(056) Non-Alcoholic Steatohepatitis (NASH) as a Risk Factor in Hepatocellular Carcinoma (HCC) Development

Background: HCC is a leading cause of cancer-related deaths. Nonalcoholic steatohepatitis (NASH), now known as metabolic dysfunction-associated steatohepatitis (MASH), is one of the fastest-growing causes of chronic liver disease (CLD) and HCC. Due to underdiagnosis, poor surveillance, and a lack of treatment options, it is suspected that NASH patients present with a more advanced stage liver disease at diagnosis and subsequently develop HCC sooner than individuals with other liver/metabolic diseases. However, the relationship between NASH and HCC is not well understood.

Objectives: To estimate the differential time-to- and time-varying probability of HCC development between NASH and non-NASH Medicare patients.

Methods: Liver disease type (NASH, other liver disease, other metabolic disease, and multiple etiologies) and index date were determined using SEER-Medicare HCC data from 1999 to 2020, with a one-year lookback period used to confirm incident disease. NASH was identified using 571.8, 571.9, and K75.81 ICD diagnosis codes, with K75.81 used for validation. Patients with idiopathic HCC and multiple etiology were excluded due to an inability to assign an index date and isolate cofounder HCC etiologies. Survival curves were constructed for NASH and non-NASH patients separately using an extension of the traditional Kaplan-Meier estimator that accounts for potential confounding through the incorporation of inverse probability of treatment weighting, and the arithmetic difference in restricted mean survival times (average time to HCC during the follow-up period for NASH vs. non-NASH patients) was estimated. 95% confidence intervals (CI) were calculated via bootstrap resampling.

Results: A total of 12,610 HCC patients were included in the final sample, 229 with NASH and 12,381 non-NASH (other liver or metabolic disease). Of the 229 NASH patients, 27% (n=62) had confirmed cirrhosis at HCC diagnosis compared with 35% (n=4,339) of non-NASH patients with cirrhosis at HCC diagnosis. Median time to HCC diagnosis was 1.13 years (95% CI: 0.60 to 1.71) in patients with NASH, and HCC was diagnosed 1.88 years (95% CI: 1.41 to 2.35) faster on average than in non-NASH patients. During the five years following CLD diagnosis, the probability of developing HCC was at least 20 percentage points higher in NASH patients than non-NASH patients.

Conclusions: Results from this analysis using clinically rich SEER-Medicare data and advanced survival analysis methodology suggest that NASH patients develop HCC sooner than those with other CLD. Increasing surveillance and effective treatment could halt the progression and subsequently reduce HCC incidence.