Analysis of hepatitis B virus genotypes and pre-core region variability during interferon treatment of HBe antigen negative chronic hepatitis B

Abstract

The clinical importance of hepatitis B virus (HBV) genome variability has been reported recently. One example is the occurrence of hepatitis B virus pre-core mutants, which arise during spontaneous or interferon-induced seroconversion from HBeAg to anti-HBe and are thought to be selected by immune pressure. A survey of HBV pre-core mutants and viral genotypes in 35 HBeAg negative patients during interferon therapy was carried out to understand viral pathogenesis in this form of chronic hepatitis B. Seventeen patients responded to interferon therapy as assessed by the sustained normalization of serum ALT levels and the significant decrease of viremia levels. The response rate to interferon was independent of both initial serum viral DNA level and interferon doses. During interferon therapy, a significant decrease of M0 (wild-type pre-core sequence at pos. 1887-1908), M1 (TGG to TAG at pos. 1896) or M2 (TGG to TAG at pos. 1896, and GGC to GAC at pos. 1899) positive viral genomes was found in 48%, 42%, and 33% of patients, respectively. A higher response rate to interferon therapy was observed in patients infected with HBV genotype A (70%) or M0 positive strains (75%) as compared to patients infected with genotype D/E (40%) or M1/M2 positive strains (44%). The data support the hypothesis that pre-core defective HBV represent viral mutants with an increased capacity to resist exogenous alpha interferon. These findings emphasize that characterization of HBV genome variability prior to interferon therapy may help to predict antiviral response in HBeAg negative patients.

Clinical features of hepatitis B virus genotype A in Japanese patients

“…However, three patients have not exhibited HBeAg seroconversion following initial therapy; these three patients subsequently underwent other treatments, but all have remained HBeAg ϩ . It has been reported that the response to INF therapy is excellent in patients with HBV genotype A chronic hepatitis compared to those with the HBV genotype D. [19][20][21] We speculate that resistance of HBeAg to seroconversion in Japanese patients characterizes the HBV genotype A, in virological terms, once the initial opportunity to treat this disease is missed.…”

Clinical characteristics of patients infected with hepatitis B virus genotypes A, B, and C

“…Genotype A, in contrast, is not common in Japan, and was not common even in the early years of HBV studies, 1,2 the G-to -A 1896 mutation in the precore region rarely occurs, and interferon therapy results in a marked response. 16,17 Because the therapeutic response of patients with genotype A is different from that in patients with genotype C who are positive for HBeAg, further studies are necessary to clarify the virological characteristics and therapeutic responses of Japanese patients with genotype A HBV.…”

Quantification and genotyping of hepatitis B virus in a single reaction by real-time PCR and melting curve analysis

“…Likewise, a study from India, where HBV genotypes A and D are dominant, noted that genotype D was associated with more severe liver disease and a higher incidence of HCC than genotype A [10]. HBV genotype was also related to the responses to antiviral therapies, including interferon and lamivudine treatments [11][12][13][14][15][16]. A relationship between HBV genotypes and mutations in the pre-core and core promoter regions that may diminish the HBeAg production has been documented [8,[17][18][19][20].…”