Patient-reported symptoms during and after direct-acting antiviral therapies for chronic hepatitis C: The PROP UP study.

A comprehensive analysis of changes in symptoms and functioning during and after direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection has not been conducted for patients treated in real-world clinical settings. Therefore, we evaluated patient-reported outcomes (PROs) in a diverse cohort of patients with HCV treated with commonly prescribed DAAs. PROP UP is a US multicenter observational study of 1,601 patients with HCV treated with DAAs in 2016-2017. PRO data were collected at baseline (T1), early on-treatment (T2), late on-treatment (T3) and 3-months post-treatment (T4). PRO mean change scores were calculated from baseline and a minimally important change (MIC) threshold was set at 5%. Regression analyses investigated patient and treatment characteristics independently associated with PRO changes on-treatment and post-treatment. Of 1,564 patients, 55% were male, 39% non-white, 47% had cirrhosis. Sofosbuvir/ledipasvir was prescribed to 63%, sofosbuvir/velpatasvir to 21%, grazoprevir/elbasvir to 11%, and paritaprevir/ombitasvir/ritonavir + dasabuvir to 5%. During DAA therapy, mean PRO scores improved slightly in the overall cohort, but did not reach the 5% MIC threshold. Between 21-53% of patients experienced >5% improved PROs while 23-36% experienced >5% worse symptoms. Of 1,410 patients with evaluable sustained virologic response (SVR) data, 95% achieved SVR. Among those with SVR, all mean PRO scores improved, with the 5% MIC threshold met for fatigue, sleep disturbance, and functioning well-being. Regression analyses identified subgroups, defined by age 35-55, baseline mental health issues and a higher number of health comorbidities as predictors of PRO improvements. In real-world clinical practices, we observed heterogeneous patient experiences during and after DAA treatment. Symptom improvements were more pronounced in younger patients, those with baseline mental health issues and multiple comorbidities. Patients who received direct-acting antiviral medications for hepatitis C at several liver centers in the US did not generally experience significant changes in baseline symptoms during treatment. We observed a full range of patient experiences with some patients experiencing substantial symptom improvements, yet others experiencing less improvements and some even experiencing a worsening of symptoms. The 1,346 patients who were cured of hepatitis C experienced improvements in fatigue, sleep disturbance, and functional well-being, and trends for improved pain and depression; whereas the 64 who were not cured experienced minimal improvements. Clinicaltrial.gov: NCT02601820.

Evon DM ，Sarkar S ，Amador J ，Lok AS ，Sterling RK ，Stewart PW ，Reeve BB ，Serper M ，Reau N ，Rajender Reddy K ，Di Bisceglie AM ，Nelson DR ，Golin CE ，Lim JK ，Fried MW ... -  《-》

High efficacy of resistance-guided retreatment of HCV patients failing NS5A inhibitors in the real world.

Pérez AB ，Chueca N ，García-Deltoro M ，Martínez-Sapiña AM ，Lara-Pérez MM ，García-Bujalance S ，Aldámiz-Echevarría T ，Vera-Méndez FJ ，Pineda JA ，Casado M ，Pascasio JM ，Salmerón J ，Alados-Arboledas JC ，Poyato A ，Téllez F ，Rivero-Juárez A ，Merino D ，Vivancos-Gallego MJ ，Rosales-Zábal JM ，García F ，GEHEP-004 Study Group ... -  《-》

Efficacy and safety of direct-acting antiviral agents for HCV in mild-to-moderate chronic kidney disease.

