Impact of Disease Severity on HCV Treatment Outcomes in HALT-C Trial

In patients with chronic hepatitis C, advanced fibrosis and cirrhosis are associated with lower rates of sustained virological response (SVR) to interferon-based therapy.

As described in the December 2006 issue of Hepatology, researchers from the University of Colorado School of Medicine assessed virological response to re-treatment with pegylated interferon alfa-2a (Pegasys) plus ribavirin as a function of baseline fibrosis score (using the Ishak staging system) and platelet count.

The study included 1046 patients enrolled in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) trial who had failed prior treatment with convention or pegylated interferon, with or without ribavirin, and had Ishak fibrosis scores of 3 or higher.

Results

4 groups of patients with increasingly severe liver disease were compared

- (A) bridging fibrosis (Ishak stage 3 or 4) with platelet counts > 125,000 cells/mm3 (n = 559);
- (B) bridging fibrosis with platelet counts </= 125,000 cells/mm3 (n = 96);
- (C) cirrhosis (Ishak stage 5 or 6) with platelet counts > 125,000 cells/mm3 (- = 198);
o (D) cirrhosis with platelet counts </= 125,000 cells/mm3 (n = 193).

SVR rates were 23%, 17%, 10%, and 9% in groups A, B, C, and D, respectively (P < 0.0001 for trend).

Reduction in SVR rates as a function of increasingly severe liver disease was independent of age, race/ethnicity, HCV genotype, HCV viral load, and type of prior therapy.

Dose reduction lowered SVR rates, but to a lesser extent than disease severity.

By logistic regression analysis, cirrhosis (P < 0.0001) was the major determinant of impaired virological response, independent of dose reduction or platelet count.

Conclusion

In conclusion, the authors wrote, "disease severity is a major independent determinant of rate of SVR in patients with advanced chronic hepatitis C. New strategies are needed to optimize antiviral therapy in these 'difficult-to-cure' patients."

12/08/06

Reference
G T Everson, J C Hoefs, L B Seeff, and others. Impact of disease severity on outcome of antiviral therapy for chronic hepatitis C: Lessons from the HALT-C trial. Hepatology 44(6): 1675-1684. December 2006.