Table 5.

Hepatic manifestations in human Wilson disease patients.

No of WD patients	Analysis	Findings in the liver	Mitochondria	Reference
8 (6 untreated, 2 treated with DPA)	Biopsy of liver tissue, EM	Excessive hepatic copper concentration, (ranging from 500 to 1300 μg/g dry weight) fatty metamorphosis of hepatocytes	Increased matrix density and intermembrane space, varying frequency of abnormally shaped mitochondria, electron-transparent inclusions, impaired fatty acid catabolism	Sternlieb, 1968 [135]
7 (before and after DPA treatment)	Biopsy of liver tissue, EM	Hepatic copper concentration between 821 and 117 μg/g dry weight	Increased matrix density, presence of granular inclusions, partial separation of inner and outer membrane of mitochondria DPA treatment reversed structural alterations of the mitochondria	Sternlieb and Feldmann, 1976 [136]
64 (untreated)	Biopsy liver tissue, EM	Increased hepatic copper content (500–1100 μg/g dry weight), fibrosis and cirrhosis in 9 of 22 patients	Mitochondria were found to be enlarged, pleomorphic, partially containing large granular vacuoles not related to patient age, hepatic copper level or AST	Sternlieb, 1992 [137]
3 (treated with DPA)	Isolated liver mitochondria, TBARS	Hepatic copper content in WD patients ∼400 μg/g dry weight, liver cirrhosis in all cases	33-fold increased copper level, increased lipid peroxidation	Sokol et al., 1994 [138]
16 (7 untreated, 9 treated with chelating therapy)	Biopsy of liver tissue, mtDNA sequencing	6 patients with cirrhosis, 14 patients with fibrosis	High prevalence of large mtDNA deletions, appearing in early stages of WD	Mansouri et al., 1997 [192]
3 (2 treated with DPA)	Liver homogenate, enzyme activity assays	All three patients presented cirrhosis, contained 300–700 μg/g dry weight of copper.	Significantly decreased activity of mitochondrial aconitase and respiratory complexes	Gu et al., 2000 [67]
11 (untreated)	Biopsy of liver tissue, EM	Portal tract fibrosis in 9, liver cirrhosis in 6	Pleomorphic mitochondria with enlarged, electron-dense granules, loss of cristae structure, increased intermembrane space	Shawky et al., 2010 [193]