Overview and Risk Factors
Nonalcoholic fatty liver disease (NAFLD) comprises a spectrum of conditions characterized by hepatic fat accumulation in the absence of alcohol abuse, with fat making up at least 10% of the liver tissue (steatosis). Nonalcoholic steatohepatitis (NASH), in which fat accumulation is accompanied by inflammation, is the most common type of NAFLD and the most common form of liver disease in the United States.1 Clinically, NASH may be indistinguishable from alcoholic hepatitis, but it is most often a subclinical disease.
The progressive accumulation of triglycerides in hepatic tissue results from increased delivery of fatty acids to the liver, decreased export of fatty acids from the liver, or impaired oxidation of fatty acids within the liver. Insulin resistance is thought to play a key role in disease development by causing alterations in lipid metabolism, leading to increased uptake of fatty acids by the liver and increased oxidation of lipids within it.
Most patients remain asymptomatic, although nonspecific symptoms, such as fatigue, malaise, and tenderness of the upper-right abdomen may occur. In more serious cases, the pathologic features resemble those of alcoholic liver disease, and may include fibrosis, inflammation, necrosis, and cirrhosis.
- States of insulin resistance (typically related to obesity, diabetes mellitus, and metabolic syndrome).
- Hyperlipidemia, especially hypertriglyceridemia.
- Severe or rapid weight loss.
- Total parenteral nutrition.
- Drugs (eg, amiodarone, tetracycline, glucocorticoids, synthetic estrogens, and certain pesticides).
- Pregnancy. Rarely, fatty liver occurs during pregnancy.
Diagnosis and Treatment
Laboratory studies include complete blood count (CBC), blood chemistry, liver function tests, and coagulation studies. It may also be useful to evaluate ammonia level for hepatic encephalopathy.
Alcoholic liver disease should be ruled out by history, physical examination, and laboratory testing, as necessary. NASH differs from alcoholic hepatitis in that the alanine aminotransferase (ALT) is generally greater than the aspartate aminotransferase (AST), and alkaline phosphatase and bilirubin are not generally elevated. However, liver function testing is not sufficient to make the diagnosis.
Ultrasound, CT scan, and MRI may be diagnostic. These tests can identify fatty liver and evaluate for other disorders, including biliary tract disease.
Liver biopsy may be useful if the cause of fatty liver is unclear. Biopsy will also reveal the grade and stage of disease to guide management and estimate prognosis.
Weight loss is essential for overweight patients with NASH. Even modest weight loss (~5% of body weight) may have significant beneficial effects by alleviating diabetes and hypertension.
Exercise may be beneficial, with or without associated weight loss. Use of pharmacologic weight loss agents may be beneficial, although this treatment has not yet been adequately studied. Morbidly obese patients (BMI > 35 kg/m2) may consider surgical options, such as gastric bypass.
Diabetes mellitus in NASH patients should be treated as appropriate. Insulin-sensitizing drugs (eg, metformin, pioglitazone) may be especially useful and are also under investigation for use in nondiabetic patients with fatty liver, as they may reduce steatosis. Treatment of hyperlipidemia may decrease the progression of disease.
Rarely, patients with advanced disease may require liver transplantation.
Obesity, diabetes, and insulin resistance syndrome are implicated in the genesis of nonalcoholic fatty liver diseases. These conditions involve steatosis and oxidative stress, both of which can be modulated by diet. Preliminary research suggests that weight reduction on a low-fat, high-fiber diet may be an effective treatment for NAFLD. Although further clinical trials are needed to establish the role of diet in treating these conditions, key nutritional issues are as follows:
Loss of excess weight may reduce the risk for NAFLD and effectively treat NASH. Compared with a rate of 20% in the general population, NAFLD affects up to 75% of obese individuals.2 Gradual, moderate weight loss (~10% of body weight) usually reduces steatosis and may lead to improvement in liver function tests and histology.3 However, rapid weight loss exceeding ~1 lb per week in children and ~ 3.5 lbs per week in adults may result in necroinflammation, portal fibrosis, steatohepatitis, and bile stasis, along with worsening fibrosis.1
Plant-based diets may be particularly helpful for both prevention and treatment of certain characteristic traits of NAFLD. Clinical trials have not yet evaluated the effect of low-fat, high-fiber vegetarian diets on NAFLD, as they have for cardiovascular disease and diabetes. However, these diets typically cause weight loss4 and can lower the concentrations of blood fats (eg, triglycerides) that contribute to nonalcoholic fatty liver disease.5 Such diets are also associated with reduced insulin resistance, another symptom of NAFLD,6 and greater antioxidant protection, compared with omnivorous diets.7,8
In addition, iron accumulation aggravates insulin resistance and oxidative stress. Plant-based diets have somewhat less iron bioavailability, and vegetarians have lower body-iron stores.9
Alcohol intake strongly predicts blood triglyceride concentrations, and dyslipidemias (including elevated triglycerides) are present in a majority of individuals with nonalcoholic fatty liver disease.10 Some evidence indicates that steatosis correlates directly with alcohol intake.11 Consumption of more than 40 grams of alcohol per day doubles the risk of fatty liver12 and other liver diseases. Women may be affected at even lower levels of intake (eg, 20-30 g/day).
Two other nutritional issues merit mention:
Balanced Glucose and Lipid
Patients receiving total parenteral nutrition should receive a balanced ratio of glucose and lipid. Excess glucose administration (> 400 g/day for a 70-kg male) may cause steatosis through excessive hepatic lipogenesis. Patients receiving total parenteral nutrition should receive two thirds of nonprotein calories as glucose and one third as either long-chain triglycerides, or a mixture of medium-chain and long-chain triglycerides.13
Some evidence suggests a role for dietary antioxidants. Oxidative stress, which is the imbalance between potentially harmful oxidants and protective antioxidants that are either diet-derived or endogenous, occurs in patients with fatty liver because of increased lipid oxidation.14 The result is depletion of ATP, DNA damage, alterations in protein stability, destruction of membranes via lipid peroxidation, and the release of proinflammatory cytokines.14 However, clinical trials have not been performed to determine the benefit of dietary or supplementary antioxidants in the prevention or treatment of this disease
What to Tell the Family
In many cases fatty liver disease is responsive to diet changes, along with medications that address the elevations in weight, blood fats, and insulin resistance associated with this condition. Family members can assist the patient by participating in and encouraging a low-fat, high-fiber diet suitable for safe and gradual weight loss, along with appropriate exercise. These measures may help the patient avoid more serious liver damage.
1. Patrick L. Nonalcoholic fatty liver disease: relationship to insulin sensitivity and oxidative stress. Treatment approaches using vitamin E, magnesium, and betaine. Altern Med Rev. 2002;7:276-291.
4. Barnard ND, Scialli AR, Turner-McGrievy G, Lanou AJ, Glass J. The effects of a low-fat, plant-based dietary intervention on body weight, metabolism, and insulin sensitivity. Am J Med. 2005;118:991-997.
5. Mach T. Fatty liver--current look at the old disease. Med Sci Monit. 2000;6:209-216.
10. Friis-Liby I, Aldenborg F, Jerlstad P, Rundstrom K, Bjornsson E. High prevalence of metabolic complications in patients with non-alcoholic fatty liver disease. Scand J Gastroenterol. 2004;39:864-869.
11. Kondili LA, Tosti ME, Szklo M, et al. The relationships of chronic hepatitis and cirrhosis to alcohol intake, hepatitis B and C, and delta virus infection: a case-control study in Albania. Epidemiol Infect. 1998;121:391-395.