Chronic hepatitis C infection is responsible for 30 percent of liver transplantations, 60 percent of hepatocellular carcinomas, and 40 percent of end-stage cirrhosis cases in industrialized countries. Until the late 1990s, interferon alfa monotherapy was the recommended treatment for this infection. However, fewer than 20 percent of patients with chronic hepatitis C developed a sustained virologic response. Combined therapy using interferon alfa plus ribavirin is now the recommended treatment for patients who are interferon naive. Kjaergard and colleagues reviewed the efficacy and safety of interferon alfa with and without ribavirin.

The authors' review included patients who had relapsed or failed to respond to interferon alfa, as well as patients who had not previously been treated. Electronic and manual searches identified relevant clinical trials involving 6,585 patients treated for a median of 26 weeks (range: six to 60 weeks) and followed to end of therapy or for a median of 24 weeks (range: 12 to 96 weeks) after therapy. Studies varied in the type of patient included and the dosage of antiviral agents used. In these trials, combination therapy reduced the risk of treatment failure (i.e., no virologic response) by 28 percent in interferon-alfa-naive patients, 47 percent in relapsing patients, and 17 percent in patients who had not responded to interferon-alfa monotherapy. These benefits lasted for at least six months. The calculated numbers needed to treat to achieve one additional sustained virologic response (i.e., six months) were six for interferon-alfa-naive patients, four for relapsers, and seven for previous nonresponders. Combination therapy was also associated with significantly better histologic and biochemical outcome measures.

There were six confirmed cases of cirrhosis in patients receiving combination therapy and 12 cases in patients receiving interferon alfa alone. Liver-related morbidity and all-cause mortality showed a trend in favor of combination therapy, but this did not reach statistical significance. Discontinuations and reductions in therapy were significantly more common in the patients who received combination therapy.

The authors' results suggest that combination therapy can lead to a sustained virologic response in approximately 37 percent of interferon-alfa-naive patients, 42 percent of relapsers, and 15 percent of previous nonresponders. These results indicate a clear advantage for combination therapy, regardless of previous treatment.

editor's note: About 15 percent of patients with hepatitis C virus infection spontaneously clear the virus, and 85 percent develop chronic infection. From 30 to 50 percent of chronically infected patients develop cirrhosis, and 5 to 15 percent develop decompensated cirrhosis or hepatoma. The factors associated with the rate of progression or the type of subsequent pathology are still unknown (Information from Gow PJ, Multimer D. Treatment of chronic hepatitis. BMJ November 17, 2001;323:1166).— a.d.w.