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

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

International audienc

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old