Clinical and molecular characterization of Wilson disease in Spanish patients.

Wilson disease (WD) results when specific mutations occur at the ATP7B gene. The presence of mutations in the ATP7B gene was studied in the coding region and the intron-exon boundaries in 15 WD Spanish patients, and their first-degree relatives when possible. A total of 20 nucleotide sequence changes were detected, 18 missense and two splicing mutations. Six of these variants were classified as disease-causing mutations, five missense, and one splicing; four of them have been previously described (M645R, A1065P, H1069Q, and 3060 + 5G > T), whereas two were novel (P768L and A990P). No mutation was clearly prevalent, although the H1069Q mutation predominated, nor did a good phenotype-genotype correlation exist. The two new mutations described were manifested as an asymptomatic increase in serum transaminases. The remaining 14 changes were classified as polymorphisms and their potential effects on protein function are discussed. The identification of mutations in the ATP7B gene has allowed a conclusive diagnosis to be made of WD in patients presenting neurological phenotype or neurological of hepatic phenotype, who would otherwise not have been diagnosed using classical criteria. WD patients could start chelating treatment earlier on and possibly modify the natural progression of the disease.

Influence of superimposed alcoholic hepatitis on the outcome of liver transplantation for end-stage alcoholic liver disease.

BACKGROUND/AIMS: Alcoholic cirrhosis is a common indication for liver transplantation. The present study was aimed to assess the influence of superimposed alcoholic hepatitis on the outcome of liver transplantation in patients with alcoholic cirrhosis. METHODS: Survival rates of 68 patients transplanted for alcoholic cirrhosis were compared with those of 101 patients transplanted for miscellaneous causes. Within the alcoholic group, explanted livers were searched for data of acute alcoholic hepatitis. The survival rate of patients with alcoholic hepatitis superimposed on liver cirrhosis was compared to that of patients with liver cirrhosis alone. Clinical severity of alcoholic hepatitis was assessed with Maddrey's score. RESULTS: Survival was similar in alcoholics and patients with other causes of liver disease. Among patients transplanted for alcoholic cirrhosis, survival was similar in patients with superimposed alcoholic hepatitis (n=36) and in cases with liver cirrhosis alone (n=32). There was no difference in survival between patients with mild (n=26) and severe (n=10) alcoholic hepatitis. Seven alcoholics (10%) returned to ethanol consumption. Recidivism was not associated with either alcoholic hepatitis in the explanted liver or graft loss. CONCLUSIONS: Survival after liver transplantation in patients with alcoholic cirrhosis plus alcoholic hepatitis detected in the explanted liver is similar to that of patients transplanted for other reasons. Even the presence of severe alcoholic hepatitis does not worsen the outcome of liver transplantation for end-stage alcoholic liver disease.