Direct-Acting Antiviral Therapy in Liver Transplant Patients With Hepatocellular Carcinoma and Hepatitis C

Abstract

Background: Direct-acting antivirals (DAA) are highly effective for the treatment of hepatitis C (HCV), although there are limited data on the safety and efficacy of DAA therapy in hepatitis C-positive individuals awaiting liver transplantation for hepatocellular carcinoma (HCC). Methods: We conducted a retrospective cohort study of HCV-positive patients who underwent liver transplantation for HCC at 3 liver transplant centers across the United States from 2014 to 2017 with follow-up to July 2018. Transplant recipients who received DAA before transplant were compared with those who did not (DAA naive) for posttransplant HCC recurrence rate, sustained virological response (SVR), allograft failure, and death using Kaplan-Meier analysis and Cox proportional hazard models. Results: A total of 171 HCV-HCC transplant recipients (99 pretransplant DAA; 72 DAA naive controls) were included, with a median follow-up of 24 months. The overall posttransplant HCC recurrence rate was 9% (15/171). Pretransplant DAA was not associated with HCC recurrence (5% versus 14%; P = 0.07), graft failure (7% versus 3%; P = 0.21), or death (12% versus 19%; P = 0.19) as compared with DAA naive patients. SVR rates were significantly lower (P < 0.01) with pretransplant DAA (75%, 39/52) than posttransplant DAA (97%, 59/61) therapies. Those who received pretransplant DAA and those who did not were not statistically different in age, gender, alpha fetal protein levels, model for end-stage liver disease scores, or transplant wait time. Conclusions: Pretransplant DAA for HCV was not associated with an increased risk of posttransplant HCC recurrence, though pretransplant DAA had lower efficacy than posttransplant DAA in HCV-HCC transplant recipients.

Prediction models of hepatocellular carcinoma recurrence after liver transplantation: A comprehensive review

“…One multicenter study of 875 HCV-HCC recipients showed no association between DAA and HCC recurrence, while another study with 171 HCV-HCC recipients showed a trend of decreased HCC recurrence in patients receiving DAAs (hazard ratio, 0.38; P=0.07). 59,60 These studies had the limitation of a relatively short follow-up period; therefore, more studies are needed to confirm the relationship between DAAs and HCC recurrence. Conversely, as HBV is predominant in the East, the potential differences in the effects of HBV and HCV on recurrence after LT should be considered.…”

“…However, the effect of DAAs on the reduction of HCC recurrence after LT remains controversial. One multicenter study of 875 HCV-HCC recipients showed no association between DAA and HCC recurrence, while another study with 171 HCV-HCC recipients showed a trend of decreased HCC recurrence in patients receiving DAAs (hazard ratio, 0.38; P =0.07) [ 59 , 60 ]. These studies had the limitation of a relatively short follow-up period; therefore, more studies are needed to confirm the relationship between DAAs and HCC recurrence.…”

Imprinted immune abnormalities in liver transplant patients cured of hepatitis C with antiviral drugs

“…Direct-acting antiviral (DAA) drugs for HCV dramatically improve outcomes for patients who undergo liver transplantation (LT) and for other patients with advanced liver disease. [1][2][3] DAAs and high-dimensional analytical techniques, such as single-cell mass cytometry (cytometry time of flight [CyTOF]), provide a unique opportunity to investigate the immune dysregulation that occurs during chronic HCV infection and to measure the ability of curative treatment for a chronic viral infection to restore immune function. Persistent abnormalities may yield insights into immunological imprinting, and they may also be clinically important, especially in patients who have undergone LT and patients with advanced liver disease who have an increased infection risk.…”

“…Direct-acting antiviral (DAA) drugs for HCV dramatically improve outcomes for patients who undergo liver transplantation (LT) and for other patients with advanced liver disease 1–3 . DAAs and high-dimensional analytical techniques, such as single-cell mass cytometry (cytometry time of flight [CyTOF]), provide a unique opportunity to investigate the immune dysregulation that occurs during chronic HCV infection and to measure the ability of curative treatment for a chronic viral infection to restore immune function.…”