|Year : 2015 | Volume
| Issue : 2 | Page : 372-376
Impact of bacterial sepsis on organ failure in patients with liver cirrhosis
Ibrahim M Boghdadi1, Tarek E Korah1, Ehab A Abd El-Atty1, Omar F Fouad MBBCh 2
1 Department of Internal Medicine, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Internal Medicine, Shebin El-Kowm Teaching Hospital, Shebin El-Kom, Egypt
|Date of Submission||14-May-2014|
|Date of Acceptance||12-Aug-2014|
|Date of Web Publication||31-Aug-2015|
Omar F Fouad
Department of Internal Medicine, Shebin El-Kowm Teaching Hospital, Shebin El-Kom
Source of Support: None, Conflict of Interest: None
The aim of this study was to examine the evidence for impact of bacterial sepsis and multiple organ failure in patients with liver cirrhosis.
A review of contemporary (1995 to present) English medical literature using the terms bacterial infection, hepatic encephalopathy, multiple organ dysfunction, and spontaneous bacterial peritonitis was conducted.
Abstracts were reviewed independently by two authors, and relevant articles were then evaluated. Exclusion criteria included editorials, non-English language, comments, and letters.
Level of evidence was assigned in accordance with the Oxford Center for Evidence-based Medicine guidance (levels I-V).
Thirty-seven articles met the inclusion criteria; of which, 11 were of level III, 22 of level IV, and four of level V evidence. Bacterial sepsis and multiple organ failure are common in patients with liver cirrhosis. There was level III evidence that third-generation cephalosporins are the treatment of choice for infections in patients with liver cirrhosis.
This review indicates that bacterial sepsis and multiple organ failure are common in patients with liver cirrhosis, supported principally by level III/IV evidence.
Keywords: bacterial infection, hepatic encephalopathy, multiple organ dysfunction; spontaneous bacterial peritonitis
|How to cite this article:|
Boghdadi IM, Korah TE, Abd El-Atty EA, Fouad OF. Impact of bacterial sepsis on organ failure in patients with liver cirrhosis. Menoufia Med J 2015;28:372-6
|How to cite this URL:|
Boghdadi IM, Korah TE, Abd El-Atty EA, Fouad OF. Impact of bacterial sepsis on organ failure in patients with liver cirrhosis. Menoufia Med J [serial online] 2015 [cited 2021 Jan 21];28:372-6. Available from: http://www.mmj.eg.net/text.asp?2015/28/2/372/163887
| Bacterial infection|| |
Despite the advancement in medical care for patients with advanced liver disease in the past decades, bacterial infections remain very common and account for significant morbidity and mortality (~30%) in these patients  . Spontaneous bacterial peritonitis and urinary infections are the most frequent infections, followed by pneumonia, cellulitis, and bacteremia. In patients with advanced cirrhosis, infection induces a systemic inflammatory response characterized by high circulating levels of proinflammatory cytokines. This excessive proinflammatory response contributes to the development of sepsis-related organ failures and septic shock in cirrhosis  .
| Pathogenesis|| |
Cirrhotic patients are in a multifactorial state of local and systemic immune dysfunction [Table 1]. Portosystemic shunting allows less bacteria and endotoxins to be cleared by the liver from the portal circulation  . The mechanisms of increased susceptibility to infections in cirrhosis are unclear. It has been suggested that there is a role for downregulation of monocyte human leukocyte antigen-DR expression (and subsequent impaired antigen presentation ability) and impairment of macrophage Fc - a receptor-mediated clearance of antibody-coated bacteria  . Systemic reticuloendothelial system function is also significantly impaired. Cirrhosis is associated with a decrease in bactericidal activity of phagocytic cells, an impaired opsonic activity, and a reduction in complement and protein C levels  . Bacterial translocation (BT) is defined as the migration of bacteria or bacterial products from the intestinal lumen to mesenteric lymph nodes and other extraintestinal sites. It has been implicated as the key step in the pathogenesis of spontaneous bacterial peritonitis (SBP) and spontaneous bacteremia in cirrhotic patients. The mechanisms of BT are complex and not yet completely understood. Immune dysfunction, intestinal bacterial overgrowth, and altered intestinal permeability are hypothesized to contribute to the development of BT  . In cirrhosis, bacterial infection is accompanied by an imbalanced cytokine response, which converts responses that are normally helpful against infections into excessive, detrimental inflammation. The pathophysiology of the exaggerating inflammatory response in cirrhotic patients has been postulated. In the early stage of sepsis, bacteria and their products, particularly lipopolysaccharides, activate toll-like receptor-4, which induces the release of proinflammatory cytokines  .
| Organ-specific infections|| |
Spontaneous bacterial peritonitis
SBP is characterized by infection of the ascetic fluid in the absence of any primary focus of intra-abdominal infection. The incidence of mortality with the first episode varies between 10 and 46%. The reported probability of spontaneous bacterial peritonitis recurrence 1 year after the first attack averages 40-69%. Cefotaxime has been the most extensively studied antibiotic for this infection  .
| Urinary tract infection|| |
Urinary tract infection is the second most common bacterial infection in cirrhosis after SBP  . Frequently found bacteria included Escherichia coli and Klebsiella pneumoniae  .
