Characteristics and outcomes of patients with imaging-defined MASLD and histological steatosis grade S0.

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver disease, and liver biopsy remains the gold standard for diagnosis. However, a subset of patients diagnosed with MASLD by imaging paradoxically exhibit steatosis grade S0 upon liver biopsy, posing a diagnostic challenge. This study investigates the outcomes and causes of "steatosis 0". "Steatosis 0" was defined as imaging-detected MASLD with a biopsy-defined steatosis grade S0. We used global cohorts to evaluate outcomes, histologic progression via paired biopsies, and possible causes. The cause analysis included MRI-PDFF for fat distribution, pathologist consistency testing, and comparison of serial biopsy sections. In a follow-up cohort of 3,273 biopsy individuals from 16 centers, 123 (3.8%) exhibited "steatosis 0". Of these, 29.3% of them had advanced fibrosis ("burnt-out" MASLD) and demonstrated a risk of liver-related events, while those without advanced fibrosis had no such events. In the paired-biopsy cohort of 1,865 patients, 74 (4.0%) individuals initially showed steatosis grade S0; among them, 93.2% retained no or mild steatosis on follow-up biopsy. MRI-PDFF assessments in 42 MASLD patients revealed heterogeneous hepatic fat distribution, with some segments showing steatosis grade S0 despite elevated average liver fat. Inter-pathologist variability and discrepancies across consecutive biopsy sections contributed to misclassification of steatosis grade. "Steatosis 0" represents a potential diagnostic gray zone in MASLD. It may be caused by "burnt-out" MASLD, uneven liver fat distribution, or variability in pathological assessment. Understanding the causes and implications of "steatosis 0" is critical for diagnosis and management.