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Unlabelled: Various critical events, liver related or not, occur in patients with compensated cirrhosis, but their respective burden remains to be prospectively assessed. The aim of this prospective cohort study involving 35 French centers was to capture the whole spectrum of complications occurring in compensated viral cirrhosis (VC) using competing risks analyses. Inclusion criteria were: histologically proven cirrhosis resulting from hepatitis C virus (HCV) or hepatitis B virus (HBV); Child-Pugh A; and no previous hepatic complications. The cohort was considered as a multistate disease model, cumulative incidences (CumIs) of events were estimated in a competing risks framework. A total of 1,654 patients were enrolled from 2006 to 2012 (HCV, 1,308; HBV, 315; HCV-HBV, 31). During a median follow-up of 34 months, at least one liver nodule was detected in 271 patients, confirmed as hepatocellular carcinoma (HCC) in 128 (4-year cumI: 10.5%) and cholangiocarcinoma in 3. HCC incidence was higher in HCV (4-year cumI: 11.4% vs. 7.4%; P = 0.05). HCC fulfilled Milan criteria in 79.3%, leading to curative treatment in 70.4%. Liver decompensation occurred more frequently in HCV patients (4-year cumI: 10.8% vs. 3.6%; P = 0.0004). Virological eradication/control was achieved in 34.1% of HCV and 88.6% of HBV patients and was associated with a marked decrease in HCC, decompensation, and bacterial infection incidences. Survival was shorter in HCV patients (4-year cumI: 91.6% vs. 97.2%; P = 0.0002). Death (n = 102; missing data: 6) was attributed to liver disease in 48 (47%; liver cancer: n = 18; miscellaneous, n = 30) and extrahepatic causes in 48 (47%; bacterial infection: n = 13; extrahepatic cancers: n = 10; cardiovascular events: n = 5; miscellaneous, n = 20)., Conclusion: After 3 years of follow-up, extrahepatic events still explained half of deaths in patients with compensated VC. A strong decrease in complications was linked to virological eradication/control., (© 2015 by the American Association for the Study of Liver Diseases.)

Background & Aims: The efficacy and tolerability of faldaprevir, a potent hepatitis C virus (HCV) NS3/4A protease inhibitor, plus peginterferon (PegIFN) and ribavirin (RBV) was assessed in a double-blind, placebo-controlled phase 3 study of treatment-naïve patients with HCV genotype-1 infection., Methods: Patients were randomly assigned (1:2:2) to PegIFN/RBV plus: placebo (arm 1, n = 132) for 24 weeks; faldaprevir (120 mg, once daily) for 12 or 24 weeks (arm 2, n = 259); or faldaprevir (240 mg, once daily) for 12 weeks (arm 3, n = 261). In arms 2 and 3, patients with early treatment success (HCV-RNA <25 IU/ml at week 4 and undetectable at week 8) stopped all treatment at week 24. Other patients received PegIFN/RBV until week 48 unless they met futility criteria. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR12)., Results: SVR12 was achieved by 52%, 79%, and 80% of patients in arms 1, 2, and 3, respectively (estimated difference for arms 2 and 3 vs. arm 1: 27%, 95% confidence interval 17%-36%; and 29%, 95% confidence interval, 19%-38%, respectively; p < 0.0001 for both). Early treatment success was achieved by 87% (arm 2) and 89% (arm 3) of patients, of whom 86% and 89% achieved SVR12. Adverse event rates were similar among groups; few adverse events led to discontinuation of all regimen components., Conclusions: Faldaprevir plus PegIFN/RBV significantly increased SVR12, compared with PegIFN/RBV, in treatment-naïve patients with HCV genotype-1 infection. No differences were seen in responses of patients given faldaprevir once daily at 120 or 240 mg., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: The impact of the IL28B genotype on the real-life treatment decisions for patients infected with the hepatitis C virus (HCV) is unknown., Objective: To prospectively analyze the impact of IL28B genotype in HCV genotype 1 (G1)- or 4 (G4)-infected patients using buccal epithelial cell samples in real-life clinical practices., Patients and Methods: From October 2011 to March 2013, 1007 CHC patients were included among 127 French clinical centers., Results: The IL28B CC, CT, and TT genotype distribution was 252 (25%), 576 (57%), and 177 (18%), respectively. The treatment decisions were recorded and matched with the initial intentions for 433 patients. Multivariate analysis on intention to start treatment showed that patients with HCV G4 were less likely to be intended to be treated than HCV G1 patients (odds ratio [OR]=0.43 [95% CI 0.19-0.97], P=0.04); similarly HIV-HCV coinfected patients were less likely to be intended to be treated than HCV monoinfected patients (OR=0.20 [0.09-0.41], P<.0001); conversely, F3-F4 patients were more likely to be intended to be treated than F0-F2 patients (OR=2.24 [1.29-3.89], P=0.004). Multivariate analysis on final decision to treat showed that Patients with F3-F4 were more likely to be treated than others (OR=2.06 [1.26-3.38], P=0.004). Conversely, although P-values are not significant, patients recruited in public hospitals tended to be less treated (OR=0.65 [0.40-1.04], P=0.069), similarly to HIV-HCV coinfected patients (OR=0.55 [0.28-1.11], P=0.095)., Conclusion: Our study showed that the IL28B genotype is used for the management of HCV-infected patients. In the context of future treatments, IL28B genotyping may remain useful if it can be used to develop individualized treatment strategies, identifying patients who can be successfully treated with shorter, simpler, or cheaper regimens., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

