Liver Disease Research

Approximately 15,000 hospitalizations occur each year for pediatric liver disease in the United States. Faculty at Nationwide Children’s are working to better understand how liver disease develops in children and working toward improved treatments and possible vaccines.

Specifically, investigators are studying the mechanisms that cause cirrhosis, one of the most common fibrotic liver diseases.  Studies focus on connective tissue growth factor (CTGF), a protein important in tissue development and healing, and its role in fibrotic diseases. Findings are intended to help determine the therapeutic value of targeting CTGF pathways to treat fibrotic disorders.

As many as 1 in 250 children are infected with hepatitis C in the United States. Hepatitis C virus infection most often becomes a chronic condition that can lead to cirrhosis of the liver and liver cancer. Investigators at Nationwide Children’s are also studying how immune responses are subverted in this viral infection, work that may contribute to hepatitis C vaccine development.  They are also investigating vertical transmission of the virus from mothers to their newborn infants.

Faculty Focused on Liver Disease Research

• David R. Brigstock, PHD
• Jonathan R. Honegger, MD
• Carol J. Potter, MD
• Christopher M. Walker, PhD

Latest Findings in Liver Disease Research

The Growth Factor CTGF Mediates Alcohol-Stimulated Differentiated Functions on Liver Stellate Cells
Connective tissue growth factor (CTGF) expression is intimately associated with the development of liver fibrosis.  This study highlights potential therapeutic benefits of targeting CTGF in alcoholic liver disease.

Access an abstract of this study: Ethanol-stimulated differentiated functions of human or mouse hepatic stellate cells are mediated by connective tissue growth factor. J Hepatol. 2011 Aug;55(2):399-406. 

CD8+ T Cells Drive Early Evolution of Hepatitis C Virus
Findings from this study suggest that during acute hepatitis C, virus evolution was driven mostly by positive selection pressure exerted by CD8+ T cells. This influence of immune pressure on viral evolution appears to subside as chronic infection is established.

Access an abstract of this study: Transmission of clonal hepatitis C virus genomes reveals the dominant but transitory role for CD8+ T cells in early viral evolution. J Virol. 2011 Sep 7. [Epub ahead of print] 

Potential Benefits of Targeting CTGF in Alcoholic Liver Disease
Connective tissue growth factor (CTGF) expression is linked to liver fibrosis development. In this study, CTGF production and action was investigated in liver cells of a mouse model or human cells of alcohol-induced liver damage. Findings highlight potential therapeutic benefits of targeting CTGF in alcoholic liver disease.

Access an abstract of this study: Ethanol-stimulated differentiated functions of human or mouse hepatic stellate cells are mediated by connective tissue growth factor. J Hepatol. 2010 Dec 11. [Epub ahead of print]

CTGF’s Role in Cell Adhesion in Fibrotic Liver Cells  
Production of connective tissue growth factor (CTGF) is a hallmark of hepatic fibrosis.  This study examined early primary cultures of hepatic stellate cells, the major cell type involved in liver fibrosis. Investigators examined how CTGF was regulated within the cells and how it interacted with other proteins in supporting cell adhesion.  Findings showed that CTGF supports hepatic stellate cell adhesion by binding to integrin alpha5beta1.  Alpha5beta1 is a novel CTGF receptor in hepatic stellate cells.

Access an abstract of this study: Integrin expression and function in the response of primary culture hepatic stellate cells to connective tissue growth factor (CCN2). J Cell Mol Med. 2010 Apr 19. [Epub ahead of print]

Current Liver Disease Grants

CTGF in Pancreatic Stellate Cell-Mediated Fibrogenesis National Institutes of Health (David Brigstock)

Pro-apoptocic BCG as an HCV vaccine vector Vanderbilt University Medical Center (Christopher Walker)

Immunological Strategies for Curing Chronic Hepatitis Virus Infections Emory University (Christopher Walker)

HCV Replication and Immunity, National Institutes of Health, National Institute of Allergy and Infectious Diseases (Christopher Walker)

Immunological Strategies for Curing Chronic Hepatitis Virus Infections, Emory University, Foundation for the National Institutes of Health (Christopher Walker)

HCV-Specific T-Cell Response, National Institute of Allergy and Infectious Diseases (Christopher Walker)