Thierry Morin

Acute hepatitis C: analysis of a 126-case prospective, multicenter cohort

Objectives To analyze the data (epidemiology, mode of transmission, course, and outcome) of a large series of patients with acute hepatitis C (AHC) in France. Methods Prospective multicenter register, observational study. Results A cohort of 126 patients with AHC was prospectively enrolled between 1999 and 2007. Fifteen (12%) were HIV coinfected. Suspected modes of hepatitis C virus transmission were drug use (38%), sexual contact (21%), nosocomial transmission (18%), and occupational exposure (12%). For 40% of the patients, AHC was revealed by jaundice. Spontaneous viral clearance occurred in 40% of the 72 patients observed for 3 months without treatment. Only jaundice and nosocomial/occupational transmission were predictive of spontaneous viral clearance. Ninety patients were treated with standard or pegylated interferon-&agr; alone (58%) or in combination with ribavirin (42%), for 24 weeks or less in 90%. In intention-to-treat, a sustained viral response was obtained in 58 of 78 (74%) hepatitis C virus monoinfected patients [19 of 22 (86%) with 24 weeks of pegylated interferon-&agr; alone], but only six of 12 (50%) of HIV coinfected patients. Conclusion AHC remains rare, and drug and sexual transmission are predominant. A 3-month follow-up after diagnosis avoids treatment for four out of 10 patients. Antiviral treatment is highly effective, 24 weeks of pegylated interferon-&agr; alone being a good option.

INFLUENCE OF HCV GENOTYPE 1 SUBTYPES ON THE VIRUS RESPONSE TO PEG INTERFERON ALPHA-2a PLUS RIBAVIRIN THERAPY

New factors that influence the viral response in HCV non‐genotype 2/3 patients must be identified in order to optimize anti‐HCV treatment. This multicenter prospective study evaluates the influence of HCV variability and pharmacological parameters on the virological response of these patients to pegylated interferon α2a (peg‐IFN‐α2a: 180 µg/week) and ribavirin (RBV; 800–1,200 mg/day) for 48 weeks. HCV subtypes were identified by sequencing the NS5B region. Serum RBV and peg‐IFN‐α2a concentrations were measured at weeks 4 and 12. The 115 patients (67 men; median age = 49, range 31–76) included 64 who had never been treated and 27 co‐infected with HIV. The mean baseline HCV RNA was 6.30 ± 0.06 log IU/ml and the HCV genotypes were: G1 (n = 93) with 1a (n = 37) and 1b (n = 50), G4 (n = 20) and G5 (n = 2). Most patients (79/108; 73%) had an early virological response. Independent predictors of an early virological response were interferon naive patients (OR = 2.98, 95% CI: 1.15–7.72) and RBV of >2,200 ng/ml at week 12 (OR = 3.41, 95% CI: 1.31–8.90). Forty of 104 patients (38%) had a sustained virological response. The only independent predictors of a sustained virological response were subtype 1b (OR = 6.82, 95% CI: 1.7–26.8), and HCV RNA <15 IU/ml at week 12 (OR = 25, 95% CI: 6.4–97.6). Thus a serum RBV concentration of >2,200 ng/ml was associated with an early virological response and patients infected with HCV subtype 1b had a better chance of a sustained virological response than did those infected with subtype 1a. J. Med. Virol. 83:437–444, 2011.

Treatment of chronic hepatitis C with pegylated interferon and ribavirin in treatment-naive patients in 'true life': a plea in favor of independent postmarketing evaluations.

Background Results of treatments for chronic hepatitis C virus are only estimated and disclosed from pivotal trials. Aim To report the ‘true life’ results of pegylated interferon and ribavirin in treatment-naive patients. Methods A prospective, multicenter observatory in 22 general hospitals. Results Five-hundred and one patients were included, with 309 men (62%), aged 46±11 years, weighting 70±13 kg, infected with the following hepatitis C virus genotypes: 1 (50%), 2 (12%), 3 (28%), 4 (7.5%), 5 (0.6%). Liver biopsy, available in 436 patients showed stage F3 fibrosis in 24% and F4 in 13%. Two-hundred and seven patients had a comorbid condition. Treatment consisted of interferon &agr;2b in 340 patients and interferon &agr;2a in 161 patients. Dose reductions were necessary in 145 patients (29%). Treatment was prematurely interrupted in 145 patients (29%) owing to lack of efficacy (n=72) or side-effects (n=73). Sustained virological response (SVR) rates were 50% for all patients, and 37.1, 70.5, and 71% for patients with genotype 1, 2 and 3, respectively. At multivariate analysis, age, genotype, and fibrosis severity were the only independent factors of SVR. Conclusion In true life, patients are older and more severe, and SVR is about 10% lower than in pivotal trials.

Favorable outcome of acute occupational hepatitis C in healthcare workers: a multicenter French study on 23 cases.

