Compared efficacy of preservation solutions in liver transplantation: A long-term graft outcome study from the european liver transplant registry

International audienceBetween 2003 and 2012, 42 869 first liver transplantations performed in Europe with the use of either University of Wisconsin solution (UW; N = 24 562), histidine-tryptophan-ketoglutarate(HTK; N = 8696), Celsior solution (CE; N = 7756) or Institute Georges Lopez preservation solution (IGL-1; N = 1855) preserved grafts. Alternative solutions to the UW were increasingly used during the last decade. Overall, 3-year graft survival was higher with UW, IGL-1 and CE (75%, 75% and 73%, respectively), compared to the HTK (69%) (p 12 h or grafts used for patients with cancer (p < 0.0001). For partial grafts, 3-year graft survival was 89% for IGL-1, 67% for UW, 68% for CE and 64% for HTK (p = 0.009). Multivariate analysis identified HTK as an independent factor of graft loss, with recipient HIV (+), donor age ≥65 years, recipient HCV (+), main disease acute hepatic failure, use of a partial liver graft, recipient age ≥60 years, no identical ABO compatibility, recipient hepatitis B surface antigen (-), TIT ≥ 12 h, male recipient and main disease other than cirrhosis. HTK appears to be an independent risk factor of graft loss. Both UW and IGL-1, and CE to a lesser extent, provides similar results for full size grafts. For partial deceased donor liver grafts, IGL-1 tends to offer the best graft outcome

Mortality after Transplantation for Hepatocellular Carcinoma: A Study from the European Liver Transplant Registry

Background and Aims: Prognosis after liver transplantation differs between hepatocellular carcinoma (HCC) arising in cirrhotic and non-cirrhotic livers and aetiology is poorly understood. The aim was to investigate differences in mortality after liver transplantation between these patients. Methods: We included patients from the European Liver Transplant Registry transplanted due to HCC from 1990 to November 2016 and compared cirrhotic and non-cirrhotic patients using propensity score (PS) calibration of Cox regression estimates to adjust for unmeasured confounding. Results: We included 22,787 patients, of whom 96.5% had cirrhosis. In the unadjusted analysis, non-cirrhotic patients had an increased risk of overall mortality with a hazard ratio (HR) of 1.37 (95% confidence interval [CI] 1.23-1.52). However, the HR approached unity with increasing adjustment and was 1.11 (95% CI 0.99-1.25) when adjusted for unmeasured confounding. Unadjusted, non-cirrhotic patients had an increased risk of HCC-specific mortality (HR 2.62, 95% CI 2.21-3.12). After adjustment for unmeasured confounding, the risk remained significantly increased (HR 1.62, 95% CI 1.31-2.00). Conclusions: Using PS calibration, we showed that HCC in non-cirrhotic liver has similar overall mortality, but higher HCC-specific mortality. This may be a result of a more aggressive cancer form in the non-cirrhotic liver as higher mortality could not be explained by tumour characteristics or other prognostic variables

Trends in liver transplantation for primary biliary cholangitis in Europe over the past three decades

BACKGROUND: The importance of primary biliary cholangitis as an indication for liver transplantation has probably been influenced by the introduction of therapies, and changes in selection criteria and disease epidemiology. AIMS: To assess the time trends in liver transplantation for primary biliary cholangitis and to evaluate the characteristics of the patient population during the past three decades. METHODS: Patients undergoing liver transplantation from 1986 to 2015 in centres reporting to the European Liver Transplantation Registry were included. We excluded combined organ transplantations and patients <18 years. Trends were assessed using linear regression models. RESULTS: We included 112 874 patients, of whom 6029 (5.3%) had primary biliary cholangitis. After an initial increase in the first decade, the annual number of liver transplantation for primary biliary cholangitis remained stable at around 200. The proportion of liver transplantations for primary biliary cholangitis decreased from 20% in 1986 to 4% in 2015 (P < 0.001). Primary biliary cholangitis was the only indication showing a consistent proportional decrease throughout all decades. From the first to the third decade, the age at liver transplantation increased from 54 (IQR 47-59) to 56 years (IQR 48-62) and the proportion of males increased from 11% to 15% (both P < 0.001). CONCLUSIONS: We have found a proportional decrease in primary biliary cholangitis as indication for liver transplantation. However, despite treatment with ursodeoxycholic acid and improved disease awareness, the absolute annual number of liver transplantations has stabilised

