Future treatment of patients with HCV cirrhosis.

Of all hepatitis C virus (HCV) patients, those with cirrhosis are most in need of treatment because of increased morbidity and mortality. Treatment with pegylated-interferon (PEG-IFN) and ribavirin (RBV) (PR) has definitely shown the benefits of successful treatment by improving fibrosis, causing the regression of cirrhosis and reducing and preventing cirrhosis-related complications. However, the sustained virological response (SVR) is lower in patients with cirrhosis. First generation protease inhibitors (boceprevir and telaprevir) in combination with PR are a major advancement in the treatment of both naïve and treatment-experienced genotype 1 patients. In naïve patients, the SVR rate with the triple regimen with boceprevir was increased by 14% in patients with severe fibrosis or cirrhosis compared with PR. This benefit was lower than that observed in patients with mild or moderate fibrosis (30%). The SVR rate of the triple regimen with telaprevir was increased by 10-30% compared with PR in patients with severe fibrosis or cirrhosis compared with nearly 30% in patients with mild or moderate fibrosis. In treatment-experienced patients, previous relapsers have the highest increase in SVR with the triple regimen compared with PR, whatever the status of fibrosis. Previous partial or non-responder patients with cirrhosis had lower SVR rates than those without cirrhosis. However, the benefits of telaprevir and boceprevir vs PR was maintained. Previous non-responder patients with cirrhosis benefited the least from treatment. The relapse rate was always higher and side effects were more frequent in patients with cirrhosis compared with those without. First generation protease inhibitors plus PR appear to be a new step forward in the management of HCV genotype 1 patients with cirrhosis.

[Sarcoidosis following pegylated interferon therapy: two cases]. / Sarcoïdose chez deux malades traités par interféron pégylé pour une hépatite chronique C.

One side effect of the immunomodulatory effect of interferon is the possible triggering or exacerbation of systemic or cutaneous sarcoidosis. We report two new cases and offer an exhaustive review of the literature. A 39-year-old man with type C chronic active hepatitis developed new respiratory symptoms and pulmonary infiltrates with hilar and mediastinal adenopathy after 7 months of treatment with pegylated interferon. The evolution was favourable after stopping treatment. The second patient developed cutaneous lesions after 6 months of treatment. Resolution occurred after the discontinuation of the treatment. In these two cases ribavirin was stopped before the first signs of sarcoidosis.

High predictive value of early viral kinetics in retreatment with peginterferon and ribavirin of chronic hepatitis C patients non-responders to standard combination therapy.

BACKGROUND/AIMS: To evaluate the efficacy of peginterferon alfa-2b and ribavirin in unselected consecutive patients with chronic hepatitis C, treated outside of trials, who were relapsers or non-responders to interferon and ribavirin combination. METHODS: One hundred and fifty-four patients were evaluated. There were 101 non-responders and 53 relapsers to standard combination therapy. Patients were retreated with peginterferon alfa-2b 1.5 microg/kg/wk plus ribavirin 1000-1200 mg/day during 48 weeks. RESULTS: Forty-four patients (28.6%) achieved sustained virological response (SVR). Rapid (week 4) and early (week 12) virological response had high negative predictive values of SVR (94% and 97%, respectively); however positive predictive values were relatively low (52% and 49%, respectively). Relapsers had higher SVR rates (58.5%) than non-responders (13%) p<0.0001. In non-responders, SVR raised to 50% in patients with genotype non-1 and mild or moderate fibrosis. In multivariate analysis, predictors of SVR were: relapse after interferon plus ribavirin combination, mild or moderate fibrosis, genotype non-1 and baseline viral load <2 million copies/ml. CONCLUSIONS: Relapsers to interferon plus ribavirin therapy, and non-responders with genotype non-1 and mild or moderate fibrosis, achieved a relatively high SVR rate following retreatment with peginterferon plus ribavirin. Early viral kinetics had a high negative predictive value of SVR.