Background: With increasing US adiposity, nonalcoholic steatohepatitis (NASH) is now a leading liver transplant (LT) indication. Given its association with hepatocellular carcinoma (HCC), the burden of NASH is substantial. We analyzed birth cohort effects among NASH LT registrants, with and without HCC.

Methods: All new LT registrants in United Network for Organ Sharing (1995-2015) were identified. Birth cohorts were defined as: 1936-1940, 1941-1945, 1946-1950, 1951-1955, 1956-1960, 1961-1965, 1966-1970, 1971-2015. Poisson regression examined trends in LT registration, by disease etiology (NASH, hepatitis C virus [HCV], other liver disease etiologies [OTHER]), and HCC.

Results: We identified 182 368 LT registrants with median age of 52 years (range, 0-86 years). Nine percent (n = 16 160) had NASH, 38% (n= 69 004) HCV, 53% (n = 97 204) OTHER. HCC was present in: 13% (n = 2181), 27% (n = 18 295), and 11% (n = 10 902), of NASH, HCV, and OTHER, respectively. Liver transplant registration for HCC increased significantly from 2002 to 2015 across all etiologies (NASH, 6%-18%; HCV, 19%-51%; OTHER, 9%-16%; P < 0.0001 for all). NASH LT registrations, with and without HCC, increased sharply in patients born from 1945 to 2015. This upward NASH trend is in stark contrast to HCV LT registrations, which showed a general decline. Notably, a sharp rise in LT registrations is occurring among younger NASH patients (35-55 years), mirroring the increasing adiposity across all age groups in the US population.

Conclusions: NASH LT registrants, with and without HCC, have increased over time, and are projected to increase unabated in the future, notably among younger birth cohorts ("Adipose Wave Effect"). HCC LT registration patterns demonstrate that, compared with HCV, NASH patients encompass younger birth cohorts. These data illustrate that the full impact of NASH on demand for LT is yet to be realized.