Has genetics eradicated the good old predictors of hepatitis C treatment response?

摘要

The ability of pegylated interferon (IFN)-alpha and ribavirin-based treatment regimens to eradicate hepatitis C virus (HCV) is under the influence of a number of parameters, including viral factors (e.g. the HCV genotype and baseline HCV RNA level), liver disease severity (i.e. the fibrosis stage assessed by means of liver biopsy or non-invasive methods), and a number of host characteristics including age, gender, body mass index and race [1]. Based on multivariate analyses of clinical trials with pegylated IFN-alpha and ribavirin in chronically infected patients, odds ratios and predictive values were calculated for these different parameters, and predictive algorithms were proposed. They led to the concept of an "a la carte" treatment of chronic hepatitis C, in which the dose and duration of administration of pegylated IFN-alpha and ribavirin are tailored to a combination of baseline parameters [2]. Nevertheless, assessment of viral kinetics early during therapy was soon shown to be a much stronger and more reliable predictor of the sustained virological response (SVR) to pegylated IFN-alpha and ribavirin therapy than any combination of baseline-parameters. HCV RNA level measurements at baseline, week 4 and week 12 (and eventually week 24) were indeed used to classify the patients into different groups of virological response, including the rapid, early, and delayed virological responses, that have been used to tailor treatment duration from 16-24 to 72 weeks, according to the HCV genotype [3].