Health-related quality of life is linked to the gut microbiome in kidney transplant recipients.

Kidney transplant recipients (KTR) have impaired health-related quality of life (HRQoL) and suffer from intestinal dysbiosis. Increasing evidence shows that gut health and HRQoL are tightly related in the general population. Here, we investigate the association between the gut microbiome and HRQoL in KTR, using metagenomic sequencing data from fecal samples collected from 507 KTR. Multiple bacterial species are associated with lower HRQoL, many of which have previously been associated with adverse health conditions. Gut microbiome distance to the general population is highest among KTR with an impaired physical HRQoL (R = -0.20, P = 2.3 × 10-65) and mental HRQoL (R = -0.14, P = 1.3 × 10-3). Physical and mental HRQoL explain a significant part of variance in the gut microbiome (R2 = 0.58%, FDR = 5.43 × 10-4 and R2 = 0.37%, FDR = 1.38 × 10-3, respectively). Additionally, multiple metabolic and neuroactive pathways (gut brain modules) are associated with lower HRQoL. While the observational design of our study does not allow us to analyze causality, we provide a comprehensive overview of the associations between the gut microbiome and HRQoL while controlling for confounders.

Comparison of reconstruction methods used during liver transplantation in case of a graft with replaced or accessory right hepatic artery: A retrospective study.

Variations in graft arterial anatomy can increase the risk of postoperative hepatic arterial thrombosis (HAT), especially in presence of a replaced or accessory right hepatic artery (RHA). We retrospectively analyzed 223 cases of liver transplantations with the presence of an RHA on the graft. Patient outcomes were compared according to the four different reconstruction methods used: (i) the re-implantation of the RHA into the splenic or gastroduodenal artery (n = 106); (ii) the interposition of the superior mesenteric artery (SMA) (n = 83); (iii) dual anastomosis (n = 24); (iv) use of an aortic patch including the origins of both the SMA and the coeliac trunk (n = 10). A competing risk analysis and Inverse Probability Weighting (IPW) were used. We found that the interposition of the SMA method was associated with a significantly lower incidence of HAT, at 4.8% compared to the re-implantation method at 17.9%, dual anastomosis at 12.5%, and aortic patch at 20%, p = .03. In the competing risk analysis with IPW, the only risk factor for RHA thrombosis was the type of reconstruction. Taking the SMA interposition group as the reference, the sub-hazard ratio (sHR) was 5.05 (CI 95 [1.72; 14.78], p < .01) for the re-implantation group, sHR = 2.37 (CI 95 [0.51; 11.09], p = .27) for the dual anastomosis group and sHR = 2.24 (CI 95 [0.35; 14.33], p = .40) for the aortic patch group. There were no differences for intraoperative transfusion, hospitalization duration (p = .37) or incidence of severe complications (p = .1). The long-term graft (p = .69) and patient (p = .52) survival was not different. In conclusion, the SMA interposition method was associated with a lower incidence of RHA thrombosis.

The Impact of Donor and Recipient Genetic Variation on Outcomes After Solid Organ Transplantation: A Scoping Review and Future Perspectives.

At the outset of solid organ transplantation, genetic variation between donors and recipients was recognized as a major player in mechanisms such as allograft tolerance and rejection. Genome-wide association studies have been very successful in identifying novel variant-trait associations, but have been difficult to perform in the field of solid organ transplantation due to complex covariates, era effects, and poor statistical power for detecting donor-recipient interactions. To overcome a lack of statistical power, consortia such as the International Genetics and Translational Research in Transplantation Network have been established. Studies have focused on the consequences of genetic dissimilarities between donors and recipients and have reported associations between polymorphisms in candidate genes or their regulatory regions with transplantation outcomes. However, knowledge on the exact influence of genetic variation is limited due to a lack of comprehensive characterization and harmonization of recipients' or donors' phenotypes and validation using an experimental approach. Causal research in genetics has evolved from agnostic discovery in genome-wide association studies to functional annotation and clarification of underlying molecular mechanisms in translational studies. In this overview, we summarize how the recent advances and progresses in the field of genetics and genomics have improved the understanding of outcomes after solid organ transplantation.

Therapeutic anticoagulation after liver transplantation is not useful among patients with pre-transplant Yerdel-grade I/II portal vein thrombosis: A two-center retrospective study.

