Extended-therapy duration for chronic hepatitis C, genotype 1: the long and the short of it

Abstract

With pegylated interferon and ribavirin, more than half of all chronically-infected hepatitis C patients can achieve a sustained virologic response; however, patients with genotype 1 infections and those with other poor prognostic factors have relatively inferior treatment response rates. Since new therapies are still years away from approval, it is incumbent upon providers to maximize the therapeutic efficacy of today's treatment. The later the virus is undetectable in serum during treatment, the less likely it will be eradicated. Patients with a delayed or slow virologic response to therapy (at least a 2-log(10) decrease in baseline hepatitis C RNA yet detectable viremia at 12 wk of therapy and undetectable virus 12 wk subsequently) may, therefore, benefit from an extended therapy course beyond one of standard duration. Although higher rates of treatment discontinuation may plague this approach, 72 wk of treatment for genotype 1-infected slow-responders may improve response rates and diminish relapse rates relative to those of 48 wk. Based on data from both viral kinetic and clinical studies, therapy prolongation in slow responders may be a reasonable strategy to improve response rates in these treatment-refractory patients.

Figure 1

Relationship between hepatitis C viremia and sustained virologic response with pegylated interferon alpha-2a and ribavirin therapy[19]. The later the virus becomes undetectable on therapy, the less likely it will be ultimately cleared. Data are from retrospective analysis[19] of a registration trial for peginterferon alpha-2a plus ribavirin involving over 1000 chronic, treatment-naive hepatitis C-infected patients[8]. Neg: Undetectable RNA; > 2 log: At least a 2 log₁₀ decrease in viral RNA compared to pre-treatment value; < 2 log: Less than a 2 log₁₀ decrease in viral RNA compared to pre-treatment value.

Figure 2

Virologic responses of slow-responders to 48 wk vs 72 wk of therapy. Treatment extension may improve chance of SVR by lessening the chance of relapse. Slow-responders to standard duration therapy (48 wk) may see relapse after an end-of-treatment response is achieved; those receiving extended duration therapy (72 wk) are not as apt to relapse after treatment is completed.