Real-world efficacy and safety of direct-acting antiviral drugs in patients with chronic hepatitis C and inherited blood disorders

International audienceBackground: Patients with inherited blood disorders (IBLD) have a high risk of hepatitis C virus (HCV) infection. The aim of this work was to assess the efficacy and safety of HCV direct-acting antiviral (DAA)-based treatment in patients with IBLD and chronic HCV infection.Methods : Twenty-seven patients (25 with sickle cell disease, 1 with β-thalassemia and 1 with hemoglobin D-Punjab), including 3 with compensated cirrhosis, were included. They were treated with sofosbuvir in combination with ribavirin, daclatasvir, ledipasvir, or velpatasvir or with grazoprevir/elbasvir for 8 or 12 weeks. In the case of treatment failure, in-vitro assessment of resistance-associated substitutions (RASs) and full-length genome sequence analysis by means of deep sequencing were performed.Results: Treatment was safe and well-tolerated and there were no drug discontinuations due to DAA-related adverse events. Twenty-five out of the 27 patients (93%) achieved sustained virological response 12 weeks post-treatment. One patient discontinued after 18 days due to adverse events unrelated to the antiviral treatment. One patient infected with ‘unusual’ genotype 2 subtype 2m relapsed. Subtype 2m naturally carries the NS5A L31M RAS. In a genotype 2a subgenomic replicon model, L31M increased daclatasvir effective concentration 50% (EC50) by 97-fold, but velpatasvir EC50 by only 3-fold, without altering the replication capacity. This patient was successfully retreated with sofosbuvir/velpatasvir for 12 weeks.Conclusion DAA-based regimens are well tolerated and highly efficacious in patients with chronic hepatitis C and IBLD in the real-world setting. Thus, DAA-based antiviral treatment should be prioritized in this thus far neglected population of HCV-infected patients

Primary resistance of hepatitis B virus to nucleoside and nucleotide analogues

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HCV Ag quantification as a one-step procedure in diagnosing chronic hepatitis C infection in Cameroon: the ANRS 12336 study

International audienceIntroduction: The diagnostic procedure for chronic hepatitis C infection (CHC) usually combines anti-HCV antibody (HCV-Ab) and HCV-RNA measurement. Quantifying HCV core antigen (cAg) as a one-step procedure could shorten the diagnostic process. We aimed to assess the performance of cAg quantification in diagnosing CHC and how it is influenced by concomitant HIV or HBV infections. Methods: The cAg was quantified by an automated assay (Abbott Diagnostics) in 465 HCV-Ab negative serum samples and 544 HCV-RNA positive serum samples (n = 1009) collected in patients from the Pasteur Center in Cameroon, some of whom were infected by HBV or HIV. Its performance was evaluated in comparison to the gold standard (ELISA or PCR) by estimating its sensitivity (Se) and specificity (Sp), and by comparing the area under ROC (AUROC) curves in each patient population: HCV mono-infected, HCV-HBV and HIV-HCV co-infected. Results: Among the 465 HCV-Ab negative patients, 51 and 79 were HIV-and HBV-infected, respectively, whereas among the 544 patients with CHC, 27 and 28 were HIV-and HBV-infected, respectively. The Spearman ρ correlation coefficient between cAg and HCV-RNA was 0.75 (p < 0.00001). The assay had a sensitivity of 95.7% (95% CI: 93.2–97.5) and a specificity of 99.7% (95% CI: 98.1–10) in diagnosing CHC, corresponding to an AUROC of 0.99 (95% CI: 0.98–1.0). Being HIV-or HBV-infected did not impact the performance of cAg (Se = 96.4%, Sp = 96.2% and AUROC = 0.98 (95% CI: 0.95–1.0) in the HBV group, Se = 100%, Sp = 88.2% and AUROC = 0.99 (95% CI: 0.97–1.0) in the HIV group, p between AUROC = 0.69). Conclusions: The cAg quantification displayed a high specificity and sensitivity for the diagnosis of CHC in Cameroon, and its performance was not significantly modified by a concomitant HIV or HBV infection. In the context of CHC elimination on a global scale, using cAg quantification as a screening tool to directly identify CHC could be a reliable tool in a " test and treat " strategy