Short versus standard treatment with Pegylated interferon alfa-2a plus ribavirin in patients with hepatitis C virus genotype 2 or 3: the CLEO trial.

Liver Unit San Camillo Forlanini Hospital, Rome, Italy.
BMC Gastroenterology (Impact Factor: 2.37). 02/2010; 10(1):21. DOI: 10.1186/1471-230X-10-21
Source: PubMed


In 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.
Two 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.
At 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.
In 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 number ISRCTN29259563.

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    • "While supporting 24 weeks as the overall standard of care, Manns et al. lend credence to the concept of truncation of therapy in patients with genotype 2 or 3 who achieve an RVR with weight-based ribavirin. The data in the overall literature, however , remain inconclusive as to whether this can be done routinely without jeopardizing the chance of SVR to any significant extent even among ''favorable'' patient populations with characteristics such as younger age [7] [10] [11] [18], no or minimal fibrosis [7] [9] [11] [19], BMI 630 kg/m 2 [11] [19] [20], low viral load [7–9,11,19], genotype 2 [8] [11], or platelet count P140,000 [20]. Despite the potential merit of a cost-effectiveness argument in support of shorter treatment, or a modest improvement in tolerability, many clinicians would find it problematic to routinely administer a regimen that had failed to demonstrate non-inferiority to patients who wish to maximize their prospects of success during the initial treatment course without incurring any incremental chance of having to undergo a repeat therapy. "

    Journal of Hepatology 04/2011; 55(3):505-6. DOI:10.1016/j.jhep.2011.04.001 · 11.34 Impact Factor
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    ABSTRACT: The drugs currently licensed for the treatment of hepatitis C are Peg-Interferon (PEG-IFN) and ribavirin. In recent years, the recommendation to treat hepatitis C virus genotype 2- and 3-infected patients with a fixed 800 mg/day dose of ribavirin in combination with PEG-IFN and for just 24 weeks has been challenged by the concept of tailoring the length of therapy according to on-treatment viral response. Therefore, the objective of the present review was to highlight the different designs of the studies on short treatment duration and the role of wk4-R as a predictor of sustained virological response after an abbreviated course of treatment. The secondary aim was to verify whether we had enough evidence to support the implementation of a short treatment course in subsets of patients with genotype 2 and 3 infection. We will also focus on how drug dosing may have influenced the outcome of treatment. To clarify reasons for discrepant results in the studies so far published, the recently discovered genetic variant near the interleukin 28B gene will be presented and its predictive role will be discussed. Finally, we will face the debated issue of whether the subset of patients with genotype 2 or 3 requires an extended treatment duration.
    Liver international: official journal of the International Association for the Study of the Liver 10/2010; 31(1):36-41. DOI:10.1111/j.1478-3231.2010.02357.x · 4.85 Impact Factor
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    ABSTRACT: Current guidelines recommend that patients with genotype 2 (G2) and 3 (G3) chronic hepatitis C be treated with pegylated interferon (PEG-IFN) plus low doses of ribavirin (800 mg/day) for 24 weeks, resulting in a sustained virological response (SVR) rate of approximately 80%. Considering these high response rates, several recent randomized trials have assessed whether shorter treatment (12-16 weeks) could be cost-effective in these patients. The results of these studies vary but suggest better responsiveness in G2 patients, and overall, do not strongly support reducing treatment to <24 weeks in all patients. On the other hand, the presence of a rapid virological response (RVR) (defined as an undetectable hepatitis C virus-RNA at 4 weeks of treatment) was always reported to be the best positive predictor of achieving SVR in both G2 and G3 patients. These results suggest that in a subgroup of subjects with RVR (G2>G3, viral load <400,000 IU, low fibrosis, no metabolic cofactors), shorter treatment is as effective as standard regimens, and that it can be proposed mainly if problems of poor tolerance or adherence are foreseen. It is possible that the SVR rate in non-RVR patients and non-responder patients could also be improved by prolonging therapy, but this must be specifically investigated in other studies along with the role of IL28B polymorphisms.
    Liver international: official journal of the International Association for the Study of the Liver 01/2011; 31 Suppl 1(s1):36-44. DOI:10.1111/j.1478-3231.2010.02382.x · 4.85 Impact Factor
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