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

International audienceBACKGROUND & 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 24weeks, 27.6% and 10.3% at 48weeks, 33.3% and 19.2% at 60weeks. The 34 patients who were inactivated showed a median improvement of 3.4 points for MELD (delta MELD, p20: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 12weeks 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 60weeks, 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

NEWS AND NOTES 1988, VOL.19, NO.3

https://digitalcommons.rockefeller.edu/news_and_notes_1988/1001/thumbnail.jp

The Eurotransplant Donor Risk Index in Liver Transplantation: ET-DRI

Transplant surger

Cyclosporine vs. tacrolimus after liver transplantation for primary sclerosing cholangitis – a propensity score-matched intention-to-treat analysis

Background & Aims: There is controversy regarding the optimal calcineurin inhibitor type after liver transplant(ation) (LT) for primary sclerosing cholangitis (PSC). We compared tacrolimus with cyclosporine in a propensity score-matched intention-to-treat analysis based on registries representing nearly all LTs in Europe and the US. Methods: From the European Liver Transplant Registry (ELTR) and Scientific Registry of Transplant Recipients (SRTR), we included adult patients with PSC undergoing a primary LT between 2000-2020. Patients initially treated with cyclosporine were propensity score-matched 1:3 with those initially treated with tacrolimus. The primary outcomes were patient and graft survival rates. Results: The propensity score-matched sample comprised 399 cyclosporine-treated and 1,197 tacrolimus-treated patients with PSC. During a median follow-up of 7.4 years (IQR 2.3-12.8, 12,579.2 person-years), there were 480 deaths and 231 re-LTs. The initial tacrolimus treatment was superior to cyclosporine in terms of patient and graft survival, with 10-year patient survival estimates of 72.8% for tacrolimus and 65.2% for cyclosporine (p <0.001) and 10-year graft survival estimates of 62.4% and 53.8% (p <0.001), respectively. These findings were consistent in the subgroups according to age, sex, registry (ELTR vs. SRTR), time period of LT, MELD score, and diabetes status. The acute rejection rates were similar between groups. In the multivariable Cox regression analysis, tacrolimus (hazard ratio 0.72, p <0.001) and mycophenolate use (hazard ratio 0.82, p = 0.03) were associated with a reduced risk of graft loss or death, whereas steroid use was not significant. Conclusions: Tacrolimus is associated with better patient and graft survival rates than cyclosporine and should be the standard calcineurin inhibitor used after LT for patients with PSC. Impact and implications: The optimal calcineurin inhibitor to use after liver transplantation in patients with primary sclerosing cholangitis has yet to be firmly established. Since randomized trials with long follow-up are unlikely to be performed, multicontinental long-term registry data are essential in informing clinical practices. Our study supports the practice of using tacrolimus instead of cyclosporine in the initial immunosuppressive regimen after liver transplantation for patients with primary sclerosing cholangitis. The retrospective registry-based design is a limitation.Peer reviewe

Locoregional treatments before liver transplantation for hepatocellular carcinoma a study from the European Liver Transplant Registry

International audienceLocoregional treatment while on the waiting list for liver transplantation (Ltx) for hepatocellular carcinoma (HCC) has been shown to improve survival. However, the effect of treatment type has not been investigated. We investigate the effect of locoregional treatment type on survival after Ltx for HCC. We investigated patients registered in the European Liver Transplant Registry database using multivariate Cox regression survival analysis. Information on locoregional therapy was registered for 4978 of 23 124 patients and was associated with improved overall survival [hazard ratio (HR) 0.84 (0.73-0.96)] and HCC-specific survival [HR 0.76 (0.59-0.98)]. Radiofrequency ablation (RFA) was the one monotherapy associated with improved overall survival [HR 0.51 (0.40-0.65)]. In addition, the combination of RFA and transarterial chemoembolization also improved survival [HR 0.74 (0.55-0.99)]. Adjusting for factors related to prognosis, disease severity, and tumor aggressiveness, RFA was highly beneficial for overall and HCC-specific survival. The effect may represent a selection of patients with favorable tumor biology; however, the treatment may be effective per se by halting tumor progression. Clinicaltrials.gov number NCT02995096