‘Real-life’ experience with direct-acting antiviral agents for HCV after kidney transplant

Introductions and Objectives: The introduction of direct-acting antiviral (DAA) agents promises to change dramatically the management of hepatitis C in kidney transplant recipients, a patient group where the treatment of hepatitis C is historically challenging. The purpose of the current study was to assess (in a ‘real-life’ setting) the safety and efficacy of all-oral, interferon-free, direct-acting antiviral agents in kidney transplant recipients with HCV. Material and Methods: We performed a single-arm, multi-center study in a cohort (n = 95) of kidney transplant recipients who underwent antiviral therapy with DAAs. The primary end-point was sustained virologic response (SVR) (serum HCV RNA < 15 IU/mL, 12 weeks after treatment ended; SVR12). We recorded data on on-treatment adverse events (AEs), serious AEs, and laboratory abnormalities. Results: Various regimens were adopted at the discretion of the treating physician: elbasvir/grazoprevir (n = 11), paritaprevir/ritonavir/ombitasvir/dasabuvir (PrOD) regimens ± ribavirin (n = 23), and sofosbuvirbased regimens ± ribavirin (n = 61). The SVR12 rate was 93.7% (89/95) (95% CI, 88%; 98%), according to intention-to-treat analysis; three patients without viral response (n = 3) were found. Ribavirin was administered in 8 (8.4%) allograft recipients. The frequency of drop-outs was 4.2% (4/95) (95% CI, 0.2%; 8.2%); these were related to arthralgia/myalgia (n = 2), fatigue (n = 1), and lowered estimated glomerular filtration rate (eGFR) (n = 1). There were no differences with regard to serum creatinine and eGFR before and after antiviral therapy and during follow-up in the whole cohort. The patient who interrupted antiviral treatment due to raised serum creatinine was on sofosbuvir/daclatasvir regimen; one of the four dropouts obtained SVR. Conclusions: All-oral, interferon-free therapy with DAAs for chronic HCV after kidney transplantation was effective and well-tolerated in a ‘real–life’ clinical setting. Identical results have been observed in patients with intact kidneys or advanced chronic kidney disease. Careful evaluation of kidney function over follow-up in kidney transplant recipients who received DAAs regimens is recommended. Clinical trials aimed to assess whether sustained viral response translates into improved patient/graft survival are under way

Disease progression in patients with hepatitis C virus infection treated with direct-acting antiviral agents

Background & Aims Little is known about how a sustained virologic response (SVR) to treatment of hepatitis C virus infection with direct-acting antivirals (DAAs) affects patient mortality and development of new liver-related events. We aimed to evaluate the incidence of disease progression in patients treated with DAAs. Methods We performed a prospective multicenter cohort study of 1760 patients who received DAA treatment at 23 hospitals in Latin America, from May 1, 2016, through November 21, 2019. We excluded patients with a history of liver decompensation, hepatocellular carcinoma (HCC), or solid-organ transplantation. Disease progression after initiation of DAA therapy included any of the following new events: liver decompensation, HCC, liver transplantation, or death. Evaluation of variables associated with the primary outcome was conducted using a time-dependent Cox proportional hazards models. Results During a median follow-up period of 26.2 months (interquartile range, 15.3–37.5 mo), the overall cumulative incidence of disease progression was 4.1% (95% CI, 3.2%–5.1%), and after SVR assessment was 3.6% (95% CI, 2.7%–4.7%). Baseline variables associated with disease progression were advanced liver fibrosis (hazard ratio [HR], 3.4; 95% CI, 1.2–9.6), clinically significant portal hypertension (HR, 2.1; 95% CI, 1.2–3.8), and level of albumin less than 3.5 mg/dL (HR, 4.1; 95% CI, 2.3–7.6), adjusted for SVR achievement as a time covariable. Attaining an SVR reduced the risk of liver decompensation (HR, 0.3; 95% CI, 0.1–0.8; P = .016) and de novo HCC (HR, 0.2; 95% CI, 0.1%–0.8%; P = .02) in the overall cohort. Conclusions Treatment of hepatitis C virus infection with DAAs significantly reduces the risk of new liver-related complications and should be offered to all patients, regardless of disease stage

Decompensated cirrhosis and liver transplantation negative lyimpact in DAA treatment response : real-world experience from HCV-LALREAN cohort

Introduction: Although the effectiveness of directacting antivirals (DAAs) for thetreatment of chronic hepatitis C virus (HCV) has been reported in realworldsettings, predictive factors of treatment failure are lacking. Therefore, we sought toexplore the baseline predictors of treatment response to DAAs.Methods: This was a prospective multicenter cohort study from the Latin AmericanLiver Research Educational and Awareness Network (LALREAN) including patientswho received DAA treatment from May 2016 to April 2019. A multivariate logisticregression model was conducted to identify variables associated with unachievedsustained virological response (SVR), defined as treatment failure (odds ratios [OR]and 95% confidence intervals [CIs]).Results: From 2167 patients (55.2% with cirrhosis) who initiated DAA therapy,89.4% completed a full course treatment (n = 1938). Median treatment duration was12 weeks, and 50% received ribavirin. Definitive suspension due to intolerance orother causes was observed in only 1.0% cases (n = 20). Overall nonSVR12 was 4.5%(95% CI, 3.55.7). There were no significant differences in treatment failureaccording to HCV genotypes and the degree of fibrosis. Independently associatedvariables with DAA failure were liver function impairment according to theChildPugh score B OR, 2.09 (P = .06), ChildPugh C OR, 11.7 (P < .0001); and livertransplant (LT) recipient OR, 3.75 (P = .01).Conclusion: In this reallife setting, higher DAA treatment failure rates were ob-served in patients with decompensated cirrhosis and in LT recipients. These pre-dictive baseline factors should be addressed to individualize the appropriatetimepoint of DAA treatmen