Is Response to Hepatitis B Treatment Influenced by HBV Genotype

		SUMMARY: It remains unclear whether hepatitis B virus (HBV) genotype has an influence on treatment response -- as is the case for hepatitis C virus (HCV) -- due to inconsistencies across studies and failure to account for differences in race/ethnicity, according to a report in the March 2010 Journal of Hepatology.

By Liz Highleyman

It is well known that viral genotype has a major impact on response to interferon-based therapy for hepatitis C, but it is unclear whether this is also true for hepatitis B. In addition, the influence of race/ethnicity -- also a major determinant of the efficacy of hepatitis C treatment -- remains poorly defined for hepatitis B.

Sara Raimondi from the European Institute of Oncology in Milan and colleagues performed a literature search on this topic, looking at studies published through April 2009.

Recently released clinical practice guidelines and consensus statements point to the importance of HBV genotyping in therapeutic algorithms for the treatment of chronic hepatitis B, they noted as background. However, this recommendation is based on information that usually comes from post hoc analyses of clinical trials that were not originally designed to study associations with HBV genotype.

From the available medical literature, the authors selected randomized clinical trials of currently approved anti-HBV drugs that provided information on HBV genotypes and baseline characteristics of study participants, treatment response, and interaction between HBV genotype and type of therapy.

"There were several intrinsic features and weaknesses in the majority of clinical trials conducted so far which make it difficult to reach firm conclusions about the role of HBV genotypes in response to antiviral therapy," they stated.

Most trials were necessarily multicenter in order to reach a sufficient number of participants to confer sufficient statistical power, the authors noted. However, pooling patients of different racial/ethnic groups "may have revealed false-positive associations between response to antiviral therapy and HBV genotype." For example, if Asian patients respond better to therapy (as appears to be the case for hepatitis C) and tend to have HBV genotype B, it could appear as if genotype B itself is a predictor of good response.

Moreover, they continued, "endpoint definitions, especially for the composite ones, varied substantially among studies, leading to lack of homogeneity." Without consistent outcome measures, it is difficult to make comparisons across trials.

Finally, they noted, possible interactions between type of therapy (e.g., interferon, direct-acting antiviral agents) and HBV genotype were seldom analyzed.

"The present review highlights several caveats regarding current indications proposed by the major clinical practice guidelines and consensus conference statements published thus far and emphasize the need for further long-term studies in the field," the authors concluded.

Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy; Liver Unit, Department of Medicine, Azienda Ospedaliera Fatebenefratelli e Oftalmico, Milan, Italy; Research Laboratories, Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy.

3/12/10

Reference
S Raimondi, P Maisonneuve, S Bruno, and others. Is response to antiviral treatment influenced by hepatitis B virus genotype? Journal of Hepatology 52(3): 441-449 (Abstract). March 2010.