efficacy of peginterferon-ribavirin-boceprevir therapy in patients infected with g1 hcv with cirrhosis, awaiting liver transplantation

Conditions: HCV Infection; Liver Cirrhosis, Experimental

Summary: evaluation of efficacy of triple therapy with pegylated interferon, ribavirin, and boceprevir in patients with genotype 1 chronic hepatitis c, who are treatment-naive, have relapsed, or are non-responders with cirrhosis and awaiting liver transplantation, with a meld score less than or equal to 18

evaluation of sustained virological response defined as the proportion of patients with undetectable hepatitis c virus rna 24 weeks after discontinuation of therapy and/or after liver transplantation in patients with genotype 1, who are treatment-naive, have relapsed, or are non-responders with cirrhosis and awaiting liver transplantation, with a meld score less than or equal to 18

Eligibility criteria:
inclusion criteria: * adult 18 years and older * chronic infection with hepatitis c virus proven with positive pcr for more than 6 months * viral genotype 1 * cirrhosis while awaiting liver transplantation * meld score \< or equal to 18 * with or without hepatocellular carcinoma * naive to antiviral c treatment * failure on a previous treatment. failure is defined as the persistence of detectable hcv rna. the previous hcv failure treatment profile must be able to be documented according to the following terminology:- relapsing patient: hcv rna undetectable at the end of treatment, becoming detectable again after the discontinuation of treatment- breakthrough: increase of viremia of 1 log or more during the treatment - non-responding patient with partial response: hcv rna detectable at w24 without ever having been undetectable and with a decrease in hcv rna ≥ 2 log at w12 - non-responding patient with nul response: decrease in hcv rna \< 2 log at w12 * no need for prior treatment wash-out * negative pregnancy test in women of child-bearing age * double method of contraception in men and women of child-bearing age during the entire duration of treatment and the 6 months following its discontinuation * free, informed, and written consent (signed on the day of pre-enrollment at the latest and before all exams required by the study) * person enrolled in or a beneficiary of a social security/universal health insurance coverage * inclusion approved by the decision support committee exclusion criteria: * previous hcv treatment with boceprevir or telaprevir * alcohol consumption \> 40 g/day * toxicomania constituting a barrier for starting therapy according to the opinion of the investigator. patients included in a methadone or buprenorphine replacement program may be enrolled * meld \> 18 * non controlled sepsis * platelets \< 50,000/mm3 * neutrophil granulocyte levels \< 1000/mm3 * creatinine clearance \< 50 ml/min (mdrd) * hb \< 10 g/dl * uncontrolled psychiatric problems * contraindications to boceprevir * contraindication to interferon or ribavirin * subject with major complications of cirrhosis * hiv coinfection * hbv coinfection (unless this is treated effectively with analogues, as proven by undetectable viremia for at least 12 months) * other infectious disease underway * neoplastic disease other than hepatocellular carcinoma during the previous year, or neoplastic disease for which the prognosis is less than 3 years * treatment with immunosuppressors (including corticosteroids), antivirals other than those for the study, except aciclovir * consumption of st. john's wort * associated treatments including a molecule or substance that could interfere with the pharmacokinetic characteristics of boceprevir * history of a lactose allergy * person participating in another study including an exclusion period that is still underway during pre-enrollment * so-called vulnerable populations (minors, people under guardianship or protection, or a private individual under protection from making legal or administrative decisions) * pregnancy, breast-feeding

Keywords: boceprevir hcv infection antiviral therapy liver transplantation