POWeR Study Finds Patients with Advanced Liver Disease Respond Poorly to Pegylated
Interferon plus Ribavirin|
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.
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.
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.
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).
In an intent-to-treat analysis, the overall SVR rate was 38%, but it differed
significantly (P < 0.0001) according to fibrosis stage:
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).
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."
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.
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."
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