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The effectiveness of a 12-week course of sofosbuvir-ledipasvir in treatment-experienced HCV genotype 1b-infected patients with cirrhosis is still under debate. Our primary endpoint was to compare the sustained virological response at post-treatment week 12 ( SVR12) of sofosbuvir-ledipasvir in combination with ribavirin for 12 weeks, and sofosbuvir-ledipasvir alone for 24 weeks. This was a prospective observational study that enrolled 424 (195 naive, 229 experienced; 164 treated for 12 weeks with Ribavirin and 260 with sofosbuvir-ledipasvir alone for 24 weeks) consecutive HCV genotype 1b-infected patients with cirrhosis. The SVR12 rates were 93.9% and 99.2% in patients treated for 12 and 24 weeks, respectively ( P = .002). The baseline characteristics of patients treated for 12 weeks were significantly different from those treated for 24 weeks as regards their younger age ( P = .002), prevalence of Child-Pugh class A ( P = .002), lower MELD scores ( P = .001) and smaller number of nonresponders ( P = .04). The shorter treatment was significantly associated with a lower SVR12 in univariate and multivariate analyses ( P = .007 and P = .008, respectively). The SVR rate was unaffected by age, gender, BMI, Child-Pugh class, MELD score or previous antiviral treatment. Patients receiving ribavirin experienced more episodes of ascites and headache but less recurrence of hepatocellular carcinoma ( HCC), and were prescribed more diuretics and cardiopulmonary drugs. No patient discontinued treatment. The therapeutic regimen of sofosbuvir-ledipasvir plus ribavirin administered for 12 weeks was less effective than sofosbuvir-ledipasvir alone given for 24 weeks. At odds with European guidelines, the recommended 12-week treatment with sofosbuvir-ledipasvir alone might be suboptimal for this setting of patients. [ABSTRACT FROM AUTHOR]

In 2016, the Global Health Sector Strategy, ratified by the 69th World Health Assembly, set the ambitious goal of eliminating hepatitis C virus (HCV) and hepatitis B virus infections by 2030, emphasizing the importance of national screening programmes. Achieving this goal depends on each country's ability to identify and treat 80% of chronic hepatitis C cases, a critical threshold set by the World Health Organization. Traditionally, estimates of HCV prevalence have been based on interferon era studies that focused on high-risk subgroups rather than the general population. In addition, the incomplete data available from national registries also limited the understanding of HCV prevalence. The 2016 report from the European Centre for Disease Prevention and Control highlighted that HCV rates varied across European counties, ranging from .1% to 5.9%. However, data were only available for 13 countries, making the overall picture less clear. Additionally, the epidemiological data may have underestimated the true burden of HCV due to lack of awareness among those with chronic infection. The main objective of this review is to provide a comprehensive summary of HCV epidemiology in Europe in the current era of direct-acting antivirals (DAAs). The data included in the analysis range from the end of 2013 to December 2023 and have been categorised according to the United Nations Geoscheme. The resulting synthesis underscores the noteworthy impact of DAA treatment on the epidemiological situation., (© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.)

Background & Aims: Despite the excellent efficacy of direct-acting antivirals (DAA) reported in clinical trials, virological failures can occur, often associated with the development of resistance-associated substitutions (RASs). This study aimed to characterize the presence of clinically relevant RASs to all classes in real-life DAA failures., Methods: Of the 200 virological failures that were analyzed in 197 DAA-treated patients, 89 with pegylated-interferon+ribavirin (PegIFN+RBV) and 111 without (HCV-1a/1b/1g/2/3/4=58/83/1/6/24/25; 56.8% treatment experienced; 65.5% cirrhotic) were observed. Sanger sequencing of NS3/NS5A/NS5B was performed by home-made protocols, at failure (N=200) and whenever possible at baseline (N=70)., Results: The majority of the virological failures were relapsers (57.0%), 22.5% breakthroughs, 20.5% non-responders. RAS prevalence varied according to IFN/RBV use, DAA class, failure type and HCV genotype/subtype. It was 73.0% in IFN group vs 49.5% in IFN free, with the highest prevalence of NS5A-RASs (96.1%), compared to NS3-RASs (75.9% with IFN, 70.5% without) and NS5B-RASs (66.6% with IFN, 20.4% without, in sofosbuvir failures). In the IFN-free group, RASs were higher in breakthrough/non-responders than in relapsers (90.5% vs 40.0%, P<.001). Interestingly, 57.1% of DAA IFN-free non-responders had a misclassified genotype, and 3/4 sofosbuvir breakthroughs showed the major-RAS-S282T, while RAS-L159F was frequently found in sofosbuvir relapsers (18.2%). Notably, 9.0% of patients showed also extra target RASs, and 47.4% of patients treated with ≥2 DAA classes showed multiclass resistance, including 11/11 NS3+NS5A failures. Furthermore, 20.0% of patients had baseline-RASs, which were always confirmed at failure., Conclusions: In our failure setting, RAS prevalence was remarkably high in all genes, with a partial exception for NS5B, whose limited resistance is still higher than previously reported. This multiclass resistance advocates for HCV resistance testing at failure, in all three genes for the best second-line therapeutic tailoring., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)