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Survival After Liver Transplant Similar With NASH and Other Causes
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AASLD The Liver Meeting Digital Experience, November 13-16, 2020
Mark Mascolini
Survival after liver transplantation proved comparable in people with nonalcoholic steatohepatitis (NASH) and people who have transplants for other indications, according to results of a 942-person US analysis [1]. Researchers working with the multicenter NAIL NASH consortium believe many of the factors driving mortality in NASH liver transplant recipients are modifiable risk factors.
NASH remains the fastest-growing reason for liver transplantation in the United States. But analyzing liver transplantation in people with NASH is difficult because reports are limited to population-based data with unadjudicated outcomes and sometimes by small numbers. To overcome these obstacles, US researchers created NAIL NASH, an initially retrospective cohort of people with NASH who got a liver transplant between January 1995 and October 2016 at 1 of 7 tertiary care academic centers. A prospective cohort began in 2018.
Inclusion criteria for the cohort included (1) liver transplantation for biopsy-confirmed NASH, (2) cryptogenic cirrhosis if meeting prespecified criteria for adjudicated NASH, (3) fatty liver with cirrhosis before liver transplant on imaging or explant with 1 or more metabolic syndrome features OR 2 or more metabolic syndrome features, and (4) no other cause of liver disease. To determine causes of death, the researchers cross-referenced all deaths with the United Network for Organ Sharing (UNOS), adjudicated at individual centers, and shared through a data agreement.
The 942 liver transplant recipients averaged 59.3 years in age, and 48.4% were women. Body mass index averaged 32.4 kg/m2, and median MELD score [2] stood at 21. Most cohort members, 79.2%, were while, while African Americans made up 2.4% of the group and Asians 2.6%. Hispanics accounted for 12.5% of the cohort.
Kaplan-Meier analysis estimated 93% survival 1 year after liver transplant for NASH, 88% after 3 years, 83% after 5 years, and 69% after 10 years-rates comparable to other indications for liver transplant [3,4]. Through 14 years after liver transplant for NASH, Kaplan-Meier curves showed significantly longer survival in people who had a transplant before age 60 (P = 0.035).
Analysis of 206 cohort members determined that the most frequent causes of death (besides "other") were infection (19%), cardiovascular disease (18%), cancer (17%), and liver-related (11%). These proportions varied over time: Infection accounted for 28% of deaths in the first year after transplant, for 24% in years 1 to 5 after transplant, for 10% in years 5 to 10, and for 10% after 10 years. Respective proportions of deaths for other reasons in those three periods were 18%, 15%, 20%, and 17% for cardiovascular disease, 20%, 8%, 7%, and 5% for liver disease, and 11%, 13%, 22%, and 25% for cancer.
Among liver-related causes of death, the most frequent was chronic rejection (37%), followed by acute rejection (27%), ischemic cholangiopathy (21%), and recurrent NASH (5%). Among cancer causes of death, the most frequent was lung/bronchial cancer (29.2%), followed by hematologic malignancy (12.5%), pancreatic cancer (12.5%), skin cancer (8.3%), colon/rectal cancer (8.3%), and hepatocellular carcinoma (8.2%).
Frequencies of metabolic comorbidities generally rose from before liver transplant to after transplantation: hypertension (54.2% to 83.0%), diabetes (60.6% to 79.3%), dyslipidemia (21.9% to 36.7%), atrial fibrillation (18.6% to 10.8%), congestive heart failure (0.98% to 9.9%), and ischemic heart failure (1.4% to 2.7%).
The NAIL NASH team suggested that "exposure to chronic immunosuppression in the context of the pre-liver transplant phenotype likely plays a central role in both short- and long-term mortality." Many variables contributing to death after liver transplant, they proposed, "are potentially modifiable risk factors that can be targeted to improve patient outcomes."
References
1. Rinella ME, Watt K, Siddiqui MB, et al. Causes of mortality following liver transplantation for NASH cirrhosis - results of a multicenter consortium (NAIL NASH) study. AASLD The Liver Meeting Digital Experience, November 13-16, 2020. Abstract 28.
2. The Model for End-stage Liver Disease (MELD) score estimates survival with liver
disease over the next 3 months. Higher scores indicate a greater need for liver transplantation. UPMC Transplant Services. What is a MELD score? https://www.upmc.com/services/transplant/liver/process/waiting-list/meld-score
3. Roberts MS, Angus DC, Bryce CL, Valenta Z, Weissfeld L. Survival after liver transplantation in the United States: a disease-specific analysis of the UNOS database. Liver Transpl. 2004;10:886-897.
https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/lt.20137
4. Jain A, Reyes J, Kashyap R, et al. Long-term survival after liver transplantation in 4,000 consecutive patients at a single center. Ann Surg. 2000;232:490-500.
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