You have reached the legacy site. Please visit our new site at

 Google Custom Search

Management of Non-responders and Relapsers Treated with Pegylated Interferon plus Ribavirin for Chronic Hepatitis C

SUMMARY: Management of patients who do not achieve sustained response to an initial course of interferon-based combination therapy for chronic hepatitis C virus (HCV) infection remains a challenge, according to a review article in the December 2009 Journal of Viral Hepatitis. Fewer than 10% of non-responders benefit from re-treatment, but the odds improve with extended duration of pegylated interferon plus ribavirin, and directly targeted anti-HCV agents offer hope for the future.

By Liz Highleyman

Fewer than half of patients with hard-to-treat HCV genotype 1 achieve sustained virological response (SVR) -- or a cure -- with their first attempt at treatment with pegylated interferon plus ribavirin.

"The probability of a previously treated patient responding to re-treatment depends on the nature of the previous regimen, the magnitude of the response to previous treatment, and the patient's characteristics," wrote Douglas Dieterich from Mount Sinai School of Medicine and colleagues.

In particular, relapsers (those who achieved undetectable HCV RNA during treatment but experienced a rise in viral load after completing therapy) have higher re-treatment SVR rates, as do people who experienced partial response (reduction but not clearance of HCV RNA) compared with complete non-responders.

Re-treatment of non-responders using a standard 48-week regimen of pegylated interferon alfa plus ribavirin resulted in sustained response rates of about 6% in the EPIC-3 program and about 8% in the REPEAT trial. In REPEAT, however, the SVR rate was twice as high -- 16% -- in those re-treated for 72 weeks (P = 0.0006). "Based on available data," Dieterich and colleagues wrote, "extended treatment is the best option for these individuals."

Undetectable HCV RNA at week 12 was an important predictor of successful re-treatment in the REPEAT and EPIC studies, as it is for initial therapy.

Based on disappointing results from trials such as HALT-C, the review authors noted that, "Maintenance therapy with pegylated interferon is generally ineffective in non-responders and cannot be recommended."

Directly acting antiviral agents, such as the experimental HCV protease inhibitors telaprevir and boceprevir, may increase sustained response rates in prior non-responders and relapsers. However, these drugs have mostly been studied in combination with interferon plus ribavirin -- therefore adding to the burden of adverse events -- and "will not be available for some years."

In conclusion, Dieterich and colleagues wrote, "after careful evaluation of an individual's benefit-risk ratio, a 72-week regimen is the preferred strategy for optimizing sustained response rates in patients who have not responded to the standard of care, provided that viral RNA is undetectable at week 12 of re-treatment."

Mount Sinai School of Medicine, New York, NY; Division of Gastro-Hepatology, Ospedale S. Giovanni Battista (Molinette), Torino, Italy; Department of Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Hannover, Germany.


DT Dieterich, M Rizzetto, and MP Manns. Management of chronic hepatitis C patients who have relapsed or not responded to pegylated interferon alfa plus ribavirin. Journal of Viral Hepatitis 16(12): 833-843 (Abstract). December 2009.



























FDA-approved Combination Therapies for Chronic HCV Infection
Pegasys + Copegus
PEG-Intron + Rebetol
Intron A + Rebetol
Roferon A + Ribavirin

Treatment Guidelines
Experimental Treatments

HCV Articles by Topic

Hepatocellular Carcinoma
Liver Transplantation
Liver Biopsy

Children / Infants / Women
Drug Abuse
Experimental Treatments
FAQs About Hepatitis C
Insulin Resistance / Diabetes
Sustained Viral Response (SVR)
Tests for HCV
Vaccines for HCV