Short versus standard treatment with pegylated interferon alfa-2A plus ribavirin in patients with hepatitis C virus genotype 2 or 3: the cleo trial

Abstract

BackgroundIn patients with chronic hepatitis C virus (HCV) genotype 2 or 3, 24 weeks' treatment with pegylated interferon alfa (PEG-IFN-alpha) and ribavirin induces a sustained virological response (SVR) in almost 80% of cases. Evidence suggests that a similar response rate may be obtained with shorter treatment periods, especially in patients with a rapid virological response (RVR). The aim of this study was to compare the efficacy of 12 or 24 weeks of treatment in patients with chronic HCV genotype 2 or 3 and to identify patients suitable for 12 weeks treatment.MethodsTwo hundred and ten patients received PEG-IFN-alpha-2a (180 ug/week) and ribavirin (800-1200 mg/day) for 4 weeks. Patients with a RVR (HCV RNA not detectable) were randomized (1:1) to either 12 (group A1) or 24 (group A2) weeks of combination therapy. Patients without a RVR continued with 24-weeks' combination therapy (group B). HCV RNA was monitored at weeks 4, 8, 12, and 24, and at week 24 post-treatment.ResultsAt study end, end of treatment response (ETR) was observed in 62 (86%) patients of group A1 and in 55 (77%) patients of group A2 (p < 0.05) Relapse rate was 3% each in groups A1 and A2, and 6% in group B. Among patients with a HCVRNA test 24 weeks after the end of treatment, SVR was observed in 60 (83%) of group A1 patients and in 53 (75%) of group A2 patients. Rapid virological response, low baseline HCV RNA levels, elevated alanine aminotransferase levels and low fibrosis score, were the strongest covariates associated with SVR, independent of HCV genotype. No baseline characteristic was associated with relapse.ConclusionIn HCV patients with genotype 2 or 3, 12-week combination therapy is as efficacious as 24-week therapy and several independent covariates were predictive of SVR.Trial registrationTrial number ISRCTN29259563

Prediction of Sustained Virological Response to Combination Therapy with Pegylated Interferon Alfa and Ribavirin in Patients with Genotype 3 Chronic Hepatitis C

“…However, some studies have shown that higher ALT levels are predictors of SVR [41]. Viral factors affecting treatment outcome include HCV RNA titers at baseline, with lower levels showing increased probability of SVR [22,31,41]. However, no difference in the SVR was observed in patients with high viral load compared to low viral load in our study.…”

“…In our study, patients with higher BMI were found to have a lower chance of achieving SVR (Table 2). However, no relationship between BMI and SVR was shown in some previous studies on hepatitis C [22,25,34]. Large trials of HCV patients with bridging fibrosis or cirrhosis have shown that PEG-IFN and RBV combination therapy achieves SVR rates of 43-44% [11,16].…”

“…However, some studies did not show a relation with age [22]. In one of the studies, patents younger than 40 years of age had markedly better outcome [31].…”

“…In most of the studies, the SVR rates vary from 44 to 83%, with higher SVR rates in HCV genotype 2 and 3. Studies indicate that, among patients infected with HCV genotype 3, SVR was achieved in 68-83% patients [20][21][22][23][24][25]. However, studies carried out in the Indian population have shown poor response to therapy [6,27,28].…”

“…Other factors, with lesser impact, include age, gender, race, bodyweight/body mass index (BMI), and the degree of fibrosis [10,11,[13][14][15][16][17][18][19]. Treatment with PEG-IFN and RBV in CHC yields SVR rates of 44-83%, with higher SVR rates seen in patients infected with HCV genotypes 2 and 3 [20][21][22][23][24][25].…”