Cirrhosis has become the major liver-related clinical endpoint in non-alcoholic steatohepatitis
(NASH). However, progression to cirrhosis is less predictable in NASH than in other
chronic liver diseases. This is due to the complex and multifactorial aetiology of
NASH, which is determined by lifestyle and nutrition, multiple genetic and epigenetic
factors, and a prominent role of hepatic and extrahepatic comorbidities. Thus, modest
changes in these cofactors can also induce fibrosis regression, at least in patients
with precirrhotic liver disease. Fibrogenesis in NASH correlates with, but is indirectly
coupled to, classical inflammation, since fibrosis progression is driven by repetitive
periods of repair. While hepatocyte lipoapoptosis is a key driving force of fibrosis
progression, activated hepatic stellate cells, myofibroblasts, cholangiocytes, macrophages
and components of the pathological extracellular matrix are major fibrogenic effectors
and thus pharmacological targets for therapies aimed at inhibition of fibrosis progression
or induction of fibrosis reversal. The advent of novel, highly sensitive and specific
serum biomarkers and imaging methods to assess the dynamics of liver fibrosis in NASH
will improve detection, stratification and follow-up of patients with progressive
NASH . These non-invasive tools will also promote the clinical development of antifibrotic
drugs, by permitting the design of lean proof-of-concept studies, and enabling development
of a personalised antifibrotic therapy for patients with rapid fibrosis progression
or advanced disease.