Unveiling the Burden of MASLD and Liver Fibrosis in India: Novel Insights from the Phenome India Study into fibrosis without MASLD

BackgroundMetabolically-dysfunction-associated steatotic liver disease (MASLD) is rising globally, including in India, yet community-based data remain scarce. We addressed this critical knowledge gap by assessing the prevalence, distribution, and characteristics of MASLD subgroups and fibrosis, leveraging the Phenome India-CSIR Health Cohort Knowledgebase (PI-CHeCK) study. MethodsIn this prospective, nationwide study, we recruited 10267 adults across 37 laboratories of the Council of Industrial Research (CSIR) from 27 Indian cities. Steatosis and fibrosis were assessed by Transient Elastography using Fibroscan, with associated clinical, biochemical, cytokine, anthropometric, and lifestyle data collected. Overall, crude and age-adjusted prevalence rates were estimated in the study population and various subgroups. FindingsOf the 10267 individuals screened, 7764 were eligible for analysis after exclusions. Among these, 3,712 (47.8%) fulfilled MASLD criteria, corresponding to an age-adjusted prevalence of 36.3%. Significant fibrosis ([≥]F2) was more frequent in MASLD (6.3% [234 of 3688]) than in cases of cryptogenic fibrosis without MASLD (1.7% [69 of 4027]), corresponding to an age-adjusted prevalence of 4.1% in MASLD. Overall age-adjusted prevalence of significant fibrosis was 2.3% in the entire cohort, which clustered in older adults (>60 years) and in those with diabetes or obesity II, with evidence of regional variation, peaking in Jorhat, Assam. Importantly, fibrosis in participants without MASLD emerged as a distinct subgroup with disproportionately elevated cytokine levels, exceeding those in MASLD with fibrosis, suggesting a cytokine-rich, high-risk phenotype. ConclusionIn this nationwide Indian cohort, MASLD affected over one-third of participants with a substantial burden of fibrosis. Notably, fibrosis without-MASLD emerged as a cytokine-rich, high-risk phenotype, underscoring an underrecognized dimension of liver disease with major public health implications.