Etiological Evaluation of Atypical Copper Related Liver Disease.

INTRODUCTION : Copper related liver disease is one of the most common etiologies of liver disease in India. Wilsons disease (WD) is the most common of the copper related liver diseases. It is a genetic disorder which follows autosomal recessive inheritance. WD is characterized by a mutation in ATP 7B gene at 13 q 14. WD generally presents as persistently elevated aspartate / alanine aminotranferases , chronic hepatitis, compensated or decompensated chronic liver disease or rarely it may present as Acute Wilsonian crisis. WD is diagnosed by Serum Ceruloplasmin levels, KF ring, 24 hr urinary copper level, hepatic copper quantification and / or ATP 7 B mutation analysis. WD is treated by copper chelation either with Pencillamine or Zinc or both. Indian childhood cirrhosis ( ICC) has fascinated the medical fraternity for almost 100 years. The peculiar features, enigmatic etiology and uniformly fatal outcome had frustrated many. In 1978, a finding almost by chance revealed a striking association of exceedingly high hepatic copper content. This finding led to the hypothesis that milk contaminated with copper caused the disease. It was characterized by occurrence of the disease in the infants with dietary history of dietary copper consumption. It is largely disappearing in India because of preventive strategies. There is a heterogeneous group of patients who do not fit into either WD or ICC. There are case reports of this uncommon disease from other countries also. It was described in Austria , Germany, Saudi Arabia, Kuwait, Japan and USA. In India largely after the disappearance of ICC it was described as Atypical copper cirrhosis. AIMS : 1. To look for evidence of increased copper intake in Atypical copper related liver disease (ACLD ) patients. 2. To study clinical features and treatment outcome of ACLD patients. CONCLUSION : The conclusions drawn from this study are, the 11 patients have features of hepatic copper overload not fitting into either WD or ICC. This condition is different from WD by not showing neurological involvement and coombs negative heamolytic aneamia with normal ceruloplasmin, and negative for Kayser Fleisher rings and ATP 7 B mutations. This condition is different from ICC by the occurrence of disease after 5 years with no dietary history of copper intake and histology different from ICC. The treatment outcome of ACLD patients with either Penicillamine or Zinc or both sequentially is good. There was no evidence for increased copper intake in drinking water in ACLD patients studied. Further studies into causation of ACLD are needed