Liver histology crucial at Wilson disease diagnosis

Wilson disease patients without cirrhosis at diagnosis generally have good long-term prognoses, but the presence of cirrhosis on diagnosis of this rare condition necessitates transplant in up to 13% of cases and is the strongest predictor of mortality, according to findings from a retrospective analysis.

The report appears in the April issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.09.025).

The finding "[reinforces] the histologic assessment of liver fibrosis to be performed in all patients suspected to have Wilson disease, regardless of whether they present with neurologic or hepatic symptoms," wrote Dr. Sandra Beinhardt of the Medical University of Vienna. She and her colleagues looked at 229 patients (48% of whom were male) who were diagnosed with Wilson disease in Austria between 1961 and 2013.

Courtesy: American Gastroenterological Association

"In patients with evaluable symptoms at diagnosis as well as reliable information on the time of the onset of symptoms" (90% of the total cohort), diagnosis of Wilson disease was established by 3 years after symptom onset in 75% of patients, the researchers noted.

Overall, 140 patients presented with predominantly hepatic symptoms; 61 with neurologic symptoms; and 23 were diagnosed by screening before any symptoms were noted.

In the remaining 5 patients, the presenting symptoms could not be determined.

Looking at long-term prognosis, the authors found that patients presenting with neurologic symptoms had a significantly longer mean follow-up period than did patients with hepatic symptoms at diagnosis (21.1 years versus 11.8 years, respectively; P less than .001).

"Nevertheless, 34% of patients predominantly presenting with neurologic symptoms at diagnosis already had developed cirrhosis," they wrote.

Overall, 30 patients received liver transplants between 1986 and 2013, because of fulminant hepatic failure in 11 patients, neurologic worsening in 1 patient, and decompensated liver cirrhosis in the remaining 18.

As for mortality, among the 17 patients who died during the study period, the researchers reported that most of the deaths could be attributed to Wilson disease. Seven patients died of liver failure, four died of complications resulting from the liver transplant.

One patient died of suicide, reportedly following severe depression stemming from the Wilson disease diagnosis.

That translated to an overall 20-year cumulative survival rate of 0.920 by Kaplan-Meier analysis. However, that figure dipped to 0.84 for patients with cirrhosis on diagnosis (compared with 0.97 for all others, P = .008).

Indeed, "By univariate logistic regression analysis, liver cirrhosis at diagnosis was the best predictor for the need of liver transplant (odds ratio, 0.07; 95% confidence interval, 0.016-0.307; P less than .001) as well as for death (OR, 6.8; 95% CI, 1.5-31.03; P = .013)," wrote the authors.

The cohort they studied represents nearly all cases of Wilson disease that could have been expected to occur in Austria during the study period, given an incidence of 30 cases per million people in that nation of 8 million inhabitants, they wrote.

And while the retrospective nature of their study limits analysis, because of the rarity of Wilson disease, "prospective studies with reasonably large sample sizes are almost impossible to perform," they noted.

Nevertheless, "the long-term prognosis in patients with Wilson disease surviving more than 10 years after diagnosis and treatment initiation is excellent," especially if the diagnosis is early, wrote Dr. Beinhardt and her colleagues.

The authors stated that they had no conflicts of interest.

Wilson disease patients without cirrhosis at diagnosis generally have good long-term prognoses, but the presence of cirrhosis on diagnosis of this rare condition necessitates transplant in up to 13% of cases and is the strongest predictor of mortality, according to findings from a retrospective analysis.

The report appears in the April issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.09.025).

The finding "[reinforces] the histologic assessment of liver fibrosis to be performed in all patients suspected to have Wilson disease, regardless of whether they present with neurologic or hepatic symptoms," wrote Dr. Sandra Beinhardt of the Medical University of Vienna. She and her colleagues looked at 229 patients (48% of whom were male) who were diagnosed with Wilson disease in Austria between 1961 and 2013.

Courtesy: American Gastroenterological Association

"In patients with evaluable symptoms at diagnosis as well as reliable information on the time of the onset of symptoms" (90% of the total cohort), diagnosis of Wilson disease was established by 3 years after symptom onset in 75% of patients, the researchers noted.

Overall, 140 patients presented with predominantly hepatic symptoms; 61 with neurologic symptoms; and 23 were diagnosed by screening before any symptoms were noted.

In the remaining 5 patients, the presenting symptoms could not be determined.

Looking at long-term prognosis, the authors found that patients presenting with neurologic symptoms had a significantly longer mean follow-up period than did patients with hepatic symptoms at diagnosis (21.1 years versus 11.8 years, respectively; P less than .001).

"Nevertheless, 34% of patients predominantly presenting with neurologic symptoms at diagnosis already had developed cirrhosis," they wrote.

