Nonalcoholic steatohepatitis is the most rapidly growing cause of HCC among US patients listed for liver transplantation.

BACKGROUND & AIMS:The profile of chronic liver disease (CLD) in the United States has changed due to obesity trends and advances in treatment of viral hepatitis. We assessed liver transplant listing trends by CLD etiology. METHODS:Adult candidates for liver transplantation were selected from the Scientific Registry of Transplant Recipients (2002 through 2019. We calculated proportion trends for common CLD etiologies at time of placement on the wait list, including chronic infection with hepatitis B virus, chronic infection with hepatitis C virus (HCV), nonalcoholic steatohepatitis (NASH, including cryptogenic cirrhosis), alcohol-related liver disease (ALD) without or with chronic HCV infection, autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis, in patients with and without hepatocellular carcinoma (HCC). RESULTS:From the 168,441 patients with known etiology and non-acute liver failure on the liver transplant waitlist, 27,799 patients (16.5%) had HCC. In 2002, the most common etiologies in patients without HCC were chronic HCV infection (37%) and ALD (16%), whereas only 5% had NASH. Among patients with HCC, 58% had chronic HCV infection and 10% had ALD and only 1% had NASH. In 2019, among patients without HCC, NASH was the second leading indication for liver transplantation (28% of patients), after ALD (38% of patients). Among patients with HCC, chronic HCV infection remained the leading indication (40% of patients) but NASH (24% of patients) surpassed ALD (16% of patients) to become the second leading indication. NASH was the leading indication in women without HCC (34%), in patients older than 54 years (36%), and in patients on Medicare (41%). In trend analysis, NASH was the most rapidly increasing indication for liver transplantation in patients without HCC (Kendall tau[0.97; P < .001) and in patients with HCC (tau[0.94; P < .0001). CONCLUSIONS:In an analysis of data from the Scientific Registry of Transplant Recipients (2002 through 2019), we found NASH to be the second most common indication for liver transplant in 2019, and the fastest increasing indication. In 2019, NASH was the leading indication for liver transplantation among women without HCC.

NASH, especially advanced NASH, is associated with high lifetime economic burden. In the absence of treatment, the total direct costs of illness for these patients will continue to grow. These costs would be even greater if the societal costs are included. This article is protected by copyright. All rights reserved.

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) and is strongly associated with type 2 diabetes mellitus (T2DM). Patients with both T2DM and NASH have increased risk for adverse clinical outcomes, leading to higher risk for mortality and morbidity. We built a Markov model with 1-year cycles and 20-year horizon to estimate the economic burden of NASH with T2DM in the U.S. RESEARCH DESIGN AND METHODS Cohort size was determined by population size, prevalence of T2DM, and prevalence and incidence of NASH in 2017. The model includes 10 health statesdNAFL, NASH fibrosis stages F0 through F3, compensated and decompensated cirrhosis, hepatocellular carcinoma, 1 year post-liver transplant, and post-liver transplantdas well as liver-related, cardiovascular, and background mortality. Transition probabilities were calculated from meta-analyses and literature. Annual costs for NASH and T2DM were taken from literature and billing codes. RESULTS We estimated that there were 18.2 million people in the U.S. living with T2DM and NAFLD, of which 6.4 million had NASH. Twenty-year costs for NAFLD in these patients were $55.8 billion. Over the next 20 years, NASH with T2DM will account for 65,000 transplants, 1.37 million cardiovascular-related deaths, and 812,000 liver-related deaths. CONCLUSIONS This model predicts significant clinical and economic burden due to NASH with T2DM over the next 20 years. In fact, this burden may be greater since we assumed conservative inputs for our model and did not increase costs or the incidence of T2DM over time. It is highly likely that interventions reducing morbidity and mortality in NASH patients with T2DM could potentially reduce this projected clinical and economic burden. Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis (.5%) in the absence of excessive alcohol consumption or other causes of fatty liver disease and chronic liver disease (1). NAFLD ranges from simple steatosis (NAFL), which has a low likelihood of progression to advanced liver disease, to nonalcoholic steatohepatitis (NASH), which has greater potential for progression. NAFLD is recognized as one of the most common causes of chronic liver disease in the U.S. and worldwide (1-3). NAFLD is

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