Clonal hematopoiesis of indeterminate potential and metabolic dysfunction-associated steatotic liver disease: Korean biopsy cohort

BACKGROUND & AIMS: Clonal hematopoiesis of indeterminate potential (CHIP) has emerged as a contributor to age-related diseases; however, its clinical relevance to metabolic liver disease remains to be established. This study investigated the association between CHIP and metabolic dysfunction-associated steatotic liver disease (MASLD) severity in a Korean biopsy cohort. METHODS: We conducted a prospective analysis of 486 individuals who underwent liver biopsy and whole genome sequencing between 2014 and 2023. CHIP status was defined by pathogenic somatic mutations in known driver genes with a variant allele frequency ≥2%. Histological assessment was performed using the NASH-CRN scoring system. Logistic regression was used for cross-sectional associations, and Cox proportional hazards models were applied for fibrosis progression outcomes. RESULTS: Among 427 eligible participants (median age 56 years), 37 (8.7%) harbored pathogenic CHIP mutation, predominantly DNMT3A (n=8) and TET2 (n=6). CHIP prevalence did not differ significantly across histological categories: no steatotic liver disease (10.9%), metabolic dysfunction-associated steatotic liver (6.5%), and metabolic dysfunction-associated steatohepatitis (10.9%; p=0.269). No clinical or histological variable was consistently associated with CHIP across definitions in adjusted or unadjusted analyses. Over a median 28-month follow-up, fibrosis progression occurred in 28 of 287 patients with serial assessments; no significant association with CHIP status was observed (HR 0.67, 95% CI 0.16-2.84; p=0.582). CONCLUSIONS: In this biopsy-based cohort, CHIP was not significantly associated with hepatic histology severity or fibrosis progression. Given the limited number of CHIP carriers and progression events, clinically meaningful associations cannot be excluded and larger, longer-term longitudinal studies are warranted.