Direct-acting antivirals for chronic hepatitis C treatment: The experience of two tertiary university centers in Brazil

Abstract

BACKGROUND Hepatitis C virus (HCV) treatment has undergone major changes in recent years. Previous interferon-based therapies have been replaced by oral direct-acting antivirals (DAA) regimens, with high sustained virologic response (SVR) rates, and a lower incidence of adverse events (AEs). AIM To evaluate the efficacy and safety of DAAs for HCV treatment in subjects from two tertiary university centers in Brazil. METHODS This is a multicenter retrospective cohort study of 532 patients with chronic hepatitis C (CHC), undergoing treatment with interferon-free regimens from November 2015 to November 2019. The therapeutic regimen was defined by the current Brazilian guidelines for HCV management at the time of treatment. Demographic, anthropometric, clinical, and laboratory variables were evaluated. SVRs were assessed at 12 to 24 wk after therapy by intention-to-treat (ITT), and modified ITT (m-ITT) analysis. AEs and serious adverse events (SAEs) were registered. In the statistical analysis, a P value of < 0.05 was considered significant. RESULTS The mean age was 56.88 years, with 415 (78.5%) being HCV genotype 1, followed by genotype 3 (20.1%). Moreover, 306 (57.5%) subjects had cirrhosis, and a third of them had decompensated cirrhosis. Sofosbuvir (SOF) plus daclatasvir ± ribavirin was the most frequently used treatment (66.9%), followed by SOF plus simeprevir (21.2%). The overall ITT SVR was 92.6% (493/532), while the m-ITT SVR was 96.8% (493/509). Variables associated with treatment failure via ITT evaluation were hepatic encephalopathy (OR: 4.320; 95%CI: 1.920-9.721, P = 0.0004), presence of esophageal varices (OR: 2.381; 95%CI: 1.137-4.988, P = 0.0215), previous portal hypertensive bleeding (OR: 2.756; 95%CI: 1.173-6.471, P = 0.02), higher model for end-stage liver disease scores (OR: 1.143, 95%CI: 1.060–1.233, P = 0.0005), lower serum albumin levels (OR: 0.528, 95%CI: 0.322-0.867, P = 0.0115), higher serum creatinine (OR: 1.117, 95%CI: 1.056-1.312, P = 0.0033), and international normalized ratio (INR) levels (OR: 5.542, 95%CI: 2.023-15.182, P = 0.0009). AEs were reported in 41.1% (211/514) of patients, and SAEs in 3.7%. The female gender, higher body mass index, esophageal varices, higher INR values, and longer treatment duration were independently associated with AE occurrence. CONCLUSION Treatment with oral DAAs attains a high SVR rate, with fewer SAEs in a real-life cohort of subjects with CHC, from two tertiary university centers in Brazil.

Effectiveness and safety of generic and brand direct acting antivirals for treatment of chronic hepatitis C

“…Similar findings were documented by other investigators and this suggests that the safety profile of both generic and brand DAAs for HCV infection treatment are good. Both the generic and brand DAA formulations resulted in significant changes in the level of serum transaminases and hemoglobin level, and this is consistent with findings of previous studies involving brand or generic DAAs[ 26 - 30 ]. Total bilirubin substantially decreased at 12 wk post treatment[ 17 , 26 , 27 , 30 , 30 ].…”

“…Both the generic and brand DAA formulations resulted in significant changes in the level of serum transaminases and hemoglobin level, and this is consistent with findings of previous studies involving brand or generic DAAs[ 26 - 30 ]. Total bilirubin substantially decreased at 12 wk post treatment[ 17 , 26 , 27 , 30 , 30 ]. ALP, ALT, and gGT all substantially declined at 12 wk post treatment when compared to baseline values in both groups in accordance with previously published reports.…”

The effect of OCT-2 inhibitor Daclatasvir on Metformin pharmacokinetics and pharmacodynamics at two dose levels: A Bayesian approach using Markov-Chain Monte Carlo simulations

“…One of the newly approved DDAs with high-sustained virologic response (SVR) rates is daclatasvir [10]. Daclatasvir is a moderate inhibitor of many membrane transporters, including organic anion transporters-1B1 (OATP1B1) and organic cation transporters (OCTs) 1 and 2 [11][12]. Metformin is known to affect males and females differently, possibly due to the differential expression of OCT2 in the basolateral membrane of renal tubules [13][14][15].…”