The metabolomic window into hepatobiliary disease

Area of Science:

• Hepatology
• Metabolomics
• Systems Biology

Background:

• Metabolomics is increasingly vital in understanding liver diseases.
• This review examines metabolomic data across various liver conditions, including NAFLD, NASH, cirrhosis, HCC, CCA, ALD, viral hepatitis, and hepatotoxicity.
• A metabolomic perspective offers insights into the biochemical shifts during liver disease progression.

Purpose of the Study:

• To review and synthesize metabolomic findings in a spectrum of liver diseases.
• To identify common metabolic alterations and distinct markers across disease phases.
• To elucidate the role of metabolomics in understanding liver pathology and disease progression.

Main Methods:

• Review of existing metabolomic data from animal models and human studies.
• Analysis of metabolic changes in relation to disease stages (Phase 0-3).
• Identification of key metabolic pathways and biomarkers.

Main Results:

• A core metabolic phenotype (CMP), involving dysregulated bile acid and phospholipid homeostasis, is identified in liver diseases.
• The CMP emerges early (Phase 1) and persists through cirrhosis (Phase 2) and cancer (Phase 3).
• Inflammation triggers CMP; Warburg effect and fatty acid oxidation upregulation are early events preceding hepatocellular carcinoma.

Conclusions:

• Metabolomics provides a systems-level view of liver pathology, revealing a common metabolic phenotype across diverse liver diseases.
• The CMP and associated metabolic shifts offer potential targets for early diagnosis and intervention.
• Understanding these metabolic transitions is crucial for deciphering the progression from healthy liver to advanced hepatobiliary diseases.