Published online Mar 28, 2018. doi: 10.3748/wjg.v24.i12.1353
Peer-review started: January 31, 2018
First decision: February 24, 2018
Revised: March 2, 2018
Accepted: March 18, 2018
Article in press: March 18, 2018
Published online: March 28, 2018
Recurrent infection with hepatitis C virus (HCV) following liver transplant (LT) treatment is the leading cause of liver graft loss and death in liver-transplanted patients infected with HCV. Before introduction of the direct-acting antiviral (DAA) therapies, treatment options for recurrent HCV in liver-transplanted patients were limited, due to significant drug-drug interactions and severe side effects. The approval of DAAs has revolutionized HCV treatment.
Despite the growing number of successfully treated patients, HCV recurrence after orthotopic LT remains one of the most challenging clinical situations. Thus, analysis of real-world cohorts of LT recipients may provide valuable insights into the safety and efficacy of DAA treatment in these cohorts.
To analyze the safety and efficiency of DAA regimens in liver-transplanted patients with HCV reinfection in a real-world cohort.
The study cohort comprises all liver transplanted patients that were treated with direct acting antiviral regimen at the Heidelberg University Hospital from January 2014 to December 2016. In total 39 patients were included. Clinical and laboratory baseline characteristics were collected at entry into the study. All patients were at least six months liver transplanted before antiviral therapy was started. HCV treatment was administered by the outpatient clinic at our tertiary center. The decision about the HCV treatment was made by specialists at our transplant center, according to current available or recommended medication. Patients were treated according recommendations of available drugs after approval by FDA and EMEA. As different drugs were approved during the course of this study therapy regimen were adapted. In the beginning Sofosbuvir was combined with pegylated interferon (Peg-INF) and ribavirin. After introduction of Daclatasvir, Simeprivir and fixed-dose combination of Sofosbuvir with Ledipasvir interferon containing regimen were no longer perpetuated.
At the end of the study period, all thirty-nine patients had attained SVR at 24 wk (SVR24). Sustained virological response at 12 wk (SVR12) was achieved in 10/13 (76.9%) of patients treated with SOF + IFN ± RBV. All patients with relapse were treated with fixed-dose combination of SOF + LDV + RBV. Patients treated with SOF + DAC + RBV or SOF + LDV + RBV achieved 100% SVR12. SVR rates after combination treatment with inhibitors of the HCV nonstructural protein (NS)5A and NS5B for 24 wk were significantly higher, as compared to all other therapy regimens (P = 0.007). Liver function was stable or even improved in the majority of patients during treatment. All antiviral therapies were safe and well-tolerated, without need of discontinuation of treatment or dose adjustment of immunosuppression. No serious adverse events or any harm to the liver graft became overt. No patient experienced acute cellular rejection during the study period.
In conclusion, DAAs are safe and very efficient in HCV patients after liver transplantation, even in cases of recurrent cirrhosis or history of relapse after Peg-IFN therapy. The high SVR rates in our cohort, despite the many patients with rrecurrent cirrhosis, may argue for a 24-wk therapy period in patients with risk factors for therapy failure in a posttransplant setting.
HCV recurrence after orthotopic LT can be safely and efficiently treated with DAAs. Optimal timing and duration of antiviral therapy remains undetermined. Patients at risk for relapse need to be identified before initiation of therapy. Long-term effects of successful antiviral therapy, especially in patients with advanced recurrent cirrhosis, need to be analyzed in future.