Patients with acute on chronic liver failure display ‘sepsis-like’ immune paralysis

Wasmuth, Hermann E.; Kunz, Dagmar; Yagmur, Eray; Timmer-Stranghöner, Annette; Vidacek, Daniel; Siewert, Elmar; Bach, Jens; Geier, Andreas; Purucker, Edmund; Gressner, A. M.; Matern, Siegfried; Lammert, Frank

doi:10.1016/j.jhep.2004.10.019

Cited by 477 publications

(459 citation statements)

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“…This phenomenon might be associated with 'sepsis-like' immune paralysis. 22 In sepsis, the downregulation of HLA-DR expression and the reduction of TNF-a levels have been identified, 23 and dysfunction of neutrophils was also reported to be associated with acquisition of nosocomial infection, 24 should aim to elucidate the mechanism underlying C5a-induced immune paralysis.…”

Section: Discussionmentioning

confidence: 99%

Complement 5a receptor-mediated neutrophil dysfunction is associated with a poor outcome in sepsis

Lin

Bao

et al. 2015

Cell Mol Immunol

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Section: Discussionmentioning

confidence: 99%

Complement 5a receptor-mediated neutrophil dysfunction is associated with a poor outcome in sepsis

Lin

Bao

et al. 2015

Cell Mol Immunol

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“…Moreover, it is notable that patients with chronic liver disease are less likely than those in the general population to be identified by either modality because of diminished cellular responses associated with cirrhosis. [14][15][16] Because both QFT and TST measure the cellular immune response to M. tuberculosis, testing with QFT is unlikely to be helpful in patients with a negative TST related to defective cellular immune responses. 11,12 The full evaluation of a patient with cirrhosis before liver transplantation should be thorough and include a detailed medical and exposure history and a review of chest radiography (see the section on the evaluation of transplant candidates and donors).…”

Section: Diagnosis Latent Tbmentioning

confidence: 99%

Mycobacterium tuberculosis infection in liver transplantation

Yehia

Blumberg

2010

Liver Transpl

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Mycobacterium tuberculosis can cause significant infections in liver transplant candidates and recipients. Its nonspecific clinical features and prolonged growth time in culture make the diagnosis difficult, and treating tuberculosis (TB) remains challenging because of significant toxicities and drug-drug interactions. The diagnosis of a latent TB infection may be accomplished with tuberculin skin testing and with the newer interferon-c release assays, although this infection may be underrecognized because of host factors. Latent TB should be treated, but the degree of liver failure and the likelihood of progression to active TB will dictate whether this should occur before or after transplantation. Patients who have a history of TB, have used muromonab-CD3 or anti-T lymphocyte antibodies, or have experienced allograft rejection or coinfection with cytomegalovirus, Pneumocystis jiroveci, or Nocardia are at the greatest risk of developing active TB. Active TB in transplant patients is difficult to treat because of drug-induced hepatotoxicity and the significant interaction between rifampin and calcineurin inhibitors. In this article, we review the epidemiology, clinical features, and evaluation of transplant candidates and recipients. In addition, we offer recommendations on the appropriate diagnostic and treatment regimens for patients with latent and active TB infections. Liver Transpl 16:1129-1135, 2010. V C 2010 AASLD.Received April 5, 2010; accepted July 6, 2010.Tuberculosis (TB) is a serious global infection with an estimated prevalence of 13.7 million cases worldwide. 1 Transplant recipients have a 36-to 74-fold higher risk of developing TB versus the general population. 2 TB in liver transplant recipients presents unique challenges, including a delayed diagnosis secondary to insensitive testing and treatment complications due to antituberculous drug toxicities and interactions with immunosuppressive agents. This review focuses on the epidemiology, clinical features, diagnosis, clinical evaluation, and treatment of liver transplant patients infected with TB. EPIDEMIOLOGYRates of 0.47% to 2.3% for active TB in adult liver transplant recipients has been reported. [2][3][4][5] Because of the difficulty of accurately diagnosing symptomatic TB, these figures most likely underestimate the burden of the disease. In addition, the frequency of the disease varies geographically, with particular regions (Asia and Africa) having a higher prevalence than other areas of the world. 6 Several factors place transplant patients at greater risk of developing active TB.A previous TB infection increases the likelihood of TB developing after transplantation. 5 The RESITRA (Spanish Network of Infection in Transplantation) cohort documented a relative risk of 4.3 for the development of symptomatic TB when the purified protein derivative (PPD) test was positive instead of negative. 4 In a systematic review of 139 cases of active TB infection after liver transplantation, 37% had a positive tuberculin skin test (TST), 23% had abnorm...

