P3759 - Metabolic Dysfunction-Associated Steatohepatitis (MASH) as a Risk Factor for Hepatocellular Carcinoma (HCC) Mortality

Yestle Kim, PharmD, MS¹, Samantha Clark, PhD², Robert Gish, MD³
1Madrigal Pharmaceuticals, West Conshohocken, PA; 2Medicus Economics LLC, Milton, MA; 3Gish Associates, Folsom, CA

Introduction: HCC is a leading cause of cancer-related deaths worldwide. MASH has become one of the fastest growing risk factors of HCC in the US. While studies suggest that individuals with MASLD are at a higher risk of HCC mortality, evidence regarding the relationship between MASH and HCC mortality death is limited. We aim to add to the existing evidence base by assessing the differential risk of HCC-related death among MASH and non-MASH patients within a competing events framework.

Methods: A retrospective cohort study including HCC patients diagnosed from 2015 - 2020 was conducted using SEER-Medicare data. The 12-month period prior to HCC diagnosis date (index date) was used for sample selection, covariate measurement, and to determine MASH status using the K75.81 diagnosis code. Patients presenting with MASH and other liver diseases (e.g., viral hepatitis) were excluded due to an inability to identify proximate HCC cause. The study period consisted of the time from a patient’s index date through first of the following events: HCC death, non-HCC death, a censoring event, or loss to follow-up. Cause-specific (CS) hazard models were fitted to evaluate the relationship between MASH, HCC death, and the competing risk of non-HCC death. Results from a separate Fine-Gray (FG) subdistribution hazard model were used to assess the extent to which differential non-HCC death rates may be driving these results. All models adjusted for year of HCC diagnosis, age at HCC diagnosis, sex, race/ethnicity, cirrhosis status, HCC stage at diagnosis, and Charlson Comorbidity Index. Model assumptions were tested via residual analysis.

Results: Of the 6,301 HCC patients included, 313 (5%) had a prior MASH diagnosis and 5,988 (95%) did not. The majority of patients (68.1%) died within 5 years of their HCC diagnosis, with 76% of these deaths attributable to HCC. CS model results indicate that the risk of HCC mortality was 23% higher in MASH patients over the follow-up period (adjusted CS hazard ratio [HR]: 1.23, 95% confidence interval (CI): 1.05 - 1.44). The minimal difference between HRs from the CS model for HCC death and FG model (adjusted FG HR: 1.17, 95% CI: 1.00 - 1.38) indicate that the impact of non-HCC death as a competing event is small.

Discussion: In this analysis, clinically rich SEER-Medicare data were combined with competing risks survival analysis to generate additional insights into the relationship between MASH and HCC death. Results suggesting that MASH patients are at a higher risk of HCC death

Disclosures:
Yestle Kim: Madrigal Pharmaceuticals – Employee, Stock Options.
Samantha Clark: Madrigal Pharmaceuticals – Consultant.
Robert Gish: Madrigal Pharmaceuticals – Consultant.

Yestle Kim, PharmD, MS¹, Samantha Clark, PhD², Robert Gish, MD³. P3759 - Metabolic Dysfunction-Associated Steatohepatitis (MASH) as a Risk Factor for Hepatocellular Carcinoma (HCC) Mortality, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.