Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) captures patients at high risk of hepatic fibrosis and cardiovascular disease. However, limited information is available on the prognosis of MASLD. This study aimed to investigate the prognosis of patients with biopsy-proven MASLD and validate a group of fatty liver patients excluded from MASLD because of no metabolic abnormalities by a multi-center longitudinal cohort. We also investigate the most important histological finding associated with the prognosis of patients with MASLD.

Methods: We enrolled 1,444 patients with fatty liver who underwent liver biopsy (age 57, female 55.1%, BMI 27.4). Patients were classified into the following three groups: the MASLD group (steatosis with metabolic abnormalities), the non-MASLD group (steatosis without metabolic abnormalities), or the Burnt-out group (no steatosis on biopsy). Cox proportional hazard analysis and Kaplan-Meier analysis were performed to identify the factor associated with the prognosis. Furthermore, decision-tree analysis was demonstrated to determine the most affected histological finding related to the prognosis of each group.

Results: The prevalence of patients with MASLD, non-MASLD, and Burnt-out group was 92.1% (1,330/1,444) and 3.1% (45/1,444), 4.8% (69/1,444), respectively. During the 9,083 person-years of observation, 4.3 person-years of deaths occurred in all patients, and 84.2% (32/38) of the deceased patients were in the MASLD group in this study. As for the histopathological features, the MASLD group showed the highest prevalence of inflammation in grades 1-3 (95.2%). Whereas the Burnt-out group showed the highest prevalence of fibrosis stages 3 and 4 (35.3%). Compared to the MASLD group, the Burnt-out group was identified as an independent factor associated with prognosis in Cox proportional hazard analysis (RR 5.91, p=0.0001). On the other hand, it could not compare the statistical analysis with the other groups because of the absence of deaths in the non-MASLD group. Kaplan-Meier analysis revealed significant differences in prognosis among the three groups (Log-rank p=0.0009). Ten-year survival rate was 95.6% in MASLD, while no patient died in the non-MASLD group until the end of the follow-up period. Decision-tree analysis revealed hepatic fibrosis was the most affected histological finding associated with the prognosis in the Burnt-out group. In contrast, we identified hepatic inflammation as the most affected prognostic finding in the MASLD group.

Conclusion: We showed MASLD was a major pathological condition related to the deaths and the prognosis of MASLD was worse than non-MASLD. Hepatic inflammation rather than fibrosis was the most affected prognostic histological finding in patients with MASLD. Thus, metabolic abnormalities may worsen the prognosis of patients with fatty liver. Inflammation may be responsible factor for the poor prognosis of MASLD.