Introduction

The progressive understanding of the natural history of chronic liver diseases (CLD) and the relative pathophysiological mechanisms have led to important improvements in the current management of these disorders. As for any cognitive course, this progress has been based on the establishment of identifiable endpoints. Along these lines, the introduction of staging systems based on the histopathological assessment of liver tissue fibrosis has allowed a reasonable understanding of what is defined as disease progression in CLD, and has facilitated the communication between clinicians and pathologists. However, there is increasing awareness that a simple semiquantitative fibrosis score does not adequately represent the complexity of the pathophysiological process leading to cirrhosis, and ultimately to life-threatening complications. Indeed, the categorisation in fibrosis stages is a clinical compromise that does not reflect the biological complexity of disease progression. This inadequacy becomes fully manifested in the stage defined ‘cirrhosis’, a phase of CLD often lasting several years, lacking appropriate clinical–pathological correlates.1 ,2

All these issues, and particularly those related to cirrhosis, are currently magnified by the increasing availability of potentially effective causative treatments (ie, antiviral agents for HCV and HBV CLD) with the emerging need of assessing/predicting disease stabilisation or even disease regression with relative accuracy. The aim of this article is to analyse this evolving area of hepatology, and focus on some relevant areas of research which will likely bring further advancement in the near future. In particular, the progression of CLD should be analysed according to aetiology-driven mechanisms, and by integrating the results of invasive and non-invasive methods with a clear mission towards the identification of predictive indexes guiding a more effective clinical management. Further complexity has been introduced by the recent description of the entity termed ‘acute on chronic liver failure’ (ACLF) which refers to a very rapid progression of …