Scavenger receptor class B type I is a key host factor for hepatitis C virus infection required for an entry step closely linked to CD81.

International audienceHepatitis C virus (HCV) is a major cause of chronic hepatitis worldwide. Scavenger receptor class B type I (SR-BI) has been shown to bind HCV envelope glycoprotein E2, participate in entry of HCV pseudotype particles, and modulate HCV infection. However, the functional role of SR-BI for productive HCV infection remains unclear. In this study, we investigated the role of SR-BI as an entry factor for infection of human hepatoma cells using cell culture-derived HCV (HCVcc). Anti-SR-BI antibodies directed against epitopes of the human SR-BI extracellular loop specifically inhibited HCVcc infection in a dose-dependent manner. Down-regulation of SR-BI expression by SR-BI-specific short interfering RNAs (siRNAs) markedly reduced the susceptibility of human hepatoma cells to HCVcc infection. Kinetic studies demonstrated that SR-BI acts predominately after binding of HCV at an entry step occurring at a similar time point as CD81-HCV interaction. Although the addition of high-density lipoprotein (HDL) enhanced the efficiency of HCVcc infection, anti-SR-BI antibodies and SR-BI-specific siRNA efficiently inhibited HCV infection independent of lipoprotein. Conclusion: Our data suggest that SR-BI (i) represents a key host factor for HCV entry, (ii) is implicated in the same HCV entry pathway as CD81, and (iii) targets an entry step closely linked to HCV-CD81 interaction

[Non invasive markers using for the assessment of fibrosis in hepatitis C]

International audienceNon invasive fibrosis markers, recently developed, are now an interesting alternative to liver biopsy in order to appreciate the severity of chronic hepatitis C. Serological markers, especially Fibrotest and Fibrometer, have a good diagnostic accuracy to discriminate patients with mild fibrosis to those with severe fibrosis. For intermediate stages, the discordance is very important and often justifies liver biopsy or using of several markers. Transient elastography (Fibroscan) is a new non invasive method subject to good conditions of utilisation. Diagnostic accuracy is improved by the using of all the markers, especially of Fibrotest. Transient elastography is also a promising method for assessing the severity of cirrhosis

[Hepatitis C, cirrhosis and hepatocellular carcinoma]

International audienceThe screening for the detection of hepatocellular carcinoma is based on ultrasound sonography which should be realised in patients with post-hepatitis C cirrhosis with a delay between 3 and 6 months according to the most identified risk factors, in particular age and sex male. In the case of discovery of hypoechogen nodule 2 cm and when the ultrasound sonography is not contributive, especially when the nodule is between 1 and 2 cm in size

[Physiopathology of bullous pemphigoid]

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[Physiopathology of herpetiform dermatitis. Current data]

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Neutralizing antibodies in hepatitis C virus infection.

International audienceHepatitis C virus (HCV) is a major cause of hepatitis world-wide. The majority of infected individuals develop chronic hepatitis which can then progress to liver cirrhosis and hepatocellular carcinoma. Spontaneous viral clearance occurs in about 20%-30% of acutely infected individuals and results in resolution of infection without sequaelae. Both viral and host factors appear to play an important role for resolution of acute infection. A large body of evidence suggests that a strong, multispecific and long-lasting cellular immune response appears to be important for control of viral infection in acute hepatitis C. Due too the lack of convenient neutralization assays, the impact of neutralizing responses for control of viral infection had been less defined. In recent years, the development of robust tissue culture model systems for HCV entry and infection has finally allowed study of antibody-mediated neutralization and to gain further insights into viral targets of host neutralizing responses. In addition, detailed analysis of antibody-mediated neutralization in individual patients as well as cohorts with well defined viral isolates has enabled the study of neutralizing responses in the course of HCV infection and characterization of the impact of neutralizing antibodies for control of viral infection. This review will summarize recent progress in the understanding of the molecular mechanisms of antibody-mediated neutralization and its impact for HCV pathogenesis

Endoscopic placement of fully covered self expanding metal stents for management of post-operative foregut leaks

Background: Fully covered self-expanding metal stent (SEMS) placement has been successfully described for the treatment of malignant and benign conditions. The aim of this study is to evaluate our experience of fully covered SEMS placement for post-operative foregut leaks. Materials and Methods: Retrospective analysis was done for indications, outcomes and complications of SEMS placed in homogeneous population of 15 patients with post-operative foregut leaks in our tertiary-care centre from December 2008 to December 2010. Stent placement and removal, clinical and radiological evidence of leak healing, migration and other complications were the main outcomes analyzed. Results: Twenty-three HANAROSTENT® SEMS were successfully placed in 14/15 patients (93%) with post-operative foregut leaks for an average duration of 28.73 days (range=1-42 days) per patient and 18.73 days per SEMS. Three (20%) patients needed to be re-stented for persistent leaks ultimately resulting in leak closure. Total 5/15 (33.33%) patients and 7/23 (30.43%) stents showed migration; 5/7 (71.42%) migrated stents could be retrieved endoscopically. There were mucosal ulceration in 2/15 (13.33%) and pain in 1/15 (6.66%) patients. Conclusions: Stenting with SEMS seems to be a feasible option as a primary care modality for patients with post-operative foregut leaks

Safety and Antiviral Activity of EGFR Inhibition by Erlotinib in Chronic Hepatitis C Patients: A Phase Ib Randomized Controlled Trial

