Bacterial translocation of enteric organisms in patients with cirrhosis

Cirera, Isabel; Bauer, Tilman; Navasa, Miguel; Vila, Jordi; Grande, Luís; Taurà, Pilar; Fuster, Josep; García‐Valdecasas, Juan Carlos; Lacy, Antonio M.; Suárez, María; Rimola, Antoni; Rodés, Juan

doi:10.1016/s0168-8278(00)00013-1

Cited by 392 publications

(294 citation statements)

References 23 publications

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“…One study demonstrated gut bacterial flora in mesenteric lymph nodes of 30.8% of patients with Child's Pugh C cirrhosis, compared with less than 10% in non-cirrhotic patients. 88 These translocated bacteria can either become a direct source of infection, 89 or translocated bacterial products including endotoxins can become a source of chronic inflammation by inducing an immune response. 90 One study showed endotoxemia, without sepsis, was seen in 92.3% of patients with cirrhosis and was completely absent in healthy controls with higher levels of endotoxemia seen in those with HE, and a high level predicted mortality.…”

Section: Systemic Inflammation and Immune Dysfunction In Acute And Chmentioning

confidence: 99%

Pathogenesis of Hepatic Encephalopathy: Role of Ammonia and Systemic Inflammation

Aldridge

Tranah

Shawcross

2015

Journal of Clinical and Experimental Hepatology

235

190

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The syndrome we refer to as Hepatic Encephalopathy (HE) was first characterized by a team of Nobel Prize winning physiologists led by Pavlov and Nencki at the Imperial Institute of Experimental Medicine in Russia in the 1890's. This focused upon the key observation that performing a portocaval shunt, which bypassed nitrogen-rich blood away from the liver, induced elevated blood and brain ammonia concentrations in association with profound neurobehavioral changes. There exists however a spectrum of metabolic encephalopathies attributable to a variety (or even absence) of liver hepatocellular dysfunctions and it is this spectrum rather than a single disease entity that has come to be defined as HE. Differences in the underlying pathophysiology, treatment responses and outcomes can therefore be highly variable between acute and chronic HE. The term also fails to articulate quite how systemic the syndrome of HE can be and how it can be influenced by the gastrointestinal, renal, nervous, or immune systems without any change in background liver function. The pathogenesis of HE therefore encapsulates a complex network of interdependent organ systems which as yet remain poorly characterized. There is nonetheless a growing recognition that there is a complex but influential synergistic relationship between ammonia, inflammation (sterile and non-sterile) and oxidative stress in the pathogenesis HE which develops in an environment of functional immunoparesis in patients with liver dysfunction. Therapeutic strategies are thus moving further away from the traditional specialty of hepatology and more towards novel immune and inflammatory targets which will be discussed in this review. ( J CLIN EXP HEPATOL 2015;5:S7-S20) H epatic encephalopathy (HE) is the term used to encapsulate the broad spectrum of neuropsychiatric disturbances associated with both acute and chronic liver failure (ALF and CLF, respectively), as well as porto-systemic bypass in the absence of hepatocellular disease. The clinical manifestations of HE can be extremely heterogeneous in nature, with symptoms presenting anywhere on a continuum spanning from seemingly normal cognitive performance, right the way through to states of confusion, stupor and coma. In between these extremes, patients with HE may exhibit signs such as inattentiveness, blunted affect, impairment of memory or reversal of the sleep-wake cycle, as well as physical manifestations such as tremor, myoclonus, asterixis and deep tendon hyperreflexia.ALF is defined by the onset of coagulopathy alongside any degree of encephalopathy in patients with no evidence of pre-existing liver disease. 1 The presence of HE in those with ALF is prognostic, with up to a quarter of cases developing raised intracranial pressure. 2 Patients presenting with ALF are at risk of developing its cardinal, lifethreatening feature, cerebral edema. Left untreated, cerebral edema can rapidly progress to cause herniation of the uncus through the falx cerebri, leading to compression of the brainstem and, ultimately, death. H...

