Abstract
Hepatic fibrosis is a major cause of morbidity and mortality worldwide, as it ultimately leads to cirrhosis, which is estimated to affect up to 2% of the global population. Hepatic fibrosis is confirmed by liver biopsy, and the erroneous nature of this technique necessitates the search for noninvasive alternatives. However, current biomarker algorithms for hepatic fibrosis have many limitations. Given that the liver is the largest organ and a major metabolic hub in the body, probing the metabolic signature of hepatic fibrosis holds promise for the discovery of new markers and therapeutic targets. Regarding individual metabolic pathways, accumulating evidence shows that hepatic fibrosis leads to alterations in carbohydrate metabolism, as aerobic glycolysis is aggravated in activated hepatic stellate cells (HSCs) and the whole fibrotic liver; in amino acid metabolism, as Fischer’s ratio (branched-chain amino acids/aromatic amino acids) decreases in patients with hepatic fibrosis; and in lipid metabolism, as HSCs lose vitamin A-containing lipid droplets during transdifferentiation, and cirrhotic patients have decreased serum lipids. The current review also summarizes recent findings of metabolic alterations relevant to hepatic fibrosis based on systems biology approaches, including transcriptomics, proteomics, and metabolomics in vitro, in animal models and in humans.
Highlights
Hepatic fibrosis, characterized by excessive extracellular matrix (ECM) deposition and fibrous scar formation in the liver [1,2], is a major cause of morbidity and mortality worldwide, as it leads to cirrhosis and hepatocellular carcinoma (HCC) [3]; cirrhosis is estimated to affect up to 2%of the global population [4,5]
The fecal metaproteomes of three cirrhotic patients with Child-Pugh scores of A, B, and C and of their spouses were surveyed by using a high-throughput approach based on denaturing polyacrylamide gel electrophoresis and LC/MS-MS, and the results showed that the proteins unique to cirrhosis were primarily involved in carbohydrate metabolism
Mounting evidence shows that activated hepatic stellate cells (HSCs) undergo aerobic glycolysis, and the whole fibrotic liver shifts from the tricarboxylic acid (TCA) cycle to aerobic glycolysis for energy generation
Summary
Hepatic fibrosis, characterized by excessive extracellular matrix (ECM) deposition and fibrous scar formation in the liver [1,2], is a major cause of morbidity and mortality worldwide, as it leads to cirrhosis and hepatocellular carcinoma (HCC) [3]; cirrhosis is estimated to affect up to 2%. Genetic polymorphisms identified in genome-wide association studies and novel proteins identified by proteomic technology offer the possibility of the further refinement and individualization of biomarkers of hepatic fibrosis [7]. Metabolomics, the identification and quantification of all or specified metabolites in a living system under a specific condition or disease [12,13,15], might be a powerful platform for discovering novel biomarkers and biochemical pathways to improve the diagnosis, prognostication and treatment of hepatic fibrosis [16]. The current review summarizes recent findings of metabolic alterations relevant to hepatic fibrosis from the aspects of individual pathways and systems biology, including transcriptomics, proteomics, and metabolomics in vitro, in animal models and in humans
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
