Secondary causes of nonalcoholic fatty liver disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) is becoming the most common cause of chronic liver disease in the developing world, found in 17-30% of the population in Western countries and 2-4% worldwide. Defined as the accumulation of fatty acid content greater than 5% of liver weight, NAFLD is a spectrum of disease ranging from simple steatosis to nonalcoholic steatohepatitis. The pathophysiology of NAFLD involves increased de novo synthesis of fatty acids in hepatocytes, the retention of lipids due to impaired hepatocyte apolipoprotein secretion or beta-oxidation. The well-known primary causes of NAFLD are obesity, type II diabetes, dyslipidemia, and insulin resistance. However, other less common conditions can cause a similar clinical and histologic picture, and should be considered in patients who present with NAFLD but do not have traditional risk factors. In this review, we discuss uncommon but important causes of NAFLD, including inborn errors of metabolism, iatrogenic causes, viral hepatitis, and nutritional disorders to provide practicing clinicians with an understanding of the less well recognized causes of NAFLD.

Keywords: fatty liver; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; secondary causes.

Figure 1.

Total parenteral nutrition induced liver injury. The liver shows marked steatosis, cholestasis, and duct proliferation with inspissated bile (arrow).

Figure 2.

Liver biopsy in a patient on nucleoside analogs. (A) The low-power view shows moderate steatosis in a nonzonal pattern, hepatocyte pallor, and mild hepatic plate thickening suggestive of reactive changes. (B) The high-power view shows the hepatocytes containing numerous swollen ‘megamitochondria’ (arrowheads), a feature of mitochondrial injury.

Figure 3.

Amiodarone toxicity. (A) Medium-power view shows diffuse ballooning degeneration of hepatocytes and sinusoidal fibrosis. (B) High-power view shows features reminiscent of alcoholic steatohepatitis, with marked ballooning degeneration of hepatocytes, Mallory–Denk bodies (arrows), and lobular neutrophil infiltrates (arrowheads).

Figure 4.

Liver biopsy in the setting of methotrexate. (A) The hepatocytes show macrovesicular steatosis, nuclear hyperchromasia, and anisonucleosis. (B) A trichrome stain shows bridging fibrosis and sinusoidal fibrosis extending from portal tracts.

Figure 5.

Liver biopsy in a young boy diagnosed with Wilson disease. The biopsy shows features indistinguishable from fatty liver secondary to metabolic syndrome with marked steatosis, irregular portal expansion, and mild portal mononuclear infiltrate. Glycogenated nuclei were also present.