Abstract
AIMS: Hepatitis B virus (HBV) reverse transcriptase (RT) mutants, which have not been well characterized according to different disease stages. This study aimed to characterize the profiles of naturally occurring mutations in the HBV RT region and their associated clinical outcomes. METHODS: HBV RT region mutations and genotypes were determined by PCR-direct sequencing and compared with p-distance model. RESULTS: Among 467 consecutive eligible patients (262 chronic hepatitis B patients, 105 cirrhotic patients and 100 hepatocellular carcinoma patients), the nucleos(t)ide analogues-related mutations (rtI169T, rtV173L, rtL180M, rtA181T, rtS202C, rtM204I/V, rtN236T) were found. The p-distance value reached a peak in the age of 20-30 years in the CHB patients and in the age of 40-45 years in the cirrhotic patients and hepatocellular carcinoma patients. The naturally occurring mutation, rtS106C mutation was higher in chronic hepatitis B patients (14/100, 14.0%) and cirrhotic patients (14/100, 14.0%) than that in hepatocellular carcinoma patients (4/100, 4.0%, P = 0.013). And the rtD134E/G/N/S mutations were also higher in chronic hepatitis B patients (22/100, 22.0%) and cirrhotic patients (21/100, 21.0%) than that in hepatocellular carcinoma patients (10/100, 10.0%, P = 0.021 and P = 0.032 respectively). The mutation frequencies in A-B interdomain were higher in cirrhotic patients (101/1900, 5.3%) than that in hepatocellular carcinoma patients (68/1900, 3.6%) (P = 0.009). CONCLUSIONS: The nucleos(t)ide analogues-related mutations do exist in treatment naive patients with different disease stages. rtS106C, rtD134E/G/N/S and A-B interdomain mutations may be associated with necro-inflammation, immune response and cirrhosis development at ages older than 40.