Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) continues to affect many people around the globe and may increase the likelihood of liver-related morbidity and mortality. Early identification of individuals at risk for progression to liver cirrhosis is crucial to the mitigation of the disease effects. This review aims to summarize the current evidence on clinical factors predicting MASLD progression to cirrhosis. A comprehensive literature search was conducted in PubMed, Cochrane, Medscape, JAMA, and Scopus covering studies from May 30, 2010, to May 30, 2025. Keywords included NAFLD, NASH, MASH, cirrhosis, risk factors, fibrosis, and progression. Key predictors identified include metabolic syndrome components (obesity, diabetes, and dyslipidemia), genetic variants such as Patatin-like phospholipase domain-containing protein 3 (PNPLA3), transmembrane 6-superfamily member 2 (TM6SF2), Ras-related protein 14 family (RAB14), lifestyle factors (sedentary behavior, high-fructose diet), demographic traits (age, sex, and ethnicity), and histological markers (fibrosis stage, non-alcoholic steatohepatitis (NASH) features). Non-invasive detection tools such as the Fibrosis-4 (FIB-4) index, non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS), enhanced liver fibrosis (ELF), and perilipin-2 (PLIN2) and elastography are valuable tests for early identification. A combination of metabolic, genetic, lifestyle, and histological factors predicts MASLD progression. Early detection and intervention are critical to prevent cirrhosis. There is a need for more standardized non-invasive tests and their availability.