Applications | Hepatology
Assess Liver Health In Vivo
Unlock the secrets of liver health with the power of metabolomics, leading the way to deeper insights and breakthrough discoveries.
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Metabolomics in Hepatology
The liver is the single most important regulator of metabolic homeostasis at the organismal level in vertebrates and performs multiple crucial biological functions including detoxification of xenobiotics, protein metabolism, degradation of waste products, vitamin storage, and bile acid production. Metabolomics is an indispensable tool for capturing an integrative profile of an individual’s liver function. As the incidence of certain liver diseases, such as metabolic dysfunction-associated steatohepatitis (MAFLD, formerly nonalcoholic fatty liver disease, NAFLD) and metabolic dysfunction-associated steatohepatitis (MASH, formerly nonalcoholic steatohepatitis, NASH) continue to rise, researchers and healthcare providers can look to Metabolon to provide much-needed diagnostic and prognostic indicators to better understand the molecular mechanisms underpinning pathological processes.
As there are no FDA-approved therapies specifically for MASH, diet and exercise are the main treatments. The lack of a clear disease taxonomy and deep mechanistic understanding of the disease is a major hindrance to drug development. Metabolon’s ability to non-invasively screen for thousands of metabolites in just one biological sample makes it an ideal solution for assessing the metabolic state. The metabolome integrates an individual’s genetic makeup, gene expression profile, and even non-genetic factors such as diet, environmental exposures, and the microbiome, making it the definitive representation of the phenotype. Therefore, layering metabolomic analysis onto genomic and transcriptomic data provides the best opportunity to understand MASH.
The Metabolon Advantage in Liver Research
Metabolon has over 20 years’ experience in metabolomics and has done over 10,000 metabolomics projects. In liver research alone, we have published over 100 times, including in high-impact journals. Our past projects have included pharmacokinetics and pharmacodynamic studies, finding biomarkers, risk assessment, and more. We also have the ability to process many sample types including liver biopsy samples. Whether your project would be best suited to untargeted or targeted metabolomics, Metabolon can help answer your research questions.
Clarify Clinical Potential and Biomarker Strategy
Global untargeted metabolomics enables researchers to discover key changes or differences between conditions such as disease stages or drug treatments. This approach has the potential to produce not only fundamental insights into disease mechanisms, but also actionable biomarkers that can be used to track disease severity and therapeutic efficacy. For example, in a study published in Gastroenterology, researchers sought to discover plasma biomarkers of response in a Phase II trial for NASH with a novel molecule (ACCi). Metabolomics results identified serum and plasma markers of fibrosis which showed improvement after the 12-week therapy.
Loomba R, Kayali Z, Noureddin M, et al. GS-0976 Reduces Hepatic Steatosis and Fibrosis Markers in Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology. 2018;155(5):1463-1473.e6. doi:10.1053/j.gastro.2018.07.027
Build Future Diagnostics and Targets
MASH is a complex disease encompassing a complex amalgam of dysregulated pathways. A narrow focus on individual markers such as lipids or liver enzymes may not be enough to fully understand and discover therapeutic targets. Leveraging global metabolomics as a wide-angle tool can support the development of diagnostics and therapeutics that have the capability to improve patients’ lives.
Loomba R, Noureddin M, Kowdley KV, et al. Combination Therapies Including Cilofexor and Firsocostat for Bridging Fibrosis and Cirrhosis Attributable to NASH. Hepatology. 2021/02/01 2021;73(2):625-643. doi:https://doi.org/10.1002/hep.31622
Metabolomics Applications for Hepatic Disease Research
- EUnderstanding molecular mechanisms of disease
- EPrediction of disease progression
- EDrug discovery and development
- EBiomarker discovery
- EDisease risk prediction
- EPrecision medicine research
- EDisease stratification
- EAssessment of therapeutics
- EPreclinical research
“By integrating clinical data with plasma metabolomics and inflammatory proteomics as well as oral and gut metagenomic data, we revealed the underlying molecular mechanisms associated with the reduced hepatic fat and inflammation in [MAFLD] patients and identified the key players involved in the host–microbiome interactions.”
Zeybel M, Altay O, Arif M, et al.
Combined metabolic activators therapy ameliorates liver fat in nonalcoholic fatty liver disease patients. Mol Syst Biol. 2021;17(10):e10459. doi:10.15252/msb.202110459. Available under CC BY 4.0.
Safety and Efficacy of Treatment for MASLD
MASLD (formerly NAFLD) is a condition in which excess fat accumulates in the liver of people who drink little or no alcohol. MASLD comprises pathologies that include hepatic steatosis, steatohepatitis, hepatic fibrosis, and cirrhosis. Current management strategies include increased physical activity and dietary intervention but have limited adherence and marginal long-term success. No drugs have been approved to treat MASLD; therefore, effective treatment options are urgently required. Although a few drugs have made it to clinical trials, the results of drugs targeting single pathways have been mostly unsuccessful. This research group recently found that the administration of combined metabolic activators (CMAs) promotes fat oxidation, attenuates the resulting oxidative stress, and eventually removes excess fat from the liver. In this phase 2 clinical trial, Metabolon helped reveal the mechanism of CMAs in MASLD patients.1
A placebo-controlled human study shows that oral administration of Combined Metabolic Activators (CMA) reduces liver fat in [MASLD] patients.
- CMA, consisting of L-serine, nicotinamide riboside, N-acetyl-L-cysteine, and L-carnitine tartrate, has a profound effect on hepatic steatosis after only 70 days of treatment in [MASLD] patients.
- CMA supplementation improved clinical parameters in [MASLD] patients, such as reductions in aspartate aminotransferase, alanine aminotransferase, uric acid, and creatinine.
- The underlying mechanisms associated with the beneficial effect of CMA were revealed by a comprehensive analysis of plasma metabolomics and inflammatory proteomics as well as oral and gut metagenomics.
The Global Discovery Panel’s unrivaled coverage of up to 5,400 semi-quantifiable metabolites offered this group the most comprehensive solution for characterizing the metabolic signature of the plasma samples, revealing the underlying molecular mechanisms associated with the decrease in liver fat in the CMA group. Metabolon also offers the Liver Fibrosis Discovery Panel to help address key factors in liver fibrosis, including mechanistic insights, personalized medicine, and drug discovery, and testing.
Source: Zeybel M, et al. Mol Syst Biol. 2021. Licensed under CC BY 4.0.
Hepatology Publications and Citations
Metabolon has contributed to publications ranging from basic research to clinical trials.
Hepatology Knowledge Base
Dive deeper by viewing our case studies and webinars. Learn more about how Metabolon furthers hepatology research and check back for more to stay up to date on the latest developments in metabolomics in hepatology.
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