Nonalcoholic Fatty Liver Disease

I. DEFINITION.

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver diseases with histologic features of alcohol-induced liver disease that occurs in individuals who do not consume significant quantities of alcohol. The spectrums of the liver diseases include hepatic steatosis (fatty liver); nonalcoholic steatohepatitis (NASH) with histologic evidence of hepatitis, hepatocellular injury, necrosis, and fibrosis; and cirrhosis with eventual portal hypertension and other complications including hepatocellular carcinoma.

NAFLD is believed to be one of the most common causes of abnormal liver chemistry tests in American adults. It is thought to be the major cause of cryptogenic cirrhosis. Ten percent to 20% of patients with NASH progress to cirrhosis or end-stage liver disease in a decade or more. The survival of patients with NAFLD is lower than in general population.

Clinically, NAFLD should be a diagnosis of exclusion. It should be suspected as a cause of chronic liver disease in patients who deny alcohol consumption and have negative serologic tests for active viral, congenital, and acquired causes of liver disease.

Hepatis C virus (HCV) or hepatitis G virus infections are not implicated as causes of NAFLD; however, NAFLD may increase the severity of HCV-related liver disease. Obesity-related steatosis seems to have deleterious effects similar to those of alcohol-induced steatosis on HCV-infected patients, exacerbating the liver damage.

In the United States the prevalence of NAFLD is estimated to be 20% and NASH 3%. The prevalence of NAFLD is 50% in people with diabetes, 74% in obese persons, and nearly 100% in morbidly obese individuals. NAFLD affects both adults and children: 2.6% of all children and 22.5% to 52.8% of obese children. Evidence for an association between arterial hypertension and atherosclerosis is accumulating. In fact, NAFLD is an independent risk factor for cardiovascular mortality.

II. ASSOCIATED CONDITIONS.

Conditions associated with NAFLD include Type 2 diabetes mellitus, obesity, and dyslipidemia, all of which are related to metabolic syndrome.

A. Obesity.

Obesity is the condition most often reported to be associated with NAFLD. Obesity is described in 40% to 100% of patients with NASH. NASH has been documented in 9% to 36% of obese patients. The prevalence and severity of hepatic steatosis has been noted to be directly proportional to the grade of obesity, and the severity of NASH has been noted to be proportional to the degree of hepatic steatosis. The distribution of body fat seems to be important in the development of hepatic steatosis. In one study, a significant correlation was found between the degree of hepatic steatosis and waist-to-hip ratio, suggesting a relationship between visceral and intraabdominal fat and accumulation of fat in the liver.

B. Hyperglycemia, insulin resistance, hyperinsulinemia, glucose intolerance, and Type 2 diabetes mellitus

have been described in 25% to 75% of adult patients with NASH.

C. Hyperlipidemias,

including hypertriglyceridemia and hypercholesterolemia or both, have been found to be present in 20% to 80% of patients with NASH.

D. Most patients with NASH

seem to have multiple risk factors including obesity, Type 2 diabetes mellitus, and hyperlipidemia.

E. Other risk factors

include female gender, rapid weight loss, acute starvation, total parenteral nutrition, and small-bowel diverticulosis.

F. Genetic conditions

associated with NAFLD include Wilson’s disease, homocystinuria, tyrosinemia, a-beta- and hypobetalipoproteinemia, and Weber-Christian disease.

G. Surgical procedures

associated with NAFLD, particularly NASH, include gastroplasty for morbid obesity, jejunoileal bypass, extensive small-bowel resection, and biliopancreatic diversion.

H. Drugs.

The use of a number of drugs has been implicated in the development of NAFLD. The list includes glucocorticoids, amiodarone, synthetic estrogens, tamoxifen citrate, 4,4′-diethylaminoethoxyhexesterol (DHEAH), isoniazid, methotrexate, perhexiline maleate, tetracycline, puromycin, bleomycin, dichloroethylene, ethionine, hydrazine, hypoglycin, l-asparaginase, azacytidine, azauridine, and azaserine. Chronic industrial exposure to petrochemicals has also been reported as a risk factor for NAFLD.

III. DIAGNOSIS

A. Clinical findings

1. Symptoms.

Most patients with NAFLD are asymptomatic; however, fatigue, malaise, or vague right upper quadrant pain or discomfort may cause patients to seek medical attention.

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