Orandi, Babak John

The prevalence of comorbid metabolic dysfunction–associated steatotic liver disease (MASLD) and obesity has increased exponentially over the last several years, with current estimates demonstrating that up to 40% of adults in the United States have MASLD. Metabolic dysfunction–associated steatohepatitis is now a leading indication for liver transplantation, and rates of obesity and MASLD pre-transplant and post-transplant are on the rise. Our understanding of the physiology of obesity and metabolic disease and the availability of effective obesity treatments have evolved over the same time frame. With the availability of new anti-obesity medications, there has been a debate over the role of pharmacotherapy versus interventional approaches in the treatment of obesity and MASLD in the liver transplantation population. In October 2024, the American Society of Transplantation (AST) Liver and Intestinal Community of Practice held a virtual Controversies Conference on obesity and liver transplantation. Experts in the field presented the available data, and smaller working groups had interactive breakout sessions that identified knowledge gaps and developed recommendations. This perspective prepared on behalf of the participants of the AST Controversies Conference on obesity and liver transplant aims to summarize the available evidence for surgical and pharmaceutical treatment in the liver transplantation population.

Objective: To examine whether body mass index (BMI) changes modify the association between kidney donation and incident hypertension. Background: Obesity increases hypertension risk in both general and living kidney donor (LKD) populations. Donation-attributable risk in the context of obesity, and whether weight change modifies that risk, is unknown. Methods: Nested case-control study among 1558 adult LKDs (1976–2020) with obesity (median follow-up: 3.6 years; interquartile range: 2.0–9.4) and 3783 adults with obesity in the Coronary Artery Risk Development in Young Adults (CARDIA) and Atherosclerosis Risk in Communities (ARIC) studies (9.2 y; interquartile range: 5.3–15.8). Hypertension incidence was compared by donor status using conditional logistic regression, with BMI change investigated for effect modification. Results: Overall, LKDs and nondonors had similar hypertension incidence [incidence rate ratio (IRR): 1.16, 95% confidence interval (95% CI): 0.94–1.43, P=0.16], even after adjusting for BMI change (IRR: 1.25, 95% CI: 0.99–1.58, P=0.05). Although LKDs and nondonors who lost >5% BMI had comparable hypertension incidence (IRR: 0.78, 95% CI: 0.46–1.34, P=0.36), there was a significant interaction between donor and >5% BMI gain (multiplicative interaction IRR: 1.62, 95% CI: 1.15–2.29, P=0.006; relative excess risk due to interaction: 0.90, 95% CI: 0.24–1.56, P=0.007), such that LKDs who gained weight had higher hypertension incidence than similar nondonors (IRR: 1.83, 95% CI: 1.32–2.53, P<0.001). Conclusions: Overall, LKDs and nondonors with obesity had similar hypertension incidence. Weight stability and loss were associated with similar hypertension incidence by donor status. However, LKDs who gained >5% saw increased hypertension incidence versus similar nondonors, providing support for counseling potential LKDs with obesity on weight management postdonation.

Background. Desensitization protocols for HLA-incompatible living donor kidney transplantation (ILDKT) vary across centers. The impact of these, as well as other practice variations, on ILDKT outcomes remains unknown. Methods. We sought to quantify center-level variation in mortality and graft loss following ILDKT using a 25-center cohort of 1358 ILDKT recipients with linkage to Scientific Registry of Transplant Recipients for accurate outcome ascertainment. We used multilevel Cox regression with shared frailty to determine the variation in post-ILDKT outcomes attributable to between-center differences and to identify any center-level characteristics associated with improved post-ILDKT outcomes. Results. After adjusting for patient-level characteristics, only 6 centers (24%) had lower mortality and 1 (4%) had higher mortality than average. Similarly, only 5 centers (20%) had higher graft loss and 2 had lower graft loss than average. Only 4.7% of the differences in mortality (P < 0.01) and 4.4% of the differences in graft loss (P < 0.01) were attributable to between-center variation. These translated to a median hazard ratio of 1.36 for mortality and 1.34 of graft loss for similar candidates at different centers. Post-ILDKT outcomes were not associated with the following center-level characteristics: ILDKT volume and transplanting a higher proportion of highly sensitized, prior transplant, preemptive, or minority candidates. Conclusions. Unlike most aspects of transplantation in which center-level variation and volume impact outcomes, we did not find substantial evidence for this in ILDKT. Our findings support the continued practice of ILDKT across these diverse centers.