Abstract
BackgroundAlcohol 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.MethodsWe 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.ResultsPathological 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.ConclusionsThe 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.
Highlights
Alcohol consumption is a major cause of liver disease in humans
We investigated transcriptomic and pathological changes observed during early stage pre-alcohol-induced liver disease (ALD) in mice fed the Lieber-Decarli liquid diet to identify biomarkers diagnostic for early stage pre-clinical stages of alcohol-induced liver disease (pre-ALD)
The present study revealed the following: Chronic alcohol treatment for periods from one to four months led to a modest increase in fatty liver seen with standard techniques of histopathology
Summary
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. 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. Diagnosis is presently based there is a need for simple non-invasive and definitive markers of early changes in the development of ALD. Indole-3-lactic acid and phenyllactic acid may be biomarker candidates for early stages of ALD [10]
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