Objectives:

This report systematically reviews the comparative benefits and harms of current antiviral treatment regimens for chronic hepatitis C virus (HCV) infection in treatment-naïve adults.

Data sources:

MEDLINE^® (1947 to August 2012), the Cochrane Central Register of Controlled Trials (through 3^rd quarter 2012), clinical trial registries, and reference lists.

Review methods:

We used predefined criteria to determine study eligibility. We selected randomized trials of dual therapy with pegylated interferon (alfa-2a or alfa-2b) plus ribavirin or triple therapy with pegylated interferon (alfa-2a or alfa-2b), ribavirin, and either boceprevir or telaprevir that reported clinical outcomes, sustained virologic response (SVR), or harms. We also selected randomized trials or cohort studies that compared clinical outcomes in patients who experienced an SVR after antiviral therapy with patients who did not experience an SVR.

Results:

We included 90 randomized trials and observational studies. No study evaluated the comparative effectiveness of current antiviral regimens on long-term clinical outcomes. In trials of treatment-naïve patients, the likelihood of achieving an SVR was slightly lower for dual therapy with pegylated interferon alfa-2b plus ribavirin than for dual therapy with pegylated interferon alfa-2a plus ribavirin, with a difference in absolute SVR rates of about 8 percentage points. There were no clear differences in estimates of relative effectiveness in patient subgroups defined by demographic or clinical characteristics, although absolute response rates were lower in older patients, Black patients, patients with high viral load, patients with more advanced fibrosis or cirrhosis, and patients with genotype 1 infection. Differences in harms were relatively small, with no difference in withdrawals due to adverse events, although dual therapy with pegylated interferon alfa-2b plus ribavirin was associated with a lower risk of serious adverse events than dual therapy with pegylated interferon alfa-2a plus ribavirin. In patients with genotype 2 or 3 infection, trials found dual therapy with pegylated interferon for 12 to 16 weeks associated with a lower likelihood of achieving SVR as compared with 24 weeks of therapy. Lower doses of pegylated interferon alfa-2b were less effective than standard doses, and limited evidence showed no clear differential effects of ribavirin dosing.

Five trials found triple therapy with pegylated interferon (alfa-2a or alfa-2b), ribavirin, and either boceprevir or telaprevir associated with higher likelihood of SVR (66–80 percent) than dual therapy with pegylated interferon plus ribavirin for genotype 1 infection, with an absolute increase in SVR rate of 22–31 percentage points. Triple therapy with boceprevir was associated with increased risk of hematological adverse events, and triple therapy with telaprevir was associated with increased risk of anemia and rash, including severe rash, versus dual therapy.

A large cohort study that controlled well for confounders found that patients with an SVR after antiviral therapy had a lower risk of all-cause mortality than patients with no SVR, with adjusted hazard ratio estimates ranging from 0.51 to 0.71, depending on genotype. Other, smaller cohort studies also found that SVR was associated with reduced risk of all-cause mortality and long-term complications of HCV infection, but had more methodological shortcomings.

Conclusions:

Although there is no direct evidence on the comparative effects of current antiviral regimens on long-term clinical outcomes, SVR rates are substantially higher in patients with HCV genotype 1 infection who receive triple therapy with pegylated interferon (alfa-2a or alfa-2b), ribavirin, and boceprevir or telaprevir compared with dual therapy with pegylated interferon plus ribavirin. Achieving an SVR following antiviral therapy appears to be associated with decreased risk of all-cause mortality compared with no SVR, although estimates are susceptible to residual confounding.