Late diagnosed Wilson disease with hepatic and neurological manifestations

A 50-year-old woman was referred to our hospital due to liver dysfunction and progressive neurological symptoms. She had previously been diagnosed with nonalcoholic steatohepatitis (NASH). Ursodeoxycholic acid (UDCA) had effectively normalized her serum aminotransferase levels, however, she presented with loss of balance, dysarthria and difficulty in handwriting. Autoantibodies and hepatitis virus markers were negative. Serum ceruloplasmin and copper levels were noted to be 9 mg/dL and 32 µg/dL, respectively. The 24-h urinary copper excretion was 331.8 µg/day. Kayser-Fleischer ring was demonstrated. Histological examination of the liver revealed inflammatory infiltrate and fibrosis, and the hepatic copper concentration was 444.4 µg/g dry weight. We diagnosed her as having Wilson disease and started treatment with trientine. Immuohistochemistry for keratin 8 and p62 demonstrated Mallory-Denk bodies. Many of the p62-expressing cells were positive for 4-Hydroxy-2-nonenal (HNE). Few Ki-67-positive hepatocytes were present in the liver. Wilson disease is one of the causes of NASH and UDCA may be a supportive therapeutic agent for Wilson disease. Cell proliferation is suppressed under copper-loaded conditions and this phenomenon may be associated with the clinical course of Wilson disease.