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

CCN2 Serum Detection May Help Determine Severity of Liver Fibrosis in Hep B Patients
This study suggests that detecting serum CCN2 in patients with hepatitis-B-induced chronic liver diseases may help determine severity of liver fibrosis.  

Access an abstract of this study: Clinical significance of connective tissue growth factor in hepatitis B virus-induced hepatic fibrosis. World J Gastroenterol. 2012 May 14;18(18):2280-6.

Mkp-1 May Help Protect the Liver during Acetaminophen Overdose
This animal model study suggests that the kinase, Mkp-1, plays a protective role during acute acetaminophen overdose.

Access an abstract of this study: Mitogen-activated Protein Kinase Phosphatase (Mkp)-1 Protects Mice against Acetaminophen-induced Hepatic Injury. Toxicol Pathol. 2012 May 23. [Epub ahead of print]

Connective Tissue Growth Factor Regulates Hepatic Stellate Cell Function
This review article focuses on how connective tissue growth factor regulates hepatic stellate cell function.

Access an abstract of this study: Regulation of hepatic stellate cells by connective tissue growth factor. Front Biosci. 2012 Jun 1;17:2495-507.

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. 

Current Liver Disease Grants

MicroRNA regulation of CTGF in hepatic stellate cells, 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)