Pathological bacterial translocation in cirrhosis: pathophysiology, diagnosis and clinical implications

Abstract

Bacterial translocation (BT) is defined by the passage of viable indigenous bacteria from the intestinal lumen to mesenteric lymph nodes (MLNs) and other territories, and its diagnostic criteria rely on the isolation of viable bacteria in MLNs. Small intestinal overgrowth, increased intestinal permeability and immunological alterations are the main factors involved in its pathogenesis. BT is obviously difficult to identify in patients with cirrhosis, and alternative methods have been proposed instead. Bacterial DNA detection and species identification in serum or ascitic fluid has been proposed as a reliable marker of BT. Bacterial products, such as endotoxin, or bacterial DNA can translocate to extra-intestinal sites and promote an immunological response similar to that produced by viable bacteria. Therefore, pathological BT plays an important role in the pathogenesis of the complications of cirrhosis, not only in infections, but by exerting a profound inflammatory state and exacerbating the haemodynamic derangement. This may promote in turn the development of hepatorenal syndrome, hepatic encephalopathy and other portal hypertension-related complications. Therapeutic approaches for the prevention of BT in experimental and human cirrhosis are summarized. Finally, new investigations are needed to better understand the pathogenesis and consequences of translocation by viable bacteria (able to grow in culture), or non-viable BT (detection of bacterial fragments with negative culture) and open new therapeutic avenues in patients with cirrhosis.

Liver disease symptoms in non-alcoholic fatty liver disease and small intestinal bacterial overgrowth

“…A number of studies have shown that SIBO is seen more in patients with cirrhosis [18][19][20]. Miele et al found that SIBO had a high prevalence in NAFLD patients compared with normal people [21].…”

Bloodstream infections in patients with liver cirrhosis

“…9 The increased gut permeability and the cirrhosis associated immune dysfunction (CAID) make this population prone to develop BSI by endogenous route, particularly during acute-on-chronic liver failure (ACLF). 10,11 Frequent need for hospitalization, invasive procedures and, use of indwelling devices such as central venous line or transjugular intrahepatic portosystemic shunt (TIPS), give to the exogenous route an additional pathogenetic rule, further increasing the overall risk, mainly in the setting of Health Care Associated or Hospital Acquired infections. 12,13 BSIs in LC are also associated with high mortality, prolonged hospitalization and faster escalation of the liver disease.…”

Markers of bacterial translocation in end-stage liver disease

“…However, increased intestinal permeability cannot fully account for the pathophysiology of BT; moreover, it is not clear whether these structural changes are the cause or the result of BT [5] . The intestinal immune system is comprised of Peyer's patches, the mesenteric lymph nodes (MLNs) and a large number of cells distributed throughout the lamina propria and epithelium of the intestine [14,15] .…”

“…The origin of such microorganisms is the enteric flora and translocation occurs via a defective mucosal barrier [4] . BT is considered the key step in the pathogenesis of SBP and bacteremia in cirrhotic patients, as well as a critical factor that triggers host immune responses and secretion of inflammatory mediators, which, ultimately, mediate the hemodynamic changes that are present in portal hypertension and cirrhosis [5] . The main three mechanisms involved in BT include bacterial overgrowth, physical disruption of the gut mucosal barrier and an impaired host defence ( Figure 1) [6] .…”