Severe sepsis in cirrhosis

Abstract

Sepsis is physiologically viewed as a proinflammatory and procoagulant response to invading pathogens. There are three recognized stages in the inflammatory response with progressively increased risk of end-organ failure and death: sepsis, severe sepsis, and septic shock. Patients with cirrhosis are prone to develop sepsis, sepsis-induced organ failure, and death. There is evidence that in cirrhosis, sepsis is accompanied by a markedly imbalanced cytokine response ("cytokine storm"), which converts responses that are normally beneficial for fighting infections into excessive, damaging inflammation. Molecular mechanisms for this excessive proinflammatory response are poorly understood. In patients with cirrhosis and severe sepsis, high production of proinflammatory cytokines seems to play a role in the worsening of liver function and the development of organ/system failures such as shock, renal failure, acute lung injury or acute respiratory distress syndrome, coagulopathy, or hepatic encephalopathy. In addition, these patients may have sepsis-induced hyperglycemia, defective arginine-vasopressin secretion, adrenal insufficiency, or compartmental syndrome. In patients with cirrhosis and spontaneous bacterial peritonitis (SBP), early use of antibiotics and intravenous albumin administration decreases the risk for developing renal failure and improves survival. There are no randomized studies that have been specifically performed in patients with cirrhosis and severe sepsis to evaluate treatments that have been shown to improve outcome in patients without cirrhosis who have severe sepsis or septic shock. These treatments include recombinant human activated C protein and protectiveventilation strategy for respiratory failure. Other treatments should be evaluated in the cirrhotic population with severe sepsis including the early use of antibiotics in "non-SBP" infections, vasopressor therapy, hydrocortisone, renal-replacement therapy and liver support systems, and selective decontamination of the digestive tract or oropharynx.

Infectious endocarditis in patients with cirrhosis of the liver: a model of infection in the frail patient

“…Liver cirrhosis has a significant impact on the mortality of patients with bacteremic infections and high production of proinflammatory cytokines seems to play a role in the worsening of 10 liver function and the development of organ-system failures such as hepato-renal syndrome or hepatic encephalopathy [18,19].…”

The burden of extended-spectrum β-lactamase-producing Enterobacteriaceae in patients with cirrhosis

“…Patients with cirrhosis have high susceptibility to bacterial infections [1]; 24 % of patients admitted to the hospital for an acute decompensation of cirrhosis have bacterial infection [2]. The most common infection is spontaneous bacterial peritonitis (SBP) [1,2].…”

“…The most common infection is spontaneous bacterial peritonitis (SBP) [1,2]. It is well known that SBP is caused by Gram-negative bacteria such as Escherichia coli or Klebsiella pneumoniae originating from the intestinal lumen [3].…”

“…It is well known that SBP is caused by Gram-negative bacteria such as Escherichia coli or Klebsiella pneumoniae originating from the intestinal lumen [3]. The translocation of intestinal bacteria is a crucial step in the process leading to SBP [1,4]. Little is known about underlying mechanisms that explain bacterial translocation [4].…”

“…Nevertheless an important question that remains to be addressed is the mechanisms of ACLF triggered by infections due to ESBL-producing bacteria. A first hypothesis is that ''persistent'' infection may elicit an excessive immune response of the host resulting in cytokine storm and subsequent tissue damage [1]. There is some evidence that some patients with cirrhosis have an excessive proinflammatory response of innate immune cells to bacterial components [18][19][20].…”