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This paper presents an overview of the outcome in combined heart-kidney transplantation performed at UZ Leuven.

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Introduction Liver transplantation, the only potentially life-saving treatment for end-stage liver failure, is associated with considerable morbidity and mortality. Although 1-year survival rates now reach 90%, recent benchmarking of low-risk liver transplant cases shows 59% of patients experience severe complications within the first year post-transplant. Most frequent complications are surgical, vascular, biliary, medical, immunological and thrombo-embolic complications as well as infection, cardio-and cerebrovascular events and malignancies. To ensure safety and quality of our programme and to identify areas where improvement is needed, continuous monitoring of morbidity and mortality is essential. Objectives The aim of this thesis is twofold: (1) the development of a tool to prospectively and systematically collect morbidity and mortality during the first 3 months after liver transplantation; (2) performance assessment of the UZ Leuven Liver Transplant Unit compared to established benchmarks. Methods The ‘M&M’ tool, integrated in the electronic patient records, was developed to prospectively register complications occurring during the first 3 months post-transplant. Severity of complications are scored by the validated Clavien-Dindo classification. Established benchmark cut-offs for low-risk transplants were compared to a retrospective cohort of low-risk transplants taking place between 2010 and 2014. Furthermore, morbidity and mortality were prospectively registered using the ‘M&M’ tool for all adult liver transplantations that occurred in our unit between 29 October 2018 and 30 April 2019. Results Between 2010-2014, 98 liver transplant cases were low-risk (33% of transplant activity). In this retrospective cohort, all postoperative indicators reached benchmark cut-offs. We observed slightly more Grade I and II complications compared to benchmark cases, though severe complications and mortality were well below benchmark cut-offs. Forty liver transplants could be monitored prospectively, of these 80% (n=32) were high-risk cases. Comparison between low- and high-risk cases showed no significant differences in baseline characteristics. High-risk patients developed significantly more minor complications compared to low-risk patients but experienced a similar rate of severe complications, with similar graft and patient survival. Comparison of the low-risk cases and the benchmark cases showed significant lower Grade I/II complications at discharge. High-risk cases have significantly higher MELD and BAR scores compared to benchmark cases with higher postoperative minor complications but high-risk patients experienced acceptable severe complication rates. Discussion The ‘M&M’ tool is an efficient and user friendly tool designed to allow continuous morbidity and mortality monitoring. Analysis of low- (retrospective and prospective) and high-risk liver transplants allows us to conclude that Liver Transplant Unit performs well with severe morbidity and mortality well within benchmark cut-offs. We observe increased rates of minor complications compared to benchmark cut-offs which deserves further exploration.

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Introduction Combined liver-kidney transplantation (CLKT) is increasingly performed. There is a lack of large CLKT cohorts described in literature and there is no information on the nature of postoperative complications in comparison with liver-only recipients. Objectives This thesis aims to: (1) describe the UZ Leuven CLKT cohort; (2) compare the post transplant complication rate and severity of complications of CLKT recipients to liver-only recipients. This was investigated in two studies. Methods (1) A retrospective study including all adult CLKT patients transplanted in UZ Leuven between 01/01/1997 and 20/12/2019 was conducted. Donor and recipient demographics as well as post transplant outcomes were summarized for the entire cohort and these were compared for four time eras (1997-2002, 2003-2008, 2009-2014, 2015-2019). (2) A retrospective study of prospectively collected morbidity & mortality (M&M) data of all adult patients receiving a CLKT or a liver-only transplantation between 01/07/2019 and 01/03/2020 was conducted. The existing “M&M tool” to collect complications after a liver-only transplantation was expanded for this purpose. In addition to descriptive analysis of complications in CLKT and liver-only recipients, the incidence and severity (Clavien-Dindo grading) of complications were compared between the two groups. Results (1) 130 CLKTs were performed in the study period; median follow-up time was five years (2-9). Recipients became older and an increase of transplantations with organs donated after circulatory death (DCD) was observed. Overall patient, liver and kidney graft survival at one, three, five, and ten years were: 92%, 85%, 83% and 67%; 89%, 83%, 81% and 61%; and 91%, 84%, 80% and 55%, respectively. Primary non function rates of liver and kidney were low. Early allograft dysfunction of the liver occurred in 20% of cases, delayed graft function of the kidney in 10%. Kidney function was good with a median estimated glomerular filtration rate at three, six, and 12 months of 58.9 ml/min/1.73m²; 58.2 ml/min/1.73m² and 51.2 ml/min/1.73m², respectively. Liver rejection occurred in 8% of patients, kidney rejection in 21%. Liver cold ischemia time (CIT) decreased in the later time eras, kidney CIT remained stable. Recipients had a significantly longer intensive care unit (ICU) stay in later time eras. (2) Nine CLKT recipients and 36 liver-only recipients were included. CLKT patients suffered from more complications compared to liver-only recipients. The proportion of severe complications and graft-related complications were similar between groups, though CLKT recipients experienced more general and minor complications compared to liver-only recipients. ICU and hospital stay were significantly longer in the CLKT group. Discussion UZ Leuven patient and graft survival for CLKT is good and comparable to reported outcomes. Short-term organ dysfunction is low to acceptable. These results are obtained despite increasing recipient age and use of DCD donors. In comparison to a temporary cohort of liver-only recipients, CLKT recipients experience more postoperative complications but these are not more serious and not more graft-specific complications. The CLKT population had a considerably longer ICU and hospital stay and needs to be readmitted to ICU and hospital more often than liver-only recipients. Larger datasets are needed to further examine these findings and identify potential areas of improvement.