[Retreatment options for patients with chronic hepatitis C]

Abstract

Despite impressive therapy improvements, there still are a huge proportion of patients that will fail to achieve undetectable HCV. On the other hand, not all patients that demonstrate some response to treatment attain a sustained viral response. Patients with HCV non-response can be classified into several groups: 1) non-response (where the patient does not achieve undetectable HCV RNA at any time); 2) partial response (when the patient experiences some drop in HCV viremia but never below the detectable limit); 3) viral breakthrough (those associated with an initial virologic response, which is subsequently lost during treatment); and 4) relapse (those with an initial virologic response, which is lost upon treatment discontinuation). Most studies suggest that the major reason for breakthrough is missing the peginterferon alfa and/or ribavirin doses for various causes (significant adverse events, poor compliance, etc.). The main reasons for relapse include treatment initiation with insufficient ribavirin dosage or failure to continue treatment long enough, especially in patients with a slow virologic response. Patients with a well-defined non-response are poor candidates for retreatment. Such patients have no significant decline in HCV RNA during treatment and are essentially refractory to the effects of interferon. Patients with partial virologic response are excellent candidates for retreatment and can achieve undetectable HCV RNA if switched to a more intensive interferon regimen. Many other patients can be retreated successfully. The likelihood of achieving SVR (Sustained Virologic Response) with peginterferon alfa plus ribavirin retreatment depends on several factors, e.g., the agents used in previous treatment courses, total dose and duration of treatment, HCV genotype, level of viremia and previous drop in viremia. Patients previously treated with standard interferon alpha monotherapy are good candidates for retreatment, regardless of baseline liver histology. In this group, those that were previous responder-relapsers are most likely to respond to a course of peginterferon/ribavirin combination therapy, whereas previous non-responders can also achieve significant rates of SVR, particularly those infected with genotype 2 or 3 HCV There are several options for peginterferon alpha/ribavirin non-responders: 1) retreatment with the same protocol if adherence was a major problem; 2) administration of a longer treatment course (72 weeks) in slow responders; 3) retreatment with another interferon-based product (different peginterferon alpha, consensus interferon); 4) maintenance therapy; 5) clinical trials; and 6) wait and watch approach (respectable in many non-responders, particularly if fibrosis is not advanced and/or the patient experienced difficulties in tolerating therapy). Ongoing retreatment trials using specific antiviral drugs (valopicitabine, boceprevir, telaprevir) are of great interest, particularly in triple combination regimens.