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The gut–liver axis is increasingly recognised as a key contributor to chronic liver disease. A failing gut barrier contributes to increased bacterial translocation, which results in an elevated risk of bacterial infection and a chronic inflammatory state that may promote the progression of chronic liver disease and the development of long-term complications such as fibrosis and HCC.1 ,2 The most important clinical consequence of increased translocation is acute bacterial infection, a common cause of hospital admissions and a major contributor to morbidity and mortality in patients with cirrhosis. Moreover, bacterial infections can lead to acute decompensation, often triggering acute-on-chronic liver injury.3 On top of a leaky gut, patients with liver cirrhosis have severe defects in the innate immune system, affecting macrophages, neutrophils and the complement system.4 The liver itself represents an important immunological organ and is the first target of gut-derived bacteria, bacterial pathogen-associated molecular patterns (PAMPs) and food products after they enter the circulation. For this reason, 80% of the body's resident macrophages are found in the liver, where they act as an important component of a firewall, that protects the body from infection from circulating bacteria.5 Following infection, a large proportion of circulating bacteria are phagocytosed by Kupffer cells rather than in the spleen; ablation of macrophages severely hampers clearance of circulating bacteria.5 Together, these findings suggest that the liver rather than the spleen is the main organ involved in the clearance of circulating bacteria. Importantly, the presence of liver fibrosis severely hampers the clearance of circulating bacteria.5 However, the mechanisms that impair the clearance of circulating bacteria in the fibrotic liver remain largely unknown. Better knowledge of the underlying pathways may lead towards novel therapeutic targets for patients with advanced liver disease.
In this issue, …
Funding National Institute on Alcohol Abuse and Alcoholism (grant no. U01AA021912).
Competing interests None declared.
Provenance and peer review Commissioned; internally peer reviewed.
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