. Among these 71 patients, 63.38% (45/71) of patients had a single mutation while 19.72% (14/71), 12.68% (9/71) and 4.23% (3/71) of patients had 2, 3 or 4 mutations, respectively. Patients with RT mutations showed significantly decreased serum baseline HBV DNA loads (p = 0.0363) and blood platelet count (p = 0.0181) than patients without RT mutations. Patients with multiple mutant sites (2) had significantly decreased baseline HBV DNA loads (p = 0.0004) and blood platelet count (p = 0.0011) than patients with single mutant site. Moreover, the number of RT mutant sites is significantly associated with severity of liver fibrosis (p = 0.0128). Conclusions. This study demonstrated that there was a prevalence of RT mutations in treatment-native chronic hepatitis B patients, which reflects a tougher liver environment for the virus and deeper liver injury for the host. Accumulation of RT mutations was associated with liver disease severity in treatment-native chronic hepatitis B patients.