Brian P Lee1, Eric Vittinghoff2, Jennifer L Dodge3, Giuseppe Cullaro1, Norah A Terrault1. 1. Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco. 2. Department of Epidemiology and Biostatistics, University of California, San Francisco. 3. Department of Surgery, University of California, San Francisco.
Abstract
Importance: Alcohol-associated liver disease (ALD) has emerged as the most common indication for liver transplant in the United States, but data on the reasons for this increase and long-term post-liver transplant outcomes among liver transplant recipients are sparse. Objective: To characterize trends and long-term outcomes of liver transplant for ALD in the United States between 2002 and 2016. Design, Setting, and Participants: This multicenter, prospective, national cohort study used data from the United Network for Organ Sharing database to evaluate all liver transplants performed in the United States between January 1, 2002, and December 31, 2016. Main Outcomes and Measures: National and regional trends in liver transplant for ALD, with a sensitivity analysis with hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC) included, and early (≤90 days after liver transplant) and late (>90 days after liver transplant) patient and graft survival. Results: The cohort consisted of 32 913 patients, including 9438 with ALD and 23 475 without ALD (patients who had HCV infection and HCC indications were excluded). Median age of patients with ALD was 54 years (interquartile range, 47-60 years) and of patients without ALD was 54 years (interquartile range, 44-61 years). Patients with ALD (vs non-ALD) were more frequently male (7197 of 9438 [76.2%] vs 11 767 of 23 475 [50.1%]; P < .001) and white (7544 [80.0%] vs 17 251 [73.5%]; P < .001). The proportion of liver transplants for ALD increased from 24.2% (433 of 1791) in 2002 to 27.2% (556 of 2044) in 2010 and 36.7% (1253 of 3419) in 2016. With HCV infection included, the proportions of liver transplant for ALD were 15.3% in 2002, 18.6% in 2010, and 30.6% in 2016, representing a 100% increase in liver transplant for ALD, of which 48% was associated with a decrease in HCV infection as an indication for liver transplant. The magnitude of increase in ALD was regionally heterogeneous and associated with changes in patient characteristics suggestive of alcoholic hepatitis: decreasing age (χ2 = 36.5; P = .005) and increasing model for end-stage liver disease score (χ2 = 69.1; P < .001). Cumulative unadjusted 5-year posttransplant survival was 79% (95% CI, 78%-80%) for ALD vs 80% (95% CI, 79%-80%) for non-ALD; cumulative unadjusted 10-year posttransplant survival was 63% (95% CI, 61%-64%) for ALD vs 68% (95% CI, 67%-69%) for non-ALD (P = .006). In multivariable analysis, ALD was associated with increased risk of late death after liver transplant (adjusted hazard ratio, 1.11; 95% CI, 1.03-1.20; P = .006). Conclusions and Relevance: The findings suggest that early liver transplant for alcoholic hepatitis may be leading to broader acceptance of ALD for liver transplant. Late survival among liver transplant recipients with ALD was inferior to that among recipients with non-ALD indications, suggesting a need for future studies to identify patient profiles associated with best outcomes. Regional differences suggest heterogeneity in policies toward liver transplant for ALD.
Importance: Alcohol-associated liver disease (ALD) has emerged as the most common indication for liver transplant in the United States, but data on the reasons for this increase and long-term post-liver transplant outcomes among liver transplant recipients are sparse. Objective: To characterize trends and long-term outcomes of liver transplant for ALD in the United States between 2002 and 2016. Design, Setting, and Participants: This multicenter, prospective, national cohort study used data from the United Network for Organ Sharing database to evaluate all liver transplants performed in the United States between January 1, 2002, and December 31, 2016. Main Outcomes and Measures: National and regional trends in liver transplant for ALD, with a sensitivity analysis with hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC) included, and early (≤90 days after liver transplant) and late (>90 days after liver transplant) patient and graft survival. Results: The cohort consisted of 32 913 patients, including 9438 with ALD and 23 475 without ALD (patients who had HCV infection and HCC indications were excluded). Median age of patients with ALD was 54 years (interquartile range, 47-60 years) and of patients without ALD was 54 years (interquartile range, 44-61 years). Patients with ALD (vs non-ALD) were more frequently male (7197 of 9438 [76.2%] vs 11 767 of 23 475 [50.1%]; P < .001) and white (7544 [80.0%] vs 17 251 [73.5%]; P < .001). The proportion of liver transplants for ALD increased from 24.2% (433 of 1791) in 2002 to 27.2% (556 of 2044) in 2010 and 36.7% (1253 of 3419) in 2016. With HCV infection included, the proportions of liver transplant for ALD were 15.3% in 2002, 18.6% in 2010, and 30.6% in 2016, representing a 100% increase in liver transplant for ALD, of which 48% was associated with a decrease in HCV infection as an indication for liver transplant. The magnitude of increase in ALD was regionally heterogeneous and associated with changes in patient characteristics suggestive of alcoholic hepatitis: decreasing age (χ2 = 36.5; P = .005) and increasing model for end-stage liver disease score (χ2 = 69.1; P < .001). Cumulative unadjusted 5-year posttransplant survival was 79% (95% CI, 78%-80%) for ALD vs 80% (95% CI, 79%-80%) for non-ALD; cumulative unadjusted 10-year posttransplant survival was 63% (95% CI, 61%-64%) for ALD vs 68% (95% CI, 67%-69%) for non-ALD (P = .006). In multivariable analysis, ALD was associated with increased risk of late death after liver transplant (adjusted hazard ratio, 1.11; 95% CI, 1.03-1.20; P = .006). Conclusions and Relevance: The findings suggest that early liver transplant for alcoholic hepatitis may be leading to broader acceptance of ALD for liver transplant. Late survival among liver transplant recipients with ALD was inferior to that among recipients with non-ALD indications, suggesting a need for future studies to identify patient profiles associated with best outcomes. Regional differences suggest heterogeneity in policies toward liver transplant for ALD.
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