Background The World Health Organisation calls for the eradication of the hepatitis C virus (HCV) by 2030. Direct-acting antivirals (DAAs) drugs promise shorter treatment times, much higher cure rates and fewer side effects. However, some patients failed to achieve sustained virological response (SVR) after DAAs regimens. Experts recommend retreatment based on an individual decision of the multidisciplinary team (MDT).

Purpose The aim of this study was to describe the cases of our hospital’s patients who failed to achieve SVR after DAAs regimens.

Material and methods The study of the MDT reports between February 2014 and July 2018 allowed us to identify retreated patients who failed to achieve SVR after DAAs regimens. Patient information was collected based on the analysis of consultations’ reports of the hepatology department: age, sex, viral genotype, co-infection with hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV), cirrhosis, presumed cause of failure of the first treatment with DAA.

Results Of the 385 cases evaluated by the MDT, 12 patients were identified. Patients mean age was 57±12 years, sex ratio M/F was 1:4, four patients were cirrhotic, one was co-infected with HBV and two were co-infected with HIV. The genotypes found were: 1 (n=4), 2 (n=2), 3 (n=2) and 4 (n=4). First DAA treatment was either combinations of NS5B+NS5A inhibitors (such as sofosbuvir with daclatasvir/ledispavir/velpatasvir, n=8), or NS5A+NS3 inhibitors (grazoprevir/elbasvir or paritaprevir/ombitasvir, n=3) or NS5B+NS5A+NS3 inhibitors (dasbuvir/ombitasvir/paritaprevir, n=1). Four treatments were associated with ribavirine. The presumed cause of failures was HCV resistance to NS5A inhibitors, since the other causes (non-compliance, drug interactions, re-infection, premature discontinuation) had been discarded. During retreatment, the duration of treatment was lengthened and/or ribavirin was added. The molecules used for retreatment were NS5B and NS3 inhibitors in 2016 and 2017 (simeprevir/sofosbuvir, n=2). In 2018, NS5B+NS5A inhibitors associated with ribavirine (sofosbuvir/velpatasvir, n=1), NS5B+NS5A+NS3 inhibitors (glecaprevir/pibrentasvir/sofosbuvir with ribavirine n=4, sofosbuvir/voxilaprevir/velpatasvir n=4) and NS5A+NS3 (glecaprevir/pibrentasvir, n=1) were used.

Conclusion Failed SVR were mainly caused by NS5A mutations. Second-generation DAAs marketing approval has allowed the retreatment of several patients. Therapeutic strategies for retreatment comply with European Association of the Study of the Liver guidelines. However, these patients should be monitored closely to evaluate SVR.

References and/or acknowledgements http://www.easl.eu/medias/cpg/2018/EASL%20Recommendations%20on%20Treatment%20of%20Hepatitis%20C%202018/English-report.pdf

No conflict of interest.