The Emerging Epidemic of Nonalcoholic Fatty Liver Disease
Nonalcoholic fatty liver disease (NAFLD) includes the clinical-pathologic entities of steatosis (nonalcoholic fatty liver, or NAFL) and nonalcoholic steatohepatitis (NASH) with or without fibrosis and cirrhosis. Ludwig and colleagues first described NASH in 1980 when they recognized a histologic pattern of fatty liver associated with lobular hepatitis, similar to alcoholic hepatitis but developing in the absence of alcoholism. Most of their patients were modestly obese and some had diabetes mellitus. NAFLD is the most frequent cause of abnormal liver tests in both adults and children.
NAFLD is common.The National Health and Nutrition Examination Survey (NHANES) III of American adults indicates that up to 23% may be affected. Hepatic steatosis is more common in white men than in white women. Hispanic whites have greater steatosis and risk for progressive liver disease than do blacks, and blacks have a reduced risk for hepatic fibrosis compared with whites. NAFLD also affects all ages: An autopsy study found fatty liver in nearly 10% of adolescents, with boys having a greater prevalence of NAFLD than girls.
Components of metabolic syndrome, including obesity, hyperlipidemia, and type 2 diabetes mellitus, are frequently present in NAFLD.Metabolic syndrome is defined by the presence of truncal obesity, increased waist circumference, hyperlipidemia with elevated triglyceride and low HDL-cholesterol levels, insulin resistance with hyperglycemia, and systemic hypertension. Affected patients are typically middle-aged (in their fifth decade), obese, and often more than 20% above their ideal body weight. NAFLD also develops in patients of normal body weight. Early cases of NASH were described following jejunoileal or jejunocolic bypass and were associated with hepatic failure and death. Non-insulin-dependent diabetes mellitus (NIDDM) is present in up to 75% of cases, although diabetes mellitus is less likely in children with NASH. Morbidly obese patients presenting for gastric bypass surgery often have NAFLD and metabolic syndrome.
Hyperlipidemia, rapid weight loss following gastric bypass for obesity, short bowel syndrome, prolonged use of total parenteral nutrition, small bowel bacterial overgrowth from jejunal diverticulosis, abetalipoproteinemia, hypobetalipoproteinemia, and Weber-Christian disease are associated with NAFLD (Table 1). Lipodystrophy with fat mobilization from peripheral fat stores can result in fat accumulation and inflammation of the liver.
Table 1. Medical Conditions Associated With NAFLD
The use of some pharmaceutical agents is also associated with NAFLD (Table 2).
Table 2. Medications and Therapies Associated With NAFLD
The Spectrum of Nonalcoholic Fatty Liver
Nonalcoholic fatty liver disease (NAFLD) includes the clinical-pathologic entities of steatosis (nonalcoholic fatty liver, or NAFL) and nonalcoholic steatohepatitis (NASH) with or without fibrosis and cirrhosis. Ludwig and colleagues first described NASH in 1980 when they recognized a histologic pattern of fatty liver associated with lobular hepatitis, similar to alcoholic hepatitis but developing in the absence of alcoholism. Most of their patients were modestly obese and some had diabetes mellitus. NAFLD is the most frequent cause of abnormal liver tests in both adults and children.
NAFLD is common.The National Health and Nutrition Examination Survey (NHANES) III of American adults indicates that up to 23% may be affected. Hepatic steatosis is more common in white men than in white women. Hispanic whites have greater steatosis and risk for progressive liver disease than do blacks, and blacks have a reduced risk for hepatic fibrosis compared with whites. NAFLD also affects all ages: An autopsy study found fatty liver in nearly 10% of adolescents, with boys having a greater prevalence of NAFLD than girls.
Associated Diseases
Components of metabolic syndrome, including obesity, hyperlipidemia, and type 2 diabetes mellitus, are frequently present in NAFLD.Metabolic syndrome is defined by the presence of truncal obesity, increased waist circumference, hyperlipidemia with elevated triglyceride and low HDL-cholesterol levels, insulin resistance with hyperglycemia, and systemic hypertension. Affected patients are typically middle-aged (in their fifth decade), obese, and often more than 20% above their ideal body weight. NAFLD also develops in patients of normal body weight. Early cases of NASH were described following jejunoileal or jejunocolic bypass and were associated with hepatic failure and death. Non-insulin-dependent diabetes mellitus (NIDDM) is present in up to 75% of cases, although diabetes mellitus is less likely in children with NASH. Morbidly obese patients presenting for gastric bypass surgery often have NAFLD and metabolic syndrome.
Hyperlipidemia, rapid weight loss following gastric bypass for obesity, short bowel syndrome, prolonged use of total parenteral nutrition, small bowel bacterial overgrowth from jejunal diverticulosis, abetalipoproteinemia, hypobetalipoproteinemia, and Weber-Christian disease are associated with NAFLD (Table 1). Lipodystrophy with fat mobilization from peripheral fat stores can result in fat accumulation and inflammation of the liver.
Table 1. Medical Conditions Associated With NAFLD
| Obesity |
| Hyperlipidemia |
| Type 2 diabetes mellitus |
| Metabolic syndrome |
| Jejunoileal bypass for obesity |
| Jejunocolic bypass for obesity |
| Gastric bypass for obesity |
| Adult polycystic ovary syndrome |
| Partial limb lipodystrophy |
| Rapid weight loss |
| Short bowel syndrome |
| Abeta- or hypobetalipoproteinemia |
| Weber-Christian disease |
| Jejunal diverticulosis |
The use of some pharmaceutical agents is also associated with NAFLD (Table 2).
Table 2. Medications and Therapies Associated With NAFLD
| Coralgil |
| Perhexilene maleate |
| Amiodarone |
| Thiazolidinediones (glitazones) |
| Total parenteral nutrition |
| Chloroquine |
| Tamoxifen |
| Glucocorticoids |
| Calcium channel blockers |
| Estrogens |
| Diethystilbestrol |
| Methotrexate |
| Thioridazine |
| Lamivudine |
| Valproic acid |
| Tetracyclines |
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