Model to Calculate Harms and Benefits of Early vs Delayed Liver Transplantation for Patients With Alcohol-Associated Hepatitis

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 157; no. 2; pp. 472 - 480.e5
• Main Authors: Lee, Brian P., Samur, Sumeyye, Dalgic, Ozden O., Bethea, Emily D., Lucey, Michael R., Weinberg, Ethan, Hsu, Christine, Rinella, Mary E., Im, Gene Y., Fix, Oren K., Therapondos, George, Han, Hyosun, Victor, David W., Voigt, Michael D., Eswaran, Sheila, Terrault, Norah A., Chhatwal, Jagpreet
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-08-2019
• Subjects: 6-month rule; ACCELERATE-AH; Adult; Alcohol Abstinence; Alcohol Drinking - adverse effects; Alcohol Drinking - prevention & control; drinking; End Stage Liver Disease - diagnosis; End Stage Liver Disease - etiology; End Stage Liver Disease - mortality; End Stage Liver Disease - surgery; Female; Hepatitis, Alcoholic - complications; Hepatitis, Alcoholic - diagnosis; Hepatitis, Alcoholic - mortality; Hepatitis, Alcoholic - surgery; Humans; Life Expectancy; Liver Transplantation - methods; Liver Transplantation - standards; Male; Markov model; Middle Aged; Models, Biological; Prospective Studies; Risk Assessment - methods; Severity of Illness Index; Survival Analysis; Time Factors; Time-to-Treatment; Treatment Outcome; Waiting Lists; 6-month rule; ACCELERATE-AH; drinking; MELD; SIM-LT; AH; LT; UNOS; Markov model
• ISSN: 0016-5085; 1528-0012; 1528-0012
• DOI: 10.1053/j.gastro.2019.04.012

Early liver transplantation (without requiring a minimum period of sobriety) for severe alcohol-associated hepatitis (AH) is controversial: many centers delay eligibility until a specific period of sobriety (such as 6 months) has been achieved. To inform ongoing debate and policy, we modeled long-term outcomes of early vs delayed liver transplantation for patients with AH.
We developed a mathematical model to simulate early vs delayed liver transplantation for patients with severe AH and different amounts of alcohol use after transplantation: abstinence, slip (alcohol use followed by sobriety), or sustained use. Mortality of patients before transplantation was determined by joint-effect model (based on Model for End-Stage Liver Disease [MELD] and Lille scores). We estimated life expectancies of patients receiving early vs delayed transplantation (6-month wait before placement on the waitlist) and life years lost attributable to alcohol use after receiving the liver transplant.
Patients offered early liver transplantation were estimated to have an average life expectancy of 6.55 life years, compared with an average life expectancy of 1.46 life years for patients offered delayed liver transplantation (4.49-fold increase). The net increase in life expectancy from offering early transplantation was highest for patients with Lille scores of 0.50–0.82 and MELD scores of 32 or more. Patients who were offered early transplantation and had no alcohol use afterward were predicted to survive 10.85 years compared with 3.62 years for patients with sustained alcohol use after transplantation (7.23 life years lost). Compared with delayed transplantation, early liver transplantation increased survival times in all simulated scenarios and combinations of Lille and MELD scores.
In a modeling study of assumed carefully selected patients with AH, early vs delayed liver transplantation (6 months of abstinence from alcohol before transplantation) increased survival times of patients, regardless of estimated risk of sustained alcohol use after transplantation. These findings support early liver transplantation for patients with severe AH. The net increase in life expectancy was maintained in all simulated extreme scenarios but should be confirmed in prospective studies. Sustained alcohol use after transplantation significantly reduced but did not eliminate the benefits of early transplantation. Strategies are needed to prevent and treat posttransplantation use of alcohol.