Key Points
-
A condition previously called fatty liver disease, now called metabolic dysfunction-associated steatotic liver disease (MASLD), is a liver condition in which excess fat accumulates in the liver.
-
A complication of MASLD is fibrosis (scarring of the liver). Liver fibrosis can cause cirrhosis and liver failure.
-
People with Down syndrome have an increased risk of developing MASLD. Obesity further increases the risk for people with Down syndrome.
-
There are lifestyle choices that can reduce the risk of MASLD and treat MASLD.
-
One medication has been approved to treat MASLD. Several other medications are being studied to treat MASLD.
What is metabolic dysfunction-associated steatotic liver disease?
Metabolic dysfunction-associated steatotic liver disease (MASLD) was previously called nonalcoholic fatty liver disease or fatty liver. MASLD is a condition in which excess fat accumulates in the liver. This accumulation of fat is caused by metabolic dysfunction such as insulin resistance, obesity, or other metabolic abnormalities. MASLD is one of the most common types of chronic liver disease.
MASLD can cause several problems in the liver. MASLD can cause hepatitis, which is inflammation in the liver. MASLD can also cause liver fibrosis, which is a “scar” in the liver. This scarring is like scarring that may form on the skin or in other organs. Liver fibrosis can cause cirrhosis of the liver (permanent scarring of the liver) and liver failure.
Why is MASLD important in Down syndrome?
MASLD is more common in people with Down syndrome. It may be more common because of differences in metabolic function in people with Down syndrome compared to people without Down syndrome. It may be more common because some of the conditions (such as obesity) that increase the risk of MASLD are more common in people with Down syndrome.
A 2017 study found that MASLD was more common in children with Down syndrome, whether they were obese or not. Other studies (included in the references below) reported that overweight and obesity further increased the risk of MASLD and liver disease in people with Down syndrome. Additionally, autoimmune liver disease and celiac disease are two autoimmune conditions that increase the risk of MASLD. People with Down syndrome have higher rates of autoimmune diseases.
Symptoms and signs
Early in the course of MASLD, there may be no symptoms. Sometimes, a health care professional will notice a sign during a physical exam, but this occurs most often later in the disease process. As the disease progresses, some individuals will report:
Often, the first sign that a person may have MASLD is found when doing routine blood testing that many people get at an annual physical.
Sometimes, when imaging such as ultrasounds or CT scans are done to assess for a different condition (e.g., constipation, abdominal pain), the abnormalities associated with MASLD may be found.
Diagnosis
An evaluation for MASLD starts with a good history and physical exam from a health care professional. However, as noted above, the history and physical exam often do not reveal any abnormal findings, particularly early in the course of the disease.
There are several blood tests that can be ordered to assess liver function including:
A variety of imaging tests can assess the liver such as ultrasounds, CT scans, or MRIs. Liver ultrasound elastography is a specific type of ultrasound that measures liver stiffness, which can indicate liver fibrosis.
A liver biopsy may also be considered.
Prevention and treatment
Weight management and dietary changes are important to prevent and treat MASLD. For those who are overweight or obese, losing weight can help prevent MASLD or improve it when present. Beneficial diets include fruits, vegetables, whole grains, and lean protein. Additionally, these diets limit saturated and trans fats, added sugars, and processed foods. For those with celiac disease, a gluten-free diet is recommended.
Additional measures to prevent the disease from progressing from MASLD to fibrosis to liver failure include:
-
Avoid alcohol and other substances that can cause injury to the liver.
-
Screen for hepatitis C (and treating when present), which can cause chronic liver disease.
-
Consider vaccination for viral hepatitis A and/or B (if the person does not have immunity) to avoid liver damage from these infections.
-
Monitor for symptoms of gall bladder disease.
-
Consider avoiding medications such as acetaminophen (Tylenol) that can affect the liver.
Resmetirom (Rezdiffra) is a medication that was FDA-approved to treat MASLD in 2024. Other medications that improve insulin sensitivity and/or treat obesity are being studied as possible treatments for MASLD.
When fibrosis of the liver is diagnosed and the cause is discovered, the goal of care is to reduce the fibrosis (called fibrous regression). It is important to address the fibrosis to prevent it from progressing to the point at which it can no longer be reduced. When that happens, cirrhosis of the liver (irreversible liver damage) can develop.
For specific treatments, we refer to a hepatologist (a specialist who diagnoses and treats liver disorders) or a gastroenterologist who has a focus on treating the liver. We are not aware of any aspects or approaches to treating liver disease that are specific to people with Down syndrome.
Resources
Down syndrome
Autoimmune Hepatitis in Down Syndrome (Down Syndrome Research and Practice)
Celiac Disease
Weight Management
General
How Liver Diseases Progress (American Liver Foundation)
Liver Function Tests (Mayo Clinic)
Metabolic Dysfunction-Associated Steatotic Liver Disease (Cleveland Clinic)
Screening for Hepatitis C Virus Infection in Adolescents and Adults (U.S. Preventive Services Task Force)
References
De Matteo A, Vajro P. Down syndrome and pediatric nonalcoholic fatty liver disease: A causal or casual relationship?. J Pediatr. 2017;189:11-13. doi:10.1016/j.jpeds.2017.07.011
Oreskovic NM, Baumer NT, Di Camillo C, et al. Cardiometabolic profiles in children and adults with overweight and obesity and Down syndrome. Am J Med Genet A. 2023;191(3):813-822. doi:10.1002/ajmg.a.63088
Pecoraro L, Ferron E, Solfa M, et al. Body composition and laboratory parameters in children with Down syndrome: The DONUT study. Clin Nutr ESPEN. 2023;57:253-257. doi:10.1016/j.clnesp.2023.07.003
Ravel A, Mircher C, Rebillat AS, Cieuta-Walti C, Megarbane A. Feeding problems and gastrointestinal diseases in Down syndrome. Arch Pediatr. 2020;27(1):53-60. doi:10.1016/j.arcped.2019.11.008
Valentini D, Alisi A, di Camillo C, et al. Nonalcoholic fatty liver disease in Italian children with Down syndrome: Prevalence and correlation with obesity-related features. J Pediatr. 2017;189:92-97.e1. doi:10.1016/j.jpeds.2017.05.077
Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology. 2015;149(2):367-e15. doi:10.1053/j.gastro.2015.04.005