Background Although risk factors and useful preventive measures are largely known, specific data about the course and prognosis of acute hepatitis C among healthcare workers is lacking. Aim To analyze the data, course, and outcome of a series of patients with occupationally transmitted acute hepatitis C in France. Methods and setting An observational multicenter study based on two consecutive acute hepatitis C cohorts, retrospective then prospective, registered between 1993 and 2007, mostly in general hospitals. Results A cohort of 23 patients with occupationally transmitted hepatitis C virus (HCV) was set up. Occupational accident registration was done in 14 (61%) cases. They were mainly women (n=14), with a mean age of 43 years. The disease was diagnosed during surveillance after exposure in 16 patients, and nine had hyperbilirubinemia. Early treatment was applied to nine of them, with eight who sustained viral response (SVR). Fourteen underwent surveillance: spontaneous viral clearance occurred in nine of them, with two relapses. Five patients with persistent HCV RNA 12 weeks after the diagnosis were then treated, with four SVR. Conclusion Information and prevention of healthcare workers concerning occupational HCV transmission need to be improved, and all blood-exposure accidents should be registered. Spontaneous viral clearance occurred in half of the patients. Antiviral treatment was highly effective, with a SVR of 86%.

High dose daily interferon-alpha induction and secondary adjunction of ribavirin in treatment-naive patients with chronic hepatitis C: A multicentric, randomised, controlled trial

OBJECTIVES To evaluate in naive patients with chronic hepatitis C 1- the efficacy and safety of one month interferon alpha (IFN-alpha) induction regimen; 2- the potential virological benefit of a secondary adjunction of ribavirin among HCV RNA negative patients after 20 weeks of IFN therapy, with or without an initial 4-week IFN induction. MATERIAL AND METHODS 151 naive HCV-RNA positive patients presenting with biopsy- proven chronic hepatitis C and elevated ALT were randomised in a 2: 1 ratio in two arms: IFN-alpha 3 MU thrice a week (tiw) for 24 weeks (non-induced patients); IFN-alpha 6 MU daily for two weeks, then 3 MU daily for two weeks then 3 MU tiw for 20 weeks (induced patients). At week 24, HCV-RNA negative patients were randomised to receive in addition or not ribavirin 1-1.2 g daily for 24 additional weeks. Induction efficacy was assessed on the early viral response (EVR) defined as undetectable HCV RNA at week 4 then week 20. Ribavirin efficacy was assessed on the proportion of maintained complete response until the end of follow-up, 24 weeks after discontinuation of treatment. Data were analysed on an intent-to-treat basis. RESULTS Efficacy of IFN-alpha induction: 104 patients were randomised to the non-induction group, 47 to the induction group. Gender, age, genotype distribution and HCV viral load at baseline did not differ significantly between the two groups. There was one treatment discontinuation because of adverse events in induced patients versus four in non-induced patients (P > 0.05). The 4 week EVR was significantly greater in induced patients in patients with HCV genotype 1, 4 or 5 (47% vs 12%, P=0.0002) only. There was no impact of induction in patients with HCV genotype 2 or 3. Efficacy of ribavirin: at week 24, 28 and 26 HCV-RNA negative patients were randomised to addition of ribavirin or not, respectively. Patients randomised to secondary additive ribavirin were more often HCV-RNA negative at the end of follow-up than patients treated with IFN-alpha alone: 18/28 (64%) vs 10/26 (39%); P=0.06. Among patients randomised to bitherapy, the relapse rate was significantly lower in patients with genotype 2 or 3 (0/12 vs 6/13, P=0.01) and not in those with genotype 1, 4 or 5 (5/11 vs 3/6, P=0.99). CONCLUSION A 4 week IFN-alpha induction significantly increases the EVR rate in patients with HCV genotype 1, 4 or 5. Late secondary adjunction of ribavirin to IFN-alpha for 6 months in HCV-RNA negative patients after 6 months of IFN-alpha significantly decreases the relapse rate in patients with HCV genotype 2 or 3, but not in patients with genotypes 1, 4 or 5.

Role of nosocomial hospital transmission in acute hepatitis C

To the Editor: We read with great interest the provocative paper by Martinez-Bauer and the Spanish Acute HCV Group attributing two-thirds of 109 cases of acute hepatitis C to hospitalization [1]. We have not observed this predominant role of nosocomial hospital transmission in our cohort of 126 patients prospectively recorded in the French Observatory of Acute Hepatitis C: in this cohort, nosocomial transmission was suspected in 24 of our patients (19%), a professional role was attributed in 15 (12%), drug use being responsible for 48 cases (38%) and sexual contacts for 26 (20%). The proportion of suspected nosocomial transmission was a little bit higher (18 patients, 29%) in our first, retrospective study of 62 cases [2], after excluding transfusion-related cases. The probable overestimation of the relative role of hospital nosocomial transmission in the Spanish study could have three main causes: (1) the inclusion of two ‘‘large” epidemics (totalizing 12/73 cases), related to obviously unsafe procedures, (2) a recruitment bias (patients being regularly admitted having systematic determinations of liver tests, which is exceptional after drug injection for example), and (3) recall bias (patients probably remembered and reported more easily hospi-