Infection as a Trigger for Portal Hypertension

Abstract

Background: Microbial infections are a relevant problem for patients with liver cirrhosis. Different types of bacteria are responsible for different kinds of infections: Escherichia coli and Klebsiella pneumoniae are frequently observed in spontaneous bacterial peritonitis or urinary tract infections, and Streptococcus pneumoniae and Mycoplasma pneumoniae in pulmonary infections. Mortality is up to 4-fold higher in infected patients with liver cirrhosis than in patients without infections. Key Messages: Infections in patients with liver cirrhosis are due to three major reasons: bacterial translocation, immune deficiency and an increased incidence of systemic infections. Nonparenchymal liver cells like Kupffer cells, sinusoidal endothelial cells and hepatic stellate cells are the first liver cells to come into contact with microbial products when systemic infection or bacterial translocation occurs. Kupffer cell (KC) activation by Toll-like receptor (TLR) agonists and endothelial sinusoidal dysfunction have been shown to be important mechanisms increasing portal pressure following intraperitoneal lipopolysaccharide pretreatment in cirrhotic rat livers. Reduced intrahepatic vasodilation and increased intrahepatic vasoconstriction are the relevant pathophysiological pathways. Thromboxane A₂ and leukotriene (LT) C₄/D₄ have been identified as important vasoconstrictors. Accordingly, treatment with montelukast to inhibit the cysteinyl-LT₁ receptor reduced portal pressure in cirrhotic rat livers. Clinical studies have demonstrated that activation of KCs, estimated by the amount of soluble CD163 in the blood, correlates with the risk for variceal bleeding. Additionally, intestinal decontamination with rifaximin in patients with alcohol-associated liver cirrhosis reduced the portal pressure and the risk for variceal bleeding. Conclusions: TLR activation of nonparenchymal liver cells by pathogens results in portal hypertension. This might explain the pathophysiologic correlation between microbial infections and portal hypertension in patients with liver cirrhosis. These findings are the basis for both better risk stratifying and new treatment options, such as specific inhibition of TLR for patients with liver cirrhosis and portal hypertension.

Clinical value of liver and spleen shear wave velocity in predicting the prognosis of patients with portal hypertension

“…In the present study, it was shown that studies have investigated the relationship between liver and spleen hardness and liver fibrosis, chronic liver, or other liver diseases[ 34 - 36 ]. However, there is lack of further research on the relationship between liver and spleen hardness and portal hypertension, and the clinical value of liver and spleen hardness in evaluating the prognosis of portal hypertension could not be determined.…”

Managing portal hypertension in patients with liver cirrhosis

“…They impair intrahepatic endothelial function by influencing nitric oxide release 138 , 139 or stimulate signaling pathways of intrahepatic contractile cells and of fibrogenesis by inducing inflammation, e.g. activation of Kupffer cells and other macrophages 140 , 141 using sensing protein families such as Nod-like receptors or Toll-like receptors 142 , 143 . Especially in fatty liver disease, an early increase in portal pressure may be caused by functional non-structural changes of the intrahepatic vascular bed 144 .…”

“…Later, endotoxin from the outer membrane of Gram-negative bacteria was more and more regarded as a cofactor for the pathogenesis of alcoholic liver disease 148 , 149 as a gut-derived stimulus. Further research showed that it mediates intrahepatic inflammation via Toll-like receptor 4 on macrophages 150 , which in turn are a trigger for portal hypertension 140 . Thus, the intestine has become a prime target for research on alcoholic liver disease and the catchword of today is gut–liver axis.…”

The role of antibiotics in upper gastrointestinal bleeding among cirrhotic patients without major complications after endoscopic hemostasis

“…Upper gastrointestinal bleeding (UGIB) is a common and fatal complication in cirrhotic patients . Increased risk of bacterial infection driven by portal hypertension and bacteria translocation was observed among patients with cirrhosis during hospitalization for UGIB . Current clinical guidelines recommend that prophylactic antibiotic should be instituted for patients with cirrhosis and UGIB, regardless of variceal hemorrhage or non‐variceal sources .…”