Background The recent development of new drugs has changed radically the treatment of chronic hepatitis C virus (HCV) infection, from interferon (IFN) based treatments to treatments based on direct acting antivirals (DAA). These drugs are thought to be better tolerated but data are still preliminary.

Purpose The aim of this study was to evaluate the safety of DAA based treatment of HCV in clinical practice.

Material and methods An observational, descriptive and prospective study was performed on monoinfected patients who had started DAA based treatments (free IFN) between January 2014 and September 2015 (minimum 8 week follow-up period).

Variables: demographic and baseline clinical data; selected DAA combinations (DCV: daclatasvir; DSV: dasabuvir; SMV: simeprevir; SOF: sofosbuvir; SOF/LDV: sofosbuvir/ledipasvir; OTP/PTV/r: ombitasvir/paritaprevir/ritonavir; RBV: ribavirina); adverse drug events (ADE) according to the Common Terminology Criteria for Adverse Events Classification (CTCAEv4), discontinued treatments; and deaths.

Results 499 patients enrolled; genotype 1, 87.4%; men, 62.1%; average age, 58.8 years (SD 11.1); grade of fibrosis, F4 (55.9%), F3 (16.0%) and F2 (21.4%); and decompensated cirrhosis, 9.8%. Major DAA combinations selected: DSV+OTP/PTV/r±RBV, 60.3% and SOF/LDV±RBV, 24.1%.

Serious ADE (grade 3/4): DSV+OTP/PTV/r±RBV, 22 patients (7.3%): hyperbilirubinaemia (9), fatigue (3), confusion (2), itching (2), anaemia (2), vomiting, diarrhoea, sleep disorders and dyspnoea; SOF/LDV±RBV, 10 patients (8.3%): hyperbilirubinaemia (3), fatigue (3), headache, diarrhoea, muscle pain and dry skin; SOF+DCV±RBV, 6 patients (20.7%): hyperbilirubinaemia (5) and sleep disorders; SOF+SMV±RBV, 5 patients (13.9%): hyperbilirubinaemia (5).

Rare ADE: DSV+OTP/PTV/r±RBV (4): acute hepatitis, priapism, sweating and syncope; SOF/LDV±RBV (2): erythroderma, significant weakness of low members and general deterioration.

Discontinued treatment: 7 patients discontinued treatment (1.4%), in treatment with different DAA combinations: SOF/LDV±RBV (4): patient decision, generalised erythroderma, extreme tiredness, significant weakness of low members and general deterioration; DSV+OTP/PTV/r±RBV (3): likely drug induced hepatitis, patient decision, previous dysphagia and inability to swallow the drug.

Deaths: 6 deaths occurred during treatment (1.2%) with different DAA combinations: SOF/LDV±RBV (2); SOF+SMV±RBV (2); and SOF+DCV; DSV+OTP/PTV/r+RBV. None of these deaths could be attributed to the treatment itself but to other causes. All patients suffered decompensated cirrhosis prior to DAA treatment.

Conclusion The study data demonstrate that most combinations were well tolerated regardless of the DAA combination. However, the results suggest further research is needed to  increase safety data and to improve detection of less frequent  ADE.

No conflict of interest.