Liver fibrosis: Pathophysiology, pathogenetic targets and clinical issues

Area of Science:

• Hepatology and immunology
• Molecular and cellular biology
• Pathophysiology of chronic liver diseases

Background:

• Chronic liver diseases (CLD) share common pathways of parenchymal injury, inflammation, and fibrogenesis, regardless of the underlying cause.
• Liver fibrogenesis, the accumulation of extracellular matrix (ECM) leading to fibrosis, is a dynamic process driven by hepatic myofibroblasts (MFs).
• While common mechanisms exist, fibrogenesis is influenced by etiology, resulting in distinct morphological patterns of fibrosis.

Purpose of the Study:

• To review established and emerging pathophysiological mechanisms of CLD progression.
• To highlight the role of key hepatic cell populations, molecular mechanisms, and signaling pathways in liver fibrogenesis.
• To discuss potential therapeutic targets and relevant clinical issues in managing CLD.

Main Methods:

• Literature review of established and emerging research on chronic liver diseases.
• Analysis of pathophysiological processes, cellular players, and molecular signaling in liver fibrogenesis.
• Examination of etiology-specific patterns and clinical implications.

Main Results:

• Identified common and etiology-independent mechanisms in CLD progression.
• Detailed the role of hepatic myofibroblasts (MFs) and ECM accumulation in liver fibrosis.
• Highlighted the influence of etiology on fibrosis development and morphology.

Conclusions:

• CLD progression involves complex interactions between injury, inflammation, and fibrogenesis.
• Hepatic myofibroblasts and associated signaling pathways are critical targets for therapeutic intervention.
• Further research into etiology-specific mechanisms and clinical management is warranted.