Identification of serum insulin-like growth factor binding protein 1 as diagnostic biomarker for early-stage alcohol-ind
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RESEARCH
Open Access
Identification of serum insulin-like growth factor binding protein 1 as diagnostic biomarker for early-stage alcohol-induced liver disease Heng-Hong Li1, Kathryn Doiron1, Andrew D Patterson2, Frank J Gonzalez3 and Albert J Fornace Jr1*
Abstract Background: Alcohol consumption is a major cause of liver disease in humans. The use and monitoring of biomarkers associated with early, pre-clinical stages of alcohol-induced liver disease (pre-ALD) could facilitate diagnosis and treatment, leading to improved outcomes. Methods: We investigated the pathological, transcriptomic and protein changes in early stages of pre-ALD in mice fed the Lieber-Decarli liquid diet with or without alcohol for four months to identify biomarkers for the early stage of alcohol induced liver injury. Mice were sampled after 1, 2 and 4 months treatment. Results: Pathological examination revealed a modest increase in fatty liver changes in alcohol-treated mice. Transcriptomics revealed gene alterations at all time points. Most notably, the Igfbp1 (Insulin-Like Growth Factor Binding Protein 1) was selected as the best candidate gene for early detection of liver damage since it showed early and continuously enhanced induction during the treatment course. Consistent with the microarray data, both Igfbp1mRNA expression in the liver tissue and the IGFBP1 serum protein levels showed progressive and significant increases over the course of pre-ALD development. Conclusions: The results suggest that in conjunction with other tests, serum IGFBPI protein could provide an easily measured biomarker for early detection of alcohol-induced liver injury in humans. Keywords: Alcohol-induced liver disease, Transcriptomics, Biomarker, Igfbp1, IGFBP1 protein
Background Alcohol consumption is responsible for about four percent of all disease world wide and is a major lifestyle-related cause of death in the United States [1], due in large part to complications from alcohol-induced liver disease (ALD). Both intrahepatic and extrahepatic stimuli triggered by alcohol abuse can cause ALD. Among the effects of interplay of these factors are metabolic dysfunctions such as fatty liver, obesity and excessive levels of hepatic free fatty acids, often followed by progressive pathologic changes such as inflammation, hepatomegaly and ultimately fibrosis and cirrhosis. Diagnosis and stage-assessment of ALD provide guidance for treatment options. Diagnosis is presently based * Correspondence: [email protected] 1 Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, 3970 Reservoir Road, NW, New Research Building, Room E504, Washington, DC 20057, USA Full list of author information is available at the end of the article
mainly on physical examination to determine general health and assessment of alcohol consumption history coupled with serum biomarker tests such as carbohydratedeficient transferrin (CDT) [2] and various laboratory tests of liver function like aspartate aminotransferase/ alanine aminotransferase ratio (AST/ALT)
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