PEG-Intron in Combination with Ribavirin Produces Sustained Viral Response of 81% in Genotype 4 Patients with HCV Viral Load Less Than 2 X 10⁶

The hepatitis C virus (HCV) genotype is an important predictive parameter for the success of pegylated interferon plus ribavirin therapy. To date, most published therapeutic trials have enrolled patients infected mainly with HCV genotypes 1, 2 and 3. Data regarding the responsiveness of genotype 4, the predominant type of HCV in the Middle East, are very limited.

To primary objective of this study was to assess the efficacy of pegylated interferon alfa-2b (PEG-Intron) in combination with ribavirin for the treatment of chronic hepatitis caused by HCV genotype 4.

44 treatment naive patients infected with HCV genotype 4 were enrolled in this open label, prospective study. Cohort characteristics included the following: 30 M/14F, mean age 44.4 + 8.9 yrs, mean weight 73.3 + 7 kg. All patients had raised ALT and were compensated.

The median pre-treatment HCV-RNA level was 2.35 x 10⁶ copies /ml (0.47 x 10⁶ iu/ml), range 0.3 x 10⁶ - 30 x 10⁶ copies/ml. 13 patients (30%) exhibited cirrhosis and 2 (4%) had bridging fibrosis on pretreatment liver biopsy specimens.

All patients were to receive pegylated interferon alfa-2b 1.5 mcg/kg/wk plus ribavirin 1000-1200 mg/day for 48 weeks. Patients were followed up for 24 weeks after completing therapy. End of treatment viral response (ETR) and sustained viral response (SVR) were defined as absence of HCV-RNA from serum (<100 copies/ml) at 48 weeks of treatment and at the end of follow-up, respectively. Data were analyzed on an intention - to- treat basis.

Study Results

• ETR and SVR were 68% and 61% respectively. Among patients with pre-treatment HCV-RNA greater than or = 2 x 10⁶_, SVR was 50% compared with SVR of 81% among patients with HCV-RNA < 2 x 10⁶ (P=0.05).
• Patients with cirrhosis or severe fibrosis had significantly lower SVR rate compared to those with mild or no fibrosis (33% vs 76%; P<0.05).
• Two patients (4.5%) discontinued therapy because of severe flu-like symptoms. One patient developed hypothyroidism.
• Dose reduction of ribavirin and pegylated interferon alfa-2b were necessary in 27% and 2% of patients respectively.

Conclusion:

Pegylated interferon alfa-2b in combination with ribavirin is effective in the treatment of HCV genotype 4. Treatment was well tolerated by most patients.

Commentary

“These findings with weight-based PEG-Intron and Rebetol combination therapy are very encouraging, especially given that genotype 4 is generally known to be difficult to treat,” said Hasan.  “To date, most therapeutic trials have enrolled patients infected with HCV genotypes 1, 2 or 3.  Data regarding the responsiveness of genotype 4 is very limited and further study is warranted,” he said.

Reference
F Hasan and others. PEGYLATED INTERFERON ALFA-2B IN COMBINATION WITH RIBAVIRIN FOR THE TREATMENT OF CHRONIC HEPATITISC GENOTYPE 4. Abstract 982 (poster). Hepatology 38:4 (Suppl). October 2003. (54^th Annual Meeting of the American Association for the Study of Liver Diseases. October 24-28, 2003. Boston, MA.)