Do directly acting antiviral agents for HCV increase the risk of hepatic decompensation and decline in renal function? Results from ERCHIVES

Abstract

Summary Background Directly acting antiviral agents (DAA) have been associated with hepatic decompensation, especially in patients with pre‐treatment cirrhosis, but this risk is not well defined. Aim To determine the incidence of hepatic decompensation, liver transplantation, death and worsening renal function in patients treated with a Paritaprevir/ritonavir, Ombitasvir, Dasabuvir (PrOD), sofosbuvir/simeprevir or sofosbuvir/ledipasvir regimen. Methods We followed ERCHIVES participants treated with the above regimens for up to 12 weeks post‐treatment. We excluded those with HIV, HBsAg+ and pre‐existing diagnosis of hepatic decompensation and hepatocellular carcinoma. Results Of 3728 persons on PrOD, 1578 on sofosbuvir/simeprevir and 10 440 on sofosbuvir/ledipasvir, incidence rates (95% CI) of hepatic decompensation/1000 patient‐years were 10.6 (5.89–17.36) for the PrOD, 32.4 (20.74–48.16) for the sofosbuvir/simeprevir and 13.0 (9.74–17.10) for the sofosbuvir/ledipasvir. Among those with baseline cirrhosis, these rates were 36.9 (19.1–64.5), 61.8 (38.2–94.5) and 41.1 (29.9–55.2) respectively, while among those without cirrhosis at baseline, these rates were 2.7 (0.6–8.0), 7.5 (1.5–21.8) and 2.7 (1.2–5.4). Advanced fibrosis was associated with increased risk of hepatic decompensation in all groups [HR (95% CI) per 0.5 unit increase in FIB‐4 score: PrOD 1.11 (1.07–1.16); sofosbuvir/simeprevir 1.03 (1.01–1.05); sofosbuvir/ledipasvir 1.02 (1.01–1.03)]. There were no deaths. Proportion of persons with eGFR decrease >30 ml/min/1.73 m2 was higher among the PrOD group, but presence of cirrhosis did not appear to affect this. Conclusions The incidence of hepatic decompensation in persons treated with PrOD, up to 12 weeks after completion of treatment, was comparable to those treated with sofosbuvir/ledipasvir regimen, and was lower than among those treated with a sofosbuvir/simeprevir regimen. Such risk was predominantly observed in those with pre‐treatment cirrhosis.

The short‐term incidence of hepatocellular carcinoma is not increased after hepatitis C treatment with direct‐acting antivirals: An ERCHIVES study

“…We conducted a retrospective cohort study among HCV‐infected persons in the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database. ERCHIVES is a large, well‐established national cohort of HCV‐infected and uninfected Veterans and has been described . All HCV‐infected Veterans at any of the nation‐wide Department of Veterans Affairs (VA) medical facilities with a positive HCV antibody test between 2002 and 2016 were identified.…”

N-Acetylcysteine Influence on Oxidative Stress and Cardiac Remodeling in Rats During Transition from Compensated Left Ventricular Hypertrophy to Heart Failure

“…By providing cysteine to glutathione synthesis, NAC replenishes glutathione, which is usually depleted in several disease states [12]. The replenishment of glutathione in deficient cells plays a central role in the effects of NAC as an antioxidant agent [10]. In fact, NAC is probably ineffective in cells replete in glutathione [10].…”

“…The replenishment of glutathione in deficient cells plays a central role in the effects of NAC as an antioxidant agent [10]. In fact, NAC is probably ineffective in cells replete in glutathione [10]. This property is important for antioxidant agents because at appropriate concentrations, reactive oxygen species also have fundamental roles in cellular function [8, 38].…”

“…Glutathione (L-γ glutamyl-cysteinyl-glycine) is an endogenous tripeptide that plays a central role in cellular defense against oxidative stress [9]. It is synthesized and maintained at high concentrations in cells [10]. In heart failure, glutathione redox status changes and its total concentration decreases in myocardium [11, 12].…”

Editorial: is sofosbuvir‐based therapy suitable for patients with advanced chronic kidney disease?

“…Patients with cirrhosis were more likely to have renal function worsening within any treatment group. However, only 1% of the patients in that report had CKD stage 4‐5 …”