Response to long‐term lamivudine treatment in patients infected with hepatitis B virus genotypes A, B, and C

Abstract

Response to lamivudine treatment longer than 1 year was compared in 15 patients persistently infected with hepatitis B virus (HBV) genotype A, 38 with genotype B, and 449 with genotype C. Patients with genotype A were younger (median age 37 [range 24-49] vs. 47 [24-67] or 44 [18-73], P = 0.015), possessed hepatitis B e antigen (HBeAg) more frequently (73% vs. 21% or 56%, P < 0.001) and HBV DNA in higher levels (8.6 [6.1-8.7] vs. 6.5 [<3.7-8.7] or 6.5 [<3.7-8.7] log genome equivalents (LGE)/ml, P = 0.024) than those with genotype B or C. During lamivudine, YMDD mutants (89% vs. 53% or 42%, P = 0.0001) and breakthrough hepatitis developed more often (47% vs. 21% or 29%, P = 0.023) in patients with genotype A than B or C. YMDD mutants elicited more frequently in patients with genotype A than B or C who were positive (82% [9/11] vs. 25% [2/8] or 48% [117/245], P = 0.037) or negative for HBeAg (75% [3/4] vs. 30% [9/30] or 33% [68/204], P = 0.003). HBeAg (hazard ratio 2.1 [95% confidence interval 1.53-2.92], P < 0.001) and genotype A (2.78 [1.08-7.12], P = 0.034) enhanced the emergence of YMDD mutants by the Cox proportional hazard model. The risk for breakthrough hepatitis was increased by the baseline alanine aminotransferase level <500 IU/L (2.56 [1.82-5.50], P = 0.018), HBeAg (2.11 [1.40-3.16], P < 0.001), cirrhosis (1.92 [1.24-2.97], P = 0.004) and HBV DNA > or =8.0 LGE/ml (1.57 [1.04-2.36], P = 0.03); it was influenced by genotypes only in patients with HBeAg. In conclusion, HBV genotypes help in predicting response to long-term lamivudine treatment and development of YMDD mutants in patients with chronic hepatitis B.

Long-term continuous entecavir therapy in nucleos(t)ide-naïve chronic hepatitis B patients

“…There was also no difference in HBeAg seronegativity with entecavir among patients infected with genotype A, B, or C virus. These results were consistent with studies on lamivudine therapy [14,18]. In this study, HBeAg positivity was a significant factor associated with detectable HBV DNA at years 1 through 3, and these results were consistent with those reported by Zoutendijk et al [10].…”

“…Previous studies showed conflicting results on the effect of HBV genotype on the response to lamivudine, with genotypes A, B, and C not affecting the antiviral response to lamivudine [14][15][16]. However, we have previously found that 47%, 84%, and 76% of patients had undetectable HBV DNA after the third year among patients of genotype A, B, and C, respectively [17,18]. The difference among these groups was probably due to the younger age of patients of genotype A and that they were often positive for HBeAg compared to those of genotype B or C. However, the genotype was not a significant predictor of HBV DNA loss after >2 years of entecavir therapy in the present study.…”

Hepatitis B virus genotyping among chronic hepatitis B patients with resistance to treatment with lamivudine in the City of Ribeirão Preto, State of São Paulo

“…Zöllner et al 13 showed the existence of differences in mutational profile during the lamivudine resistance selection between genotypes A and D, but did not show the possibility that these genotypes might develop resistant variants at different rates. Other recent studies have suggested that the rate of lamivudine resistance was higher among patients infected with HBV genotype A than among those with genotype D 42,43 . In Brazil, some studies have observed this relationship 23 but, like in the present study, the number of samples was insufficient to correlate lamivudine resistance mutations and genotype.…”

Correlation between serum hepatitis B virus core‐related antigen and intrahepatic covalently closed circular DNA in chronic hepatitis B patients

“…Several reports indicate that HBsAg seroclearance confers favorable long-term outcomes in patients without hepatocellular carcinoma or decompensated liver cirrhosis Kobayashi et al, 2006]. However, studies show that intrahepatic HBV DNA still remains in HBsAg seroclearance cases , and that 10-20% of patients have 50-100 copies/ ml of serum HBV DNA for 5 and 10 years after seroclearance of HBsAg [Arase et al, 2007].…”