P78 Progression to decompensation or hepatocellular carcinoma and risk factors for mortality and disease progression in individuals with early-stage liver disease

<h3>Background/Objectives</h3> Patients with early-stage liver disease are at increased risk of progression to advanced conditions, including cirrhosis, decompensation, and hepatocellular carcinoma (HCC). Fibrosis progression is a major determinant of adverse outcomes, yet the natural history of disease progression and associated risk factors remains insufficiently understood. Our previous work established a novel methodology that classifies liver disease into five discrete stages. Early-stage liver disease includes stage 1 (underlying aetiological process without cirrhosis), stage 2 (cirrhosis without portal hypertension or synthetic failure), and stage 3 (cirrhosis with portal hypertension but without decompensation). Late-stage liver disease (stages 4 and 5) includes decompensation and HCC. This study aimed to estimate the cumulative incidence of liver disease progression and identify factors associated with progression and all-cause mortality among individuals with early-stage liver disease. <h3>Methods</h3> We conducted a retrospective cohort study of adults (18 years or older) newly diagnosed with early-stage liver disease between January 1st, 2004, and December 31st, 2023. Eligible participants had at least 12 months of continuous data available before and after diagnosis. Kaplan-Meier curves were used to estimate the probability of progression and all-cause mortality. Cox proportional hazards models identified independent predictors of these outcomes. <h3>Results</h3> A total of 70,899 individuals met the inclusion criteria. Of these, 4111 progressed to late-stage liver disease, 6059 progressed within early-stage categories, and 60,729 showed no progression during follow-up. Comorbidities such as cardiovascular disease, hypertension, and diabetes were more common in those who progressed. Compared to non-progressors, all-cause mortality was significantly higher among early-stage progressors and those who progressed to late-stage disease (early-stage progressors: HR = 1.72, 95% CI: 1.65–1.79, p &lt; 0.001; late-stage progressors: HR = 3.21, 95% CI: 3.08–3.33, p &lt; 0.001). Independent predictors of mortality included older age, male sex, alcohol use, smoking, overweight, cardiovascular disease, hypertension, diabetes, renal disease, and hyperlipidemia. Patients initially diagnosed with stage 2 or 3 disease had higher hazards of progression to late stage (stage 2: HR = 5.47, 95% CI: 5.04–5.93, p &lt; 0.001; stage 3: HR = 5.11, 95% CI: 4.72–5.54, p &lt; 0.001). Additional predictors of progression included age, sex, alcohol use, smoking, overweight, diabetes, and hyperlipidemia. <h3>Conclusions</h3> Progression to late-stage liver disease is significantly associated with increased mortality. Individuals with cirrhosis at diagnosis are more likely to progress. Early detection and management of modifiable risk factors are essential to improving long-term outcomes.