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.

[How to investigate and diagnose autochthonous hepatitis E?]. / Quand rechercher et comment diagnostiquer une hépatite E autochtone?

In developed countries, HEV infection was still recently considered as rare, and as an imported disease from endemic areas by travellers. Hepatitis E virus is now recognized mainly as an autochthonous disease in these countries. Although the source and the route of contamination remain uncertain, several cases of food-borne (zoonotic transmission) and blood-borne transmission have been recently reported. The mortality rates in industrialized countries seems to be higher than in endemic areas, since the infection occurs more frequently in elderly people with underlying chronic liver disease (mortality rate approaching 70% in this subgroup of patients). By contrast, whereas mortality rate rises by 20% during pregnancy in developing countries, no death in pregnant woman from developed countries secondary to an autochthonous case has been reported so far. Lastly, HEV infection may be a cause of chronic hepatitis in immunocompromised patients (mostly in solid organ-transplant recipients) which can evolve to cirrhosis.

Coeliac disease in chronic hepatitis C: a French multicentre prospective study.

BACKGROUND: A prevalence of 1.2% of coeliac disease (CD) in patients with chronic hepatitis C was recently reported, suggesting a possible epidemiological link between these two diseases. However, other studies have not found this relationship. AIM: To conduct a French multicentre prospective study to assess the prevalence of CD in hepatitis C virus (HCV)-infected patients. METHODS: Between June 2003 and November 2005, 624 consecutive HCV-positive out-patients were tested for antiendomysial IgA antibodies (AEA), antigliadin IgA and IgG antibodies (AGA). Patients with positive AEA or IgA AGA and positive IgG AGA in a context of a high suspicion of CD were asked to undergo gastroscopy with duodenal biopsies. RESULTS: Isolated IgA AEA, IgA AGA and IgG AGA were 0.16%, 5.7% and 4.4%, respectively. Gastroscopy was required for 39 patients, 31 were performed (eight refusals), but only 25 duodenal biopsies were performed as six patients had cirrhosis. CD was never detected. CONCLUSIONS: The prevalence of CD in HCV-positive patients was 0% (95% confidence interval: 0-0.59%), but there is a low prevalence of CD in the whole French population.

[Hepatitis E as a zoonosis]. / L'hépatite E: une zoonose méconnue.

Hepatitis E virus (HEV) is responsible for large waterborne epidemics of acute hepatitis in endemic regions and for autochthonous sporadic cases in non endemic regions. In contrast to endemic regions where the water vector has been well characterised, very little is known about the way of contamination in non endemic regions. Unlike the other hepatitis viruses, HEV has an animal reservoir. Several lines of evidence, such as phylogenic analysis and direct contamination through infected food products, suggest that animal to human transmissions occur. Despite these observations, all origins of possible human contamination in non endemic areas remain unknown and need to be investi- gated. The high genetic variability of HEV might also be an important risk factor for human contamination and need further survey.

Extrahepatic manifestations associated with hepatitis C virus infection. A prospective multicenter study of 321 patients. The GERMIVIC. Groupe d'Etude et de Recherche en Medecine Interne et Maladies Infectieuses sur le Virus de l'Hepatite C.

From January 1996 to January 1997, 321 patients with an average age of 46 +/- 16 years and chronically infected with hepatitis C virus (HCV) were prospectively enrolled in a study designed to determine the prevalence of extrahepatic manifestations associated with HCV infection in a large cohort of HCV patients, to identify associations between clinical and biologic manifestations, and to compare the results obtained in human immunodeficiency virus (HIV)-positive versus HIV-negative subsets. In a cross-sectional study, clinical extrahepatic manifestations, viral coinfections with HIV and/or hepatitis B virus, connective tissue diseases, and a wide panel of autoantibodies were assessed. Thirty-eight percent (122/321) of patients presented at least 1 clinical extrahepatic manifestation including arthralgia (60/321, 19%), skin manifestations (55/321, 17%), xerostomia (40/321, 12%), xerophthalmia (32/321, 10%), and sensory neuropathy (28/321, 9%). Main biologic abnormalities were mixed cryoglobulins (110/196, 56%), thrombocytopenia (50/291, 17%), and the presence of the following autoantibodies: antinuclear (123/302, 41%), rheumatoid factor (107/280, 38%), anticardiolipin (79/298, 27%), antithyroglobulin (36/287, 13%) and antismooth muscle cell (27/288, 9%). At least 1 autoantibody was present in 210/302 (70%) of sera. By multivariate logistic regression analysis, 4 parameters were significantly associated with cryoglobulin positivity: systemic vasculitis (p = 0.01, odds ratio OR[ = 17.3), HIV positivity (p = 0.0006, OR = 10.2), rheumatoid factor positivity (p = 0.01, OR = 2.8), and sicca syndrome (p = 0.03, OR = 0.27). A definite connective tissue disease was noted in 44 patients (14%), mainly symptomatic mixed cryoglobulinemia and systemic vasculitis, HIV coinfection (23%) was associated with 3 parameters: anticardiolipin (p = 0.003, OR = 4.18), thrombocytopenia (p = 0.01, OR = 3.56), and arthralgia or myalgia (p = 0.017, OR = 0.23). HIV-positive patients presented more severe histologic lesions (p = 0.0004). Extrahepatic clinical manifestations in HCV patients involve primarily the skin and joints. The most frequent immunologic abnormalities include mixed cryoglobulins, rheumatoid factor, antinuclear, anticardiolipin, and antithyroglobulin antibodies. Cryoglobulin positivity is associated with systemic vasculitis and rheumatoid factor and HIV positivity. HIV coinfection is associated with arthralgia or myalgia, anticardiolipin antibodies, and thrombocytopenia.

