The causes of death in patients with nonalcoholic steatohepatitis following liver transplantation stratified using pre-liver transplant BMI.

Abstract

Determining the effects of pre-liver transplant (LT) BMI independent of underlying ascites on the post-LT outcomes of patients with nonalcoholic steatohepatitis (NASH) is needed to clarify the paradoxical and protective effects of obesity on post-LT endpoints. In order to accomplish this, we used graded severities of ascites to stratify the NASH-LT population and to perform an ascites-specific strata analysis with differing pre-LT BMI levels. 2005-2019 United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research (STAR) database was queried to select patients with NASH, who were categorized into specific sets of ascites severity: no ascites (n = 1188), mild ascites (n = 4463), and moderate ascites (n = 3525). Then, BMI classification (underweight: < 18.5, normal: 18.5-25, overweight: 25-30, obese: ≥ 30kg/m2) was used to stratify each ascites-specific group and to compare to the post-LT mortality endpoints. Those under 18years old and those who received living/multi-organ transplants were excluded. Among each ascites category, there were the following numbers of normal, underweight, overweight, and obese BMI patients respectively; no ascites: 161, 4, 359, 664; mild ascites: 643, 28, 1311, 2481; and moderate ascites: 529, 25, 1030, 1941. The obese BMI cohort was at a lower risk of all-cause mortality compared to recipients with normal BMI with mild ascites (aHR: 0.79, 95% Confidence Interval (CI) 0.65-0.94, p-value = 0.010; case-incidence 47.10 vs 56.81 deaths per 1000 person-years) and moderate ascites (aHR: 0.77, 95% CI 0.63-0.94, p-value = 0.009; case-incidence 53.71 vs 66.17 deaths per 1000 person-years). In addition, the overweight BMI cohort with mild ascites demonstrated a lower hazard of all-cause mortality (aHR: 0.80, 95% CI 0.66-0.97, p-value = 0.03; case-incidence 49.09 vs 56.81 deaths per 1000 person-years). There was no difference in graft failure for the three BMI groups (underweight, overweight, and obese) in comparison to normal BMI. Furthermore, the overweight BMI group with mild ascites cohort demonstrated a lower hazard of death due to general infectious causes (aHR: 0.51, 95% CI 0.32-0.83, p = 0.006; case-incidence 6.12 vs 11.91 deaths per 1000 person-years) and sepsis (aHR: 0.49, 95% CI 0.27-0.86, p = 0.01; case-incidence 4.31 vs 8.50 deaths per 1000 person-years). The paradoxical effects of obesity in reducing the risks of all-cause death appears to be in part modulated by ascites. The current study emphasizes the need to evaluate BMI with concomitant ascites severity pre-LT to accurately prognosticate post-LT outcomes when evaluating NASH patients with advanced liver disease.