We assessed the burden of nonalcoholic fatty liver disease (NAFLD) related acute on chronic liver failure (ACLF) among transplant candidates in the United States (US), along with waitlist outcomes for this population. We analyzed the United Network for Organ Sharing (UNOS) registry from 2005-2017. Patients with ACLF were identified using the EASL-CLIF criteria and categorized into NAFLD, alcoholic liver disease (ALD), and hepatitis C virus (HCV) infection. We used linear regression and Chow’s test to determine significance in trends and evaluated waitlist outcomes using Fine and Gray’s competing risks regression and Cox proportional hazards regression. Between 2005 and 2017, waitlist registrants for NAFLD-ACLF rose by 331.6% from 134 to 574 candidates (p<0.001), representing the largest percentage increase in the study population. ALD-ACLF also increased by 206.3% (348 to 1,066 registrants, p<0.001), while HCV-ACLF declined by 45.2% (p<0.001). As of 2017, the NAFLD-ACLF population consisted primarily of individuals age 60 or older (54.1%), and linear regression demonstrated a significant rise in the proportion of patients age ≥ 65 in this group (β=0.90, p=0.011). Since 2014, NAFLD-ACLF grade 1 was associated with a greater risk of waitlist mortality relative to ALD-ACLF (SHR=1.24, 95% CI 1.05-1.44) and HCV-ACLF (SHR=1.35, 95% CI 1.08-1.71), among patients ≥ 60 years old. Mortality was similar among the three groups for patients with ACLF grade 2 or 3. CONCLUSION: NAFLD is the fastest rising etiology of cirrhosis associated with ACLF among patients listed in the US. As the NAFLD population continues to grow and age, patients with NAFLD-ACLF will likely have the highest risk of waitlist mortality.
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