Hepatitis E virus emergence in north eastern France

International audienc

Hepatitis E virus emergence in north eastern France

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Variability in molecular characteristics of Hepatitis E virus quasispecies could modify viral surface properties and transmission

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Plasma mSEPT9: A Novel Circulating Cell-free DNA-Based Epigenetic Biomarker to Diagnose Hepatocellular Carcinoma

Summary: Background: Patients with cirrhosis are at high risk of hepatocellular carcinoma (HCC). The SEPT9 gene is a key regulator of cell division and tumor suppressor whose hypermethylation is associated with liver carcinogenesis. The primary aim of this study was to evaluate the diagnostic accuracy of a PCR-based assay for the analysis of SEPT9 promoter methylation in circulating cell-free DNA (mSEPT9) for diagnosing HCC among cirrhotic patients. Methods: We report two phase II biomarker studies that included cirrhotic patients with or without HCC from France (initial study) and Germany (replication study). All patients received clinical and biological evaluations, and liver imaging according to current recommendations. The primary outcome was defined as the presence of HCC according to guidelines from the American Association for the Study of Liver Diseases. The diagnosis of HCC was confirmed by abdominal contrast-enhanced computed tomography scan and systematically discussed in a multidisciplinary consultation meeting. HCC-free cirrhotic patients were recruited if the screening abdominal ultrasound showed no evidence of HCC at the time of blood sampling for the mSEPT9 test and on the next visit six months later. The adjudicating physicians were blinded to patient results associated with the mSEPT9 test. Findings: We included 289 patients with cirrhosis (initial: 186; replication: 103), among whom 98 had HCC (initial: 51; replication: 47). The mSEPT9 test exhibited high diagnostic accuracy for HCC diagnosis, with an area under the receiver operating characteristic curve (AUROC) of 0.944 (0.900–0.970, p < 0.0001) in the initial study (replication: 0.930 [0.862–0.971, p < 0.0001]; meta-analysis: AUROC = 0.940 [0.910–0.970, p < 0.0001], no heterogeneity: I2 = 0%, p = 0.67; and no publication bias). In multivariate logistic regression analysis, the number of positive mSEPT9 triplicates was the only independent variable significantly associated with HCC diagnosis (initial: OR = 6.30, for each mSEPT9 positive triplicate [2.92–13.61, p < 0.0001]; replication: OR = 6.07 [3.25–11.35, p < 0.0001]; meta-analysis: OR = 6.15 [2.93–9.38, p < 0.0001], no heterogeneity: I2 = 0%, p = 0.95; no publication bias). AUROC associated with the discrimination of the logistic regression models in initial and validation studies were 0.969 (0.930–0.989) and 0.942 (0.878–0.978), respectively, with a pooled AUROC of 0.962 ([0.937–0.987, p < 0.0001], no heterogeneity: I2 = 0%, p = 0.36; and no publication bias). Interpretation: Among patients with cirrhosis, the mSEPT9 test constitutes a promising circulating epigenetic biomarker for HCC diagnosis at the individual patient level. Future prospective studies should assess the mSEPT9 test in the screening algorithm for cirrhotic patients to improve risk prediction and personalized therapeutic management of HCC. Keywords: Cirrhosis, Hepatocellular carcinoma, Circulating cell-free DNA-based epigenetic biomarker, DNA methylation, mSEPT

Cannabis Use Is Inversely Associated with Overweight and Obesity in Hepatitis B Virus-Infected Patients (ANRS CO22 Hepather Cohort)

International audienceBackground: Chronic hepatitis B virus (HBV) infection may evolve into cirrhosis and hepatocellular carcinoma, and this progression may be accelerated by specific risk factors, including overweight and obesity. Although evidence for a protective effect of cannabis use on elevated body weight has been found for other populations, no data are available for HBV-infected patients.Aims: We aimed to identify risk factors (including cannabis use) for overweight and obesity in patients with HBV chronic infection.Methods: Using baseline data from the French ANRS CO22 Hepather cohort, we performed two separate analyses, one using “central obesity” (based on waist circumference) and the other “overweight” and “obesity” (based on body mass index) as outcomes. Logistic and multinomial regressions were used to model central obesity and overweight/obesity, respectively.Results: Among the 3706 patients in the study population, 50.8% had central obesity, 34.7% overweight, and 14.4% obesity. After multivariable adjustment, current cannabis use was associated with a 59% lower risk of central obesity compared with no lifetime use (adjusted odds ratio [95% CI]: 0.41 [0.24 to 0.70]). It was also associated with a 54% and 84% lower risk of overweight (adjusted relative risk ratio [95% CI]: 0.46 [0.27 to 0.76]) and obesity (0.16 [0.04 to 0.67]), respectively.Conclusions: Cannabis use was associated with lower risks of overweight and obesity in patients with HBV chronic infection. Future studies should test whether these potential benefits of cannabis and cannabinoid use translate into reduced liver disease progression in this high-risk population

Similar 5-year HCC occurrence in Tenofovir- and Entecavir-treated HBV chronic infection in the French AFEF/ANRS CO22 Hepather cohort.

