Abstract

Background:

High prevalence of obesity in the U.S. is driving the burden of non-alcoholic steatohepatitis (NASH) and associated adverse clinical outcomes including NASH-related end-stage liver disease and hepatocellular carcinoma (HCC). Our aim was to assess the most recent trends in patients with chronic liver disease (CLD) listed for liver transplantation (LT) in the U.S. using a national registry.

Methods:

The Scientific Registry of Transplant Recipients (SRTR) was used to select adult (≥18 years at listing) LT candidates included between 2013-2022. Primary and secondary listing etiologies were used to identify patients with the most common etiologies of CLD.

Results:

There were 116,292 LT candidates with a known etiology of CLD. In candidates without HCC, the most common CLD etiology was alcoholic liver disease (ALD) which increased from 23% (2013) to 48% (2022); the most rapid increase happened between 2019-2022 (from 38% to 48%). The second most common indication for non-HCC LT was NASH, the proportion of which increased from 19% (2013) to 27% (2022). In contrast, rates of chronic hepatitis C (CHC) decreased from 28% (2013) to 4% (2022) and chronic hepatitis B (CHB) declined from 1.8% (2013) to 1.1% (2022) (all trend p<0.01). Cumulatively, 21% (n=24,657) of candidates listed for LT had HCC. However, the proportion of HCC decreased from 24-25% (2013-2016) to 17% (2021-2022). Among candidates with HCC, the proportion of CHC decreased from 60% (2013) to 27% (2022) while NASH increased from 10% to 31% and ALD from 9% to 24%, respectively (all trend p<0.0001) (Figure). On the other hand, the proportion of CHB remained stable between 5 to 7% (trend p=0.62). Among candidates with HCC, the rapid increase in the proportion of NASH continued during the most recent study years: 20% (2018) to 28% (2020) to 31% (2022), and the increasing trend remained significant overtime after adjustment for candidates’ age, sex, ethnicity, obesity, and type 2 diabetes. The average magnitude of increase in the proportion of NASH in candidates with HCC in 2018-2022 was +2.8 percentage points per year (p<0.0001).

Conclusion:

The impact of different etiologies of CLD to LT burden in the U.S. has been changing over the last decade. ALD and NASH remain the two most common indications for non-HCC-LT, while NASH is currently the most common indication for HCC-LT.