New era in treatment options of chronic hepatitis C: focus on safety of new direct-acting antivirals (DAAs)

Abstract

New direct-acting antivirals have changed hepatitis C virus infection management extremely. Areas covered: The pharmacological management of HCV infection and the main characteristics of new DAA therapies have been discussed. In order to analyse safety data regarding DAA therapies, a narrative review was performed searching for safety results of main second generation DAAs pivotal and post-marketing studies. Data on main DAAs drug-drug interactions have also been discussed. Results of main DAAs pivotal studies revealed that these drugs were frequently associated to adverse events such as asthenia, headache, nausea, and insomnia. Although some of post-marketing studies confirmed the good tolerability profile already detected in the pre-marketing phase, real-world safety data showed that second generation DAAs can be associated to cutaneous, metabolic, pulmonary, hepatic, and renal adverse events. Expert opinion: Safety results of pivotal and post-marketing studies indicated that the most recently approved DAAs are well tolerated. However, considering the recent marketing approval of new DAAs, further observational studies and post-marketing surveillance activities will be necessary in order to improve the knowledge of their safety.

Campania Preventability Assessment Committee (Italy): A Focus on the Preventability of Non-steroidal Anti-inflammatory Drugs' Adverse Drug Reactions

“…In fact, it resulted that from 2012 to 2015, the use of NSAIDs in Campania Region was 9.6 (in 2012), 10.2 (in 2013), 11.0 (in 2014), and 10.7 DDD/1000 ab die (in 2015) higher than Italian average (The Medicines Utilisation Monitoring Centre., 2015). According to previous studies on Campania Region spontaneous reporting system (Parretta et al, 2014; Sessa et al, 2015, 2016a,b,c,d; Mascolo et al, 2016, 2017; Rafaniello et al, 2016; Scavone et al, 2016), also for ICSRs reporting NSAIDs, the hospital physicians was the primary source of reports for both preventable and not preventable cases. Interestingly, more than 50% of preventable cases required a hospitalization or prolongation of hospitalization with more than 85% of cases requiring pharmacological and/or non-pharmacological treatments, drug switch or withdrawal to treat ADRs.…”

Rationale for treating hepatitis C virus infection in patients with mild to moderate chronic kidney disease

“…Most RCT of DAA in the general population included patients with normal renal function, and trials for patients with CKD primarily included CKD stage 4 and 5 patients. Therefore, information about treatment safety in CKD patients is based on post marketing and real‐world studies . Recently, many results have been presented at international meetings in abstract format related to this topic.…”

“…Treatment with DAA regimens in HCV patients with mild CKD are highly effective and also appear to slow CKD progression and possibly improve kidney function as well. Although RCT do not report any safety concern regarding kidney function, we should take into account that patients included in these trials have normal kidney function and have gone through a rigorous selection process to include almost “ideal” candidates …”

“…Therefore, information about treatment safety in CKD patients is based on post marketing and real-world studies. 40 Recently, many results have been presented at international meetings in abstract format related to this topic. The TRIO Network reported their real-world experience in 440 patients with chronic HCV infection treated with EBR/GZR.…”

Successful treatment of chronic hepatitis C in a hemodialysis

“…Direct acting antivirals (DAAs) provide shorter treatment duration with higher sustained virological response (SVR) rates, greater efficacy and safety, and less adverse events (AE) in comparison to interferon-based therapy [1]. DAAs can be used in patients with comorbidities, in which interferon-based therapy was unsuccessful or contraindicated [1].…”