Impact of Hepatitis C Virus (HCV) Antiviral Treatment on the Need for Liver Transplantation (LT)

Esteban Sáez-González; Carmen Vinaixa; Fernando San Juan; Vanesa Hontangas; Salvador Benlloch; Victoria Aguilera; Angel Rubín; María García; Martín Prieto; Rafa López-Andujar; Marina Berenguer


Liver International. 2018;38(6):1022-1027. 

In This Article

Abstract and Introduction


Background: Therapies for hepatitis C virus (HCV) infection have revolutionized the treatment of patients with chronic HCV infection. The effect of these therapies on the epidemiology of liver transplantation (LT) has yet to be elucidated.

Aim: To establish whether the indications for LT have changed as a result of the introduction of new therapies for HCV.

Materials and methods: We conducted a retrospective study based on a prospectively maintained registry of patients who undergo LT at La Fe Hospital in Valencia from 1997 to 2016. An analysis of outcome measures over time stratified by LT indications was performed.

Results: From January 1997 to December 2016, 2379 patients were listed for LT. Of these, 1113 (47%) were listed for HCV cirrhosis±hepatocellular carcinoma (HCC). This percentage varied significantly over time declining from 48.8% in the 1997–2009 initial period (IFN–based regimens) to 33% in the 2014–2016 final period (DAAs regimens) (P = .03). However, during that period, the proportion of those included in the waiting list (WL) due to HCV–HCC increased significantly (P = .001). In addition, among HCV–positive waitlisted patients with decompensated cirrhosis without HCC, the proportion of those with an HCV–alcohol mixed etiology also increased significantly over time (P = .001). Of all HCV–positive waitlisted patients, 203 were eventually removed from the WL due to either clinical improvement (n = 77) or more frequently worsening/death (n = 126).

Conclusions: The proportion of patients wait–listed for LT for decompensated HCV cirrhosis has significantly decreased over time. These changes are possibly related to the large–scale use of direct–acting antivirals.


Chronic Hepatitis C Virus (HCV) infection is associated with substantial mortality, with over 350.000 deaths per year attributed to HCV–related cirrhosis and hepatocellular carcinoma (HCC).[1,2] The development of cirrhosis and HCC due to HCV infection represent the most common indications for liver transplantation (LT) in western countries.[3,4] Hepatitis C therapies in current clinical practice have revolutionized the natural history of patients with chronic HCV.[5,6] New direct acting antivirals (DAAs) have changed the approach to HCV infection and also the prognosis of patients with HCV–related liver disease. Indeed, DAAs are highly effective at eradicating HCV infection in most circumstances, included in patients with advanced liver disease.[7–12] An improvement in liver function, indirectly assessed through the Model for End–Stage Liver Disease (MELD) and Child–Pugh–Turcotte (CPT) scores, has been observed in the majority of patients. Such functional improvement can result, in some cases, in a significant clinical improvement with reversal of decompensation.[5]

The long–term impact of HCV treatment in patients with HCV cirrhosis and its effect on LT candidacy, however, remain to be seen.[13] Indeed, by treating waitlisted patients and eradicating HCV, reduction in MELD score together with clinical improvement may result in delisting from the waiting list (WL).[14,15] In some cases though, the improvement of the MELD score may not reach the point of delisting and/or may not be followed by relevant clinical improvement, leaving the patient with a lower MELD score that reduces the probability of receiving a LT under the current MELD allocation system (the so–called MELD purgatory or limbo).

The treatment goal of chronic HCV is to achieve virological cure. The approval of the first–generation DAAs in 2011, boceprevir and telaprevir, marked the beginning of a new era in the treatment of chronic HCV. Although extremely toxic in patients with advanced liver disease, their use in Spain was initially restricted to those with bridging fibrosis and/or compensated cirrhosis. Previously, they had been used as compassionate use. In turn, all–oral DAAs therapies were available in Spain since 2014, first within the context of compassionate programs and since 2015 within the Spanish National Strategic Plan for the treatment of HCV. Within this plan, patients prioritized to receive therapy in 2015 were those with advanced liver disease including patients in the setting of LT.

Chronic HCV infection has been the leading indication for LT in our center, La Fe University Hospital, ever since the first LT was performed more than 20 years ago. On average, 100 liver transplants are performed every year. In Spain, non–biliary cirrhosis, particularly alcohol– and HCV–related cirrhosis (60%), and tumors, mainly HCC (19%), are the most common indications for LT.[16] Allocation in Spain is mostly but not uniquely MELD–based. In our region, where allocation is based on MELD score, the median MELD at transplantation is 17 (range: 6–38) with a median time spent in the waiting list of 141 days, ranging from 49 to 346 days (data from 2014, www.SETH).

The aims of our study were to establish whether LT indications in our center have changed overtime, particularly in recent years, as a result of the introduction of HCV therapies based on DAAs, as well as to determine the impact of DAA on WL delisting due to clinical improvement.