Interferon-free regimens for the treatment of hepatitis C virus in liver transplant candidates or recipients

• Published in: World journal of gastroenterology : WJG 2015-08, Vol.21 (32), p.9526-9533
• Main Authors: Cholongitas, Evangelos, Pipili, Chrysoula, Papatheodoridis, George
• Format: Article
• Language: English
• Subjects: acting; agents; Liver; antiviral; Antiviral Agents - adverse effects; Antiviral Agents - therapeutic use; C; Direct; Drug Interactions; Drug Therapy, Combination; End Stage Liver Disease - diagnosis; End Stage Liver Disease - surgery; End Stage Liver Disease - virology; Hepatitis; Hepatitis C, Chronic - complications; Hepatitis C, Chronic - diagnosis; Hepatitis C, Chronic - drug therapy; Humans; Liver Cirrhosis - diagnosis; Liver Cirrhosis - surgery; Liver Cirrhosis - virology; Liver Transplantation - adverse effects; Minireviews; Patient Selection; Recurrence; Risk Assessment; Risk Factors; Treatment Outcome
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v21.i32.9526

The goal of therapy in chronic hepatitis C virus(HCV) infection is sustained virological response(SVR) which reflects HCV eradication. Treatment against HCV has dramatically improved with the recent availability of direct-acting antivirals(DAAs) including sofosbuvir, simeprevir, daclatasvir, ledipasvir/sofosbuvir, paritaprevir/ombitasvir and dasabuvir. Carefully selected combinations of these DAAs offer the potential for highly effective all-oral safe regimens even for patients with decompensated cirrhosis or liver transplant(LT) recipients. Like all current protease inhibitors, simeprevir and paritaprevir should not be used in patients with Child C cirrhosis, while sofosbuvir and ledipasvir/sofosbuvir should not be given in patients with severe renal impairment and glomerular filtration rate less than 30 m L/min. Drug-drug interactions may still occur with the current DAAs particularly in postLT patients, in whom simeprevir should not be coadministered with cyclosporine and dose adjustments of calcineurin inhibitors are required in case of regimens including the ritonavir boosted paritaprevir. Phase Ⅱ clinical trials and real life cohort studies have shown that sofosbuvir based combinations are safe and can achieve improvements of clinical status, high SVR rates and even prevention of post-LT HCV recurrence in patients with decompensated cirrhosis or LT-candidates. In the post-LT setting, sofosbuvir based regimens and the combination of paritaprevir/ombitasvir and dasabuvir have been reported to be safe and achieve high SVR rates, similar to those in non-transplantpatients, being effective even in cases with cholestatic fibrosing hepatitis. Ongoing clinical trials and rapidly emerging real life data will further clarify the safety and efficacy of the new regimens in these settings.