Which histologic findings are characteristic of hepatic Wilson disease?

Updated: Feb 14, 2019
  • Author: Richard K Gilroy, MBBS, FRACP; Chief Editor: Praveen K Roy, MD, AGAF  more...
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The earliest changes detectable with light microscopy include glycogen deposition in the nuclei of periportal hepatocytes and moderate fatty infiltration. The lipid droplets, which are composed of triglycerides, progressively increase in number and size, sometimes resembling the steatosis induced by ethanol. Hepatocyte mitochondria typically exhibit heterogeneity in size and shape, with increased matrix density, separation of the normally apposed inner and outer mitochondrial membranes, widened intercristal spaces, and an array of vacuolated and crystalline inclusions within the matrix. With progression of disease, copper protein is sequestered in lysosomes and is visible as electron-dense pericanalicular granules.

Despite consistently elevated hepatic copper levels in patients with Wilson disease, histochemical staining of liver biopsy specimens for copper is of little diagnostic value. Early in the disease, copper distribution is primarily cytoplasmic and is not readily apparent with rhodamine or rubeanic acid staining.

The rate of progression of the liver histology from fatty infiltration to cirrhosis is variable, although it tends to occur by 1 of 2 general processes, either with or without hepatic inflammation. The histologic picture may be histologically indistinguishable from that of chronic active hepatitis. Pathologic features include mononuclear cell infiltrates, which consist mainly of lymphocytes and plasma cells; piecemeal necrosis extending beyond the limiting plate; parenchymal collapse; bridging hepatic necrosis; and fibrosis.

The histologic pattern is one of a macronodular or mixed micro-macronodular cirrhosis, with fibrous septa (containing predominantly types I and III collagen), bile ductule proliferation, and variable septal round cell infiltration. Hepatocytes at the periphery of the nodules frequently contain Mallory hyalin. One proposed mechanism implicates copper as the inducer of fibrogenesis.

Interestingly, hepatocellular carcinoma is exceedingly rare in patients with Wilson disease compared with patients with hemochromatosis. This may be attributable to the significantly shortened life expectancy in untreated patients with Wilson disease, which does not allow time for carcinoma to develop. An increasing number of case reports suggest that the incidence will likely increase with improved survival. It has been proposed that the diminished cancer risk is due to the relatively low inflammatory component in the pathogenesis of Wilson disease.

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