[Recurrence after surgical treatment of epidermoid cancers of the esophagus. Therapeutic approach in 19 patients]. / Récidives après traitement chirurgical des cancers épidermoïdes de l'oesophage. Approche thérapeutique chez 19 malades.

OBJECTIVES: The aim of this study was to report the management of 19 patients with recurrence of esophageal squamous cell carcinoma after surgical treatment. PATIENTS-METHODS: Nineteen patients with loco-regional recurrent invasion (n = 13) or metastasis (n = 6) of esophageal squamous cell carcinoma were included. Four of the 13 patients with loco-regional recurrent invasion had tracheal involvement. The treatment of the recurrence was a combined radiochemotherapy (n = 12) for loco-regional recurrent invasion in 11 cases and for metastasis in 1 case, associated with a tracheal prosthesis in 1 patient. The other treatments were chemotherapy alone (n = 5), esophageal prosthesis (n = 1) and surgical treatment (n = 1). RESULTS: There were 7 objective responses among the 12 patients treated with combined radiochemotherapy and none in the group treated with chemotherapy alone. Grade 3-4 toxicity was noticed in 2 cases (severe mucositis). Survival rate of the 19 patients was 52.6% at 1 year and 13.1% at 2 years; it was linked with general health (P = 0.09) and with tracheal involvement (P = 0.04). Survival rate of the 12 patients treated by combined radiochemotherapy was higher: 66% at 1 year and 22.2% at 2 years (median survival time = 16 months). CONCLUSION: Active medical treatment of recurrence of esophageal squamous cell carcinoma by combined radiochemotherapy can provide a median survival time of 16 months, with a moderate toxicity.

Influence of insulin resistance on hepatic fibrosis and steatosis in hepatitis C virus (HCV) mono-infected compared with HIV-HCV co-infected patients.

BACKGROUND: Insulin resistance (IR), the major feature of the metabolic syndrome, is also common in patients with chronic HCV infection. Liver fibrosis and steatosis are known potential outcome of chronic hepatitis B or C infection. Studies have shown that HIV positive individuals co-infected with HCV have more rapid live disease progression than those with HIV alone. Few data have reported the influence of IR on steatosis and fibrosis in the context of HIV-HCV coinfection. AIM: To test the association among insulin resistance (IR), liver fibrosis and liver steatosis in HIV-HCV and HCV-infected patients. PATIENTS AND METHODS: A total of 170 HIV-HCV-infected patients matched by age, gender and genotype with 170 HCV mono-infected patients were included. Patients were considered to be IR when the homeostasis model assessment of IR >2. Significant fibrosis was considered if METAVIR >or=F2 and significant steatosis if >or=10%. RESULTS: Insulin resistance was independently associated in HCV patients with fibrosis [odds ratio (OR) = 2.04 (95% CI 1.02-4)], a body mass index (BMI) >25 kg/m(2) [OR = 3.33 (1.47-7.69)] and steatosis [OR = 3.33 (1.67-6.67)]. Fibrosis >or=F2 was associated in HCV patients with high liver activity grade (>or=A2) [OR = 8.33 (3.85-16.67)], male gender [OR = 3.03 (1.33-7.14)] and IR [OR = 2.44 (1.15-5)]. In HIV-HCV patients, >or=A2 [OR = 5.56 (1.64-20)] was associated with fibrosis. Steatosis >or=10% was associated in HCV patients with IR [OR = 3.13 (1.59-6.25) and >or=F2 (OR = 2.22 (1.15-4.17)]. In HIV-HCV, a BMI >25 kg/m(2) [OR = 3.85 (1.64-9.10)], >or=A2 [OR = 2.16 (1.02-4.55); P = 0.044] and nucleoside reverse transcriptase inhibitor [OR = 3.61 (1.19-10.96); P = 0.023] were independently associated with significant liver steatosis. CONCLUSIONS: Insulin resistance is associated with liver fibrosis and steatosis in HCV mono-infected, but not in HIV-HCV co-infected patients. Significant liver fibrosis is associated with IR independent of liver steatosis only in HCV mono-infected patients.

