Liver Disease

Study Goals and Findings

Chronic hepatitis C (HCV) is the most common blood-borne infection in Western countries and affects close to 4 million people in the U.S. alone. It is now the most common reason for liver transplantation in developed nations. This viral infection results in progressive inflammation and scarring of the liver, which can lead to liver failure. Few treatment options exist, and the most common – interferon-based therapies – have significant side effects and work in only half of all treated patients. Compounding these clinical challenges, responsiveness to treatment varies by ethnic group with African Americans, for example, significantly less responsive to treatment on average than people in other ethnic groups. Identifying the causes of this variable responsiveness may lead to the development of more effective and individualized therapies.

This Horizon 1 project investigated biological factors that could help explain why some people do not respond to interferon treatment. In pursuit of developing more personalized treatment regimens, researchers analyzed biospecimens from hepatitis C patients and identified proteins in their blood correlated with treatment responsiveness. The research team focused on the identification of individuals that might benefit the most from standard-of-care treatments. Testing hepatitis C patients for biological indicators of treatment efficacy may help improve disease outcomes and eliminate wasteful therapeutic interventions.

Related Publications and Abstracts
  1. Thompson JW, Dubois, LG, Lucas J, Patel, K, McCarthy JJ, McHutchison JG, Moseley, MA. Comprehensive Biomarker Discovery Platform Reveals Qualified MRM Assay for Prediction of INF/Riboflavirin Treatment Response in Hepatitis C Patients. Poster presentation at the Association of Biomolecular Resource Facilities Meeting, San Antonio, TX, February 19, 2011.
  2. Cyr D, Lucas JE, Thompson JW, Patel D, Thompson A, Tillmann H, Clark PJ, Moseley MA, McHutchison JG, McCarthy JJ. Characterization of serum proteins associated with IL28B genotype among patients with chronic hepatitis C. PLoS One. 2011;6:e21854.
  3. Patel K, Lucas J, Thompson JW, Dubois LG, Tillmann H, Thompson A, Uzarski D, Califf RM, Moseley MA, Ginsburg GS, McHutchison JG, McCarthy JJ. High Predictive Accuracy of an Unbiased Proteomic Profile for Sustained Virologic Response in Chronic Hepatitis C Patients. Hepatology. 2011; 53(6):1809-18.
  4. McCarthy JJ, Li JH, Thompson A, Suchindran S, Lao XQ, Patel K, Tillman H, Muir A and McHutchison J. Replication of an interferon lambda genetic polymorphism strongly associated with treatment response in patients with chronic hepatitis C infection in a tertiary care setting. Gastroenterology. 2010 Jun;138(7):2307-14. PMID: 20176026.
  5. McCarthy JJ, Cyr D, Lucas J, Thompson JW, Patel K, Thompson A, Tillmann H, Clark PJ, Moseley MA and McHutchison JG. Serum Proteomic Profiles Associated with IL28B Genotype among CHC Patients. Hepatology. 2010 (52): 4 (suppl):727A.
  6. Rowell J, Thompson A, Guyton JR, Lao XQ, Patel K, McHutchison J, McCarthy JJ. The MURDOCK Study. Serum Apolipoprotein C-III levels are independently associated with hepatic fibrosis in patients with chronic hepatitis C infection. Poster presentation, American Association for the Study of Liver Diseases (AASLD) November 2009.
  7. Patel K, Lucas J, Thompson J, Moseley M, Uzarski D, Tillmann H, Califf R, McCarthy J, McHutchison J. High Predictive Accuracy of an Unbiased Proteomic Profile to Predict Sustained Virologic Response in Genotype I Chronic Hepatitis C Patients. Hepatology. 2008;48(suppl 4)210: AASLD October 2008.

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MURDOCK study and more