Primary Prophylaxis of Spontaneous Bacterial Peritonitis Delays Hepatorenal Syndrome and Improves Survival in Cirrhosis

Fernández, Javier; Navasa, Miquel; Planas, Ramón; Montoliu, Silvia; Monfort, David; Soriano, Germán; Vila, Carmen; Pardo, A.; Quintero, Enrique; Vargas, Vı́ctor; Such, José; Ginès, Pere; Arroyo, Vicente

doi:10.1053/j.gastro.2007.06.065

Cited by 647 publications

(480 citation statements)

References 34 publications

(50 reference statements)

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“…Several lines of evidence support gut derived bacterial translocation being of particular importance [3,[15][16][17]. However, the reason why the intestinal barrier fails in cirrhosis, and the molecular events at the gut wall associated with translocation remain poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Activated intestinal macrophages in patients with cirrhosis release NO and IL-6 that may disrupt intestinal barrier function

Plessis

Vanheel

Janssen

et al. 2013

Journal of Hepatology

155

123

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Background & Aims: Bacterial infections commonly occur in decompensated cirrhosis resulting from bacterial translocation from the intestine. We studied the role of intestinal macrophages and the epithelial barrier in cirrhosis. Methods: Forty-four patients with NASH/ASH cirrhosis (decom-pensated n = 29, compensated n = 15) and nineteen controls undergoing endoscopy were recruited. Serum was obtained and LPS and LBP levels determined. Intestinal macrophages were characterized by flow cytometry, immunohistochemistry, and nitric oxide (NO) production measured in supernatant of cultured duodenal samples. Quantitative RT-PCR was performed on duo-denal biopsies assessing 84 inflammatory genes. Protein levels of cytokines/chemokines were assessed in serum and superna-tant. The duodenal wall was assessed by electron microscopy, tight junction protein expression determined by RT-PCR, immu-nohistochemistry, and Western blot and, functional analysis performed by transepithelial resistance measurement and per-meability studies. Results: Increased plasma LPS, LBP levels and higher numbers of duodenal CD33 + /CD14 + /Trem-1 + macrophages, synthesizing iNOS and secreting NO were present in decompensated cirrhosis. Upregulation of IL-8, CCL2, CCL13 at the transcriptional level, and increased IL-8, and IL-6 were detected in supernatant and serum in cirrhosis. IL-6 and IL-8 co-localised with iNOS + and CD68 + , but not with CD11c + cells. Electron microscopy demon-strated an intact epithelial barrier. Increased Claudin-2 was detected by Western blot and immunohistochemistry, while decreased transepithelial resistance and increased duodenal per-meability were detected in decompensated cirrhosis. Conclusions: Our study shows the presence of activated CD14 +-Trem-1 + iNOS + intestinal macrophages, releasing IL-6, NO, and increased intestinal permeability in patients with cirrhosis, sug-gesting that these cells may produce factors capable of enhancing permeability to bacterial products.

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Section: Discussionmentioning

confidence: 99%

Activated intestinal macrophages in patients with cirrhosis release NO and IL-6 that may disrupt intestinal barrier function

Plessis

Vanheel

Janssen

et al. 2013

Journal of Hepatology

155

123

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“…This is due to perforation or inflammation of an intra-abdominal organ, and its mortality is much higher than that of SBP (66% vs 10%) [28] . Secondary peritonitis must be suspected in patients with inadequate response to therapy or when multiple organisms are identified in the ascitic fluid [29] . A diagnosis of secondary peritonitis is probable when at least two of the Runyon's criteria are present: glucose level < 50 mg/dL; protein concentration > 10 g/L; or lactate dehydrogenase > 225 mU/mL [8] .…”

Section: Diagnosis Of Spontaneous Bacterial Peritonitismentioning

confidence: 99%

Diagnosis and management of bacterial infections in decompensated cirrhosis

Pleguezuelo

Benítez²,

Jurado³

et al. 2013

WJH

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Bacterial infections are one of the most frequent complications in cirrhosis and result in high mortality rates. Patients with cirrhosis have altered and impaired immunity, which favours bacterial translocation. Episodes of infections are more frequent in patients with decompensated cirrhosis than those with compensated liver disease. The most common and life-threatening infection in cirrhosis is spontaneous bacterial peritonitis followed by urinary tract infections, pneumonia, endocarditis and skin and soft-tissue infections. Patients with decompensated cirrhosis have increased risk of developing sepsis, multiple organ failure and death. Risk factors associated with the development of infections are severe liver failure, variceal bleeding, low ascitic protein level and prior episodes of spontaneous bacterial peritonitis (SBP). The prognosis of these patients is closely related to a prompt and accurate diagnosis. An appropriate treatment decreases the mortality rates. Preventive strategies are the mainstay of the management of these patients. Empirical antibiotics should be started immediately following the diagnosis of SBP and the first-line antibiotic treatment is third-generation cephalosporins. However, the efficacy of currently recommended empirical antibiotic therapy is very low in nosocomial infections including SBP, compared to community-acquired episodes. This may be associated with the emergence of infections caused by Enterococcus faecium and extended-spectrum β-lactamaseproducing Enterobacteriaceae, which are resistant to the first line antimicrobial agents used for treatment. The emergence of resistant bacteria, underlines the need to restrict the use of prophylactic antibiotics to patients with the greatest risk of infections. Nosocomial infections should be treated with wide spectrum antibiotics. Further studies of early diagnosis, prevention and treatment are needed to improve the outcomes in patients with decompensated cirrhosis.

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“…Furthermore, another randomised controlled trial reported that primary prophylaxis with norfloxacin reduced the incidence of SBP, delayed the development of HRS and improved survival in patients with cirrhosis, ascites and either advanced liver failure or impaired renal function (13). The phosphodiesterase inhibitor, pentoxifylline, which has anti-inflammatory properties through inhibition of leukotriene and TNFα synthesis, was included in management for prevention of HRS.…”

Section: Prevention Of Hrsmentioning

confidence: 99%

An Update on Hepatorenal Syndrome

Chan¹,

Francis³

et al. 2017

jrenhep

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Hepatorenal syndrome (HRS) is one of the many potential causes of acute kidney injury (AKI) in patients with decompensated liver disease. HRS is associated with poor prognosis and represents the end-stage of a sequence of reductions in renal perfusion induced by progressively severe hepatic injury. The pathophysiology of HRS is complex with multiple mechanisms interacting simultaneously, although HRS is primarily characterised by renal vasoconstriction. A recently revised diagnostic criteria and management algorithm for AKI has been developed for patients with cirrhosis, allowing physicians to commence treatment promptly. Vasopressor therapy and other general management, such as antibiotic prophylaxis, need to be initiated whilst patients are assessed for eligibility for transplantation. Liver transplantation remains the treatment of choice for HRS but is limited by organ shortage. Other management options, such as transjugular intrahepatic portosystemic shunt, renal replacement therapy and molecular absorbent recirculating system, may provide short-term benefit for patients not responding to medical therapy whilst awaiting transplantation. Clinicians need to be aware of the pathophysiology and management principles of HRS to provide quality care for patients with multi-organ failure.

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Primary Prophylaxis of Spontaneous Bacterial Peritonitis Delays Hepatorenal Syndrome and Improves Survival in Cirrhosis

Cited by 647 publications

References 34 publications

Activated intestinal macrophages in patients with cirrhosis release NO and IL-6 that may disrupt intestinal barrier function

Activated intestinal macrophages in patients with cirrhosis release NO and IL-6 that may disrupt intestinal barrier function

Diagnosis and management of bacterial infections in decompensated cirrhosis

An Update on Hepatorenal Syndrome

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