Sepsis in cirrhosis: report on the 7th meeting of the International Ascites Club

Abstract

Sepsis is a systemic inflammatory response to the presence of infection, mediated via the production of many cytokines, including tumour necrosis factor (TNF-), interleukin (IL)-6, and IL-1, which cause changes in the circulation and in the coagulation cascade. There is stagnation of blood flow and poor oxygenation, subclinical coagulopathy with elevated D-dimers, and increased production of superoxide from nitric oxide synthase. All of these changes favour endothelial apoptosis and necrosis as well as increased oxidant stress. Reduced levels of activated protein C, which is normally anti-inflammatory and antiapoptotic, can lead to further tissue injury. Cirrhotic patients are particularly susceptible to bacterial infections because of increased bacterial translocation, possibly related to liver dysfunction and reduced reticuloendothelial function. Sepsis ensues when there is overactivation of pathways involved in the development of the sepsis syndrome, associated with complications such as renal failure, encephalopathy, gastrointestinal bleed, and shock with decreased survival. Thus the treating physician needs to be vigilant in diagnosing and treating bacterial infections in cirrhosis early, in order to prevent the development and downward spiral of the sepsis syndrome. Recent advances in management strategies of infections in cirrhosis have helped to improve the prognosis of these patients. These include the use of prophylactic antibiotics in patients with gastrointestinal bleed to prevent infection and the use of albumin in patients with spontaneous bacterial peritonitis to reduce the incidence of renal impairment. The use of antibiotics has to be judicious, as their indiscriminate use can lead to antibiotic resistance with potentially disastrous consequences.

Figures

Figure 1

Pathogenesis of sepsis: endotoxin signalling pathway. IL, interleukin, LPS, lipopolysaccharides, LP, lipopeptides, MAP-k, mitogen activated protein kinase, NFκB, nuclear factor κB; PGN, peptidoglycan; TLR, toll-like receptors; TNF-α, tumour necrosis factor α. Flash points represent changes that occur in cirrhosis that make them more susceptible to the development of infection.

Figure 2

Pathogenesis of sepsis: changes in the circulation during sepsis. D, deformed red blood cells; IL, interleukin; mon, monocytes; neu, neutrophil; NO, nitric oxide; TNF-α, tumour necrosis factor α. Flash points represent changes that occur in cirrhosis that make them more susceptible to the development of infection.

Figure 3

Incidence, risk factors, and complications of bacterial infections within seven days from variceal bleeding (blue area), and the improvement following antibiotic prophylaxis (red area).

Figure 4

Prevalence and type of severe hospital acquired bacterial infections in patients with cirrhosis who either did or did not receive norfloxacin prophylaxis. BE, bacteraemia; SBP, spontaneous bacterial peritonitis; Px+, prophylactic norfloxacin; Px−, no prophylactic norfloxacin. *Significantly different from Px−.