Review
Immune Dysfunction and Infections in Patients With Cirrhosis

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Patients with cirrhosis are immunocompromised and susceptible to infections. Although detection and treatment of spontaneous bacterial peritonitis (SBP) have improved, overall survival rates have not increased greatly in recent decades—infection still increases mortality 4-fold among patients with cirrhosis. Hospitalized patients with cirrhosis have the highest risk of developing infections, especially patients with gastrointestinal (GI) hemorrhage. Bacterial infections occur in 32% to 34% of patients with cirrhosis who are admitted to the hospital and 45% of patients with GI hemorrhage. These rates are much higher than the overall rate of infection in hospitalized patients (5%–7%). The most common are SBP (25% of infections), urinary tract infection (20%), and pneumonia (15%). Bacterial overgrowth and translocation from the GI tract are important steps in the pathogenesis of SBP and bacteremia—these processes increase levels of endotoxins and cytokines that induce the inflammatory response and can lead to septic shock, multiorgan dysfunction, and death. A number of other bacterial and fungal pathogens are more common and virulent in patients with cirrhosis than in the overall population. We review the pathogenesis of infections in these patients, along with diagnostic and management strategies.

Section snippets

State of Immune Dysfunction in Cirrhosis

Cirrhosis-associated immune dysfunction syndrome (CAIDS) is a multifactorial state of systemic immune dysfunction (Figure 1), which decreases their ability to clear cytokines, bacteria, and endotoxins from circulation. The liver contains 90% of the reticuloendothelial (RE) cells,7 such as Kupffer and sinusoidal endothelial cells, that are central to clearing bacteria. When radiolabeled E. coli and P. aeruginosa were injected intravenously, 70% and 96% of their populations, respectively, were

Bacterial Translocation

Bacterial translocation is the migration of bacteria or bacterial products from the intestinal lumen to mesenteric lymph nodes (Figure 2).24 Bacterial translocation is known to be increased in cirrhosis and has been pathogenetically linked to the development of SBP.5, 6 It has also been implicated as a cause of recurrent SBP.25 Patients with cirrhosis have slowed intestinal motility, which leads to intestinal bacterial overgrowth.26 This overgrowth, along with portosystemic shunting, enables

SIRS, Sepsis, and Cirrhosis

Systemic inflammatory response syndrome (SIRS) is not uncommon in cirrhosis, and sepsis is defined as SIRS in the presence of confirmed bacterial infection (Figure 3).1, 2, 11, 27, 28, 29, 30 Bacterial derived toxins, such as peptidoglycans from gram-positive bacteria or lipopolysaccharides from gram-negative bacteria, bind to Toll-like receptors which initiate a cascade of cell signaling. Toll-like receptors trigger either nuclear factor μB or mitogen activated protein kinase, which in turn

Gastrointestinal Bleeding–Associated Infections and Prophylaxis

GI bleeding is associated with an increased incidence of infection, and approximately 17% to 45% of cases lead to an episode of SBP or bacteremia.46 Conversely, the presence of infection has been found to increase the risk of early bleeding.47, 48 Goulis et al49 hypothesize that bacterial endotoxins stimulate hepatic stellate cell contraction and endothelial NO production, which then increase sinusoidal pressure and inhibit platelet aggregation, respectively.

Patients who present with acute

Urinary Tract Infection

UTI occurs in approximately 15% to 20% of hospitalized patients with cirrhosis; it is twice as frequent in patients with cirrhosis compared with matched controls.3, 99 Women have a 4 times higher rate of bacteriuria than men.99 Gram-negative bacilli, such as E. coli and Klebsiella spp., are the primary causative agents. Notably, bacteriuria is not associated with an increased risk of sepsis, SBP, or other infections often seen in patients with cirrhosis.99 Although more frequent among those

Summary

Patients with cirrhosis are in a multifactorial immunocompromised state which predisposes them to a higher risk of infection. Bacterial infections, particularly SBP and bacteremia, are an important cause of morbidity and mortality in these patients. Gram-negative enteric bacteria appear to be the most common causative organisms. However, other unusual bacteria and fungi are also frequently observed and more virulent in patients with cirrhosis relative to those without liver disease. Moreover,

Acknowledgments

The authors appreciate the in-depth review and comments of Dr Jasmohan Bajaj from Virginia Commonwealth University.

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    Conflicts of interest The authors disclose no conflicts.

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