The current treatment of patients with chronic HCV infection since ten years is pegylated interferon combined with ribavirin. This association allows a virological eradication in 55% of patients, all genotype and 40% of those infected with genotype 1, the most prevalent. Two protease inhibitors (telaprevir and boceprevir) were approved in 2011, in combination with pegylated interferon and ribavirin in both naïve and non-responder patients infected with HCV genotype 1. These new drugs allow obtaining a viral eradication in 70% of cases. Other direct acting antiviral drugs are also currently being tested and likely to radically change treatment strategies for patients with chronic hepatitis due to HCV., (Copyright © 2012. Published by Elsevier Masson SAS.)

About half of patients with chronic hepatitis C do not respond to the current treatment combining pegylated interferon and ribavirin. One must distinguish the "false" non responders who did not receive an optimal treatment and the "true" non responders who received an optimal treatment. In "false" non responders, the management of the factors of non response (alcohol consumption, body overweight...) or the improvement of tolerability to therapy (anti-depressive therapy, erythropoietin...) may allow an optimized retreatment with a chance of viral eradication. On the opposite, in "true" non responders, the probability to obtain with retreatment a viral eradication is very low and one must envisage, in case of severe liver disease (fibrosis stage F3 or F4), maintenance therapy. The objective of maintenance therapy is to decrease the activity of the chronic hepatitis and stabilize fibrosis in order to decrease the risk of complications and hepatocellular carcinoma. The ongoing trials will determine the optimal schedule of maintenance therapy. The new antivirals, mainly protease inhibitors and polymerase inhibitors, will probably be used in triple therapy with pegylated interferon and ribavirin. The drugs, currently in phase 1 and 2, which will demonstrate their efficacy and safety, should not be available before several years.

SERIOLOGICAL TESTS IN FIRST INTENTION: Aimed at revealing antibodies demonstrating the contact of the patient with the hepatitis C virus. There are two types of serological tests: ELISA for the global screening of various antibodies and immunoblot for the isolation of the various antibodies. QUALITATIVE RNA OF HCV: The positive qualitative detection of RNA of the hepatitis C virus in a patient exhibiting anti-HCV antibodies confirms an active infection. In the case of negative qualitative detection in a patient exhibiting anti-HCV antibodies, viral eradication is probable and should be controlled later on. MEASURING THE VIRAL LOAD: Two types of measuring techniques are used to quantify the circulating viral RNA: gene amplification and amplification of the signal. The extent of the viral load will help to guide the selection and duration of the anti-HCV dual therapy, associating pegylated interferon and ribavirin. The kinetics of the decrease in viral load are part of the therapeutic follow-up. HCV typing Many viral strains have been isolated, demonstrating its genetic variability and have led to the development of genotyping. The latter is useful in selecting the right therapy and duration of treatment, because the response depends on the genotype (better response rate for the genotypes 2 and 3).

Various complementary actors are implied in the management of HCV infections: virologists, general practitioners, hepato-gastroenterologists and hospital residents, and they should all cooperate together. The role of biologist is crucial in assisting the practitioners in the choice of examinations to be prescribed for the diagnosis of HCV infections (search for RNA HCV), in establishing a prognosis and in deciding on the therapeutic strategy (genotyping, Fibrotest and Actitest). The role of the general practitioner is important at all stages of the management. The practitioner's involvement is also crucial in the recognition and follow-up of the concomitant diseases. THE ROLE OF THE SPECIALIST: The hepatologist, together with the general practitioner, are inseparable partners in the management of a patient suffering from hepatitis C. The specialist should only see patients exhibiting hepatitis C who are participating in a treatment program, since the indication for treatment is usually decided on by the specialist. The hepatologist should be informed of the various concomitant diseases and the treatments (replacement therapy or others) prescribed for them. CRUCIAL QUESTIONS: For the management of an HCV infection, in general 3 questions require an answer: who should be screened for such infections, what explorations should be performed in the case of positive serology and what follow-up is required during and after anti-HCV treatment?

INCREASE IN ALANINE AMINOTRANSFERASE (ALAT): Used for many Years in the diagnosis and follow-up of chronic hepatic diseases related to HCV, the determination of ALAT presents various limits: variation from one patient to the other and in the same patient over time, absence of specificity and inconstant increase. HISTOLOGICAL ASSESSMENT OF THE INVOLVEMENT OF THE LIVER: The hepatic needle-biopsy remains the best means of assessing precisely the hepatic impact. Several scores of hepatic involvement exist, the most frequently used is the Metavir score that takes into account not only the necrotic-inflammatory activity but also the fibrosis. OTHER THAN THE HEPATIC NEEDLE-BIOPSY: There are complications with the hepatic needle-biopsy and non-invasive markers of fibrosis and hepatic necrotic-inflammatory activity have been looked for. Two scores have hence been developed from the measurement in the blood of 4 proteins (apolipoprotein A1, alpha2 macroglobulin, haptoglobin and bilirubin) and 2 enzymes (alanine aminotransferase and gamma-glutamyl transpeptidase) which provide an acurate assessment of the fibrosis (Fibrotest) and the necrotic-inflammatory activity (Actitest).

