Study defines early-onset cirrhosis caused by fatty liver disease

Researchers at University of California San Diego School of Medicine have published the first study to define early-onset cirrhosis caused by metabolic dysfunction-associated steatotic liver disease (MASLD), a condition known as fatty liver disease.

The study results, published in the September 16, 2026, online edition of Clinical Gastroenterology and Hepatology, found that people who develop cirrhosis before the age of 50 have a distinct risk profile shaped by both inherited genetic factors and metabolic conditions, specifically type 2 diabetes.

Rohit Loomba, MD, senior author of the study, gastroenterologist and hepatologist at UC San Diego Health and chief of the Division of Gastroenterology and Hepatology, UC San Diego School of MedicineOur findings show that younger adults who develop cirrhosis from MASLD are not simply experiencing the same disease earlier. They appear to have a unique combination of genetic susceptibility and metabolic risk factors that accelerate progression to advanced liver disease."

Using data from about 2,400 adults with biopsy-confirmed MASLD enrolled in the national NASH Clinical Research Network, investigators found that approximately 25% of cirrhosis cases occurred before the age of 50. The study defined this group as having "early-onset MASLD cirrhosis" and identified key risk factors associated with the condition.

Although cirrhosis typically develops later in life, some individuals progress to advanced liver scarring much sooner, and little has been known about why. The findings also highlight limitations in current screening approaches. Many commonly used liver fibrosis assessment tools incorporate age, which may reduce their sensitivity in younger patients. In the study, nearly one-third of participants with early-onset cirrhosis had scores that would not typically trigger further evaluation using standard screening thresholds.

"As current screening tools incorporate age, they miss almost a third of patients with early-onset MASLD cirrhosis," said Veeral Ajmera, MD, first author of the study, hepatologist at UC San Diego Health, and associate professor of medicine at UC San Diego School of Medicine. "This study helps us identify which patients are at greatest risk and need a more accurate assessment of their liver disease."

"Cirrhosis is frequently silent until serious complications develop," said Loomba. "These results suggest that younger adults with type 2 diabetes, obesity or elevated genetic risk may benefit from more proactive liver assessment."

Loomba, who is a member of UC San Diego Moores Cancer Center, added that cirrhosis is an important risk factor for hepatocellular carcinoma, the most common form of liver cancer. Identifying high-risk patients earlier may create opportunities for appropriate cancer surveillance and intervention before liver cancer develops.

UC San Diego Health is home to one of the nation's leading programs for the diagnosis, treatment and research of MASLD and related liver conditions. Through its multidisciplinary MASLD program, patients have access to hepatologists, endocrinologists, obesity medicine specialists, dietitians and clinical trials evaluating emerging therapies for fatty liver disease and advanced fibrosis.

Patients at risk for or diagnosed with liver cancer may also receive care at Moores Cancer Center at UC San Diego Health, where researchers and clinicians are focused on reducing liver cancer risk through earlier detection and appropriate hepatocellular carcinoma surveillance.

The authors say the study provides a foundation for improving risk prediction and screening strategies and advancing more personalized approaches to liver disease prevention and treatment.

As rates of obesity and type 2 diabetes continue to rise, researchers expect MASLD-related liver disease to become increasingly common, emphasizing the need to identify those most likely to progress to an advanced stage of the disease.

Co-authors include Linus Schwantes-An, Indiana University School of Medicine; Luis Antonio Díaz, UC San Diego School of Medicine and Pontificia Universidad Católica de Chile; Callie Zaborenko, Indiana University School of Medicine; Katherine P. Yates, Johns Hopkins Bloomberg School of Public Health; and Naga P. Chalasani, Indiana University School of Medicine.

Funding was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (U01DK061734, U01DK130190, P30DK120515, U01DK061737, U01DK061730 and U24DK061730); the National Center for Advancing Translational Sciences (NCATS) (UL1TR000006); the John C. Martin Foundation; the David W. Crabb Endowed Professorship; the Terance Kahn Endowed Liver Disease Research Program; and additional National Institutes of Health grants supporting the investigators and the NASH Clinical Research Network.

Source:

University of California - San Diego

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