Interferon-free regimens for the treatment of hepatitis C virus in liver transplant candidates or recipients.
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 mL/min. Drug-drug interactions may still occur with the current DAAs particularly in post-LT patients, in whom simeprevir should not be co-administered 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-transplant patients, 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.
Evangelos Cholongitas, 4 Department of Internal Medicine, Medical School of Aristotle University, Hippokration General Hospital of Thessaloniki, 54642 Thessaloniki, Greece.
Evangelos
E
Cholongitas
Evangelos Cholongitas, 4 Department of Internal Medicine, Medical School of Aristotle University, Hippokration General Hospital of Thessaloniki, 54642 Thessaloniki, Greece.
Chrysoula
C
Pipili
Evangelos Cholongitas, 4 Department of Internal Medicine, Medical School of Aristotle University, Hippokration General Hospital of Thessaloniki, 54642 Thessaloniki, Greece.
George
G
Papatheodoridis
D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D058625:End Stage Liver Disease / Q000175:diagnosis / Q000601:surgery* / Q000821:virology; D019698:Hepatitis C, Chronic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000601:surgery* / Q000821:virology; D016031:Liver Transplantation / Q000009:adverse effects; D018579:Patient Selection; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
D000998:Antiviral Agents
Decompensated cirrhosis; Direct acting antiviral agents; Hepatitis C; Liver transplantation; Sofosbuvir