Pathogenesis, Non-Invasive Assessments and Treatment of Hepatic Fibrosis in Autoimmune Liver Diseases

Abstract

Background and Aims

Autoimmune liver diseases (AILD), including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), can lead to progressive liver fibrosis, development of cirrhosis, decompensation, hepatocellular carcinoma (HCC), and need for liver transplantation (LT).

Methods

This review aims to provide a comprehensive overview of the mechanisms of liver fibrogenesis, non-invasive methods to assess hepatic fibrosis and potential anti-fibrotic interventions in AILD.

Results and Conclusions

Current management for AILD should incorporate non-invasive methods to evaluate changes in hepatic fibrosis and consider potential interventions aiming at controlling the progression of the disease, interruption and, potentially, reversal of liver fibrosis. Several laboratory tests can help distinguish patients with advanced fibrosis or cirrhosis but their utility in discriminating earlier histological stages of fibrosis is unclear. A current shift toward non-invasive radiological methods, such as vibration-controlled transient elastography, shear wave elastography, acoustic radiation force impulse imaging and magnetic resonance elastography, opens promising avenues for their wide application; however, their performances may be compromised by hepatic inflammation, ascites, biliary obstruction, or concomitant obesity and metabolic dysfunction-associated steatotic liver disease. Corticosteroids and immunomodulators have been shown to regress fibrosis in AIH patients. In PBC, treatment with either synthetic bile acids, farnesoid X receptor agonists or peroxisome proliferator-activated receptor agonist leads to the improvement or stabilization in the fibrosis stage. There is an urgent need for effective medical treatment in PSC, and available evidence of antifibrotic treatment is particularly limited. Promising anti-fibrotic interventions in AILD encompass conventional pharmacological agents as well as potential new treatments, such as fibrates, monoclonal antibodies, and site- and organelle-specific agents.