Background and importance It is well documented that direct acting antiviral (DAA) combinations in the treatment of hepatitis C virus (HCV) achieve high rates of sustained virologic response. However, studies on retreatment options for patients who have failed several DAA treatment regimens that include non-structural protein 5A (NS5A) inhibitors remain scarce.

Aim and objectives To assess the efficacy of glecaprevir/pibrentasvir plus sofosbuvir and ribavirin for 12 weeks in genotype 1b patient with compensated cirrhosis who had virologic failure to multiple treatments including regimens containing NS5A inhibitors.

Material and methods A 50-year-old man failed multiple hepatitis C treatments, including peginterferon plus ribavirin (2003) for 9 months, sofosbuvir/ledipasvir plus ribavirin (2014) for 24 weeks, sofosbuvir/simeprevir plus ribavirin (2015) for 24 weeks and sofosbuvir/velpatasvir plus ribavirin (2018) for 24 weeks. Adherence to these treatments was correct according to the dispensing records. Headache, fatigue, anaemia, nausea and pruritus were reported with oral treatments, but drug withdrawal was not required. However, peginterferon was stopped due to anxiety and depression.

There are no specific algorithms to guide retreatment decisions. These must be guided by the drugs administered in previous treatment courses or, if resistance testing is performed, by probabilities of response according to the resistance profile and the treating team’s experience. Resistance testing showed resistance to NS5A inhibitors: daclatasvir, elvasvir, ledipasvir, ombitasvir and velpatasvir, but not to pibrentasvir. The multidisciplinary team decided on a new treatment with glecaprevir/pibrentasvir plus sofosbuvir and ribavirin for 12 weeks and it was started in November 2019. Prior to treatment, drug interactions were checked. An undetectable HCV RNA level 12 weeks after completion of therapy (SVR12) defined treatment success.

Results Two potential drug interactions were detected: (1) gemfibrozil was discontinued because of the increased risk of gastrointestinal side effects; (2) due to the potential increase in carvedilol concentrations, close monitoring of heart rate and blood pressure was recommended. The patient achieved SVR12 with the fifth hepatitis C treatment with glecaprevir/pibrentasvir plus sofosbuvir and ribavirin for 12 weeks. The treatment was well tolerated, and adherence was correct.

Conclusion and relevance In this particularly difficult to cure cirrhotic patient previously exposed to NS5A inhibitors, the combination of glecaprevir/pibrentasvir plus sofosbuvir and ribavirin administered for 12 weeks achieved SVR12.

Conflict of interest No conflict of interest