Metabolic Dysfunction-Associated Steatohepatitis
Synonyms
MASH, NASH, nonalcoholic steatohepatitis, non alcoholic steatohepatitis,Overview
Metabolic dysfunction-associated steatohepatitis (MASH), previously known as nonalcoholic steatohepatitis (NASH), is liver inflammation caused by a buildup of fat in the liver. MASH is part of a group of liver diseases, known as nonalcoholic fatty liver disease, in which fat builds up in the liver and sometimes causes liver damage that gets worse over time (progressive liver damage). Although the cause is not known, MASH seems to be related to certain other conditions, including obesity, high cholesterol and triglycerides, and diabetes. Treatment for MASH involves controlling those underlying diseases
Symptoms
MASH is usually a silent disease with few or no symptoms. Patients generally feel well in the early stages and only begin to have symptoms—such as fatigue, weight loss, and weakness—once the disease is more advanced or cirrhosis develops. The progression of MASH can take years, even decades. The process can stop and, in some cases, reverse on its own without specific therapy. Or MASH can slowly worsen, causing scarring or “fibrosis” to appear and accumulate in the liver. As fibrosis worsens, cirrhosis develops; the liver becomes seriously scarred, hardened, and unable to function normally. Not every person with MASH develops cirrhosis, but once serious scarring or cirrhosis is present, few treatments can halt the progression. A person with cirrhosis experiences fluid retention, muscle wasting, bleeding from the intestines, and liver failure. Liver transplantation is the only treatment for advanced cirrhosis with liver failure, and transplantation is increasingly performed in people with MASH. MASH ranks as one of the major causes of cirrhosis in America, behind hepatitis C and alcoholic liver disease.
Causes
Although MASH has become more common, its underlying cause is still not clear. It most often occurs in persons who are middle-aged and overweight or obese. Many patients with MASH have elevated blood lipids, such as cholesterol and triglycerides, and many have diabetes or pre-diabetes, but not every obese person or every patient with diabetes has MASH. Furthermore, some patients with MASH are not obese, do not have diabetes, and have normal blood cholesterol and lipids. MASH can occur without any apparent risk factor and can even occur in children. Thus, MASH is not simply obesity that affects the liver. While the underlying reason for the liver injury that causes MASH is not known, several factors are possible candidates: * insulin resistance * release of toxic inflammatory proteins by fat cells (cytokines) * oxidative stress (deterioration of cells) inside liver cells
Treatment
Currently, no specific therapies for MASHexist. The most important recommendations given to persons with this disease are to * reduce their weight (if obese or overweight) * follow a balanced and healthy diet * increase physical activity * avoid alcohol * avoid unnecessary medications These are standard recommendations, but they can make a difference. They are also helpful for other conditions, such as heart disease, diabetes, and high cholesterol. A major attempt should be made to lower body weight into the healthy range. Weight loss can improve liver tests in patients with NASH and may reverse the disease to some extent. Research at present is focusing on how much weight loss improves the liver in patients with MASH and whether this improvement lasts over a period of time. People with MASH often have other medical conditions, such as diabetes, high blood pressure, or elevated cholesterol. These conditions should be treated with medication and adequately controlled; having MASH or elevated liver enzymes should not lead people to avoid treating these other conditions. Experimental approaches under evaluation in patients with MASH include antioxidants, such as vitamin E, selenium, and betaine. These medications act by reducing the oxidative stress that appears to increase inside the liver in patients with MASH. Whether these substances actually help treat the disease is not known, but the results of clinical trials should become available in the next few years. Another experimental approach to treating MASH is the use of newer antidiabetic medications—even in persons without diabetes. Most patients with MASH have insulin resistance, meaning that the insulin normally present in the bloodstream is less effective for them in controlling blood glucose and fatty acids in the blood than it is for people who do not have MASH. The newer antidiabetic medications make the body more sensitive to insulin and may help reduce liver injury in patients with MASH. Studies of these medications—including metformin, rosiglitazone, and pioglitazone—are being sponsored by the National Institutes of Health and should answer the question of whether these medications are beneficial in MASH.