Electrophysiological Adverse Effects of Direct Acting Antivirals in Patients With Chronic Hepatitis C

Abstract

Recently, several cases of symptomatic, sometimes fatal bradycardia during the first days of direct-acting antiviral (DAA) (eg, sofosbuvir [SOF]) administration have been reported. We analyzed in detail electrocardiographic (ECG) changes during SOF- or non-SOF-based chronic hepatitis C (CHC) treatment, specifically focusing on bradyarrhythmias. All 39 consecutive patients treated at our center with any interferon-free regimen between June and December 2015 were included in this study (26 SOF-based therapy vs 13 no-SOF interferon-free regimens). ECG tracings were obtained from all patients the first day of treatment and after 7, 14, and 28 days. ECG parameters (P-wave, QRS, QT interval, JT interval, T -T interval duration) were compared between the 2 groups at baseline and at the 3 different time points during antiviral therapy. There were no cases of symptomatic bradycardia/syncope. In the SOF group, QTc duration rose after 1 week (from 424.3 to 431.2 milliseconds; P = .013) and returned to baseline during therapy. QT dispersion dropped since week 1 (from 85.6 to 67.2 milliseconds) and remained significantly reduced until the end of the observation period (72.9 msec) (P = .003). JT dispersion reduced up to week 2 (P = .010) and returned to baseline at week 4; in the no-SOF group, QRS dispersion transiently reduced (from 41 to 34.5 milliseconds, day 7). No other significant changes were observed in the remaining parameters. In CHC patients treated with SOF and other DAAs, ECG parameter changes were mild and/or transient and did not translate into clinically significant electrophysiological effects in the absence of amiodarone coadministration.

Virological and Clinical Outcome of DAA Containing Regimens in a Cohort of Patients in Calabria Region (Southern Italy)

“…All these characteristics (advanced age, comorbidities, and high burden of comedications) could potentially affect tolerability of HCV treatment and adherence in this subgroup [7]. Moreover, some possible side effects and biomarker alterations, as well as increased risk of liver cancer, have been reported by several authors, especially in elderly people [8][9][10][11][12][13]. In addition, the presence of some side effects was in particular reported among those who had concurrent comorbidities (such as liver cirrhosis, cardiac failure, and advanced age) [14,15].…”

Assessing the impact of a combination of sofosbuvir and daclatasvir treatment for hepatitis C virus infection on heart rate, rhythm and heart rate variability using 24-hour ECG monitoring

“…Such changes were not clinically significant, and no cases of symptomatic bradycardia or syncope were reported. All patients in this study did not receive amiodarone or other medications affecting heart rate [19].…”

Electrophysiological Adverse Effects of Direct-Acting Antivirals in Patients With Chronic Hepatitis C

“…We read with great interest the article by Durante‐Mangoni et al . Sofosbuvir (SOF) has recently been correlated with bradyarrhythmias, especially if coadministered with amiodarone.…”

“…We read with great interest the article by Durante-Mangoni et al 1 Sofosbuvir (SOF) has recently been correlated with bradyarrhythmias, especially if coadministered with amiodarone. In this study, Durante-Mangoni et al assessed several electrocardiographic (ECG) parameters in 26 subjects who were consecutively treated with various SOF-based regimens.…”