From Journal of Viral Hepatitis
Management of Chronic Hepatitis C Patients Who have Relapsed or Not Responded to Pegylated Interferon Alfa Plus Ribavirin
- Abstract and Introduction
- Definition of Relapse and Nonresponse
- Which Patients are Most Likely to Relapse or Not Respond to the Standard of Care?
- Re-treatment of Relapsers
- Re-treatment of Nonresponders
- Predictors of SVR in Relapsers and Nonresponders
- Maintenance Therapy for Nonresponders and Relapsers
- Future Therapies for Nonresponders to Pegylated Interferon Plus Ribavirin
- Current Management of Previously Treated Patients
Abstract and Introduction
Development of therapeutic strategies for patients with chronic hepatitis C who experience virological breakthrough, relapse or nonresponse lag behind those for treatment-naïve patients. 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. Relapsers have higher sustained virological response rates than nonresponders when re-treated with pegylated interferon plus ribavirin. Re-treatment of nonresponders to pegylated interferon plus ribavirin with the standard 48-week regimen resulted in an approximate 6% sustained response rate in the EPIC-3 program. In the REPEAT trial, the sustained response rate was significantly higher in nonresponders to pegylated interferon alfa-2b (12 kD) plus ribavirin randomized to 72 weeks of peginterferon alfa-2a (40 kD) plus ribavirin, compared with a 48-week regimen (16% vs 8%, P = 0.0006). Based on available data, extended treatment is the best option for these individuals. Undetectable viral RNA at week 12 is an important criterion for re-treatment in the REPEAT and EPIC studies. Maintenance therapy with pegylated interferon is generally ineffective in nonresponders and cannot be recommended. Directly acting antivirals may increase response rates and the burden of adverse events when combined with the standard of care, but will not be available for some years. In conclusion, 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.
Infection with hepatitis C virus (HCV) often results in chronic hepatitis C, a progressive liver disease that is associated with significant morbidity and mortality. Chronic HCV can lead to liver cirrhosis and hepatocellular carcinoma and is one of the leading indications for liver transplantation worldwide. However, effective treatment is available. The current standard of care for chronic HCV infection is the combination of pegylated interferon plus ribavirin. With this combination, more than 50% of previously untreated patients achieve a sustained virological response (SVR).[2–5]
SVR has been described as 'tantamount to a cure' by the American Gastroenterological Association. Cure of chronic hepatitis C is associated with resolution of symptoms, improvements in health-related quality of life and liver histology and reductions in liver-related morbidity and mortality.[7–14]
Cure rates for chronic hepatitis C have improved significantly with each major evolutionary step in the treatment paradigm for the disease. As the willingness to treat patients and the indications for treatment have expanded, so too have the number of patients in whom HCV has not been eradicated by a first course of treatment. Thus, there is a large and growing pool of 'relapsers' and 'nonresponders' to the standard of care in urgent need of effective treatment.
Much progress has been made in optimizing treatment regimens for patients with chronic hepatitis C.[15,16] However, the development of therapeutic strategies for relapsers and nonresponders lags behind those for treatment-naïve patients. As a result, current treatment guidelines recommend that re-treatment should only be contemplated if the previous course of treatment included conventional (i.e. nonpegylated) interferon. This recommendation is now in need of re-evaluation as recent data have provided insight into how best to re-treat patients with pegylated interferon plus ribavirin.