Comparison of hepatitis B virus genotypes B and C among chronically hepatitis B virus‐infected patients who received nucleos(t)ide analogs: A multicenter retrospective study

Abstract

Aim Hepatitis B virus genotype B (HBV/B) has been reported to have less risk of liver cirrhosis and hepatocellular carcinoma (HCC), but long‐term observation has rarely been reported. We aimed to clarify the characteristics of HBV/B in nucleos(t)ide analog‐treated patients in an area where HBV/B is more prevalent than in other areas of Japan. Methods A total of 498 chronically HBV‐infected patients treated with nucleos(t)ide analog (lamivudine, entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide fumarate) for >6 months (mean 70.6 months) were included from nine hospitals in northeast Japan. The frequencies of hepatitis B surface antigen loss and HCC occurrence were analyzed. Results Among 427 patients whose genotype could be determined, 34.0% and 64.4% were infected with HBV/B and genotype C (HBV/C), respectively. The age of patients with HBV/B was significantly older than those with HBV/C (57.7 vs. 48.1). The cumulative rate of hepatitis B surface antigen loss was significantly higher in HBV/B than in HBV/C (3.6% vs. 0.7% at 10 years). Among 480 patients without HCC history, HCC occurrence was found in 40 patients (13.4% at 10 years). There was no cumulative rate difference of HCC occurrence among the genotypes, but after propensity score matching for age/sex, it was significantly lower in HBV/B than in HBV/C (5.3% vs. 18.5% at 10 years). Conclusions Although a lower rate of HCC occurrence in HBV/B was shown by an age/sex‐matched analysis than that in HBV/C, patients with HBV/B were significantly older and had a comparative risk of HCC occurrence in nucleos(t)ide analog‐treated patients.

Hepatitis B genotyping: The utility for the clinicians

“…In a recent study of patients chronically infected with HBV, HCC incidence was 13.4% at 10 years. In these patients, the incidence of HCC was lower in genotype B (5.3% at 10 years) than in genotype C (18.5% at 10 years) [40]. Another recent study from Japan recorded higher incidence of HCC in genotype B patients compared with genotype C during the first 20 years of follow up; however, the HCC incidence was similar in genotypes B and C, after 20 years [41].…”

“…In vitro studies showed that wild-type HBV strains (genotypes A-H) and drug-resistant hepatitis B strains were susceptible to tenofovir alafenamide [56]. In chronically HBV-infected patients treated with different nucleos(t)ide analogues-lamivudine, entecavir, tenofovir (disoproxil fumarate or alafenamide fumarate)-for > 6 months (mean duration of treatment 71 months), patients with genotype B had a significantly higher cumulative rate of HBsAg loss (3.6% at 10 years) than those with genotype C (0.7% at 10 years) [40].…”

Hepatitis B surface antigen reduction as a result of switching from long‐term entecavir administration to tenofovir

“…Recently, nucleotide/nucleoside analog (NA) therapy has been widely used, which enables viral suppression and HCC suppression . However, considering the low rate of HBsAg elimination during NA therapy, administration must be continued for a long period of time . Therefore, new therapeutic strategies are required which target HBsAg clearance in patients undergoing long‐term NA administration.…”

Cross-Protection of Hepatitis B Vaccination among Different Genotypes

“…Subgenotypes in HBV genotype C may be associated with the increase of HCC occurrence in patients with HBeAg-positivity [ 40 ]. Patients infected with HBV genotype C progress rapidly to cirrhosis and HCC than patients infected with genotype B in Asia [ 41 , 42 , 43 , 44 ]. Moreover, more patients infected with HBV genotype D developed to cirrhosis and HCC than patients infected with HBV genotype A [ 24 , 45 , 46 , 47 ].…”