Timing of Hepatitis C Virus Treatment in Liver Transplant Candidates in the Era of Direct-acting Antiviral Agents

Abstract

Chronic hepatitis C virus (HCV) infection remains the leading indication for liver transplantation (LT) in the United States. While most patients with chronic HCV infection remain asymptomatic, up to one-third develop progressive liver disease resulting in cirrhosis. LT is often the only curative treatment once significant hepatic decompensation develops. However, antiviral therapy for HCV infection has advanced markedly in the past 5 years with the discovery and approval of direct-acting antiviral agents. These new regimens are well tolerated, of short duration and highly effective, unlike the traditional treatment with pegylated-interferon and ribavirin. As achieving sustained virological response becomes increasingly attainable for a majority of HCV-infected patients, concerns have been raised regarding the optimal timing of treatment for HCV infection in the setting of end-stage liver disease and during the peri-transplant period. On one hand, HCV treatment may improve hepatic function and negate the need for LT in some, which is crucial given the scarcity of donor organs and mortality on the waiting list in certain regions. On the other hand, HCV treatment may result in lowering the priority for LT without improving quality of life, thereby delaying potentially curative LT surgery. This review evaluates the evidence supporting the use of direct-acting antiviral agents in the period before and following LT.

The impact of direct-acting antiviral agents on liver and kidney transplant costs and outcomes

“…24,29 Pretransplant patients who are pre-cirrhotic or who have well-compensated disease may benefit from early HCV treatment with stabilization or regression of chronic liver disease, potentially avoiding LT entirely. Ahmed et al recently reported a Markov analysis comparing delayed or immediate HCV treatment among patient waiting for LT. 30 The benefit of HCV treatment varied according to clinical condition.…”

Optimal Timing of Administration of Direct-acting Antivirals for Patients With Hepatitis C-associated Hepatocellular Carcinoma Undergoing Liver Transplantation

“…Currently, there is limited data regarding the optimal time to initiate DAAs in the liver transplant population. 42,43 A study by Gorgen et al sought to answer this question among 516 patients with underwent LT for HCV with concomitant HCC who received DAA therapy either pre or post-LT. 44 The investigators reported an SVR rate of 93.4% and a 5-year RFS of 93.4% for patients who received DAAs pre-LT and an SVR rate of 96.5% and a recurrence rate of 2.9% for those who received DAAs post-LT. However, the study time period included patients from 2005 to 2015, while DAAs were only widely disseminated in 2015.…”

“…Currently, there is limited data regarding the optimal time to initiate DAAs in the liver transplant population 42,43 . A study by Gorgen et al sought to answer this question among 516 patients with underwent LT for HCV with concomitant HCC who received DAA therapy either pre or post-LT 44 .…”

A Focused Review on Recent Advances in the Diagnosis and Treatment of Viral Hepatitis

“…Those with MELD scores between 16 and 20 require individualized treatment regimens regarding when to initiate DAA given the potential to precipitate liver failure or other complications with antiviral therapy. DAA therapy in those with MELD > 20 has been shown to have optimal benefit when initiated following liver transplantation at the earliest point of clinical stability (2 - 4 weeks post-transplant) [ 94 , 95 ].…”