Clinical Pearls & Morning Reports
Despite the increasing prevalence of infections among patients with cirrhosis, developing strategies for prevention, early detection, and treatment has been challenging. Read the NEJM Review Article here.
Q: What are some of the factors that increase susceptibility to infection in patients with cirrhosis?
A: Cirrhosis is associated with inherent and external factors that synergize to increase susceptibility to and progression of infections. The major internal factors that confer susceptibility to infection are cirrhosis-associated immune dysfunction, reduction in bile flow, and changes in gut microbial composition and function.
Q: What are the most prevalent infections in patients with cirrhosis?
A: The most prevalent infections in patients with cirrhosis are spontaneous bacterial peritonitis and urinary tract infections, followed by pneumonia, spontaneous bacteremia, skin and soft-tissue infections, and Clostridioides difficile infection, with variations in the risk of death. Fungal infections occur at a frequency of 10 to 13% among patients with cirrhosis, and patients with dual bacterial and fungal infections have lower survival rates than those with bacterial infections alone.
A: The intestinal barrier, which consists of multiple physical and immune layers, is progressively impaired with advancing stages of cirrhosis. Alterations in the gut microbiota, the mucus layer, epithelial cells, and immune function of the lamina propria contribute to an increased rate of bacterial translocation among patients with cirrhosis. This immune impairment in cirrhosis leads to microbial dysbiosis in the stool, upper and lower intestinal mucosa, blood, skin, and saliva. In the gut, these changes include a reduction in autochthonous, or “beneficial,” taxa and an increase in pathobionts such as gram-negative rods belonging to Enterobacteriaceae and gram-positive cocci belonging to Streptococcaceae and Enterococcaceae, as well as altered bacterial function. Ultimately, bacterial translocation leading to clinically relevant infections is a balance between pathogen factors, such as causative organisms and virulence, and host factors, such as the severity of liver disease and status with respect to diabetes and malnutrition, as well as to the use of alcohol, proton-pump inhibitors, and glucocorticoids in the context of cirrhosis-associated immune dysfunction.
A: Spontaneous bacterial peritonitis is an infection most commonly associated with cirrhosis, and affected patients may be asymptomatic or may present with abdominal pain, diarrhea and ileus, fever or hypothermia, leukocytosis, hepatic encephalopathy, or worsening of hepatic and renal function. An ascitic fluid neutrophil count of 250 per cubic millimeter has the highest sensitivity for the diagnosis of spontaneous bacterial peritonitis, but a cutoff point of 500 neutrophils per cubic millimeter has the highest specificity. Bacterascites, the term used when bacterial cultures of ascitic fluid are positive but the neutrophil count in the fluid is normal, represents colonization of ascitic fluid and typically does not require treatment. Some cases of bacterascites may represent early spontaneous bacterial peritonitis, and antibiotic therapy may be required if the patient is, or becomes, symptomatic. Follow-up paracentesis is recommended to confirm the absence of neutrophilic ascites. Daily antibiotics for prophylaxis against spontaneous bacterial peritonitis should be considered in three high-risk groups of patients with cirrhosis: patients with acute gastrointestinal bleeding, those with advanced cirrhosis who are at high risk for infection, and those with a history of spontaneous bacterial peritonitis. Long-term secondary prophylaxis against a subsequent bout of spontaneous bacterial peritonitis is recommended until liver transplantation or death. However, prophylactic strategies are associated with the risk of antibiotic resistance.