[ad_1]
January 05, 2026
2 min read
Key takeaways:
- In a population of 2,395 adults with MASLD, 234 had cirrhosis, with 53 identified as having early-onset disease.
- Early-onset disease was defined as patients aged younger than 50 years.
Nearly one-quarter of adults with metabolic dysfunction-associated steatotic liver disease and cirrhosis presented before age 50 years, with genetics and presence of type 2 diabetes mellitus both increasing the risk for early-onset disease.
The HSD17B13 cirrhosis variant was also found to be less prevalent when MASLD-related cirrhosis presented early, according to a poster presentation during The Liver Meeting.
“Although the risk of MASLD-related cirrhosis rises with age, a subset of adults presents with advanced fibrosis and cirrhosis at an early age,” Veeral Ajmera, MD, MAS, associate professor of medicine and medical director of liver transplantation in the division of gastroenterology and hepatology at University of California, San Diego, told Healio. “We wanted to define early-onset MASLD cirrhosis and evaluate for any unique clinical or genetic features in this population.”
The study included 2,395 adults with biopsy-confirmed MASLD from the multicenter NASH CRN cohort, of whom 234 had cirrhosis (9.8%; mean age, 56.9 years; 71% women; mean BMI, 35.6 kg/m2). Of those with cirrhosis, 66% had diabetes.
“Early-onset cirrhosis was defined as patients with MASLD cirrhosis under 50 years old, which was the lowest quartile of age with cirrhosis in the multicenter NASH CRN study,” Ajmera said.
Results showed 53 individuals had early-onset disease. This population was more likely to be men (40% vs. 25%), have a higher steatosis grade and have a “markedly lower” Fibrosis-4 score (2.3 vs. 3.4; P < .001).
Ajmera and colleagues also found the HSD17B13 cirrhosis variant to be less prevalent in patients with vs. without early-onset disease (24% vs. 34%; P = .004), whereas TM6SF2 and PNPLA3 variants were more prevalent, although this difference was not statistically significant.
Among patients with MASLD younger than 50 years, those with cirrhosis were significantly more likely to be older (42.9 vs. 39.2 years) than those without cirrhosis. They also were more likely to be white (81% vs. 68%), have diabetes (57% vs. 26%), have a BMI greater than 35 kg/m2 (58% vs. 42%), have lower alanine aminotransferase (63.4 U/L vs. 77.6 U/L) and have higher alkaline phosphatase (110.2 U/L vs. 78.8 U/L).
“Individuals with early-onset cirrhosis exhibited a distinct clinical-genetic profile, including a higher genetic risk and a markedly greater prevalence of [type 2 diabetes mellitus] and obesity class II ( 35 kg/m²),” Ajmera said.
“Importantly, this population may be at higher risk of misclassification with current clinical care pathways given 30% of participants in this study with early MASLD cirrhosis had a [Fibrosis-4 score of less than 1.3], which would classify them as low risk,” he continued.
Elevated genetic risk is not routinely assessed in clinical practice, Ajmera said, and therefore younger patients with MASLD who have this risk along with diabetes “may benefit from a lower [Fibrosis-4] threshold or proceeding directly to liver stiffness measurement in order to minimize the risk of being misclassified as low risk.”
While emerging data support genetic testing in MASLD, Ajmera told Healio that further research is needed.
“There are multiple compounds targeting genes associated with [metabolic dysfunction-associated steatohepatitis] and fibrosis. Patients with early-onset MASLD cirrhosis may have higher genetic risk and be a population which could benefit from these emerging therapies as we move toward a future with more personalized treatments for individuals with MASH,” Ajmera said.
For more information:
Veeral Ajmera, MD, MAS, can be reached at v1ajmera@health.ucsd.edu.
Sources/Disclosures
Source:
Ajmera V, et al. Risk factors and definition of early onset metabolic dysfunction-associated steatotic liver disease (MASLD) cirrhosis. Presented at: The Liver Meeting; Nov. 7-11, 2025; Washington (hybrid meeting).
Disclosures:
Healio could not confirm relevant financial disclosures at the time of publication.
Ask a clinical question and tap into Healio AI’s knowledge base.
- PubMed, enrolling/recruiting trials, guidelines
- Clinical Guidance, Healio CME, FDA news
- Healio’s exclusive daily news coverage of clinical data
[ad_2]
Source link
