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Biomarkers Used To Predict Recurrent Disease In Hepatitis C Transplant Patients

Date:
October 10, 2005
Source:
John Wiley & Sons, Inc.
Summary:
Two new studies on Hepatitis C (HCV) patients who underwent liver transplants examined a potential biomarker that could be used to predict who might develop hepatic fibrosis, a formation of scar-like tissue that can lead to cirrhosis. The studies found that changes in a certain type of liver cell were useful in determining those who were at the greatest risk for developing this serious complication.

Two new studies on Hepatitis C (HCV) patients who underwent livertransplants examined a potential biomarker that could be used topredict who might develop hepatic fibrosis, a formation of scar-liketissue that can lead to cirrhosis. The studies found that changes in acertain type of liver cell were useful in determining those who were atthe greatest risk for developing this serious complication.

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The results of these studies appear in the October 2005 issue ofLiver Transplantation, the official journal of the American Associationfor the Study of Liver Diseases (AASLD) and the International LiverTransplantation Society (ILTS). The journal is published on behalf ofthe societies by John Wiley & Sons, Inc. and is available onlinevia Wiley InterScience at http://www.interscience.wiley.com/journal/livertransplantation.

Hepatitis C is the leading cause of liver transplants andrecurrence of the disease following transplant is a serious problem. Itis estimated that up to 20 percent of HCV patients will developfibrosis or cirrhosis within two years of undergoing a transplant.Antiviral therapy is not highly effective in transplant patients andposes additional problems for these individuals, who may havedifficulty tolerating the potent drugs it involves. However, antiviraltherapy might be useful for those patients likely to develop fibrosis,if they could somehow be identified. Hepatic stellate cells (HSC)normally store vitamin A in the liver, but in HCV patients these cellsproduce collagen and other proteins that can lead to fibrosis.Researchers tried to determine if HSC activation could help predictwhich patients would later develop fibrosis by using laboratoryanalysis of alpha smooth muscle actin (alpha-SMA), a reliable markerfor HSC activation.

In one study, led by Samer Gawrieh of the Division ofGastroenterology and Hepatology at the Mayo Clinic College of Medicinein Rochester, MN, 26 patients who underwent HCV-related livertransplants at the Mayo Clinic between April 1993 and July 1999 wereincluded. Biopsies obtained 4 months and 1 year post-transplant wereevaluated and given a score for alpha-SMA. The results showed that HSCactivation of one particular type of cell (mesenchymal cells, whichgive rise to connective tissue) was highly reliable in predicting thedevelopment of fibrosis. "Staining early post-LT liver biopsies foralpha-SMA may help identify patients with hepatitis C at risk forsevere recurrence who may benefit from early anti-HCV or anti-fibrotictherapy," the authors conclude.

In another study, led by Mark W. Russo, M.D., M.P.H. of theDivision of Gastroenterology and Hepatology of the University of NorthCarolina in Chapel Hill, 46 patients who underwent HCV-related livertransplants at the University of Florida between 1997 and 2001 wereincluded. Patients were divided into two groups: those who developedadvanced fibrosis within 2 years of liver transplant and those whodeveloped mild or no fibrosis in the same period. Biopsies from 4months, 1 year and 2 years post-transplant were scored for alpha-SMA.The results showed that HSC activation was significantly higher in the4 month biopsies for those who developed advanced fibrosis within 2years. The authors note that alpha-SMA "is an attractive biomarkerbecause it is determined from the organ of interest and there isbiological plausibility for why increased stellate cell activity wouldlead to advanced fibrosis."

In an accompanying editorial by A.J Demetris and J.G. Lunz IIIof the Thomas E. Starzl Transplantation Institute at the University ofPittsburgh Medical Center in Pittsburgh, the authors note that theability of alpha-SMA to predict disease at 4 months after transplantsuggests that something triggers a chain of events that begins withmesenchymal and/or HSC activation and leads to the development offibrosis. They speculate as to what the trigger might be and how itmight explain the mechanism of liver disease, examining risk factorsfor recurrent HCV that might offer clues, as well as substances such asviral proteins and proteins secreted by liver cells. In particular,they cite their research on p21, a protein made in the liver, whichshowed that progression of fibrosis was related to the effect of p21 onliver cell proliferation. "This model better fits observations aboutdisease pathogenesis," they conclude. "It explains why any hepatocytestressors, such as steatosis [accumulation of fat in the liver], iron,inflammation, HCV replication or spontaneously increased 21 expression,such as occurs with aging, can accelerate liver disease progression."

###

Article: "Early Hepatic Stellate Cell Activation Predicts SevereHepatitis C Recurrence After Liver Transplantation," Samer Gawrieh,Bettina G. Papouchado, Lawrence J. Burgart, Shogo Kobayashi, Michael R.Charlton, Gregory J. Gores, Liver Transplantation; October 2005 (DOI:10.1002/lt.20455).

Article: "Early Hepatic Stellate Cell Activation is Associatedwith Advanced Fibrosis After Liver Transplantation in Recipients withHepatitis C," Mark Russo, Roberto Firpi, David Nelson, RobertSchoonhoven, Roshan Shrestha, Michael Fried, Liver Transplantation;October 2005 (DOI: 10.1002/lt.20432).

Editorial: "Early HCV-Associated Stellate Cell Activation inAggressive Recurrent HCV: What Can Liver Allografts Teach About HCVPathogenesis?" A.J. Demetris, J.G. Lunz III, Liver Transplantation;October 2005 (DOI: 10.1002/lt.20506).


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The above story is based on materials provided by John Wiley & Sons, Inc.. Note: Materials may be edited for content and length.


Cite This Page:

John Wiley & Sons, Inc.. "Biomarkers Used To Predict Recurrent Disease In Hepatitis C Transplant Patients." ScienceDaily. ScienceDaily, 10 October 2005. <www.sciencedaily.com/releases/2005/10/051010101045.htm>.
John Wiley & Sons, Inc.. (2005, October 10). Biomarkers Used To Predict Recurrent Disease In Hepatitis C Transplant Patients. ScienceDaily. Retrieved October 23, 2014 from www.sciencedaily.com/releases/2005/10/051010101045.htm
John Wiley & Sons, Inc.. "Biomarkers Used To Predict Recurrent Disease In Hepatitis C Transplant Patients." ScienceDaily. www.sciencedaily.com/releases/2005/10/051010101045.htm (accessed October 23, 2014).

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