The candidate is currently an Associate Professor of Medicine at the University of Washington and is nationally recognized for his work in hepatology, in particular hepatic iron overload disorders. He has reached a stage of rapid and productive growth in his career. Heavy clinical responsibilities have limited his ability to focus on patient-oriented research. This award will protect his time and help him sustain the momentum and productivity he has generated. He will also strengthen and build on his knowledge of biostatistics, epidemiology and molecular biologic techniques. The candidate will be able, with the protected time afforded by this award, to achieve the following career goals: 1. Conduct excellent patient-oriented research in liver disease. 2. Develop into a leader in his field and make significant scientific contributions that will improve clinical care. 3. Serve as a mentor and role model in the training of new and junior patient-oriented investigators. During the period of funding, the candidate will develop and expand a multidisciplinary research program in two broad areas: 1. The role of iron and HFE mutations in liver disease and 2. Genotype/phenotype correlations in hereditary hemochromatosis. The candidate will lead studies examining the relationship between hepatic iron stores, HFE genotype and disease severity in hepatitis C and nonalcoholic steatohepatitis (NASH). He will continue and expand a current study funded by an NIH planning grant to examine the effect of iron overload on outcome after liver transplantation. These studies will provide definitive data on the role of iron and HFE mutations in the expression and clinical severity of hepatitis C, NASH and in end-stage liver disease. Hereditary hemochromatosis is a genetic disease caused by an autosomal recessive defect in the recently identified HFE gene. There is currently much debate about the clinical expression (penetrance) of HFE mutations in hemochromatosis, the natural history of this disease, and the appropriate use of genetic testing and liver biopsy in this condition. The candidate has established the only multidisciplinary clinic in the region dedicated to the care and study of patients with iron overload. The large patient database that will be generated from this clinic will be used to answer current important clinical questions about the relationship between genotype and phenotype in hemochromatosis. The University of Washington, as the only referral center for liver disease and iron overload in a five-state region, is uniquely positioned to enable the candidate to achieve these patient oriented research goals. The candidate has strong institutional support, facilities and resources to help him achieve these goals.