Targeting Gut–Liver Axis for Treatment of Liver Fibrosis and Portal Hypertension

Abstract

Antifibrotic therapies for the treatment of liver fibrosis represent an unconquered area of drug development. The significant involvement of the gut microbiota as a driving force in a multitude of liver disease, be it pathogenesis or fibrotic progression, suggest that targeting the gut–liver axis, relevant signaling pathways, and/or manipulation of the gut’s commensal microbial composition and its metabolites may offer opportunities for biomarker discovery, novel therapies and personalized medicine development. Here, we review potential links between bacterial translocation and deficits of host-microbiome compartmentalization and liver fibrosis that occur in settings of advanced chronic liver disease. We discuss established and emerging therapeutic strategies, translated from our current knowledge of the gut–liver axis, targeted at restoring intestinal eubiosis, ameliorating hepatic fibrosis and rising portal hypertension that characterize and define the course of decompensated cirrhosis.

Obesity Management in the Primary Prevention of Hepatocellular Carcinoma

“…A promising therapeutic approach is the development of drugs that target steatosis, hepatitis, and fibrosis through multiple modes of action, such GLP-1, GCGR, and/or GIP-1. Many of these drugs are effective in reducing body weight and have demonstrated preclinical efficacy in the treatment of MAFLD and are now in phase 1 and 2 clinical trials [ 153 ]. Overall, there is limited data available from both pre-clinical models and humans to conclude whether pharmacological treatment of obesity prevents HCC, but newer obesity medications display promise as they pertain to cancer prevention.…”