Potential Research Questions
Who is likely to progress from NAFLD/NASH to cirrhosis and liver cancer?
Which patient will benefit from preventative strategies?
Which role does the liver play in the pathogenesis of type 2 diabetes?
How to predict and detect drug induced liver damage?
Status Quo and Medical Need
The liver is probably the most important metabolic organ, and is known to interact with numerous organ systems, such as the gut, heart, muscles, adipose tissue, CNS, and many more. It is also involved in the breakdown of many drugs and a frequent target of toxicity. The Fischer ratio (ratio of branched chain to aromatic amino acids) is well established as a marker associated with liver function.
As the interactions between the liver and other organs are multifaceted, further basic and clinical research will be needed to improve the knowledge about liver involvement in complex diseases. Circulatory markers assessing the risk for progression of liver disease, or the response to medication targeting liver disease are largely missing. Not least, liver disease is often only diagnosed at a late stage. Given the importance of the liver in metabolic processes, metabolomics is a promising tool for the development of better biomarkers for liver disease.
Relevant Metabolite Classes
Amino acids and biogenic amines:
- Leucine, isoleucine are essential metabolites, associated with microbiome interaction, and part of the Fischer ratio.
- Amino acid metabolism may help predict hepatobiliary cancers.
- Altered mitochondrial beta oxidation of fatty acids contributes to the progression of liver disease.
- Produced and metabolized by the liver, bile acids interact with the microbiome: they regulate intestinal microbiota and are themselves regulated by the gut flora.
- Bile acids have important signaling functions in the liver and in other organs, via nuclear receptors.
- Typical clinical routine tests only assess total bile acids pool, which negates the vast differences in function between individual bile acid species.
- Phospholipids are required to form micelles with bile acids and cholesterol, to protect bile duct epithelium
- Lipid breakdown may be altered in malign vs. benign non-alcoholic fatty liver
Eicosanoids & prostaglandins:
- May be involved in inflammation and failure of the liver
- Disturbances in fatty acid metabolism contribute to non-alcoholic fatty liver and steatosis
- Omega 3 fatty acids may be protective of fatty liver disease
- Slopianka et al.: Quantitative targeted bile acid profiling as new markers for DILI in a model of methapyrilene-induced liver injury in rats; Toxicology 2017
- Wu et al.: Serum lipid alterations identified in chronic hepatitis B, hepatitis B virus-associated cirrhosis and carcinoma patients; Scientific Reports 2017.
- Mouzaki et al.: Bile acids and dysbiosis in non-alcoholic fatty liver disease; PLOS One 2016
- Feldman et al.: Clinical and Metabolic Characterization of Lean Caucasian Subjects With Non-alcoholic Fatty Liver; The American journal of gastroenterology 2016
- Schröder et al.: Mitochondrial gene polymorphisms alter hepatic cellular energy metabolism and aggravate diet-induced non-alcoholic steatohepatitis; Molecular Metabolism 2016
- Stepien et al.: Alteration of amino acid and biogenic amine metabolism in hepatobiliary cancers: Findings from a prospective cohort study; International Journal of Cancer 2015
- Bhattacharyya et al.: Targeted liquid chromatography–mass spectrometry analysis of serum acylcarnitines in acetaminophen toxicity in children; Biomarkers Med. 2014
- Lehmann et al.: Circulating Lysophosphatidylcholines Are Markers of a Metabolically Benign Nonalcoholic Fatty Liver; Diabetes Care 2013
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For Research Use Only. Not for use in diagnostic procedures.