Fibrosis in chronic liver diseases: diagnosis and management

Abstract

The increasing knowledge on the mechanisms responsible for hepatic fibrogenesis together with the introduction of potentially more effective therapeutic strategies for chronic liver diseases (CLDs) have led to the compelling need of acquiring more adequate clinical approaches for the evaluation of the fibrogenic progression of CLDs. This need has led to critically re-evaluating classic standard approaches such as liver biopsy and the search for noninvasive methods for the longitudinal follow-up of the disease. Overall, the situation appears rather confused, prone to significant speculation and the urgent need for clarification and consensus. A similar consideration can be made for the area of the so-called ‘anti-fibrogenic’ drugs, where in spite of a remarkable number of proposed agents, no drugs have been so far thoroughly tested and approved for use in humans. Progressive accumulation of fibrillar extracellular matrix (ECM) in the liver is the consequence of reiterated liver tissue damage due to infective (mostly hepatitis B—HBVand C—HCV-viruses), toxic/druginduced, metabolic and autoimmune causes and the relative chronic activation of the wound healing reaction. Liver fibrosis results from a dynamic process in which the accumulation of fibrillar ECM is associated with ECM degradation and remodeling in a balanced process that can result in an advanced stage defined as ‘cirrhosis’ or reversed to restore normal hepatic structure and function [1]. Cirrhosis is characterized by the formation of regenerative nodules of liver parenchyma that are separated by and encapsulated in fibrotic septa and is associated with major angio-architectural changes. In light of these important structural changes, cirrhotic liver tissue can be ‘remodeled’ in response to removal of the primary cause of damage. This does not mean that cirrhosis in its complete expression is