ONGOING / FUTURE RESEARCH 

 Dr. Aasim Sheikh:

One major research and clinical focus has been in developing a comprehensive care program for Hepatitis C at UAB. Our current clinical research program involves 8 industry sponsored trials ranging from phase I– phase IV protocols. These studies involve 3 research nurses and 5 different companies. We currently have 84 patients enrolled in studies, with ongoing weekly enrollment in each study. We have an active collaboration with the Division of Nephrology in treating patients with chronic renal disease and with the Liver transplant program in initiating a trial of treatment early after transplantation. In addition, we have an active patient education program and a large consultative practice in Hepatitis C.

For further information regarding our Hepatitis C program, please contact one of the research nurses below:

Dr. Gary Abrams:

Dr Abrams has recently focused on obesity induced liver injury called nonalcoholic fatty liver disease (NAFLD).  We have characterized the histologic spectrum of NAFLD associated with the various components of the metabolic syndrome. Our current aims are to: 1- understand the role of mitochondrial dysfunction in the pathogenesis of nonalcoholic steatohepatitis (NASH) - the progressive form of NAFLD, 2- identify adipose tissue cytokines from specific depots and the role of adipose tissue as an endocrine organ in NAFLD and 3- detect noninvasive biomarkers to differentiate fatty liver from NASH. A clinical repository has been established including liver tissue, adipose tissue (omental and subcutaneous) and blood from morbidly obese subjects undergoing gastric bypass surgery. Collaborations include Drs Ronald Clements (Surgery), Victor Darley-Usmar and Shannon Bailey (Pathology and Center for Free Radical Biology - mitochondrial dysfunction and animal models of NAFLD), Carroll Harmon (Pediatric Surgery - adipose tissue analysis), Arron Xu (Ciphergen, Inc. - serum proteomic analysis). A R21 will be submitted in 2005 in response to PA-04-081: Proteomics: Diabetes, Obesity and Digestive Diseases.

Dr. Miguel Arguedas:

Dr. Arguedas’ major research focus is outcomes studies in Hepatology and Gastroenterology. His specific expertise is in decision analysis and Markov modeling which examine the cost-effectiveness and outcomes of particular preventive and therapeutic interventions in liver and gastrointestinal diseases and health-resource utilization in clinical care. He is a co-investigator in a multicenter "Pulmonary Vascular Complications of Liver Disease" group funded by two RO3 awards, one to UAB and one to Columbia University. Dr. Arguedas has an ongoing collaboration within UAB with the Division of General Internal Medicine and outside UAB with the University of Modena and Reggio Emilia (Italy). His long term goal is to define optimal preventive/treatment strategies in Hepatology and Gastroenterology that maximize patient outcomes at a lesser cost of care.

Dr. Joseph Bloomer:

Dr. Bloomer has received NIH research support since 1976, including a MERIT Award from 1994-2002, to investigate the pathogenesis of clinical and biochemical features in the porphyrias.  His laboratory was the first to define the enzyme defects in two of these eight human genetic disorders, erythropoietic protoporphyria (EPP) and variegate porphyria, and the first to show that liver disease in EPP is caused by the toxic effect of protoporphyrin on liver structure and function.  Most recently his laboratory has demonstrated that symptomatic disease in EPP is associated with a mutation in one ferrochelatase allele that causes a detrimental alteration in enzyme structure, together with a polymorphism in the other allele that causes low gene expression.  This has profound implications regarding genetic counseling that is given to families with EPP, and for gene therapy which may be developed for patients with severe disease.  Further studies are being done to evaluate other genetic factors that may affect phenotype, such as methylation in the ferrochelatase promoter and modifiying genes.  The human studies are complemented by a mouse model of EPP in which a heterozygous deletion of exon 10 in  the ferrochelatase gene has been backcrossed into two strains of mice that have different levels of expression of the ferrochelatase gene.  These mice will be used to identify quantitative trait loci that alter ferrochelatase gene expression and phenotype in EPP.  Molecular features of EPP liver disease in humans are also being examined by DNA microarray analysis of hepatic genes in liver explants of patients who have undergone transplantation.