Compared with noncirrhotic patients, cirrhotic patients with community-acquired pneumonia are more frequently associated with bacteremia, multilobar involvement, impaired consciousness, renal failure, septic shock, and death  . Careful monitoring and empirical treatment with intravenous β-lactams plus macrolides or intravenous antipneumococcal quinolones is recommended  .
Bacteremia without particular organ-specific source is increasingly common in cirrhosis and can be arbitrarily divided into two entities: primary or spontaneous bacteremia and secondary bacteremia  . Bacteremia and/or SBP occur in 17-45% of patients following an episode of gastrointestinal bleeding and, like those patients with primary bacteremia, the causative organisms are typically gram-negative enteric bacteria  .
Spontaneous bacterial empyema
The pathogenesis of spontaneous bacterial empyema, SBP, and spontaneous bacteremia are closely interconnected; thus, they share the same types of common pathogens  . Treatment with intravenous third-generation cephalosporin should be initiated immediately when pleural fluid polymorphonuclear count is 250 cells/mm 3 or greater while awaiting culture result. In cases with slow clinical recovery, a repeat thoracocentesis is suggested to document the treatment response. Chest tube drainage can be harmful in cirrhotic patients with hepatic hydrothorax and should not be used in the treatment of spontaneous bacterial empyema  .
| Skin and soft tissue infection|| |
Soft tissue infections account for 11% of infections overall in cirrhotic patients, and the severe form of necrotizing infection carries a high mortality rate  . The common causative organisms are gram-positive cocci Staphylococcus aureus (β-hemolytic streptococci) and gram-negative enteric bacteria (occasionally polymicrobial)  .
The mortality rate of cirrhotic patients with infective endocarditis is high (27-51%) despite treatment, especially in those patients with advanced cirrhosis and staphylococcal infection  .
When patients with liver cirrhosis develop disturbed consciousness, seizures, and septicemia, immediate neuroimaging and cerebrospinal fluid studies should be undertaken to determine whether bacterial meningitis is the cause. Early diagnosis and treatment are essential for survival  . Prompt empirical central nervous system-dosed antibiotics and an appropriate diagnostic approach are key to decreasing morbidity and mortality in patients with bacterial meningitis  .
All cirrhotic patients should be aware of the risk of infections and contact their physicians instantly when they are febrile or ill  . Prophylactic antibiotics should be utilized in cirrhotic patients at high risk of developing infection, in those with gastrointestinal bleeding, and in patients undergoing invasive endoscopic or surgical procedures  . Long-term prophylaxis is recommended for patients with a history of SBP and those who have low ascitic fluid protein (<1.5 g/dl)  . In contrast, overuse of antibiotic prophylaxis can lead to the development of resistant organisms. The rate of culture-positive infection caused by quinolone-resistant gram-negative bacilli was found to be very high (65%) in patients on long-term norfloxacin prophylaxis  .
Prompt and appropriate antibiotic treatment is essential in the management of patients with cirrhosis who have infection. Meanwhile, third-generation cephalosporins continue to be the gold standard antibiotic treatment of many of the infections acquired in the community  .
Treatment with intravenous albumin (1.5 g/kg at diagnosis and 1 g/kg on day 3) reduces the incidence of hepatorenal syndrome (from 33 to 10%) and improves short-term survival in patients with SBP  .
Norepinephrine and dopamine are first-line vasopressors to correct hypotension in septic shock  .
Patients with cirrhosis and septic shock may have a high incidence of adrenal insufficiency (51-68%), which may be related to a reduction in adrenal blood flow and high cytokine expression  . Hydrocortisone could shorten the duration of shock resolution and improves survival  .
Hyperglycemia and insulin resistance are common in sepsis. Hyperglycemia may act as procoagulant, induce apoptosis, impair neutrophil function, and is associated with increased risk of death  .
Multiple organ dysfunction in cirrhosis
Multiple organ failure is common in patients with cirrhosis and severe sepsis. Although the mechanisms leading to this multiorgan failure are poorly understood, an excessive production of proinflammatory cytokines seems to play an important role  . In cirrhotic patients, once an overt infection occurs, it may lead to systemic inflammatory response syndrome (SIRS), which can precipitate hypotension (severe sepsis), renal dysfunction, encephalopathy, and coagulopathy - that is, multiorgan failure  .