The advent of direct-acting antiviral agents promises to change the management of hepatitis C virus infection (HCV) in patients with chronic kidney disease (CKD), a patient group in which the treatment of hepatitis C was historically challenging. We investigated the safety and efficacy of all-oral, interferon-free direct-acting antiviral agents for the treatment of hepatitis C in a 'real-world' cohort of patients with CKD. We performed an observational single-arm multi-centre study in a large (n=198) cohort of patients with stage 1-3 CKD who underwent antiviral therapy with DAAs for the treatment of HCV. The primary end-point was sustained virologic response (serum HCV RNA <15IU/mL, 12 weeks after treatment ended) (SVR12). We collected data on on-treatment adverse events (AEs), severe AEs, and laboratory abnormalities. The average baseline eGFR (CKD-EPI equation) was 70.06±20.1mL/min/1.72m2; the most common genotype was HCV 1b (n=93, 51%). Advanced liver scarring was found in 58 (46%) patients by transient elastography. Five regimens were adopted: elbasvir/grazoprevir (n=5), glecaprevir/pibrentasvir (n=4), ritonavir-boosted paritaprevir/ombitasvir/dasabuvir (PrOD) regimen (n=40), simeprevir±daclatasvir (n=2), and sofosbuvir-based combinations (n=147). The SVR12 rate was 95.4% (95% CI, 93.8%; 96.8%). There were nine virological failures - eight being relapsers. Adverse events occurred in 30% (51/168) of patients, and were managed clinically without discontinuation of therapy or hospitalization. One of the most common AEs was anaemia (n=12), which required discontinuation or dose reduction of ribavirin in some cases (n=6); deterioration of kidney function occurred in three (1.7%). All-oral, interferon-free therapy with DAAs for chronic HCV in mild-to-moderate CKD was effective and well-tolerated in a 'real-world' clinical setting. Studies are in progress to address whether sustained viral response translates into better survival in this population.

Ridruejo E ，Garcia-Agudo R ，Mendizabal M ，Aoufi-Rabih S ，Dixit V ，Silva M ，Fabrizi F ... -  《-》

Direct-acting antivirals for the treatment of hepatitis C virus infection: optimizing current IFN-free treatment and future perspectives.

There has been a revolution in the treatment of chronic hepatitis C. Several oral regimens combining direct-acting antivirals (DAAs) from different families [NS5B nucleotide inhibitors, NS5B non-nucleoside inhibitors, NS5A replication complex inhibitors and NS3/4A protease inhibitors (PI)] have been developed. These regimens result in an increase in sustained virological response (SVR) rates to above 90% and reduce the duration of treatment to 12 weeks or less. As of 2016 several regimens will be approved with additive potencies, without cross-resistance and with a good safety profile. Remaining issues will include increasing screening and access to care so that HCV may become the first chronic viral infection eradicated worldwide. This review summarizes results obtained with oral DAA combinations that have been approved and/or have completed phase 3 clinical trials for HCV infection and discusses future perspectives.

Asselah T ，Boyer N ，Saadoun D ，Martinot-Peignoux M ，Marcellin P ... -  《-》

Effect of Paritaprevir/Ritonavir/Ombitasvir/Dasabuvir and Ledipasvir/Sofosbuvir Regimens on Survival Compared With Untreated Hepatitis C Virus-Infected Persons: Results From ERCHIVES.

Interferon-based regimens are associated with a substantial survival benefit for persons infected with hepatitis C virus (HCV). Survival data with direct-acting antiviral agents are not available. We conducted this study to quantify the effect of paritaprevir/ritonavir, ombitasvir, dasabuvir (PrOD) and ledipasvir/sofosbuvir (LDV/SOF) regimens upon mortality. In the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), a well-established national cohort of HCV-infected Veterans, we identified HCV-infected persons initiated on PrOD or LDV/SOF, excluding those with human immunodeficiency virus, hepatitis B surface antigen positivity, hepatocellular carcinoma, or missing HCV RNA or FIB-4 scores. For each case, we identified a propensity score-matched control never initiated on treatment. Primary outcome was survival. Outcomes were assessed using frequency of events, Kaplan-Meier curves, and Cox proportional hazards regression analyses. We identified 1473 persons on PrOD, 5497 on LDV/SOF, and 6970 propensity score-matched untreated persons. Treated persons were more likely to be obese and have cirrhosis, but less likely to have stage 3-5 chronic kidney disease (CKD), alcohol or drug abuse or dependence diagnosis, and anemia. The proportion of persons who died was higher in the untreated group compared with either treatment group (PrOD, 0.3%; LDV/SOF, 1.4%; untreated controls, 2.5%; P < .001). A significantly larger percentage of treated patients survived to 18 months of follow-up, compared with untreated controls (P < .001). In multivariable Cox regression analysis, treatment with either regimen (hazard ratio [HR], 0.43; 95% confidence interval [CI], .33-.57) and attainment of sustained virologic response (SVR) were associated with significantly lower mortality (HR, 0.57; 95% CI, .33-.99). Treatment with PrOD or LDV/SOF and SVR are associated with a significant mortality benefit, apparent within the first 18 months of treatment.

Butt AA ，Yan P ，Simon TG ，Abou-Samra AB ... -  《-》