Long-term outcomes of patients with Wilson disease in a large Austrian cohort.
OBJECTIVE
Wilson disease is an autosomal recessive disorder that affects copper metabolism, leading to copper accumulation in liver, central nervous system, and kidneys. There are few data on long-term outcomes and survival from large cohorts; we studied these features in a well-characterized Austrian cohort of patients with Wilson disease.


METHODS
We analyzed data from 229 patients diagnosed with Wilson disease from 1961 through 2013; 175 regularly attended a Wilson disease outpatient clinic and/or their physicians were contacted for information on disease and treatment status and outcomes. For 53 patients lost during the follow-up period, those that died and reasons for their death were identified from the Austrian death registry.


RESULTS
The mean observation period was 14.8 ± 11.4 years (range, 0.5-52.0 years), resulting in 3116 patient-years. Of the patients, 61% presented with hepatic disease, 27% with neurologic symptoms, and 10% were diagnosed by family screening at presymptomatic stages. Patients with a hepatic presentation were diagnosed younger (21.2 ± 12.0 years) than patients with neurologic disease (28.8 ± 12.0; P < .001). In 2% of patients, neither symptoms nor onset of symptoms could be determined with certainty. Most patients stabilized (35%) or improved on chelation therapy (26% fully recovered, 24% improved), but 15% deteriorated; 8% required a liver transplant, and 7.4% died within the observation period (71% of deaths were related to Wilson disease). A lower proportion of patients with Wilson disease survived for 20 years (92%) than healthy Austrians (97%), adjusted for age and sex (P = .03). Cirrhosis at diagnosis was the best predictor of death (odds ratio, 6.8; 95% confidence interval, 1.5-31.03; P = .013) and need for a liver transplant (odds ratio, 07; 95% confidence interval, 0.016-0.307; P < .001). Only 84% of patients with cirrhosis survived 20 years after diagnosis (compared with healthy Austrians, P =.008).


CONCLUSIONS
Overall, patients who receive adequate care for Wilson disease have a good long-term prognosis. However, cirrhosis increases the risk of death and liver disease. Early diagnosis, at a precirrhotic stage, might increase survival times and reduce the need for a liver transplant.
Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University Vienna, Austria.
Sandra
S
Beinhardt
Department of General Internal Medicine, Bern University Hospital, Bern, Switzerland.
Waltraud
W
Leiss
Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University Vienna, Austria.
Albert Friedrich
AF
Stättermayer
Department of Gastroenterology and Hepatology, Medical University Innsbruck, Austria.
Ivo
I
Graziadei
Department of Gastroenterology and Hepatology, Medical University Innsbruck, Austria.
Heinz
H
Zoller
Division of Gastroenterology and Hepatology, Medical University Graz, Austria.
Rudolf
R
Stauber
Hospital Elisabethinen, Linz, Austria.
Andreas
A
Maieron
Hospital Oberndorf, Salzburg, Austria.
Christian
C
Datz
Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University Vienna, Austria.
Petra
P
Steindl-Munda
Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University Vienna, Austria.
Harald
H
Hofer
Department of Gastroenterology and Hepatology, Medical University Innsbruck, Austria.
Wolfgang
W
Vogel
Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University Vienna, Austria.
Michael
M
Trauner
Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University Vienna, Austria. Electronic address: peter.ferenci@meduniwien.ac.at.
Peter
P
Ferenci
D000293:Adolescent; D000328:Adult; D001317:Austria / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006527:Hepatolenticular Degeneration / Q000453:epidemiology* / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
Genetic Liver Disease; Inherited Liver Disease; Mortality; Population