OBJECTIVES: HCC is a leading cause of cancer-related deaths worldwide. Nonalcoholic steatohepatitis (NASH) has become one of the fastest-growing causes of HCC in the US. Although HCC occurs more frequently in cirrhosis patients, it’s estimated that up to 50% of NASH HCC patients are non-cirrhotic at HCC diagnosis. Currently, little evidence exists regarding characteristics of non-cirrhotic NASH patients who develop HCC.

METHODS: A retrospective cohort study including NASH HCC patients diagnosed from 1999-2020 in SEER-Medicare data was conducted. NASH was defined as the presence of ICD-10 K75.81 or ICD-9 571.8/571.9 (with a subsequent K75.81 code) diagnosis codes, with a one-year lookback period used to confirm incident disease. Demographic and clinical factors associated with non-cirrhotic HCC were identified using separately specified logistic regression models. Average marginal effects were estimated via recycled predictions. Standard errors and 95% confidence intervals were generated using bootstrap resampling.

RESULTS: Of 435 total NASH HCC patients, 73% (318) had cirrhosis at HCC diagnosis and 27% (117) did not. On average, non-cirrhotic NASH patients had a shorter time-to-HCC diagnosis (1.57 years vs 2.6 years in cirrhotic patients). The likelihood of developing HCC without cirrhosis in NASH patients was estimated to be 44% lower in women, 24% lower in obese individuals, 13% lower in diabetics, and 20% lower in individuals with a Charlson Comorbidity Index of 2+ compared to those with a score of 0. Older patients with hypertension were more likely to develop non-cirrhotic HCC, with a 1.2 percentage point increase in risk per year of age and a 43% higher risk in hypertensives.

CONCLUSIONS: We found that non-cirrhotic NASH patients developed HCC sooner, on average, and were more likely to be otherwise healthy, older, male, and hypertensive. Results highlight the potential role of expanded surveillance and effective early-stage NASH treatment in reducing HCC disease burden in this population.