Topic of Current Interest
Nonalcoholic Fatty Liver Disease
(Previous topics are available in the Archives)
Nonalcoholic Fatty Liver Disease (NAFLD) is a very common form of liver disease in the United States which is indistinguishable from alcoholic liver disease except that it occurs in people without significant alcohol consumption (less than 2 drinks per day). It encompasses a wide spectrum of disease, from simple fatty liver or steatosis to cirrhosis. Fatty liver or steatosis is defined as a fatty change in hepatocytes (liver cells). It affects about 34% of the general U.S. population, and 70-80% of obese individuals. Steatosis can progress to steatohepatitis which is a fatty change in the liver associated with inflammation. Nonalcoholic steatohepatitis (NASH) is present in about 2.7% of lean individuals and 18.5% of obese individuals. NASH can progress to cirrhosis. There are an estimated 600,000 Americans with cirrhosis due to NAFLD.
NAFLD is present in all age groups and ethnicities. However, the highest prevalence of NAFLD is seen in people ages 40 to 49 and in Mexican- and European-Americans. There is an equal frequency in men and women. There are several risk factors for NAFLD. Certain metabolic disorders, abdominal surgeries, and medications can predispose individuals to develop NAFLD. However, the most common risk factor for NAFLD is the metabolic syndrome or Syndrome X. The metabolic syndrome is defined by the presence of central obesity, impaired fasting glucose or diabetes, hypertriglyceridemia, low high density lipoprotein (HDL), and hypertension. There is a 40% prevalence of the metabolic syndrome in individuals over the age of 60. The metabolic syndrome is characterized by insulin resistance. The likelihood of NAFLD is directly correlated with the number and severity of metabolic risk factors.
It is believed that insulin resistance causes the normal liver to progress to fatty liver. The cause of progression of fatty liver to steatohepatitis is not well understood, but is likely some form of oxidative stress.
Most people with NAFLD are asymptomatic. Some people may notice fatigue or right upper abdominal discomfort. Generalized itching, poor appetite, and nausea are other possible symptoms. Jaundice usually occurs only late in the course of disease. On physical exam, most patients are obese. Some may demonstrate an enlarged liver. The most common bloodwork abnormality is an abnormal ALT or AST occurring in 50-90% of patients. In fact, NAFLD is the most common cause for unexplained persistent ALT elevation.
Liver biopsy is the most accurate method of diagnosing NAFLD and is the only accurate method to distinguish between steatosis and NASH. Noninvasive methods of diagnosing NAFLD include ultrasound, CT scan, and MRI. Ultrasound typically demonstrates a diffuse hyperechoic echotexture. The role of liver biopsy in NAFLD is controversial. Some experts argue against liver biopsy because the overall prognosis with NAFLD is good, there is no proven therapy, and there are risks associated with liver biopsy. However, a liver biopsy is helpful to exclude other causes of liver disease, determine the degree of fibrosis, and to determine long-term prognosis.
The natural progression of NAFLD is unclear as few patients have undergone sequential liver biopsies. At initial presentation, about 30-40% and 10-15% of NAFLD patients will have advance fibrosis and established cirrhosis respectively. However, spontaneous improvement in liver biopsy findings has been demonstrated in some patients. Age of 45 years or older, and body mass index of 30 kg/m2 or higher, type 2 diabetes mellitus, and an AST/ALT ratio greater than one are all predictors of advanced disease.
There is currently no proven therapy for NAFLD, but several medications are under investigation. Weight loss has been shown to improve liver size and ALT. Gradual weight loss of 1-2 pounds per week is recommended. The initial target should be 10% of baseline weight. A heart healthy or diabetic diet is recommended to achieve weight loss. Aggressive weight management such as gastric bypass surgery may be indicated in some individuals if their BMI is greater than 35 kg/m2. Other potential therapies include insulin sensitizing agents such as metformin, lipid lowering agents, vitamin E, and others. However, these are all still considered experimental therapies.
In conclusion, NAFLD is the most common cause of an unexplained ALT in the United States. There is a strong association of NAFLD with the metabolic syndrome. Liver biopsy is the only method to differentiate between fatty liver and NASH. There is no proven therapy, but the current recommendation is gradual weight loss.
Dr. Jayaraman-October 2006
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