A national survey of acute hepatitis E in France.

BACKGROUND: Few data are available on the incidence, risk factors and contamination pathways involved in acute indigenous hepatitis E in developed countries. AIMS: To draw up an overall picture of hepatitis E cases, to confirm whether or not the majority of the cases were indigenous and to attempt to identify the risk factors and contamination pathways involved in hepatitis E. METHODS: This study was performed in the framework of a national network (ANGH) including 96 participating centres. The 19 centres with at least one case of acute HEV reported a total number of 53 cases. RESULTS: A decreasing South-to-North geographic gradient was observed. A nonspecific clinical profile was observed in many cases. Acute hepatitis E was of indigenous origin in 90% of the patients. The most relevant and/or frequent possible risk factors among the 47 indigenous metropolitan cases were water consumption from a personal water supply, uncooked shellfish consumption and the recent acquisition of a pet pig. CONCLUSIONS: This national survey confirmed that acute indigenous hepatitis E is an emerging disease in developed countries such as France, and suggests that various risk factors are responsible for acute indigenous hepatitis E contamination in non-endemic countries.

Optimized stepwise combination algorithms of non-invasive liver fibrosis scores including Hepascore in hepatitis C virus patients.

BACKGROUND: Non-invasive liver fibrosis scores such as Hepascore (HS) have been proposed as an alternative to liver biopsy in hepatitis C virus (HCV)-infected patients. AIM: To validate HS as an alternative to liver biopsy and Fibrotest (FT) and propose five optimized combination algorithms to improve diagnostic accuracy. METHODS: The cohort included 467 patients with HCV. There were 274/467 (59%) men, and mean age was 47 +/- 12 years. RESULTS: Hepascore area under ROC curves (AUC) for > or =F2, F3F4 and F4 diagnosis were 0.82, 0.84 and 0.90 respectively, in the same range as FT. HS and FT were concordant in 387/467 (82%) for fibrosis staging. Among these patients, 342/387 (88%) were concordant with liver biopsy. AUCs of aspartate aminotransferase (AST) to Platelets Ratio Index (APRI) and Forns for > or =F2 were 0.76 and 0.73 (0.65-0.79) respectively. The algorithm combining APRI and HS had the highest rate of avoided liver biopsies (45%) with a high diagnostic accuracy (91%). CONCLUSIONS: Hepascore is an accurate non-invasive marker for > or =F2 and F4 diagnosis in HCV patients. In a pragmatic approach, a stepwise optimized algorithm combining APRI and FT or HS considerably increases diagnostic accuracy and avoided liver biopsies.

Validation and comparison of indexes for fibrosis and cirrhosis prediction in chronic hepatitis C patients: proposal for a pragmatic approach classification without liver biopsies.

Noninvasive indexes have been developed to predict fibrosis staging. The aim of this study was to assess the diagnostic accuracy of these indexes in comparison with liver histology in hepatitis C virus (HCV)-infected patients. A total of 235 consecutive patients with HCV infection from the Fibropaca multicentre independent study were included in this paper. FibroTest (FT), aspartate aminotransferase to platelet ratio index (APRI) and Forns score were assessed in the cohort and compared with liver histology performed on the same day. The main end point was the area under characteristic curves (AUCs) for the diagnosis of significant fibrosis (F2-F4) and cirrhosis (F4) by the METAVIR classification. Mean age was 46 (+/-11) years, 55% were males, 42% (n = 99) had significant fibrosis (F2-F4) and 7% (n = 16) had cirrhosis (F4). For the diagnosis of significant fibrosis, respective AUCs of FT, APRI and Forns score were 0.81 (95% confidence interval: 0.76-0.86), 0.71 (0.67-0.79) and 0.76 (0.70-0.82); for cirrhosis prognosis, AUCs of FT and APRI were 0.82 (0.77-0.87) and 0.81 (0.76-0.86) (AUCs not significantly different). Using each index independently, all patients were classified by FT, 214 (91%) patients were classified by APRI and 129 (55%) by Forns score. There were significantly more cases of discordances between APRI and liver biopsy than between FT or Forns score and liver biopsy (P < 0.05). Performing all scores (FT, Forns and APRI) without liver biopsy allowed fibrosis to be well evaluated in 191 patients (81.3%), including patients with FT failure. Liver biopsy remained mandatory to evaluate fibrosis in 44 patients (18.7%). Our study shows that performing all the tests and liver biopsy improves the diagnostic accuracy for liver fibrosis in chronic hepatitis C patients without patent comorbidities. The combination of all tests with liver biopsy allowed 225/235 (96%) patients to be correctly classified. The combination of all tests without liver biopsy allowed 191/235 (81.3%) patients to be correctly classified; liver biopsy remained mandatory in some patients (18.7%).