关键词: 慢性HBV相关肝病, HBV基因型, 核苷(酸)类似物, 耐药突变, 疾病进展

Abstract: Objective To explore the relationship of hepatitis B virus (HBV) genotypes and drug resistance mutation sites to disease progression in patients with HBV-related chronic liver diseases. Methods Two hundred and thirty patients with HBV-related chronic liver diseases treated with nucleos(t)ide analogues (NAs) were selected as study subjects. HBV genotypes and drug-resistant mutations within reverse transcriptase (RT) region were detected. Results Among the 230 patients with HBV-related chronic liver disease, 100 cases (43.47%) were found to have NA-resistant mutations, with lamivudine (LAM)/telbivudine (LdT) resistance being the most common (30.00%, 69/230), adefovir (ADV) resistance being the second (7.83%, 18/230), entecavir (ETV) resistance being the least (5.65%, 13/230), and there was statistically significant difference among them (χ²=67.392, P<0.001). Among the cases with LAM/LdT-resistant mutations, 55 were single-point mutant (79.71%), most being rtM204V/I mutations (17.39%, 40/230); 14 were multi-point mutant (20.29%), most being rtL180M+rtM204V/I mutations (5.65%, 13/230). Among the cases of ADV resistant mutations, most were single-point mutant (61.11%, 11/18), Rta181t mutations being the most prevalent (3.91%, 9/230). And all cases of ETV-resistant mutations were multi-point mutant, most being rtm204v/I+rta181t+rts202g/I mutations (3.04%, 7/230). In all the patients with HBV-related chronic liver diseases, HBV genotypes were B (70.43%, 162/230) and C (29.57%, 68/230), with no genotype A, D, E, F, G, H or J. There was significant difference in mutation rates of rt180 and rt181 between genotype B and C of HBV (χ²=11.545, P=0.001; χ²=4.845, P=0.028), no significant difference in rates of other mutations (P>0.05). The distribution of HBV genotypes was statistically different between chronic hepatitis B group and hepatitis B-related cirrhosis group (χ²=25.012, P<0.001). The rate of rt204 mutation was significantly different among chronic hepatitis B group, hepatitis B-related cirrhosis group and hepatitis B-related liver cancer group (P=0.015), and rates of other mutations were not (P>0.05). Conclusion The genotypes of HBV in this area are mainly B and C, and the detection rate of main resistant mutations against NAs is relatively high. The disease progression and resistant mutations in patients infected with HBV of different genotypes are different, and the rate of rt204 mutation is different in different disease stages. It is suggested that patient infected with HBV should be routinely tested for HBV genotypes and resistance against NAs for individualized treatment and improvement of disease progression.

Key words: Hepatitis B virus-related chronic liver disease, Hepatitis B virus genotype, Nucleos(t)ide analogue, Drug resistance mutation, Disease progression