Reports of hepatobiliary malignancies in Wilson disease are sparse. The aim of this study was to evaluate hepatobiliary malignancies in Wilson disease patients concerning the clinical course of tumour disease and pathological analysis of tumour tissue.

Multicenter cohort study of patients with confirmed diagnosis of Wilson disease treated at the Second Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland, the university hospitals Heidelberg, Duesseldorf and Dresden, Germany, and the Department of Hepatology, University Leuven, Belgium. Occurrence, treatment and outcome of hepatobiliary tumours were analysed retrospectively.

Of a total of 1186 patients, fourteen developed hepatobiliary malignancies. Eight were hepatocellular carcinomas (HCC) and six were intrahepatic cholangiocellular carcinomas (ICC). The prevalence of hepatobiliary malignancies in the cohort was 1.2% and the incidence was 0.28 per 1000 person years. Pathological analysis of tumour material showed no abnormal copper concentration.

The rate of hepatobiliary malignancies in Wilson disease is very low, even in cirrhotic patients. As a result of the relevant number of ICC in addition to HCC histological analysis through surgical resection or biopsy should be mandatory when a suspect liver lesion is detected. The influence of copper depletion from Wilson disease-specific medical treatment on tumour activity remains to be elucidated.

Wilson's disease is a hereditary disorder of copper metabolism that results in the accumulation of copper in the body, primarily in the liver, brain, and cornea. Hepatocellular carcinoma, in contrast to other causes of cirrhosis, is seldom associated with Wilson's disease. We present a 12-yr-old boy with Wilson's disease in whom hepatocellular carcinoma was incidentally diagnosed in the pathologic specimen examined after liver transplantation.

We report a 66-year-old male patient with hepatocellular carcinoma (HCC) associated with Wilson's disease. The patient presented with unresolving abnormal liver function test, decreased serum ceruloplasmin levels and increased 24-hour urine copper excretion. Liver biopsy specimen revealed the presence of increased levels of copper and features suggestive of Wilson's disease. Abdominal imaging showed the existence of a small HCC. Three years after chemoembolization and microwave coagulation therapy for HCC, he died of hepatic failure, which apparently resulted from chemoembolization. Patients with Wilson's disease should be screened for HCC. We should elude therapies such as chemoembolization in these patients.

A 23-year-old man was admitted to our department due to hemorrhage from gastric varices. He had been diagnosed as having Wilson's disease at the age of 17. Abdominal ultrasonography and computed tomography (CT) showed portal thrombosis and a large mass occupying most of the right lobe in the liver. The tumor was diagnosed as hepatocellular carcinoma (HCC) by image views and tumor markers. He died 3 months after the diagnosis, and an autopsy was performed. Histologic examination of the tumor showed moderately to poorly differentiated HCC. The nontumorous lesion of the liver revealed cirrhosis. HBX-DNA sequence was not detected in the liver. Hepatic cirrhosis is a well-recognized complication of Wilson's disease, but HCC is extremely rare. We describe the clinical findings of this patient and discuss the relationship of the development of HCC with a review of the relevant literature.

During the last 90 years, Wilson's hepatolenticular degeneration has evolved from a disease presenting insurmountable challenges to the clinician's diagnostic acumen to a metabolic disorder which is diagnosable woth certainty, treatable successfully, and even preventable. It may be long before the genetic defect becomes amenable to correction and a cure of the disease becomes possible.

Certain features of Wilson's disease (WD) in Asia have been found to be different from those in other continents. The higher prevalence rate in Japan is presumably due to a higher consanguinity rate. In Chinese there is a tight linkage between WD and two gene loci for esterase D and retinoblastoma in the long arm of chromosome 13. The high proportion of patients with hepatic presentation accounts for early onset of WD in the Japanese and Chinese series. Skeletal involvement, leg hyperpigmentation, dark complexion, amenorrhea, epileptic seizures, and cerebral white matter degeneration are relatively more common among WD patients in Asia. Excessive copper in the liver appears to have a protective effect against hepatocellular carcinoma and type B hepatitis. Electrophysiological studies suggest widespread functional disturbances of the CNS in WD. Side-effects from penicillamine are rather frequent and often lead to interruption of the therapy. Trien is found to be effective without adverse reactions. Oral zinc therapy may be a suitable alternative for long-term management of WD patients in developing Asian countries.

Hepatocellular carcinoma has rarely been reported in Wilson's disease, particularly in women. We describe the case of a female patient who was diagnosed with Wilson's disease at the age of 39 years, after presenting with severe neurological symptoms. She had significant neurological improvement following penicillamine therapy and succumbed to hepatocellular carcinoma at the age of 72 years, following 33 years of penicillamine therapy. The patient described here was the oldest and only the third female patient with hepatocellular carcinoma complicating Wilson's disease to be reported in the literature.

A 27 year old woman with hepato-lenticular degeneration (Wilson's disease) was found to have primary hepatocellular carcinoma (PHC) three and a half years after she was started on treatment with D-penicillamine. The tumour was resected since when she has remained well. Her liver function tests were normal throughout the course of her disease. The available literature is reviewed and possible mechanisms for this association proposed.

A male patient with Wilson's disease developed a hepatocellular carcinoma after treatment for nine years with D-penicillamine. Examination at necropsy showed that excess liver copper had been effectively removed. As copper has been shown to protect against chemically induced hepatocellular carcinoma in rats, this may be the reason for the extreme rarity of hepatocellular carcinoma in patients with Wilson's disease and possibly in other liver diseases with hepatic copper overload.