Dr. Michael Fallon:

The major investigative focus in our group is understanding the pathogenesis and clinical features of pulmonary vascular complications of chronic liver disease. Our approach involves both translational studies based around animal models and a multicenter clinical study group. Translational studies are funded through an RO1, a Regional American Heart Association and a VA Merit Review award. Our multicenter "Pulmonary Vascular Complications of Liver Disease" group includes 7 transplant programs across the US and is currently funded by two RO3 awards, one to UAB and one to Columbia University. We have ongoing collaborations within UAB with the Vascular Biology and Hypertension Program, the Center for Free Radical Biology, the Gene Therapy Center, the Cell Adhesion and Matrix Research Center, the Pharmacology Department and with the Liver Transplant program. Our ongoing outside collaborations include the 6 participating transplant centers, the Cholangiocyte Biology program at Texas A&M University, the Vascular Biology program at the Medical College of Georgia, the Pulmonary Vascular Biology Program at The University of Colorado and The Physiology Department at the University of South Alabama. Our long term goals are to define the clinical features of the hepatopulmonary syndrome and to elucidate the pathogenesis in order to develop effective medical therapies. 

Dr. Brendan McGuire: 

My research focus has been in the clinical management of complications in patients with end-stage liver disease.  I have been involved in industry sponsored multi-center studies using two liver assist devices for treating acute and chronic liver disease.  I am the primary investigator at UAB of the acute liver failure study group, which is an NIH funded RO1 including 27 US adult and pediatric liver programs. I am the primary investigator of a pilot study looking at the prevalence of kidney pathology in patients with hepatitis C cirrhosis undergoing liver transplantation at UAB, with funding provided by Roche Pharmaceuticals.  In addition, I have obtained funding through the Protective Life Clinical Initiative, Roche Pharmaceuticals, and Schering Corporation for the UAB Interdisciplinary Cirrhosis Clinic.  Our goal is to use this clinic as a platform to expand outpatient clinical trials while providing state-of-the art medical and preventive therapy for patients with cirrhosis.   

My clinical research forecast looks favorable with the interdisciplinary cirrhosis clinic and additional trials which are anticipated to start in 2005.  Other trials include a study using the Molecular Adsorbent Recirculating System (an albumin based dialysis device) and a new Bioartificial Liver Assist Device (HepaHope) that uses sheets of pig liver tissue.  We also plan to utilize the preliminary data generated from our kidney pathology study in patients with hepatitis C cirrhosis undergoing liver transplantation at UAB to apply for NIH funding through the project announcement (PA-04-043) entitled, “Research Grants for Studies of Hepatitis C in the Setting of Renal Disease” for the June 1, 2005 deadline.  My new initiative for 2005 is “A Phase II, Randomized, Active-Controlled Study of the Safety and Efficacy of Ammonul (Sodium phenylacetate/sodium benzoate) in Patients with Grade III to IV Hepatic Encephalopathy.” for which I am the overall principal investigator.  I designed the protocol with Robert Gish, MD, at California Pacific, and Kevin Mullen, MD, at Case Western, presented the trial to the pre-IND meeting with the FDA, and coordinated 5 university hospitals to begin our trial in spring of 2005. This study is funded by Ucyclyd Pharma.  My long term goals are to expand our center of excellence into a leading national center for clinical care and research in patients with end-stage liver disease. 

Dr. Steven King:

My research interests are focused on initiating a pediatric arm to the ongoing work in the pulmonary vascular complications of chronic liver disease.  We are currently underway in establishing a multi-center clinical study group through collaborations with an NIH funded pediatric multicenter liver transplant network . I am also a sub-investigator on a study investigating kidney disease in HCV cirrhosis and  on a planned industry sponsored study investigating  early use of interferon and ribavirin post transplant (Roche).  My goal is to establish a pediatric site of excellence for the care and research of important complications of chronic liver disease.

UAB Interdisciplinary Cirrhosis Clinic was created to improve patient care by educating patients of the potential complications of cirrhosis and offering preventative strategies to prolong life and maximize quality of life.  The clinic offers appropriate vaccinations, cancer screening, variceal bleeding prevention, and appropriate referral for liver transplantation. With our proactive, comprehensive approach to the management of cirrhosis the clinic will serve as a model for patients with cirrhosis throughout the United States.  For more information for the UAB Interdisciplinary Cirrhosis Clinic please go to www.uabcirrhosis.edu.