What Are MASLD and MASH?
Metabolic dysfunction-associated steatotic liver disease (MASLD) (formerly called nonalcoholic fatty liver disease/NAFLD) and metabolic dysfunction-associated steatohepatitis (MASH) (formerly called nonalcoholic steatohepatitis/NASH) are ways in which metabolic syndrome shows up in the liver. Metabolic syndrome is a cluster of conditions that include obesity, hypertension, insulin resistance, and high cholesterol.
MASLD and MASH develop due to fat deposition in the liver, resulting in inflammation and injury to the liver which can then progress to cirrhosis (end-stage liver disease). MASLD and MASH are now the most common causes of cirrhosis worldwide, surpassing alcohol and virus-induced hepatitis and cirrhosis.
MASLD is characterized by fat deposition in the liver without liver injury. MASH is a later-stage condition with both fat deposition and liver cell injury. MASH has a higher risk of progression to end-stage liver scarring (cirrhosis), as well as liver cancer (hepatocellular carcinoma).
The Link between MASLD, Diabetes, Obesity, and Sleep Disturbances
Insulin resistance and obesity are the main drivers of MASLD and MASH. Any condition that increases the risk of obesity and insulin resistance – such as type 2 diabetes – puts people at risk for fat deposition in the liver with progression to liver injury.
With the incidence of obesity and overnutrition rising two to threefold in Western countries, the rates of MASLD and MASH are also increasing. Liver damage from obesity and diabetes is also happening more frequently in younger populations. MASLD is more common in men than in women. However, since estrogen is protective in preventing MASLD, post-menopausal women are at increased risk for MASLD as their estrogen levels fall. Although MASLD is more commonly associated with obesity, people with a BMI <25 can still be at risk for MASLD if they have insulin resistance, hypertension, and cholesterol problems.
Obstructive sleep apnea (OSA) is also independently associated with MASLD.
Complications of MASLD
Since MASLD is a liver manifestation of metabolic syndrome, patients are at risk for cardiovascular comorbidities like heart disease and stroke. In addition, if MASLD progresses to MASH, patients may experience cirrhosis. Liver cancer is also more common in those who have MASH.
How Are MASLD and MASH Diagnosed?
The gold standard for diagnosis is a liver biopsy. However, liver enzymes like ALT and AST (commonly in your normal blood work listed in the metabolic panel) may initially be elevated, signaling to the medical provider that in the absence of excessive alcohol use, MASLD or MASH may be the culprit. Liver function testing, however, can also be normal, missing these conditions 10% of the time. If liver function testing is elevated, an ultrasound of the liver is the next best option to evaluate fat deposition and any evidence of fibrosis/scarring in the liver. A multidisciplinary team approach with a primary care provider, an endocrinologist (if there is uncontrolled diabetes and/or obesity), and a hepatologist will be beneficial for diagnosis and management.
Treatment of MASLD
First-line treatment in preventing the progression of MASLD to MASH and then to fibrosis is weight loss of 7% to 10% of your body weight through lifestyle modifications (diet and exercise) and medications that lead to weight loss. A sedentary lifestyle has been shown to contribute to the onset of MASLD and its progression to fibrosis. Therefore, aerobic activity and dietary modifications are the mainstays of treatment. For those with severe obesity, gastric bypass surgery may also be recommended to reduce the progression of MASLD to MASH and cirrhosis.
Although there are no FDA-approved medications available for the treatment of MASLD and MASH, small case reports are available for anti-diabetic medications like metformin, GLP1 agonists, and SGLT2 inhibitors. Another diabetes medication called pioglitazone (brand name Actos), also reduces insulin resistance by helping reduce glucose production in the liver, leading to a lower risk of fatty liver. Any interventions that reduce weight and control insulin resistance should help reduce the progression of MASLD. There are many pharmacotherapy trials currently recruiting patients with MASLD, and there have been some promising results.
Prevention of MASLD
Eating a Mediterranean diet that’s low in saturated fats and enriched in complex carbohydrates and fiber has been shown to be preventative of MASLD, independent of weight loss. Management of obstructive sleep apnea with a CPAP machine, weight loss, and strict control of diabetes have all been shown to prevent the development of MASLD. Plain coffee intake has been shown to reduce the development of MASLD as well. In post-menopausal women, short-term use of hormone replacement therapy with estrogen at the onset of menopause can provide protection against MASLD, as well as other cardiovascular risks. Overall, an active lifestyle with a focus on a low intake of saturated fats may be the best route of prevention.
Early detection is key to preventing and slowing the progression of liver disease. MASLD and MASH often do not have noticeable symptoms, so if you have risk factors such as obesity, hypertension, insulin resistance, and/or high cholesterol, talk to your doctor about being tested. Until we have medications dedicated to treating MASLD and MASH, lifestyle modifications play a vital role in preventing and managing the conditions, as well as benefiting overall health.