Long-term mortality and extrahepatic outcomes in 1096 children with MASLD: A retrospective cohort study

Abstract

Background and aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease in children, but its long-term outcomes are poorly understood. This study aimed to quantify mortality rates, identify causes of death, and evaluate the incidence of cirrhosis and extrahepatic outcomes in children with pediatric-onset MASLD.

Approach and results: The Longitudinal InVestigation Evaluating Results of Steatosis (LIVERS) study is a single-center, retrospective cohort study conducted at Rady Children's Hospital San Diego. We included 1096 children aged 2-18 years who were diagnosed with MASLD between 2000 and 2017 and followed for a mean of 8.5 years. Mortality was ascertained through the National Death Index, and comorbidities were assessed through follow-up research visits and medical records. Overall, 3.4% of children died, yielding a mortality rate of 398 per 100,000 person-years; nearly half of these deaths were liver-related. Male sex and lower HDL levels independently predicted increased mortality risk. The cumulative incidence of cirrhosis was 4.7%. High incidence rates of extrahepatic comorbidities were observed, including dyslipidemia (3664 per 100,000 person-years), hypertension (1901), obstructive sleep apnea (1185), and type 2 diabetes (911).

Conclusions: Pediatric MASLD is associated with significant premature mortality and a substantial burden of hepatic and extrahepatic comorbidities. These findings highlight the need for timely screening, early intervention, and long-term management strategies to improve outcomes for children with MASLD.

Keywords: cirrhosis; dyslipidemia; epidemiology; hypertension; obstructive sleep apnea; steatohepatitis; type 2 diabetes.