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Section: Systemic Inflammation and Immune Dysfunction In Acute And Chmentioning

confidence: 99%

Pathogenesis of Hepatic Encephalopathy: Role of Ammonia and Systemic Inflammation

Aldridge

Tranah

Shawcross

2015

Journal of Clinical and Experimental Hepatology

235

190

View full text Add to dashboard Cite

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“…34,35 In a study including 80 cirrhotic patients and 24 controls assessed for intestinal permeability, the risk of SPB and BSI were directly related to the grade of intestinal barrier dysfunction measured by the expression of tight junction protein Claudin-2. 36 …”

Section: Pathophysiology Of Bsis In Patients With Liver Cirrhosis: Inmentioning

confidence: 99%

Bloodstream infections in patients with liver cirrhosis

et al. 2016

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Bloodstream infections are a serious complication in patients with liver cirrhosis. Dysregulated intestinal bacterial translocation is the predominant pathophysiological mechanism of infections in this setting. For this reason enteric Gram-negative bacteria are commonly encountered as the first etiological cause of infection. However, through the years, the improvement in the management of cirrhosis, the recourse to invasive procedures and the global spread of multidrug resistant pathogens have importantly changed the current epidemiology. Bloodstream infections in cirrhotic patients are characterized by high mortality rate and complications including metastatic infections, infective endocarditis, and endotipsitis (or transjugular intrahepatic portosystemic shunt-related infection). For this reason early identification of patients at risk for mortality and appropriated therapeutic management is mandatory. Liver cirrhosis can significantly change the pharmacokinetic behavior of antimicrobials. In fact hypoproteinaemia, ascitis and third space expansion and impairment of renal function can be translated in an unpredictable drug exposure.

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“…It has been postulated that intestinal bacterial overgrowth, altered gut permeability, and bacterial translocation, all common in cirrhosis with ascites, may exert continuous pressure on the immune system. [1][2][3][4] This disturbance is thought to lead to activation of monocytes and lymphocytes and increased serum levels of proinflammatory cytokines such as tumor necrosis factor ␣ (TNF-␣). Exposure to bacteria and their endotoxins, directly or involving host cytokines, has been associated with increased synthesis of nitric oxide, 5 which may exacerbate the circulatory disarrangement of cirrhosis.…”

mentioning

confidence: 99%

Increased lipopolysaccharide binding protein in cirrhotic patients with marked immune and hemodynamic derangement

et al. 2003

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Intestinal bacterial overgrowth and translocation, both common in cirrhosis with ascites, may lead to the activation of monocytes and lymphocytes, increased levels of proinflammatory cytokines, and enhanced synthesis of nitric oxide present in cirrhosis. Bacterial endotoxin promotes the synthesis of lipopolysaccharide (LPS)-binding protein (LBP), and forms a LPS-LBP complex that binds to CD14. This study was designed to evaluate LBP levels and their correlation to the immune response and the hemodynamic status in cirrhotic patients. Plasma LBP, endotoxin, soluble CD14 (sCD14), cytokines, renin, nitrites, and systemic vascular resistance were determined before and 4 weeks after norfloxacin or placebo in 102 cirrhotic patients and 30 controls. LBP was elevated in 42% of ascitic cirrhotic patients (15.7 ؎ 0.7 versus 6.06 ؎ 0.5 g/mL, P < .01). In 60% of high LBP patients, endotoxin was within normal range. Among ascitic patients, those with high LBP showed greater (P < .05) levels of sCD14, tumor necrosis factor ␣ (TNF-␣), interleukin 6 (IL-6), nitrites ؉ nitrates (NOx)/creatinine, and renin, and lower vascular resistance. In the cirrhotic patients with high LBP, norfloxacin normalized (P < .01) LBP (from 16.6 ؎ 0.5 to 5.82 ؎ 0.8 g/mL) and sCD14; reduced the level of cytokines, NOx/creatinine, and renin; and increased vascular resistance; but lacked effect in patients with normal LBP. Portal pressure was unchanged after norfloxacin in another group of 18 cirrhotic patients with high and 19 with normal LBP. In conclusion, the subset of ascitic cirrhotic patients with marked immune and hemodynamic derangement is identified by increased LBP levels. Amelioration of these abnormalities by norfloxacin suggests the involvement of enteric bacteria or their products in the triggering of the process. (HEPATOLOGY 2003;37:208-217.)

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Bacterial translocation of enteric organisms in patients with cirrhosis

Cited by 392 publications

References 23 publications

Pathogenesis of Hepatic Encephalopathy: Role of Ammonia and Systemic Inflammation

Pathogenesis of Hepatic Encephalopathy: Role of Ammonia and Systemic Inflammation

Bloodstream infections in patients with liver cirrhosis

Increased lipopolysaccharide binding protein in cirrhotic patients with marked immune and hemodynamic derangement

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