Introduction: Significant hepatocellular carcinoma (HCC) risk persists after chronic hepatitis C (CHC) cure. Preclinical studies have shown that erlotinib, an oral epidermal growth factor receptor (EGFR) inhibitor, has an antiviral activity and HCC chemopreventive effect. Erlotinib is metabolized in the liver, and its safety in patients with CHC is unknown. This study aimed to assess the safety and antiviral activity of erlotinib in patients with CHC.Methods: In this investigator-initiated dose-escalation phase Ib prospective randomized double-blind placebo-controlled study, noncirrhotic hepatitis C virus (HCV) patients received placebo or erlotinib (50 or 100 mg/d) for 14 days with a placebo-erlotinib ratio of 1:3. Primary end points were safety and viral load reduction at the end of treatment (EOT). The secondary end point was viral load reduction 14 days after EOT.Results: This study analyzed data of 3 patients receiving placebo, 3 patients receiving erlotinib 50 mg/d, and 3 patients receiving erlotinib 100 mg/d. One grade 3 adverse event was reported in the placebo group (liver enzymes elevation), leading to treatment discontinuation and patient replacement, and 1 in the erlotinib 100 mg/d group (pericarditis), which was not considered to be treatment-related. Grade 2 skin rash was observed in 1 erlotinib 100 mg/d patient. No significant HCV-RNA level reduction was noted during treatment, but 2 of the 3 patients in the erlotinib 100 mg/d group showed a decrease of >0.5 log HCV-RNA 14 days after EOT.Discussion: Erlotinib demonstrated to be safe in noncirrhotic CHC patients. An antiviral activity at 100 mg/d confirms a functional role of EGFR as an HCV host factor in patients. These results provide perspectives to further study erlotinib as an HCC chemopreventive agent in patients with CHC

Dietary components modulate the risk of hepatocellular carcinoma in cirrhotic patients

Eighty percent of hepatocellular carcinoma (HCC) cases occur after cirrhosis from various etiologies. The association between diet and cancer is well accepted, but the links with cirrhosis progression and HCC risk have been poorly investigated. However, we hypothesized that diet could be a modifiable preventive factor for HCC. Thus, the aim of our study was to explore the relationships between dietary factors and the risk of HCC in a population of cirrhotic patients. A total of 582 cirrhotic patients were studied: 401 without HCC (controls) and 181 with HCC (cases). These patients were recruited between 2008 and 2012 for the "CiRCE" case-control study conducted in six French university hospitals. Information about the consumption of 208 food items and 23 nutrients were collected through a diet history questionnaire. Unconditional multivariate logistic regressions were performed for each residual food group and nutrients in tertiles. HCC patients were more often men, diabetic and older than controls. After adjustment, a significant positive association was found between HCC risk and carbonated beverages (ORTertile3vsTertile1=2.44 [1.17-5.09] p-trend=0.021), total cereals (ORT3vsT1=1.87 [1.09-3.22] p-trend=0.035), processed meat (ORT3vsT1=1.97 [1.14-3.41] p-trend=0.028) and sodium (ORT3vsT1=2.00 [1.14-3.53] p-trend=0.043). Conversely, the consumption of fiber (ORT3vsT1=0.49 [0.28-0.86] p-trend=0.012), vitamin E (ORT3vsT1=0.52 [0.30-0.89] p-trend=0.017), vitamin B9 (folate and folic acid) (ORT3vsT1=0.56 [0.33-0.95] p-trend=0.036), manganese (ORT3vsT1=0.56 [0.32-0.97] p-trend=0.038) and potassium (ORT3vsT1=0.44 [0.25-0.76] p-trend=0.004) were significantly lower in HCC patients compared with cirrhotic controls. Although these findings must be confirmed in prospective studies, using dietary patterns or biological parameters, they suggest that certain dietary components may modulate HCC risk in cirrhotic patients

Characteristics and care of chronic hepatitis C treated with direct-acting antivirals in migrants

BACKGROUND AND AIMS: Hepatitis C is poorly documented in migrants. The published studies mainly concern the screening in this population and are limited to some countries in Europe and North America. This study aimed to evaluate the characteristics and care of chronic hepatitis C in this population compared to the nonmigrant population, in the era of direct-acting antivirals (DAAs). METHOD: We performed a retrospective analysis based on data presented at the multidisciplinary team meetings of our tertiary care center between 2015 and 2019. RESULTS: We included 277 migrant- and 1390 nonmigrant patients mono-infected with hepatitis C virus (HCV) and treated with DAAs. The majority of the migrants were from Eastern European countries. In multivariable analysis, BMI classes associated with more obesity (OR = 1.84; 95% CI, 1.37-2.49; P < 0.001) and therapeutic patient education (OR = 3.91; 95% CI, 2.38-6.49; P < 0.001) were positively associated with migrant status, whereas age (OR = 0.92; 95% CI, 0.90-0.94; P < 0.001), female gender (OR = 0.46; 95% CI, 0.28-0.74; P = 0.002), modes of contamination with less drug use, transfusion history or nosocomial risk, as well more unknown mode (OR = 0.70; 95% CI, 0.50-0.96; P = 0.031), alcohol consumption (OR = 0.48; 95% CI, 0.29-0.73; P = 0.001), types of structures with less care in a general hospital or health network of general practitioners and more care in a university hospital or primary addictology center (OR = 0.78; 95% CI, 0.60-0.99; P = 0.046) and opioid substitution therapy (OR = 0.25; 95% CI, 0.08-0.68; P = 0.008) were negatively associated with migrant status. The substained virologic response 12 was close to 97% in both groups. CONCLUSION: Despite multiple differences in characteristics and therapeutic care between the two populations, the chances of healing hepatitis C were the same among migrant- compared with nonmigrant patients