Hepatitis B infection in HIV-1-infected patients receiving highly active antiretroviral therapy in Lomé, Togo: Prevalence and molecular consequences

Background. No data are available on HIV/hepatitis B virus (HBV) or hepatitis C virus coinfection in Togo, and patients are not routinely tested for HBV infection.Objectives. To determine the prevalence of HBV and the risk of HBV drug resistance during antiretroviral treatment in HIV-coinfected patients in Togo.Method. This cross-sectional study was carried out in Lomé, Togo, from January 2010 to December 2011 among HIV-infected patients who had been on antiretroviral therapy (ART) for at least 6 months.Results. In total, 1 212 patients (74.9% female) living with HIV/AIDS and treated with ART were included in the study. The seroprevalence of hepatitis B surface antigen (HBsAg) was 9.7% (117/1 212; 95% confidence interval (CI) 8.04 - 11.45). Of these 117 HBsAg-positive patients, 16 (13.7%) were hepatitis B e antigen (HBeAg)-positive, and 115 (98.3%) were on lamivudine. The HBV DNA load was >10 IU/ mL in 33/117 patients overall (38%), and in 87.5% of 16 HBeAg positive patients (p<0.0001). In multivariate analysis, factors associated with HBV DNA load >10 IU/mL were HBeAg positivity (adjusted odds ratio (aOR) 6.4; p=0.001) and a higher level of education (aOR 6.5; p=0.026). The prevalence of HBV resistance to lamivudine was 13.0% (15/115; 95% CI 7.0 - 19.0). The detected resistance mutations were rtL180M (14/15 patients) and rtM204V/I (15/15).Conclusion. The seroprevalence of HBV among ART-treated HIV-infected patients in Togo was 9.7%. The prevalence of HBV lamivudine resistance mutations after 2 years of ART was 13.0%. These results suggest that HBV screening before ART initiation can be based on HBsAg testing

Burden of liver disease progression in hospitalized patients with type 2 diabetes mellitus

BACKGROUND AND AIMS: There are uncertainties on the burden of liver disease in patients with type-2 diabetes (T2D). METHODS: We measured adjusted hazard ratios of liver disease progression to hepatocellular cancer and/or decompensated cirrhosis in a 2010-2020 retrospective, bicentric, longitudinal, cohort of 52,066 hospitalized patients with T2D. RESULTS: Mean age was 64±14 years and 58% were men. Alcohol use disorders accounted for 57% of liver-related complications and were associated with all liver-related risk factors. Non-metabolic liver-related risk factors accounted for 37% of the liver burden. T2D control was not associated with liver disease progression. The incidence (95% confidence interval) of liver-related complications and of competing mortality were 3.9 (3.5-4.3) and 27.8 (26.7-28.9) per 1000 person-years at risk, respectively. The cumulative incidence of liver disease progression exceeded the cumulative incidence of competing mortality only in the presence of a well-identified risk factors of liver disease progression, including alcohol use. The incidence of hepatocellular cancer was 0.3 (95% CI, 0.1-0.5) per 1000 person-year in patients with obesity and it increased with age. The adjusted hazard ratios of liver disease progression were 55.7 (40.5-76.6), 3.5 (2.3-5.2), 8.9 (6.9-11.5), and 1.5 (1.1-2.1), for alcoholic liver disease, alcohol use disorders without alcoholic liver disease, non-metabolic liver-related risk factors, and obesity, respectively. The attributable fractions of alcohol use disorders, non-metabolic liver risk-related risk factors, and obesity to the liver burden were 55%, 14%, and 7%, respectively. CONCLUSIONS: In this analysis of data from two hospital-based cohorts of patients with T2D, alcohol use disorders, rather than obesity, contributed to most of the liver burden. These results suggest that patients with T2D should be advised to drink minimal amounts of alcohol. LAY SUMMARY: • There is uncertainty on the burden of liver-related complications in patients with type-2 diabetes • We studied the risks of liver cancer and complications of liver disease in over 50,000 patients with type-2 diabetes • We found that alcohol was the main factor associated with complications of liver disease • This finding has major implications on the alcohol advice given to patients with type-2 diabetes

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Effect of resistance-associated substitutions on retreatment of direct acting antiviral-exposed patients in the real-world setting (ANRS CO22 HEPATHER)

International audienceRe-treatment of patients with decompensated chronic hepatitis C virus cirrhosis using 24 weeks of sofosbuvir and NS5A inhibitor, with or without ribavirin after failing a 12 week cours

Anti-HBV DNA vaccination does not prevent relapse after discontinuation of analogues in the treatment of chronic hepatitis B: a randomised trial—ANRS HB02 VAC-ADN

International audienceObjective: The antiviral efficacy of nucleos(t)ide analogues whose main limitation is relapse after discontinuation requires long-term therapy. To overcome the risk of relapse and virological breakthrough during long-term therapy, we performed a phase I/II, open, prospective, multicentre trial using a HBV envelope-expressing DNA vaccine.Design: 70 patients treated effectively with nucleos(t)ide analogues for a median of 3 years (HBV DNA 120 IU/mL) or impossibility of stopping treatment at week 48.Results: Reactivation occurred in 97% of each group after a median 28 days without liver failure but with an HBV DNA <2000 IU/mL in 33%; 99% of adverse reactions were mild to moderate. Immune responses were evaluated by enzyme-linked immunosorbent spot and proliferation assays: there was no difference in the percentage of patients with interferon-γ secreting cells and a specific T-cell proliferation to HBcAg but not to HBsAg after reactivation in each group.Conclusions: Although it is fairly well tolerated, the HBV DNA vaccine does not decrease the risk of relapse in HBV-treated patients or the rate of virological breakthrough, and does not restore the anti-HBV immune response despite effective viral suppression by analogues

Reporter gene assay for the quantification of the activity and neutralizing antibody response to TNFα antagonists.

A cell-based assay has been developed for the quantification of the activity of TNFα antagonists based on human erythroleukemic K562 cells transfected with a NFκB regulated firefly luciferase reporter-gene construct. Both drug activity and anti-drug neutralizing antibodies can be quantified with a high degree of precision within 2h, and without interference from cytokines and other factors known to activate NFκB. The assay cells also contain the Renilla luciferase reporter gene under the control of a constitutive promoter that allows TNFα-induced firefly luciferase activity to be normalized relative to Renilla luciferase expression. Thus, results are independent of cell number or differences in cell viability, resulting in intra and inter assay coefficients of variation of 10% or less. Normalization of results relative to the expression of an internal standard also provides a means for correcting for serum matrix effects and allows residual drug levels or anti-drug neutralizing antibodies to be quantified even in serum samples with a relatively high degree of cytotoxicity