Inherited metabolic disease of the liver.

PURPOSE OF REVIEW: Progress in the dissection of the molecular pathogenesis of most prevalent inherited liver diseases such as hereditary hemochromatosis, Wilson's disease, and alpha1-antitrypsin deficiency is continuing. This review highlights recent achievements that have clarified defective molecular pathways and shed new lights on the complex interplay of genetic and environmental factors in determining disease phenotype. This advancement paves the way for development of new strategies to diagnose and cure metabolic liver diseases.

RECENT FINDINGS: Hepcidin, the iron hormone that is defective in hemochromatosis, is controlled not only by iron signals but also by a number of circulatory and membrane-associated regulators. Serum and urinary hepcidin can be now measured. New studies have provided important information on variable clinical expressivity of the genetic defect in hemochromatosis. The molecular and cellular events that accompany Wilson's disease and alpha-1-antitrypsin deficiency are being elucidated. In both, an unexpected pathogenic link with early metabolic abnormality in lipid or glycogen metabolism has emerged. Interference with apoptotic pathways may offer new therapeutic tools to prevent liver disease progression and acute liver failure associated with inherited metabolic diseases of the liver.

SUMMARY: The field of inherited diseases of the liver is rapidly evolving. Understanding molecular pathogenesis of these disorders is improving our ability to diagnose and treat them. The most recent findings are detailed in this review.