International audienceBackground: Chronic hepatitis B virus (HBV) infection results in a high risk of cirrhosis and its complications, cirrhosis decompensation (DC), hepatocellular carcinoma (HCC), liver transplantation (LT), death or any of these outcomes (composite endpoint [CE]). Nucleos(t)ide analogues (NUCs) such as tenofovir or entecavir are associated with a reduction in these complications.Aim: To compare the impact of tenofovir and entecavir on these outcomes in patients treated for HBV infection and included in the prospective Hepather cohort.Methods: All patients with HBV infection who had received tenofovir or entecavir for more than 6 months at or after entry in the ANRS CO22 cohort were selected. Patients with HDV and HCV co-infection or prior liver event were excluded. Incidence rates of events were compared using inverse probability of treatment weighting (IPW).Results: The cohort included 1800 patients (986 tenofovir and 814 entecavir). Median follow-up was 4.2 years. The incidences of HCC, DC, LT, ACD, LRD and CE were not different between tenofovir- (1.8 (0.9; 3.2), 0.6 (0.2; 1.6), 0.2 (0.0; 0.8), 1.7 (0.8; 3.0), 0.8 (0.2, 1.8) and 4.1 (3.0; 5.4) per 1000 person-years) and entecavir-treated patients (1.6 (0.7; 3.0), 0.7 (0.2; 1.8), 0.2 (0.0; 1.0), 3.0 (1.7, 4.8), 0.5 (0.1; 1.5) and 5.0 (3.3; 7.2)) per 1000 person-years, respectively.Conclusion: The risk of liver-related events or death was not different between tenofovir- and entecavir-treated patients in this large prospective cohort of predominantly non-cirrhotic French patients.Trial registration number: NCT019553458

Cannabis Use Is Inversely Associated with Overweight and Obesity in Hepatitis B Virus-Infected Patients (ANRS CO22 Hepather Cohort)

International audienc

Cannabis use as a factor of lower corpulence in hepatitis C-infected patients: results from the ANRS CO22 Hepather cohort

International audienceBackground: Patients with chronic hepatitis C virus (HCV) infection are at greater risk of developing metabolic disorders. Obesity is a major risk factor for these disorders, and therefore, managing body weight is crucial. Cannabis use, which is common in these patients, has been associated with lower corpulence in various populations. However, this relationship has not yet been studied in persons with chronic HCV infection.Methods: Using baseline data from the French ANRS CO22 Hepather cohort, we used binary logistic and multinomial logistic regression models to test for an inverse relationship between cannabis use (former/current) and (i) central obesity (i.e., large waist circumference) and (ii) overweight and obesity (i.e., elevated body mass index (BMI)) in patients from the cohort who had chronic HCV infection. We also tested for relationships between cannabis use and both waist circumference and BMI as continuous variables, using linear regression models.Results: Among the 6348 participants in the study population, 55% had central obesity, 13.7% had obesity according to their BMI, and 12.4% were current cannabis users. After multivariable adjustment, current cannabis use was associated with lower risk of central obesity (adjusted odds ratio, aOR [95% confidence interval, CI]: 0.45 [0.37-0.55]), BMI-based obesity (adjusted relative risk ratio (aRRR) [95% CI]: 0.27 [0.19-0.39]), and overweight (aRRR [95% CI]: 0.47 [0.38-0.59]). This was also true for former use, but to a lesser extent. Former and current cannabis use were inversely associated with waist circumference and BMI.Conclusions: We found that former and, to a greater extent, current cannabis use were consistently associated with smaller waist circumference, lower BMI, and lower risks of overweight, obesity, and central obesity in patients with chronic HCV infection. Longitudinal studies are needed to confirm these relationships and to assess the effect of cannabis use on corpulence and liver outcomes after HCV cure.Trial registration: ClinicalTrials.gov identifier: NCT01953458

Early Hepatocellular Carcinoma Detection Using Magnetic Resonance Imaging Is Cost-Effective in High-Risk Patients with Cirrhosis

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