Early-Life Indicators Could Predict Future Risk of Liver Disease

Fahim Ebrahimi, MD, MSc

Credit: Karolinska Institutet

A nationwide study in Sweden found that young individuals with low birth weight or those classified as small for gestational age (SGA) had a higher risk of developing metabolic dysfunction–associated steatotic liver disease (MASLD) and progressive liver disease, highlighting the importance of early screening in high-risk populations.

MASLD currently affects more than one-third of young people with obesity and has become the most common chronic liver disease, with pediatric-onset MASLD steadily increasing worldwide. MASLD is more aggressive in children compared with adults, and a higher incidence of young people with the condition already exhibit advanced fibrosis or cirrhosis when they are diagnosed.

“Therefore, it has been hypothesized that MASLD and particularly MASLD-associated progressive liver disease may have developmental origins in early life,” wrote a team of investigators led by Fahim Ebrahimi, MD, MSc, a postdoctoral researcher at Karolinska Institutet and gastroenterologist at Clarunis University Center for Gastrointestinal and Liver Diseases in Switzerland.

This increase in pediatric-onset MASLD is particularly concerning because these patients have a significantly increased risk of cardiovascular disease, including heart failure and other major adverse cardiovascular events. It is also linked to a high risk of developing cirrhosis or end-stage liver disease that requires liver transplant.

To determine any associations between perinatal conditions and the risk of developing MASLD and other progressive liver disease, a population-based, case-control study analyzed biopsy-confirmed cases of MASLD among people living in Sweden registered in the Epidemiology Strengthened by Histopathology Reports in Sweden (ESPRESSO) cohort. A group of patients aged 25 years or younger with a MASLD diagnosis from January 1992 through December 2016 were matched with controls from the general population.

Birth weight was categorized as low, reference or high. Gestational age and birth weight for gestational age data were collected and participants were labeled small, appropriate or large for gestational age. These data were compared between the two groups.

A total of 165 patients with MASLD were matched with 717 controls. In the MASLD cohort, the mean age at diagnosis was 12 years and 60.6% were male. Among patients with MASLD, 46.1% had progressive liver disease with either liver fibrosis or cirrhosis.

Investigators discovered a link between low birth weight and the future development of MASLD, but not between high birth weight and an increased risk of developing MASLD, compared with babies born within the normal birth weight range.

SGA babies were more likely to develop MASLD compared with the reference group, although this association was not observed among babies who were large for gestational age. Additionally, progressive liver disease was more common among babies with low birth weight.

Investigators warn that findings should be interpreted with caution due to a few limitations, including the possibility of residual confounding. They were also unable to track weight trajectories through infancy and childhood and could not ascertain if the mothers breastfeed—which may reduce the risk of MASLD and progressive liver disease. Additionally, they could not adjust for ethnic background as that information is not available in Swedish registries.

“The study findings suggest that MASLD and MASLD-associated progressive liver disease have developmental origins, and it highlights the need for intensified preventive measures to reduce the number of small, vulnerable newborns and to implement structured screening measures to diagnose MASLD-associated progressive liver disease early in high-risk individuals,” investigators concluded.