BACKGROUND: Portal vein thrombosis (PVT) is no longer a contraindication for liver transplantation (LT). While therapeutic anticoagulation (tAC) is recommended during the waiting period, there is no evidence for its usefulness in the prevention of PVT recurrence after LT. OBJECTIVES: The aim of our study was to evaluate the role of tAC post-LT in the prevention of PVT recurrence. PATIENTS/METHODS: All adult LTs performed in two high-volume centers between 2003 and 2018 were retrospectively analysed. Only patients with PVT classified as Yerdel grade I or II and with standard portal reconstruction were included. PVT recurrence and tAC-associated morbidity within 1 year were compared between patients receiving tAC or not. RESULTS: During the study period, of 2612 LTs performed, 235 (9%) patients with PVT were included; 113 patients (48.1%) received post-LT tAC (tAC group) while 122 (51.9%) did not (non-tAC group). The incidence of bleeding events was significantly higher in the tAC group (26 [23%] vs. 5 [4.1%], P < .01) and the initial hospitalization duration was longer (21 vs. 17.5 days, P < .01). Within the first year, PVT recurrence was observed for 9 (3.8%) patients without any difference between the tAC and non-tAC groups (6 [5.1%] vs. 3 [2.5%], P = .39). The only identified risk factor for PVT recurrence was the recipients' age (odds ratio= 0.94, P = .03). Graft (P = .11) and patient (P = .44) survival were similar between the two groups. CONCLUSION: Therapeutic anticoagulation is not necessary in the prevention of grade I/II PVT recurrence and is associated with higher morbidity and longer hospital stay.

Donor genetic variants as risk factors for thrombosis after liver transplantation: A genome-wide association study.

Thrombosis after liver transplantation substantially impairs graft- and patient survival. Inevitably, heritable disorders of coagulation originating in the donor liver are transmitted by transplantation. We hypothesized that genetic variants in donor thrombophilia genes are associated with increased risk of posttransplant thrombosis. We genotyped 775 donors for adult recipients and 310 donors for pediatric recipients transplanted between 1993 and 2018. We determined the association between known donor thrombophilia gene variants and recipient posttransplant thrombosis. In addition, we performed a genome-wide association study (GWAS) and meta-analyzed 1085 liver transplantations. In our donor cohort, known thrombosis risk loci were not associated with posttransplant thrombosis, suggesting that it is unnecessary to exclude liver donors based on thrombosis-susceptible polymorphisms. By performing a meta-GWAS from children and adults, we identified 280 variants in 55 loci at suggestive genetic significance threshold. Downstream prioritization strategies identified biologically plausible candidate genes, among which were AK4 (rs11208611-T, p = 4.22 × 10-05 ) which encodes a protein that regulates cellular ATP levels and concurrent activation of AMPK and mTOR, and RGS5 (rs10917696-C, p = 2.62 × 10-05 ) which is involved in vascular development. We provide evidence that common genetic variants in the donor, but not previously known thrombophilia-related variants, are associated with increased risk of thrombosis after liver transplantation.

Donor tobacco smoking is associated with postoperative thrombosis after primary liver transplantation.

BACKGROUND: Thrombosis after liver transplantation is a leading cause of graft loss, morbidity, and mortality. Several known recipient- and surgery-related characteristics have been associated with increased risk of thrombosis after transplantation. Potential donor-related risk factors, however, remain largely undefined. OBJECTIVES: We aimed to identify risk factors for early post-transplantation thrombosis (<90 days) and to determine the impact of early postoperative thrombosis on long-term graft and patient survival. PATIENTS/METHODS: A post hoc analysis was performed of an observational cohort study including all primary, adult liver transplantations performed between 1993 and 2018. Donor-, recipient-, and surgery-related characteristics were collected. Competing risk model analyses and multivariable regression analyses were performed to identify risk factors for developing early post-transplant thrombosis and graft failure. RESULTS: From a total of 748 adult liver transplantations, 58 recipients (7.8%) developed a thrombosis after a median of 7 days. Post-transplantation thrombotic events included 25 hepatic artery thromboses, 13 portal vein thromboses, and 22 other thrombotic complications. Donor history of smoking was independently associated with early postoperative thrombosis (odds ratio [OR] 2.42; 95% confidence interval [CI], 1.29-4.52). Development of early post-transplant thrombosis was independently associated with patient mortality (hazard ratio [HR] 3.61; 95% CI 1.54-8.46) and graft failure (HR 5.80, 95% CI 3.26-10.33), respectively. CONCLUSION: Donor history of smoking conveys a more than two-fold increased risk of thrombosis after liver transplantation, independent of other factors. Post-transplant thrombosis was independently associated with decreased patient and graft survival.