Unlabelled: Little is known about the management of HCV infected patients after screening in general medicine. On May 2000, 75 General Practitioners (GP) from South Eastern France were involved in an HCV screening campaign. Fifteen per cent of 6321 patients seen during this period presented at least one of the following risk factors: blood transfusion before 1991, drug abuse, imprisonment. Among the 238 HCV positive patients, 9 new cases were reported., Aim of the Study: To describe the management of these patients., Results: One hundred and fifty-nine of these 238 cases were studied (100 males and 59 females). Mean age was 42 +/- 12 years. Mean delay between contamination and the discovery of HCV positive status was 8 +/- 6 years. Main routes of infection were: drug abuse (78%), transfusion before 1991 (15%), imprisonment (7%). The GP performed the entire follow up of cases in 34%. The following investigations were performed: ALT dosage in 98% (elevated: 59%, normal: 41%), qualitative HCV RNA detection in 77% (positive 78%, negative 22%), quantitative HCV RNA detection in 27%. A liver biopsy was performed in 62 patients (39%). Among the 159 patients 39 (19%) were treated with Interferon (with or without Ribavirin). Treatment and liver biopsy were not performed for the following reasons: patient refusal (26%), normal ALT values (26%), HIV co-infection (27%), elderly patients (3%), decompensated cirrhosis (5%), drug abuse or excessive alcohol intake (12%)., Conclusion: The main reasons that adequate management in hepatitis C patients failed was fear of liver biopsy and/or Interferon therapy, and a population difficult that was difficult to treat (HIV coinfected, drug abuse or chronic alcoholism), A better collaboration between general practitioners and specialists could help improve the management of these patients.

Background: This study was performed to assess screening and management of hepatitis C by community-based practitioners in the Alpes Maritimes district in the South of France and to compare their practices with the recommendations issued by the consensus conferences in 1997 and 1999. This information was to be used to adapt continuing medical education to the needs of practitioners in the area., Method: Two hundred and nineteen general practitioners who were members of eighteen continuing medical education associations accepted to complete a questionnaire containing eighteen closed questions. It was issued late 1999 during one of the monthly meetings and completed by all the participating physicians., Results: Only 32% of general practitioners knew the conclusions of one of the two French and European consensus conferences concerning hepatitis C. General practitioner practices were in accordance with recommendations for targeted screening in case of transfusion before 1991 (88%), intra-venous drug use (94%) and increased ALT (91%); however intra nasal drug use (35%) and imprisonment (46%) were underestimated risk factors. Frequency of screening was correlated to duration of practice (P<0.01), size of practice (P<0.02) and follow-up of hepatitis C infected patients, regardless of treatment (P<0.03). Upon discovery of a positive HCV status, 80% of general practitioners prescribed initial investigations but these included costly and needless procedures such as hepatic imaging (56%), RNA quantification (39%) and viral genotype (6%). On the other hand, 79% general practitioners recommended a liver biopsy for patients with elevated transaminase levels. When transaminase levels were normal, only 13% requested qualitative detection of viral RNA. Generally, general practitioners were confused concerning the indications for qualitative or quantitative viral RNA investigations. Few general practitioners followed treated HCV-infected patients and renewed interferon therapy prescriptions. Condom use was advised by 56% of GPs for couples in which one of the partners had a positive HCV status., Conclusions: This study demonstrates the weak impact of consensus conferences on hepatitis C management for general practitioners in the Alpes Maritimes. It provides an opportunity to identify the need for specific training which will be developed within the Côte d'Azur Hepatitis C Network.

Objective: To perform a descriptive analysis of patients with chronic hepatitis C based on a local registry of liver biopsies., Patients and Method: Collection of clinical, biological and histological data from all HCV-infected patients who underwent liver biopsy between January 1997 and December 1998 in the Alpes-Maritimes (France)., Results: One thousand and fifty six patients including 924 who lived in the Alpes-Maritimes (515 male, 409 female, mean age: 44.9 years old) were included. Intravenous drug use (30.1%) was the major suspected source of infection before blood transfusion (28.2%). Among intravenous drug users, 38% of patients were infected with genotype 1a and 37.4% with genotype 3. The METAVIR fibrosis severity score was distributed as follows: F0: 10.8%, F1: 53.7%, F2: 15.9%, F3: 14.7%, and F4: 4.9%. In a multivariate analysis adjusted for the duration of infection, independent risk factors associated with the severity of fibrosis were age at contamination >=30 years, genotype other than 1a and alcohol intake >=50 g/day. Determination of HCV antibody and liver biopsy were performed an average of 12.5 and 14 years after presumed date of contamination, respectively., Conclusions: These data provide a clearer view of the impact of this condition in this area and could help to define a comprehensive policy for patient management.