Changes in characteristics of patients with hepatitis C virus-related cirrhosis from the beginning of the interferon-free era

BACKGROUND Nearly 290000 patients with chronic hepatitis C die annually from the most severe complications of the disease.One of them is liver cirrhosis,which occurs in about 20%of patients chronically infected with the hepatitis C virus(HCV).Direct-acting antivirals(DAAs),which replaced interferon(IFN)-based regimens,significantly improved the prognosis of this group of patients,increasing HCV eradication rates and tolerability of therapy.Our study is the first to assess changes in patient profile,effectiveness,and safety in the HCV-infected cirrhotic population in the IFN-free era.AIM To document changes in patient characteristics and treatment regimens along with their effectiveness and safety profile over the years.METHODS The studied patients were selected from 14801 chronically HCV-infected individuals who started IFN-free therapy between July 2015 and December 2021 in 22 Polish hepatology centers.The retrospective analysis was conducted in real-world clinical practice based on the EpiTer-2 multicenter database.The measure of treatment effectiveness was the percentage of sustained virologic response(SVR)calculated after excluding patients lost to follow-up.Safety data collected during therapy and the 12-wk post-treatment period included information on adverse events,including serious ones,deaths,and treatment course.RESULTS The studied population(n=3577)was balanced in terms of gender in 2015-2017,while the following years showed the dominance of men.The decline in the median age from 63 in 2015-2016 to 61 years in 2021 was accompanied by a decrease in the percentage of patients with comorbidities and comedications.Treatment-experienced patients dominated in 2015-2016,while treatment-naive individuals gained an advantage in 2017 and reached 93.2%in 2021.Genotype(GT)-specific options were more prevalent in treatment in 2015-2018 and were supplanted by pangenotypic combinations in subsequent years.The effectiveness of the therapy was comparable regardless of the period analyzed,and patients achieved an overall response rate of 95%,with an SVR range of 72.9%-100%for the different therapeutic regimens.Male gender,GT3 infection,and prior treatment failure were identified as independent negative predictors of therapeutic success.CONCLUSION We have documented changes in the profile of HCV-infected cirrhotic patients over the years of accessibility to changing DAA regimens,confirming the high effectiveness of IFN-free therapy in all analyzed periods.

European Association for the Study of the Liver and French hepatitis C recent guidelines: The paradigm shift

The latest Association Fran?aise pour l'Etude du Foie-French Association for Study of the Liver(AFEF) and European Association for the Study of the Liver(EASL) recommendations announce a change of paradigm, for the management of patients infected with hepatitis C virus(HCV). The AFEF recommendations focus on the elimination of HCV infection on a national level by preventing reinfection, in less than ten years. This goal involves the facilitation of patients' management in a simplified pathway by increasing screening procedures and access to pangenotypic treatments mainly in the "reservoir" population of people who inject drugs and migrants. Even in the complex pathway of patients with previous comorbidities, AFEF takes the option of a therapeutic simplification. The EASL guidelines position themselves on the state of the art with a precise description of all therapeutic options available, without separating simplified and complex pathways even if they take into account the epidemiological evolution of difficult-to-treat populations.

Genotype 3-hepatitis C virus’last line of defense

Chronic infection with hepatitis C virus(HCV)is one of the leading causes of liver disease globally,affecting approximately 71 million people.The majority of them are infected with genotype(GT)1 but infections with GT3 are second in frequency.For many years,GT3 was considered to be less pathogenic compared to other GTs in the HCV family due to its favorable response to interferon(IFN)-based regimen.However,the growing evidence of a higher rate of steatosis,more rapid progression of liver fibrosis,and lower efficacy of antiviral treatment compared to infection with other HCV GTs has changed this conviction.This review presents the specifics of the course of GT3 infection and the development of therapeutic options for GT3-infected patients in the era of direct-acting antivirals(DAA).The way from a standard of care therapy with pegylated IFNalpha(pegIFNα)and ribavirin(RBV)through a triple combination of pegIFNα+RBV and DAA to the highly potent IFN-free pangenotypic DAA regimens is discussed along with some treatment options which appeared to be dead ends.Although the implementation of highly effective pangenotypic regimens is the most recent stage of revolution in the treatment of GT3 infection,there is still room for improvement,especially in patients with liver cirrhosis and those who fail to respond to DAA therapies,particularly those containing inhibitors of HCV nonstructural protein 5A.

Best therapy for the easiest to treat hepatitis C virus genotype 1binfected patients

BACKGROUND The revolution in treatment of patients with chronic hepatitis C virus(HCV)infection dates back to the introduction of direct-acting antivirals(DAAs).The increase in efficacy was most pronounced in patients infected with genotype(GT)1b,as this was the most poorly responsive population to treatment during the interferon era.AIM To identify the most effective interferon-free therapy for GT1b-infected patients and to determine positive and negative predictors of virological response.METHODS This real-world retrospective analysis included patients chronically infected with GT1b HCV whose data were obtained from the multicenter observational EpiTer-2 database.Treatment effectiveness was evaluated for each therapeutic regimen as the percentage of sustained virological responses(SVR).Assessment of the safety was based on the evaluation of the course of therapy,the occurrence of adverse events including serious ones,deaths during treatment and in the post 12-wk follow-up period.RESULTS The studied population consisted of 11385 patients with a mean age of 53±14.8 years and a female predominance(53.4%).The majority of them were treatment-naïve(74.6%)and patients with cirrhosis accounted for 24.3%.Of the DAA regimens used,76.9%were GT-specific with ombitasvir/paritaprevir/ritonavir+dasabuvir±ribavirin being the most used option(32.4%).A total of 10903 patients responded to treatment resulting in a 98.1%in the per-protocol analysis after excluding 273 patients without SVR data.The effectiveness of all regimens exceeded 90%and the highest SVR of 98.9%was achieved in patients treated with a combination of glecaprevir/pibrentasvir.Logistic regression analyses showed that the virologic response was independently associated with female sex[odds ratio(OR)=1.67],absence of decompensated cirrhosis at baseline(OR=2.42)and higher baseline platelets(OR=1.004 per 1000/μL increase),while the presence of human immunodeficiency virus(HIV)coinfection significantly decreased the odds of response(OR=0.39).About 95%-100%of patients completed therapy irrespective of the drug regimen.At least one adverse effect occurred in 10.9%-36.3%and most of them were mild.No treatment related deaths have been reported.CONCLUSION We documented very high effectiveness and a good safety profile across all DAA regimens.Positive predictors of SVR were female sex,absence of decompensated cirrhosis at baseline and higher platelet count while HIV coinfection reduced the effectiveness.