Prediction of response to treatment of chronic hepatitis B with pegylated interferon in the Philippines

Abstract

The response marker for interferon has not been investigated fully for hepatitis B viruses (HBVs) in the Philippines where novel subtypes B5 and C5 were recognized recently. The prediction parameters for interferon treatment were assessed, with emphasis on the mutation patterns in the basal core promoter and precore regions in patients with chronic hepatitis B. Seventeen HBeAg-positive patients were stratified according to response to treatment with pegylated interferon based on HBe seroconversion and HBV load. Intra-patient distributions of wild-type strains (A1762, G1764) and variants (T1762, A1764) were analyzed using HBV-DNA amplification and subsequent molecular cloning. The rate of variants (T1762, A1764) harbored by a patient was higher among responders (41.2% and 31% per person on average) than among non-responders (2.4% and 2.4%) to treatment with pegylated interferon at the baseline, respectively (P < 0.05). The rate of variants (T1762, A1764) harbored by responders (41.2% and 31%) decreased to 1.7% and 1.7%, and wild-type strains (A1762, G1764) conversely became majority (98.3% and 98.3%) after treatment with pegylated interferon, respectively. HBV strains harbored by two of six responders and a patient with lower baseline load (1.0 x 10(4) copies/ml) showed genotype shift from A to other genotypes, where genotype A disappeared preferentially after the loss of HBeAg and genotypes B and C formed a major population. These results suggest that the HBV variants (T1762, A1764) and HBV genotype A in the Philippines have an advantage in the response to pegylated interferon. These results warrant a large-scale examination for further precise prediction of the response to treatment with interferon.

The Role of the Basal Core Promoter (BCP) and Precore Codon 28 Mutations in the Treatment Response to the Pegylated Interferon

“…In this respect, BcP mutations have an important role to follow-up of chronic HBV. Although there is not much study on the effects of the mutations on the pegylated interferon response, it has been reported that especially the T1762, A1764 were advantage in response to pegylated interferon therapy (31,32). similarly, in our study the virological response rate was higher in groups with BcP mutations than in the group have no mutations, but there was no statistically significant differences between the groups (p>0.05).…”