Non -alcoholic fatty liver disease (NAFLD), as the name implies, refers to the infiltration of fat in the liver that is NOT due to excessive alcohol use.
This fatty accumulation is known as steatosis, and NAFLD is sometimes also called non-alcoholic steatosis. The basic cause of NAFLD is the insulin resistance that decreases the effect of insulin, and is typically found with prediabetes-metabolic syndrome and diabetes. The most frequent risk factor for insulin resistance is obesity, especially abdominal visceral obesity at your mid-section. Many people know that insulin is important for blood sugar regulation, but insulin also plays an important role in blood fat (lipid) management. Insulin resistance leads to changes in glucose and lipid metabolism. The result of these changes is an increased uptake (infiltration and accumulation) of triglyceride fat into liver cells. The triglycerides are absorbed from the diet as well as channeled from abdominal fat and peripheral muscles to the liver. Simple fatty liver is not overly harmful and disappears with weight loss, however a minority of those affected go on to develop non-alcoholic steatohepatitis (NASH), which is the more harmful inflammatory stage of NAFLD.
NAFLD is a diagnosis of exclusion made after other causes of secondary fatty liver disease (alcohol, hepatitis, autoimmune disease, drug-induced, etc.) have been ruled out. A liver biopsy is required to make a definitive diagnosis and to determine the severity of the condition. The disease process is asymptomatic and the liver can become fatty without initially disturbing liver function. The presumptive diagnosis of NAFLD or NASH is made in people who are insulin resistant, have mildly elevated liver enzymes (transaminases) in the blood, and have signs of fatty liver on an ultrasound study. These patients will have no other known cause for these liver enzyme elevations or for fatty liver, along with no significant alcohol use. If weight loss results in a decrease or normalization of elevated liver enzymes, the diagnosis of NAFLD is likely. Only a liver biopsy, however, can confirm the diagnosis of NAFLD and NASH and determine the severity of the disease. Whether or not it is important to do a liver biopsy in people with suspected NAFLD or NASH is still debated among liver specialists since no specific treatments are available.
NAFLD is typically related to high BMI individuals with diabetes and prediabetes metabolic syndrome, and may respond to the treatments used for these insulin-resistant conditions such as improving nutritional status, proper diet, exercise and weight loss for better blood sugar and lipid management. Pharmaceuticals such as metformin and thiazolidinediones are used. These medications reduce insulin resistance by improving the sensitivity of insulin receptors in muscle, liver, and fat cells.
If inflammation develops in the fatty liver, the condition can progress to non-alcoholic steatohepatitis (NASH). NASH is the most extreme inflammatory form of NAFLD, and is a major cause of cirrhosis of the liver. The exact reasons and mechanisms by which the disease progresses from one stage to the next are not known.
A simple “NAFLD and NASH” search of PubMed/MEDLINE shows how this area of medicine is undergoing a significant amount of research from a number of different perspectives. This research has given rise to a number of theories about how NASH develops. One theory is that the simple process of the accumulation of fat in the liver eventually leads to the development of NASH. According to this theory, the large amount of fat in the liver is thought to be a source of peroxidation that results in the generation of free radicals. These free radicals then damage proteins and other structures important to liver cell function. This damage leads to cell death and/or an inflammatory cascade that removes the damaged liver cells.
There is also a growing body of work in animal models of fatty liver disease that suggests a so-called two-hit hypothesis. In this theory, the first hit is the fatty liver (steatosis). Then, a second event, or second hit, leads to the development of NASH. Multiple potential second hits have been suggested such as: cytokine activity, mitochondrial malfunction, peroxidation, and insulin receptor pathology. Others are examining the involvement of adipohormones . Quite an advanced subject for the casual lay reader.
Regardless of the cause, the bottom line is that the single most effective treatment for obese people with NAFLD or NASH is to simply lose weight through diet and exercise. Granted this is not an easy undertaking , however weight loss is achievable if you set your mind to it. It could be a matter of life or death. Ask your doctor what you can do regarding lifestyle changes as part of managing this problem.