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“…21 Recently, reduced monocyte HLA-DR expression has been reported in patients with septic decompensation of acute-on-chronic liver failure. 26 Acetaminophen-induced acute liver failure (AALF) is characterized by progressive vasodilatory shock and multiple organ failure and shares striking similarities with septic shock. [27][28][29] Both conditions result in uncontrolled activation of the inflammatory cascade, despite being triggered by different events.…”

Section: S Ystemic Inflammatory Response Syndrome (Sirs) Ismentioning

confidence: 99%

Reduced monocyte HLA-DR expression: A novel biomarker of disease severity and outcome in acetaminophen-induced acute liver failure

et al. 2006

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Acute liver failure (ALF) shares striking similarities with septic shock where a decrease in HLA-DR expression on monocytes is associated with disease severity and predicts outcome. We investigated monocyte HLA-DR expression in ALF in relation to inflammatory mediator levels and clinical outcome. Monocyte HLA-DR expression was determined in 50 patients with acetaminophen-induced ALF (AALF) and 20 non-acetaminophen-induced ALF (NAALF). AALF patients were divided into dead/transplanted (AALF-NS, n ‫؍‬ 26) and spontaneous survivors (AALF-S, n ‫؍‬ 24). Fifty patients with chronic liver disease (CLD) and 50 healthy volunteers served as controls. Monocyte HLA-DR expression was determined by double-color flow-cytometry with monoclonal antibodies detecting HLA-DR and monocyte specific CD14. Serum levels of interleukin (IL) -4, -6, -10, tumor necrosis factor (TNF)-␣ and interferon (IFN)-␥ were concomitantly measured by ELISA. Compared to healthy volunteers (75%) and CLD (67%) monocyte HLA-DR percentage expression was lower in AALF (15%, P < .001) and NAALF (22 %, P < .001). Compared to AALF-S, AALF-NS had lower monocyte HLA-DR % (11% vs. 36%, P < .001) and higher levels of IL-4, IL-6, IL-10 and TNF-␣ (P < .001). HLA-DR percentage negatively correlated with INR, blood lactate, pH and levels of encephalopathy (r ‫؍‬ ؊0.8 to ؊0.5, P < .01), IL-10 (r ‫؍‬ ؊0.8, P < .0001), TNF-␣ (r ‫؍‬ ؊0.4, P ‫؍‬ .02). HLA-DR percentage level <15% has a 96% sensitivity and 100% specificity and 98% accuracy in predicting poor prognosis. In conclusion, the strong relationship of monocyte HLA-DR expression with indices of disease severity, mediators of inflammation and outcome indicates a key role for this molecule as a biomarker of disease severity and prognosis. (HEPATOLOGY 2006;44:34-43.)

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Patients with acute on chronic liver failure display ‘sepsis-like’ immune paralysis

Cited by 477 publications

References 48 publications

Complement 5a receptor-mediated neutrophil dysfunction is associated with a poor outcome in sepsis

Complement 5a receptor-mediated neutrophil dysfunction is associated with a poor outcome in sepsis

Mycobacterium tuberculosis infection in liver transplantation

Reduced monocyte HLA-DR expression: A novel biomarker of disease severity and outcome in acetaminophen-induced acute liver failure

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