By Liz Highleyman

It is well established that chronic hepatitis C patients with advanced liver fibrosis or cirrhosis respond poorly to interferon-based therapy, but this group has the most urgent need for effective treatment.

The Canadian POWeR program evaluated the impact of advanced fibrosis or cirrhosis on sustained virological response (SVR) rates in treatment-naive genotype 1 chronic hepatitis C patients treated with pegylated interferon plus ribavirin in "real-life" clinical settings between 2000 and 2007. Results were reported at the recent 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2008) in San Francisco.

This prospective, non-interventional, observational study included participants at 138 community and academic medical centers across Canada. Patients were treated with 1.5 mcg/kg/week pegylated interferon alfa-2b (PegIntron) plus 800-1200 mg/day weight-adjusted ribavirin for up to 48 weeks. HIV-HCV coinfected patients were excluded.

The intent-to-treat population included 718 patients who had available biopsy specimens and received at least 1 treatment dose. At baseline, 60% had mild to moderate fibrosis (stages F1-F2) and 40% had advanced fibrosis or cirrhosis (F3-F4). 55% had high baseline viral load (HCV RNA > 600,000 IU/mL).

Results

• In an intent-to-treat analysis, the overall SVR rate was 38%, but it differed significantly (P < 0.0001) according to fibrosis stage:

• F1: 52%;
• F2: 46%;
• F3: 26%;
• F4: 18%.

• End-of-treatment (EOT) response rates were significantly higher in patients with F1-F2 fibrosis versus F3-F4 fibrosis or cirrhosis (59% vs 34%; P < 0.0001).

• Corresponding SVR rates in the F1-F2 versus F3-F4 groups were 48% and 22%, respectively (P < 0.0001).

• Relapse after EOT response was more frequent in patients with F3-F4 fibrosis or cirrhosis than in those with F1-F2 fibrosis (35% vs 18%; P = 0.0009).

• Patients with F1-F2 fibrosis and low baseline viral load were significantly more likely to achieve SVR than those with the same degree of fibrosis and high viral load (58% vs 41%; P = 0.0008).

• The effect of baseline viral load on SVR was not apparent, however, among patients with F3-F4 advanced fibrosis or cirrhosis (20% vs 21%; P = non-significant).

Based on these findings, the researchers concluded, "Advanced hepatic fibrosis clearly diminished SVR rates in treatment-naive genotype 1 HCV patients treated with pegylated interferon alfa-2b plus weight-based ribavirin therapy."

"Advanced fibrosis/cirrhosis superseded the impact of viral load, as high viral load reduced SVR rates in patients with mild/moderate fibrosis but not those with advanced disease," they continued.

Finally, they recommended, "These results suggest that genotype 1 patients with advanced fibrosis require additional therapeutic approaches, including modified dose and/or duration of treatment, to optimize outcomes."

11/21/08

Reference
P Marotta, C Cooper, DK Wong, and others. Impact of Advanced Fibrosis and Cirrhosis on Sustained Virologic Response of HCV G1-Infected Patients: Results of the Canadian POWeR Program. 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2008). San Francisco. October 31-November 4, 2008. Abstract 1216.