Chronic hepatitis C and liver fibrosis

Abstract

Chronic infection with hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide and predisposes to liver fibrosis and end-stage liver complications. Liver fibrosis is the excessive accumulation of extracellular matrix proteins, including collagen, and is considered as a wound healing response to chronic liver injury. Its staging is critical for the management and prognosis of chronic hepatitis C (CHC) patients, whose number is expected to rise over the next decades, posing a major health care challenge. This review provides a brief update on HCV epidemiology, summarizes basic mechanistic concepts of HCV-dependent liver fibrogenesis, and discusses methods for assessment of liver fibrosis that are routinely used in clinical practice. Liver biopsy was until recently considered as the gold standard to diagnose and stage liver fibrosis. However, its invasiveness and drawbacks led to the development of non-invasive methods, which include serum biomarkers, transient elastography and combination algorithms. Clinical studies with CHC patients demonstrated that non-invasive methods are in most cases accurate for diagnosis and for monitoring liver disease complications. Moreover, they have a high prognostic value and are cost-effective. Non-invasive methods for assessment of liver fibrosis are gradually being incorporated into new guidelines and are becoming standard of care, which significantly reduces the need for liver biopsy.

Keywords: Biopsy; Cirrhosis; Fibroscan; Hepatitis C virus; Liver fibrosis.

Figure 1

Hepatic stellate cells are retinoid-storing cells that play a key role in liver fibrogenesis. During liver injury, they undergo transformation from a quiescent state to proliferative, contractile myofibroblasts. Activated HSCs are the main source for production of collagen and other ECM proteins. Several molecules and pathways regulate the equilibrium between deposition and degradation of ECM proteins. HSCs: Hepatic stellate cells; ECM: Extracellular matrix; PDGF: Platelet-derived growth factor; EGF: Epidermal growth factor; TGF: Transforming growth factor; VEGF: Vascular endothelial growth factor; CCR5: C-C chemokine receptor 5; MMP-2: Matrix metalloproteinase 2.