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Response to Interferon-Alfa Depends Upon HBV Genotype



By Brian Boyle, MD



The response of different hepatitis B virus (HBV) genotypes to interferon-alfa (IFN-alfa) treatment is not known. Since the use of IFN-alfa or pegylated interferon alfa in combination with other antiviral agents is being explored in the treatment of chronic HBV, this information may have increasing importance in the coming years.



In a study presented at the 52nd AASLD, researchers evaluated the relationship between the outcome of IFN-alfa treatment and HBV genotype, the ability of each HBV genotype to develop mutations, and the variability in the HBV core gene. The study included 148 European or Chinese patients with HBeAg-positive chronic hepatitis B. Treatment response was defined as sustained loss of HBeAg.



In European patients, HBV genotypes were A 46/103 (45%) and D 35/103 (34%) were most common, while in Chinese patients genotypes C 29/45 (64%) and B 16/45 (36%) were most common. The response to IFN-alfa ?treatment was higher in genotype A vs. D in the European patients and in genotype C vs. B in the Chinese patients.



At baseline, core promoter mutations were more frequent in treatment responders than non-responders (p=0.005) and, in the responder group, but not the non-responder group, the prevalence of these mutations increased by the end of treatment (p=0.01). In contrast, the precore stop mutation was equally distributed between responders and non-responders at baseline and there was no significant change in the prevalence of this mutation at the end of treatment. The treatment response was also associated with a lower variation in the HBV core gene. Failure to respond to IFN-alfa was not associated with the selection of HBV strains containing new core gene mutations at the end of treatment.



Based upon these data, the authors conclude that "the response to IFN-alfa treatment differs between HBV genotypes, depending on the molecular characteristics of the core promoter and core gene variability. The higher response to treatment, observed in HBV genotype A, is associated with its greater tendency to develop core promoter mutations and with less variations in the nucleocapsid protein." A multivariate analysis, evaluating other factors that may have led to improved results due to the HBV genotype present, including ALT and HBV viral load levels, is in progress, but was not reported at this conference.



11/16/01