Entero-Hepatic Discord: Consequences for Liver Disease Pathogenesis and the Risk of Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most debilitating malignancies of hepatic origin and does not only contribute significantly to global cancer-related mor- tality but also global disease burden. Malfunctioning and dysregulation of the entero-hepatic axis culminating from chronic ingestion of dietary and other non-specific food substances have been implicated in liver disease patho- genesis and this has the potential to increase risk of HCC. As a result, there have been increased efforts to advance understanding of the role played by the perturbed gut in liver disease and the key cell and molecular players in- volved. Luckily, growing evidence from many independ- ent studies seem to lend credence to the phenomenon of bidirectional pathogenesis of entero-hepatic diseases. This has raised hopes of finding more sensitive and specific biomarkers for prognosis and diagnosis of entero-hepatic diseases as well as identification of new therapeutic tar- gets, more specifically for therapy against major risk fac- tors (NAFLD, NASH, liver fibrosis, and cirrhosis) of HCC. This chapter takes a panoramic view of the interactions between the perturbed gut and the susceptible liver. Spe- cifically, the chapter highlights the consequences of gut dysbiosis for liver disease pathogenesis and the risk of HCC.