Early Discontinuation of Ribavirin May Be Appropriate for Selected Genotype 2 or 3 Chronic Hepatitis C Patients

By Liz Highleyman

An adequate dose of ribavirin helps prevent relapse after interferon-based therapy for chronic hepatitis C, but the drug can cause hemolytic anemia that may necessitate dose reduction or discontinuation.

In a recent review article published in the February 2009 Journal of Hepatology, K. Rajender Reddy and colleagues discussed the current state of knowledge about optimal ribavirin use.

Studies to date indicate that "optimal ribavirin dose should be maintained over the whole treatment period," the authors wrote. For patients with HCV genotype 1, ribavirin dosages vary by body weight (1000 mg/day for patients < 75 kg and 1200 mg/day for patients > 75 kg), but 800 mg/day is considered "sufficient to ensure optimal response in all genotype 2/3 patients." The standard duration of pegylated interferon/ribavirin is 48 weeks for HCV genotype 1 and 24 weeks for genotypes 2 or 3.

"Recent data suggest treatment success is dependent on cumulative ribavirin exposure, as patients who receive < 60% of the planned dose have lower response rates, regardless of whether reductions are from temporary interruptions or premature cessation of therapy," they continued. "All patients should be monitored for hemolytic anemia, as early diagnosis allows management through small dose reductions and stepwise return to the target dose, maximizing cumulative exposure."

GI Division, University of Pennsylvania, Philadelphia, PA; Division of Gastroenterology, Hepatology, and Nutrition, University of Florida College of Medicine, Gainesville, FL; Department of Medicine I, JW Goethe University Hospital, Frankfurt, Germany.

Early Ribavirin Discontinuation

In a related study published in the January 2009 Journal of Viral Hepatitis, Italian researchers sought to determine whether chronic hepatitis C patients with easier-to-treat HCV genotypes 2 or 3 could safely stop ribavirin sooner, given that prior trials showed that half of these patients can achieve sustained virological response (SVR) using pegylated interferon monotherapy. The aim of the current study was to identify patient characteristics that might help identify individuals likely to benefit from early ribavirin discontinuation.

In this trial, 144 genotype 2 or 3 chronic hepatitis C patients started standard combination treatment with 180 mcg/week pegylated interferon alfa-2a (Pegasys) plus 1000 or 1200 mg/day ribavirin. Participants who experienced viral clearance at week 4 were then randomly assigned either to continue on combination therapy (n = 61) or to stop ribavirin and continue on pegylated interferon monotherapy (n = 59) through week 12.

Results

All but 1 patient with a rapid virological response (RVR) at week 4 had continued response at the end of treatment.

The overall SVR rate was significantly lower in patients who discontinued ribavirin compared with those who remained on combination therapy (54% vs 82%; P < 0.001).

In patients who achieved RVR and discontinued ribavirin, low baseline HCV RNA levels helped predict SVR (odds ratio 11.2).

SVR rates were similar in patients with low (< 300 000 IU/mL) and intermediate baseline viral load receiving pegylated interferon monotherapy or continued combination therapy:

Low viral load: 86% monotherapy vs 81% combination therapy;

Intermediate viral load: 70% monotherapy vs 71% combination therapy.

Among patients with high (>700 000 IU/mL) baseline viral load, however, those who stopped ribavirin had a significantly lower SVR rate than those who continued combination therapy (37% vs 88%; P = 0.004).

Based on these findings, the study authors concluded, "[I]n HCV-2- and HCV-3 infected patients, withdrawal of ribavirin and continuation of [pegylated interferon alfa-2a] monotherapy may be appropriate to attain an SVR, providing viremia is cleared early during therapy and associated with low baseline viral load."

"These results warrant future investigations," they added, "as discontinuing ribavirin could lead to considerable savings in cost and quality of life related to over-treatment."

Gastroenterology and Hepatology Units, San Giovanni Rotondo, Bologna, Castellana Grotte, Canosa, Casarano, and Napoli, Italy; Internal Medicine, University of Palermo, Italy.

1/20/09

References

KR Reddy, DR Nelson, and S Zeuzem. Ribavirin: Current role in the optimal clinical management of chronic hepatitis C. Journal of Hepatology 50(2): 402-411. February 2009. (Abstract).

A Andriulli, C Cursaro, R Cozzolongo, and others. Early discontinuation of ribavirin in HCV-2 and HCV-3 patients responding to Peg-interferon alpha-2a and ribavirin. Journal of Viral Hepatitis 16(1): 28-35. January 2009. (Abstract).