Overall, 30 patients received liver transplants between 1986 and 2013, because of fulminant hepatic failure in 11 patients, neurologic worsening in 1 patient, and decompensated liver cirrhosis in the remaining 18.

As for mortality, among the 17 patients who died during the study period, the researchers reported that most of the deaths could be attributed to Wilson disease. Seven patients died of liver failure, four died of complications resulting from the liver transplant.

One patient died of suicide, reportedly following severe depression stemming from the Wilson disease diagnosis.

That translated to an overall 20-year cumulative survival rate of 0.920 by Kaplan-Meier analysis. However, that figure dipped to 0.84 for patients with cirrhosis on diagnosis (compared with 0.97 for all others, P = .008).

Indeed, "By univariate logistic regression analysis, liver cirrhosis at diagnosis was the best predictor for the need of liver transplant (odds ratio, 0.07; 95% confidence interval, 0.016-0.307; P less than .001) as well as for death (OR, 6.8; 95% CI, 1.5-31.03; P = .013)," wrote the authors.

The cohort they studied represents nearly all cases of Wilson disease that could have been expected to occur in Austria during the study period, given an incidence of 30 cases per million people in that nation of 8 million inhabitants, they wrote.

And while the retrospective nature of their study limits analysis, because of the rarity of Wilson disease, "prospective studies with reasonably large sample sizes are almost impossible to perform," they noted.

Nevertheless, "the long-term prognosis in patients with Wilson disease surviving more than 10 years after diagnosis and treatment initiation is excellent," especially if the diagnosis is early, wrote Dr. Beinhardt and her colleagues.

The authors stated that they had no conflicts of interest.

Wilson disease patients without cirrhosis at diagnosis generally have good long-term prognoses, but the presence of cirrhosis on diagnosis of this rare condition necessitates transplant in up to 13% of cases and is the strongest predictor of mortality, according to findings from a retrospective analysis.

The report appears in the April issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.09.025).

The finding "[reinforces] the histologic assessment of liver fibrosis to be performed in all patients suspected to have Wilson disease, regardless of whether they present with neurologic or hepatic symptoms," wrote Dr. Sandra Beinhardt of the Medical University of Vienna. She and her colleagues looked at 229 patients (48% of whom were male) who were diagnosed with Wilson disease in Austria between 1961 and 2013.

Courtesy: American Gastroenterological Association

"In patients with evaluable symptoms at diagnosis as well as reliable information on the time of the onset of symptoms" (90% of the total cohort), diagnosis of Wilson disease was established by 3 years after symptom onset in 75% of patients, the researchers noted.

Overall, 140 patients presented with predominantly hepatic symptoms; 61 with neurologic symptoms; and 23 were diagnosed by screening before any symptoms were noted.

In the remaining 5 patients, the presenting symptoms could not be determined.

Looking at long-term prognosis, the authors found that patients presenting with neurologic symptoms had a significantly longer mean follow-up period than did patients with hepatic symptoms at diagnosis (21.1 years versus 11.8 years, respectively; P less than .001).

"Nevertheless, 34% of patients predominantly presenting with neurologic symptoms at diagnosis already had developed cirrhosis," they wrote.

Overall, 30 patients received liver transplants between 1986 and 2013, because of fulminant hepatic failure in 11 patients, neurologic worsening in 1 patient, and decompensated liver cirrhosis in the remaining 18.

As for mortality, among the 17 patients who died during the study period, the researchers reported that most of the deaths could be attributed to Wilson disease. Seven patients died of liver failure, four died of complications resulting from the liver transplant.

One patient died of suicide, reportedly following severe depression stemming from the Wilson disease diagnosis.

That translated to an overall 20-year cumulative survival rate of 0.920 by Kaplan-Meier analysis. However, that figure dipped to 0.84 for patients with cirrhosis on diagnosis (compared with 0.97 for all others, P = .008).

Indeed, "By univariate logistic regression analysis, liver cirrhosis at diagnosis was the best predictor for the need of liver transplant (odds ratio, 0.07; 95% confidence interval, 0.016-0.307; P less than .001) as well as for death (OR, 6.8; 95% CI, 1.5-31.03; P = .013)," wrote the authors.

The cohort they studied represents nearly all cases of Wilson disease that could have been expected to occur in Austria during the study period, given an incidence of 30 cases per million people in that nation of 8 million inhabitants, they wrote.

And while the retrospective nature of their study limits analysis, because of the rarity of Wilson disease, "prospective studies with reasonably large sample sizes are almost impossible to perform," they noted.

Nevertheless, "the long-term prognosis in patients with Wilson disease surviving more than 10 years after diagnosis and treatment initiation is excellent," especially if the diagnosis is early, wrote Dr. Beinhardt and her colleagues.

The authors stated that they had no conflicts of interest.