Long-term Effect of Peginterferon Alfa-2b (Peg-Intron) Plus Ribavirin (Rebetol) on Incidence of Hepatocellular Carcinoma in Patients with HCV-related Cirrhosis

The objective of the current study was to assess the treatment efficacy of interferon (IFN) alfa-2b (Peg-Intron) plus ribavirin (Rebetol) therapy and to determine whether these therapies influence the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related cirrhosis.
 

One hundred twenty-five patients with HCV-related cirrhosis who received IFN alfa-2b (3 or 5 MU thrice weekly) and oral ribavirin (1000-1200 mg per day) for 24 or 48 weeks were analyzed. Sustained virological response (SVR) was defined as negative HCV RNA at 6 months after therapy. Any other pattern of response was defined as non-response (NR).
 

Results

A total of 111 patients completed therapy. Forty-eight % of patients were of genotype 1b. Seventy-two (58%) achieved a SVR. Multivariate analysis of the factors (age, gender, genotype, viral load and IFN dosage) revealed that non-genotype 1b (p=0.000) and low viral load (p=0.000) were independent variables of treatment efficacy.

Over a median follow-up of 37 (12-60) months, HCC developed in 10 patients with NR and 5 with SVR. The incidence was significantly higher in patients with NR than that of sustained responders (p=0.0281).
 

Conclusions

In conclusion, the authors write, “These results suggest that successful HCV eradication by using IFN alfa-2b plus ribavirin therapy may decrease the incidence of HCC in patients with HCV-related cirrhosis.”

11/10/04

Reference
C H Hung and others. LONG-TERM EFFECT OF INTERFERON ALFA-2B PLUS RIBAVIRIN THERAPY ON INCIDENCE OF HEPATOCELLULAR CARCINOMA IN PATIENTS WITH HEPATITIS C VIRUS-RELATED CIRRHOSIS. Abstract 408 (poster). 55^th AASLD. October 29-November 2, 2004

http://www.hivandhepatitis.com/2004icr/aasld/docs/hcv/111004_c.html

The objective of this study was to determine sustained virological response (SVR) rates, sustained biochemical response (SBR) rates and safety of combination therapy with Pegasys plus Copegus in patients with CHC and compensated cirrhosis/bridging fibrosis who were enrolled in two pivotal phase III studies (Fried et al. NEJM 2002; 347:975 and Hadziyannis et al. 2004; 140:346).
 

Patients enrolled in the trials were interferon-naïve, had detectable HCV RNA in serum (≥2000 copies/ml) and elevated serum ALT levels and compensated liver disease.

Cirrhosis/bridging fibrosis was determined by a liver biopsy obtained ≤15 months of initiation of therapy. Patients received Pegasys 180 μg/wk plus either a low dose (LD, 800 mg/d) or standard dose (SD, 1000/1200 mg/d) of Copegus for 24 or 48 weeks.

In one study, patients in one arm received interferon alfa-2b 3 MIU tiw plus ribavirin 1000/1200 mg/day for 48 weeks. SVR was defined as an undetectable HCV RNA (<50 IU/mL, COBAS AMPLICOR HCV Test, v 2.0) during weeks 12-24 of follow-up. SBR was defined as normal ALT during follow-up.
 

Results (see Table below)

Overall SVR rates were higher in patients treated with Pegasys plus Copegus than in those treated with conventional interferon/ribavirin. Among the different regimens, SVR rates ranged from 26% to 37% in genotype 1 patients and from 69% to 75% in genotype 2/3 patients. The majority of patients with an SVR had an SBR and few patients had an isolated SBR without an SVR.

 

The safety profile of Pegasys/Copegus in patients with compensated cirrhosis was similar to that in the overall study population. There were no cases of decompensation or hepatocellular carcinoma.

Conclusion

The authors conclude, “Pegasys/Copegus is effective and safe in patients with CHC and compensated cirrhosis.”

11/10/04

Reference
P Marcellin and others. SUSTAINED VIROLOGICAL AND BIOCHEMICAL RESPONSES TO PEGINTERFERON ALFA-2A (40KD) (PEGASYS®) PLUS RIBAVIRIN (COPEGUS®) IN PATIENTS WITH CHRONIC HEPATITIS C (CHC) AND COMPENSATED CIRRHOSIS/BRIDGING FIBROSIS. Abstract 531 (poster). 55^th AASLD. October 29-November 2, 2004.

Table of Contents for all 55th AASLD Articles [by topic]
http://www.hivandhepatitis.com/2004icr/aasld/docs/hcv/111004_b.html