Metabolome and Liver Diseases

The liver is the hub of the body's metabolism and is responsible for most of the body's metabolic processes such as synthesis, catabolism and transformation. Currently, the diagnosis of liver diseases is confirmed based on histological examination or a combination of clinical and imaging findings, but these methods are often invasive and lack specificity and sensitivity. Therefore, the early, non-invasive diagnosis of liver disease is a challenging task.

Metabolomics is an important part of systems biology, which is a comprehensive analysis of all metabolites in a biological system and can be used for physiological evaluation, disease diagnosis and disease prognosis. Unlike traditional biochemical methods that often focus on a single metabolite, metabolomics allows simultaneous qualitative and quantitative analysis of all metabolites, such as lipids, amino acids, organic acids and other small molecules, to obtain characteristic metabolic markers and provide comprehensive information on pathophysiological processes, the impact of pharmacological interventions and metabolic kinetics.

Metabolomics Research Methods

Metabolomics research relies on various high-throughput techniques such as nuclear magnetic resonance spectroscopy, gas chromatography-mass spectrometry (CC-MS), and liquid chromatography/mass spectrometry (LC/MS). Commonly used procedures include biological sample collection, sample pretreatment, data collection, principal component analysis in multivariate statistics, orthogonal partial least squares discriminant analysis and partial least squares discriminant analysis, statistical analysis and categorization of the obtained data such as mass number, retention time and peak intensity to obtain the relevant markers.

As a powerful tool for structural analysis, NMR can be used for the rapid, non-invasive and unbiased detection of complex mixtures of biological fluids without the need for cumbersome sample processing and simultaneous determination of multiple components. The limitations of NMR are its relatively low sensitivity and limited dynamic range, which makes it unsuitable for the analysis of large quantities of low concentration metabolites.

MS technology is fast when used alone, and has become the technology of choice for metabolomics research because of its high sensitivity, selectivity, and ability to quantify multiple metabolites in combination with other technologies. Creative Proteomics uses ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) technology, which offers high chromatographic selectivity, better peak resolution, higher sensitivity, faster separation from complex mixtures, and low ion suppression, making it particularly suitable for large-scale, untargeted metabolomics studies.

Metabolomics in the Study of Liver Diseases

Nonalcoholic fatty liver disease (NAFLD)

Non-alcoholic fatty liver disease is a metabolic disease associated with obesity, insulin resistance and genetic factors, and is the most important cause of cryptogenic cirrhosis. 70% of cryptogenic cirrhosis is caused by non-alcoholic hepatitis. Liver biopsy is the gold standard for its clinical diagnosis. It is an invasive technique, so its clinical dissemination is limited. Some studies have shown that stearoylcarnitine is stably elevated in different phenotypes of NAFLD, providing a sensitive and non-invasive method for clinical diagnosis of fatty liver.

The gut microbiota contributes to hepatic steatosis. (Delzenne et al., 2018)

Cirrhosis and chronic hepatitis

Cirrhosis is a diffuse liver damage formed by one or more etiologies acting for a long time or repeatedly, and metabolomics techniques are now widely used in the diagnosis of cirrhosis. Researchers performed metabolomic analysis of serum from cirrhotic patients and showed that serum lysophosphatidylcholines (LPCs) levels were decreased and bile acids, hypoxanthines and stearamide levels were increased in cirrhotic patients, all of which are suggested to be common biomarkers of cirrhosis.

Oleic acid amide and myristic acid amide are increased in alcoholic cirrhosis and decreased in hepatitis B cirrhosis and can be used as specific markers for the differential diagnosis between the two.

Liver failure

Liver failure is a serious liver damage caused by multiple factors, resulting in severe impairment or even loss of its synthesis, detoxification and excretion functions, with a very high morbidity and mortality rate. In a metabolomic characterization study of a murine model of liver failure, a significant difference in peak serum bile acids was found between the liver failure group and the control group, suggesting that serum bile acid levels could provide a basis for etiological analysis and further study of liver failure.

Hepatocellular carcinoma (HCC)

Failure to diagnose HCC early is one of the main reasons for the low survival rate of patients. The discovery of sensitive and specific biomarkers is of great importance in the early diagnosis of HCC. Alpha-fetoprotein (AFP) is a powerful objective co-marker, but AFP is not unique to HCC and is partially associated with hepatocyte regeneration after hepatic necrosis in severe hepatitis. The use of metabolomics can help in disease differentiation and assist in early diagnosis.

Metabolomic analysis of liver tissues for characterization of hepatocellular carcinoma (Ferrarini et al., 2019)

Other liver diseases

Non-cirrhotic portal hypertension (INCPH) is a rare and life-threatening disease of the liver. It is often misdiagnosed as cryptogenic cirrhosis due to the lack of specific diagnostic methods. Idiopathic portal hypertension (IPH) is a rare cause of portal hypertension and is usually diagnosed after other possible causes of portal hypertension have been excluded. The search for specific diagnostic markers for this condition through the metabolome is a breakthrough for rapid diagnosis.

References

1. Delzenne, N. M., & Bindels, L. B. (2018). Microbiome metabolomics reveals new drivers of human liver steatosis. Nature medicine, 24(7), 906-907.
2. Ferrarini, A., Di Poto, C., He, S., Tu, C., Varghese, R. S., Kara Balla, A., ... & Ressom, H. W. (2019). Metabolomic analysis of liver tissues for characterization of hepatocellular carcinoma. Journal of proteome research, 18(8), 3067-3076.

Related Sections

Metabolomics Service

Untargeted Metabolomics Service

Blood & Plasma & Serum Metabolomics

Urine Metabolomics