Sustained response to combination therapy in patients with chronic hepatitis C who failed to respond to interferon.

Abstract

BACKGROUND/AIMS:

The best treatment for chronic hepatitis C patients who do not respond to interferon is still unknown. Reported rates of response to treatment vary as the result of heterogeneous definitions of non-responders and small study size.

METHODS:

One hundred nineteen hepatitis C virus (HCV) RNA-positive non-responders to high-dose interferon monotherapy received alpha-interferon, 5 MU tiw plus oral ribavirin, 1000-1200 mg/day for 48 weeks (Group A, n=74) or alpha-interferon, 5 MU daily for 4 weeks, followed by 5 MU tiw plus oral ribavirin, 1000-1200 mg/day for 44 weeks (Group B, n=45) according to the Institution where they were followed. Persistently normal alanine aminotransferase and negative HCV RNA up to 72 weeks from treatment onset defined a sustained response.

RESULTS:

Eighteen patients discontinued treatment (13 developed anemia, two mucositis, one granulocytopenia; two were dropouts), none for serious adverse events. There were 24 (20%) sustained responders, with similar final response rates in Groups A and B. Sustained response was more frequent in patients aged </=40 years (36% vs. 13%; P=0.006) and in those with non-1 genotype (44% vs. 14%; P=0.002). Among genotype 1 patients, the younger ones showed higher response rates (32% vs. 7%; P=0.005). Compared with patients harboring non-1 genotypes, the odds ratio of being a non-responder was 1.68 (confidence interval (CI): 0.53-5.37; P=0.381) in younger genotype 1 patients and 9.53 (CI: 2.84-32; P<0.001) in older genotype 1 patients.

CONCLUSIONS:

Chronic hepatitis C patients who are non-responders to interferon monotherapy and infected by non-1 genotypes should undergo re-treatment with combination therapy. Treatment should be extended to younger genotype 1 patients who are more susceptible to liver disease worsening because of longer life expectancy and have a higher probability of being long lasting responders than their older counterparts.

• Authors: Silvia Fargion, Savino Bruno, Mauro Borzio, Pier Maria Battezzati, Franco Bissoli, Roberto Ceriani, Annarosa Orlandi, Alessandra Maraschi, Alberto Chiesa, Lorenzo Morini, Anna Ludovica Fracanzani, Andrea Crosignani, Gemino Fiorelli, Mauro Podda
• Journal: Journal of hepatology (J Hepatol) Vol. 38 Issue 4 Pg. 499-505 (Apr 2003) ISSN: 0168-8278 [Print] Netherlands
• PMID: 12663243 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Interferon-alpha
• Ribavirin

Topics

• Adult
• Aged
• Antiviral Agents (administration & dosage, adverse effects)
• Drug Resistance, Viral
• Drug Therapy, Combination
• Female
• Genotype
• Hepacivirus (drug effects, genetics)
• Hepatitis C, Chronic (drug therapy)
• Humans
• Interferon-alpha (administration & dosage, adverse effects)
• Male
• Middle Aged
• Ribavirin (administration & dosage, adverse effects)