NEW YORK (Reuters Health) – In patients with chronic hepatitis B virus (HBV) infection who are hepatitis B e antigen-positive, viral genotype is one of the strongest predictors of a sustained response to pegylated interferon-alfa (PEG-IFN), investigators report.
Only a minority of patients with chronic HBV develops a sustained response to PEG-IFN, and substantial side effects are common, principal investigator Dr. Harry L. A. Janssen and colleagues note in the December issue of Gastroenterology.
Therefore, Dr. Janssen, from Erasmus MC University Medical Center in Rotterdam, the Netherlands, and his team looked for markers that would predict the likelihood of a sustained response to PEG-IFN in hepatitis B e antigen-positive patients. Their cohort involved the combined populations of the two largest randomized trials in this patient population (n = 721).
Patients were treated with PEG-IFN-alfa-2a 180 mcg/wk for 48 weeks or PEG-IFN-alfa-2b 100 mcg/wk for 52 weeks. The researchers defined sustained response as clearance of hepatitis B e antigen from serum and HBV DNA < 2000 IU/mL at 6 months post-treatment.
Overall, 158 patients (22%) had a sustained response. Rates of sustained response were 37% with genotype A, 25% with genotype B, 20% with genotype C, and 8% with genotype D.
Apart from genotype, other pre-treatment predictors of sustained response were high levels of alanine aminotransferase (ALT 2 or more times the upper limit of normal), low levels of HBV DNA (< 200 million IU/mL), female sex, older age (average 34.8 vs. 32.4 years), and absence of previous IFN therapy.
Assuming an average predicted probability of sustained viral response of at least 30%, the investigators recommend PEG-IFN for patients with genotype A who have either a high ALT or a low level of HBV DNA. They also recommend it for patients with genotypes B and C when ALT is high and HBV DNA is low.
They also recommend against PEG-IFN for patients with genotype D, and note that the drug is also not generally advised for hepatitis B e antigen-negative patients because of poor therapeutic response.
Based on their findings, Dr. Janssen and his colleagues take issue with a recent recommendation from the European Association for the Study of the Liver against HBV genotyping: Such genotyping “is essential” if doctors want to see a sustained response once patients are no longer being treated, they write.
They predict that currently ongoing clinical trials will “allow for further validation of the model in the near future.”
Reference:
Gastroenterology 2009;137:2002-2009.
