Delisting of liver transplant candidates with chronic hepatitis C after viral eradication: A European study

Background & Aims All oral direct acting antivirals (DAA) have been shown to improve the liver function of patients with decompensated cirrhosis but it is presently unknown whether this clinical improvement may lead to the delisting of some patients. The aim of this study was to assess if and which patients can be first inactivated due to clinically improvement and subsequently delisted in a real life setting. Methods 103 consecutive listed patients without hepatocellular carcinoma were treated with different DAA combinations in 11 European centres between February 2014 and February 2015. Results The cumulative incidence of inactivated and delisted patients by competing risk analysis was 15.5% and 0% at 24 weeks, 27.6% and 10.3% at 48 weeks, 33.3% and 19.2% at 60 weeks. The 34 patients who were inactivated showed a median improvement of 3.4 points for MELD (delta MELD, p <0.0001) and 2 points for Child-Pugh (CP) (delta-CP, p <0.0001). Three variables emerged from the most parsimonious multivariate competing risk model as predictors of inactivation for clinical improvement, namely, baseline MELD classes (MELD 16–20: HR = 0.120; p = 0.0005, MELD >20:HR = 0.042; p <0.0001), delta MELD (HR = 1.349; p <0.0001) and delta albumin (HR = 0.307; p = 0.0069) both assessed after 12 weeks of DAA therapy. Conclusions This study showed that all oral DAAs were able to reverse liver dysfunction and favoured the inactivation and delisting of about one patient out-of-three and one patient out-of-five in 60 weeks, respectively. Patients with lower MELD scores had higher chances to be delisted. The longer term benefits of therapy need to be ascertained. Lay summary The excellent efficacy and safety profile of the new drugs against Hepatitis C virus, “direct acting antivirals” or DAAs, have made antiviral therapy possible also for patients with advanced liver disease and for those on the waiting list for liver transplantation (LT). This study shows for the first time that the DAAs may lead to a remarkable clinical improvement allowing the delisting of one patient out of 5. Abbreviations DAAs, direct acting antivirals; HCV, hepatitis C virus; LT, liver transplantation; HCC, hepatocellular carcinoma; MELD, model for end-stage liver disease; ELITA, European Liver and Intestine Transplant Association; HIV, human immunodeficiency virus; HBV, hepatitis B virus; HE, hepatic encephalopathy; HPS, hepato-pulmonary syndrome; HCV-RNA, hepatitis C virus-ribonucleic acid; SOF, sofosbuvir; RBV, ribavirin; DCV, daclatasvir; LDV, ledipasvir; SMV, simeprevir; INR, international normalized ratio; SD, standard deviation; IQR, interquartile range; CP, Child-Pugh; WL, waiting list; RVR, rapid virological response; EVR, early virological response; SVR, sustained virological response; EOT, end of treatment; EMA, European Medicines Agency; FDA, Food and Drug Administration.