Ammonia dysmetabolism cannot single handedly explain all the neurological changes that are seen in patients with hepatic encephalopathy. In patients with cirrhosis and infection, induced hyperammonemia results in a significant deterioration of neuropsychological test scores in patients with evidence of SIRS, but not after its resolution, suggesting that SIRS mediators, such as nitric oxide (NO) and proinflammatory cytokines, may be important in modulating the cerebral effect of ammonia in cirrhosis. This 'sepsis-associated encephalopathy' has been linked to the production of reactive oxygen species, the direct effect of inflammatory cytokines on cerebral endothelial cells, astrocytes, and vagal afferents, and a reduction in cerebral blood flow  . The development of hepatic encephalopathy has a significant negative effect on survival in patients with cirrhosis. The Model of End-stage Liver Disease system, used to prioritize patients on liver transplant lists, does not include information on neuropsychiatric status. Thus, at present, no priority is given to patients with severe recurrent or persistent hepatic encephalopathy. The features of overt hepatic encephalopathy usually resolve following liver transplantation, even in patients with major physical manifestations  .
Coagulation abnormalities in cirrhosis are attributed to a reduction in the hepatic synthesis of factors VII, V, X, and prothrombin, vitamin K deficiency, and quantitative and qualitative platelet defects. Coagulation abnormalities are greater in cirrhotic patients with sepsis, perhaps as a result of more severe liver dysfunction  . The release of cytokines tumor necrosis factor-α, interleukin-1 (IL-1), and IL-6 with sepsis impairs platelet function and increases fibrinolysis, the consumption of clotting factors, and the production of endogenous heparin-like substances. Bacterial infections are common in cirrhotic patients with variceal hemorrhage. Conversely, the presence of infection may precipitate variceal hemorrhage by increasing portal pressure and altering hemostasis, thereby increasing mortality  . The balance between the levels of procoagulant and anticoagulant proteins determines the overall effect on hemostasis and resulting risk of hemorrhage and thrombosis. Although bleeding occurs more frequently, the hemostatic imbalance in end-stage liver disease occasionally favors hypercoagulability, predisposing to thrombosis. Deficiencies of anticoagulation proteins are common and correlate with the severity of disease  .
The pathogenesis of renal dysfunction in the setting of infection is related to worsening splanchnic and systemic vasodilation leading to a further decrease in effective arterial blood volume, with the consequent activation of neurohumoral systems (renin-angiotensin-aldosterone) that leads to renal vasoconstriction and renal dysfunction. A prospective study performed in patients with SBP shows that, in those who develop renal failure, the mean arterial pressure is lower and plasma renin, aldosterone, and norepinephrine concentrations are higher. The increases in renin and aldosterone inpatients with SBP-related renal failure have been clearly associated with increases in inflammatory cytokines (tumor necrosis factor, IL-6) and vasodilatory hormones (NO)  .
Acute respiratory distress syndrome
Acute respiratory distress refers to hypoxia and bilateral radiographic infiltrates in the absence of an elevated left atrial pressure. Several studies have suggested that cirrhosis is an independent predictor of mortality in a patient who develops acute respiratory distress syndrome. The other complications from the association between cirrhosis and acute respiratory distress syndrome have been linked to an increase in serum cytokines, NO, and pulmonary leukotrienes  .
Hepatopulmonary syndrome (HPS) is defined as the presence of the triad of an arterial oxygenation defect, intrapulmonary vasodilation, and the presence of liver disease  . Liver transplant remains the only effective treatment for HPS, although post-transplant survival is often reduced compared with patients without HPS  .
| Summary|| |
Bacterial infections are an important cause of morbidity and mortality in cirrhotic patients due to their relative immunocompromised state. BT plays a major role in the pathogenesis of infections and in the hyperdynamic circulatory state of cirrhosis. Hemodynamic alterations worsen with the development of overt infection and can progress to severe sepsis and septic shock. Endotoxin, cytokines, and NO are key elements in the pathogenesis of circulatory abnormalities in cirrhosis and sepsis. Early diagnosis and prompt treatment of spontaneous bacterial peritonitis and other infections can significantly reduce morbidity and improve survival, particularly when associated with intravenous albumin in patients with a high risk of developing renal failure. Antibiotic prophylaxis is indicated in patients admitted with gastrointestinal hemorrhage and in those who have recovered from an episode of SBP. As the widespread use of antibiotic prophylaxis will lead to antimicrobial resistance, it would be important to develop nonantibiotic measures to inhibit BT and infections. Bacterial infection can lead to a systemic inflammatory response and multisystem organ dysfunction including circulatory dysfunction, renal failure, and death. In these patients, treatment is mainly directed at treating the infection and circulatory abnormalities through the use of antibiotics, vasoconstrictors, albumin, hydrocortisone, and liver support devices. As critically ill septic cirrhotic patients have a poor prognosis and as resources are not unlimited, it is important to use prognostic models to better identify when further care is futile, as well as identify optimal timing and outcomes of liver transplantation.
| Acknowledgements|| |
Conflicts of interest
There are no conflicts of interest.
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