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

Disclosures

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

In This Article

Discussion

The two main indications for wait–listing patients with HCV are HCC and decompensated cirrhosis. Oral DAAs have radically changed the management of patients with chronic HCV infection, and a sustained viral response (SVR) higher than 90% is now obtained in patients with compensated cirrhosis. In patients with decompensated cirrhosis, SVR rates are very high but lower than in compensated cirrhosis.[7,8,10–16,18] Interestingly, in these patients, viral clearance can result in significant laboratory and clinical improvement.[11,12] Indeed, data from a few clinical trials indicate that new DAAs may improve liver function in patients with decompensated cirrhosis and can lead, in some cases, to a significant clinical improvement with reversal of decompensation.[7] Some patients listed for LT due to decompensated cirrhosis may reach a sufficient improvement in their liver function to be inactivated from the WL and eventually delisted.[14,15] However, the long–term impact of HCV treatment in patients with HCV cirrhosis and the effects on liver transplant candidacy after viral eradication remain to be determined.

In Spain, oral therapies against HCV were introduced in 2011, first in combination with IFN and more recently as all oral combination treatments. Our LT centre is the largest in Spain and HCV–related cirrhosis has been the most common indication since the program started in 1991. By analysing transplant indications, wait–listing and delisting over time, we aimed at assessing the impact that new oral antivirals have had in liver transplantation. The main findings from this study can be summarized as follows: (i) the incidence of WL for HCV patients decreased by 19.5% in the DAA era compared to the IFN era and by 15% when compared to the PI era; (ii) the number of patients who are delisted due to clinical improvement has significantly increased in recent years; (iii) these trends are not observed in some subgroups of HCV infected patients, namely those with additional causes of liver damage, such as alcohol, or those with concomitant HCC.

Recently, Flemming et al,[17] reported the US trends in LT WL in order to explore the potential impact of effective medical therapy using data from the Scientific Registry of Transplant Recipients database. As in our study, era of listing was divided into IFN (2003–2010), first–generation PI (2011–2013), and DAA era (2014–2015). Adjusted incidences of LT WL for decompensated cirrhosis in HCV patients decreased by 5% in the PI era and 32% in the DAA era compared to the IFN era, results that are similar to our findings. These two studies highlight the impact that DAA regimens have had on the epidemiology of LT and their positive effect in patients with HCV infection.[19] Interestingly, and probably because the duration of follow up is still too short, the number of patients wait–listed for HCC among HCV–infected patients has continued to increase in the DAA era. In addition, the presence of comorbidities, such as alcohol or non–alcoholic steatohepatitis, may also influence outcome following successful therapy. Indeed, in our centre, the proportion of waitlisted patients due to mixed aetiology did not follow the same trend as those with HCV–infection alone.

In addition to the reduction in the number of HCV–infected candidates who are waitlisted, we also observed an increase in delisting due to functional and clinical improvement, a circumstance that is being increasingly documented in the literature.[5,12,14,15] Belli et al,[15] showed that oral DAAs were able to reverse liver dysfunction leading to inactivation and delisting in approximately one–third and one–fifth of patients, respectively, 60 weeks from treatment initiation. Patients with lower MELD scores had a higher probability of being delisted. In our study, the highest number of delisted patients occurred during the last 2014–2016 period corresponding to the all DAA era.

The direct consequence of the changes in WL and delisting was a reduction in the number of HCV–positive patients who were eventually transplanted in the last 3 years. Reducing the need of LT among HCV–infected cirrhotic patients will not only have significant consequences from an individual patient point of view but also in terms of organ sparing.[11,20,21]

In contrast to patients with decompensated HCV–cirrhosis, HCV–infected patient with HCC may either undergo transplantation or be delisted due to HCC progression or death. In these cases, achieving an SVR with DAAs regimens will probably not affect these outcomes. Furthermore, in some regions where anti–HCV (+) donors is a frequent source of donation, delaying therapy to post–transplant may be a safer option given the shorter waiting list time associated with the use of these organs.[22] This strategy may be the best alternative for patients with low possibilities of being delisted, such as those with HCC and/or those with high MELD scores.[15]

While we believe that the large–scale use of DAAs is one of the major reasons behind the observed changes, we cannot exclude the possibility that the epidemiology of HCV infection in our country has also played a significant role. Indeed, data extracted from the Spanish National Plan (data not shown) indicates that most treated patients (mostly F3 and F4) belong to a cohort of patients born between 1945 and 1975. In contrast, the number of patients treated during these years, where prioritization was given to patients with advanced liver disease, who belong to younger cohorts (born after 1975) is very low suggesting that the Spanish HCV–infected population is an aged population that would eventually decline as an indication of LT regardless of the introduction of new DAA therapies.

In summary, although the number of patients is small and the follow up still short, we have demonstrated in this study the positive effect that HCV eradication can have on LT indications, with reduction in those transplanted for decompensated HCV cirrhosis, thus sparing donor organs for HCC and non–HCV indications.

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