Infection and the progression of hepatic encephalopathy in Acute Liver Failure

Division of Gastroenterology and Hepatology , Northwestern University, Evanston, Illinois, United States
Gastroenterology (Impact Factor: 16.72). 09/2003; 125(3):755-64. DOI: 10.1016/S0016-5085(03)01051-5
Source: PubMed

ABSTRACT Progression of hepatic encephalopathy (HE) is a major determinant of outcome in acute liver failure (ALF). Our aim was to identify predictive factors of worsening HE, including the relation of encephalopathy with the systemic inflammatory response (SIRS) and infection.
We included 227 consecutive patients with stage I-II HE prospectively enrolled in the U.S. Acute Liver Failure Study. Univariate and multivariate analysis of 27 variables at admission were performed separately for acetaminophen (n = 96) and nonacetaminophen (n = 131) etiologies.
On multivariate analysis, acquisition of infection during stage I-II HE (P < 0.01), increased leukocyte levels at admission (P < 0.01), and decreased platelet count (P < 0.05) were predictive factors of worsening HE in the acetaminophen group. By contrast, only increased pulse rate (P < 0.05) and AST levels (P < 0.05) at admission were predictors in nonacetaminophen patients. In patients who progressed to deep HE, the first confirmed infection preceded progression in 15 of 19 acetaminophen patients compared with 12 of 23 nonacetaminophen patients. In patients who did not demonstrate positive microbiologic cultures, a higher number of components of SIRS at admission was associated with more frequent worsening of HE (25% vs. 35% vs. 50% for 0, 1, and >or=2 components of SIRS, P < 0.05). CONCLUSIONA: This prospective evaluation points to infection and/or the resulting systemic inflammatory response as important factors contributing to worsening HE in ALF, mainly in patients with acetaminophen- induced ALF. The use of prophylactic antibiotics in these patients and the mechanisms by which infection triggers hepatic encephalopathy require further investigation.

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    • "Immune dysregulation is central to the pathogenesis of ALF, in which massive leucocyte infiltration of the injured liver is contrasted by a depletion and dysfunction of immune cells in the circulation [2]. From a clinical perspective, it is widely accepted that the mortality in ALF is a consequence of profound activation of systemic inflammatory responses (SIRS) and its attendant complications of recurrent sepsis and extra-hepatic organ dysfunction [3] [4]. "
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    ABSTRACT: Acute liver failure (ALF) is a condition with a high mortality and morbidity for which new treatments are desperately required. We contend that although the initial event in ALF is liver cell death, the clinical syndrome of ALF and its complications including multi-organ dysfunction and sepsis, are largely generated by the immune response to liver injury. Hepatic macrophages fulfil a diversity of roles in ALF, from pro-inflammatory to pro-resolution. Their inherent plasticity means the same macrophages may have a variety of functions depending on the local tissue environment at different stages of disease. A better understanding of the mechanisms that regulate macrophage plasticity during ALF will be an essential step towards realising the potential of immune-modulating therapies that re-orientate macrophages to promote the desirable functions of attenuating liver injury and promoting liver repair/regenerative responses. The key dynamics: temporal (early vs. late phase), regional (hepatic vs. systemic), and activation (pro-inflammatory vs. pro-resolution) are discussed and the potential for novel ALF therapies that modulate monocyte/macrophage function are described.
    Journal of Hepatology 08/2014; 61(2). DOI:10.1016/j.jhep.2014.03.031 · 11.34 Impact Factor
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    • "An interesting point of this study is that we investigated variable factors such as DM, BMI, RDW, and the SIRS score, which had not yet been applied to prediction of HA outcome. Recently, the SIRS score, the clinical manifestation of inflammation, was reported to be associated with the prognosis of ALF patients.25 Several studies have revealed that SIRS worsens the grade of HEP and increases the mortality rates as the number of SIRS fulfilled components increases. "
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    ABSTRACT: Purpose Due to the seroepidemiological shift in hepatitis A (HA), its severity, mortality, and complications have increased in recent years. Thus, the aim of this study was to identify predictive factors associated with poor prognosis among patients with HA. Materials and Methods A total of 304 patients with HA admitted to our institution between July 2009 and June 2011 were enrolled consecutively. Patients with complications defined as acute liver failure (ALF) were evaluated, and mortality was defined as death or liver transplantation. Results The mean age of patients (204 males, 100 females) was 32 years. Eighteen (5.9%) patients had progressed to ALF. Of the patients with ALF, 10 patients (3.3%) showed spontaneous survival while 8 (2.6%) died or underwent liver transplantation. Multivariate regression analysis showed that Model for End-Stage Liver Disease (MELD) and systemic inflammatory response syndrome (SIRS) scores were significant predictive factors of ALF. Based on receiver operating characteristics (ROC) analysis, a MELD ≥23.5 was significantly more predictive than a SIRS score ≥3 (area under the ROC: 0.940 vs. 0.742, respectively). In addition, of patients with a MELD score ≥23.5, King's College Hospital criteria (KCC) and SIRS scores were predictive factors associated with death/transplantation in multivariate analysis. Conclusion MELD and SIRS scores ≥23.5 and ≥3, respectively, appeared to be related to ALF development. In addition, KCC and SIRS scores ≥3 were valuable in predicting mortality of patients with a MELD ≥23.5.
    Yonsei Medical Journal 07/2014; 55(4):953-9. DOI:10.3349/ymj.2014.55.4.953 · 1.29 Impact Factor
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    • "Pathophysiologically, astrocyte metabolism of ammonia produces accumulation of osmotically active glutamine to produce brain oedema and intracranial hypertension (Haussinger et al. 1994; Cordoba et al. 1996; Tofteng et al. 2006). In patients with ALF, SIRS (often secondary to infection) correlates with advancing stages of HE and intracranial hypertension (Rolando et al. 2000; Vaquero et al. 2003). We have previously reported a correlation between intracranial hypertension and both circulating and brain levels of proinflammatory cytokines in ALF patients (Jalan et al. 2004; Wright et al. 2007a). "
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    ABSTRACT: Acute-on-chronic liver failure (ACLF) is a newly defined clinical entity with significant morbidity and mortality (~40-90 % at 1 year dependent on need for organ support at presentation). It defines a presentation with acute severe liver injury, often with multiorgan dysfunction, on a background of previously known or unknown cirrhosis. In its severest form, it is almost indistinguishable from acute liver failure, as similarly in around 5 % may rapidly progress to intracranial hypertension and cerebral oedema culminating in coma and/or death. Our understanding of such cerebral sequelae is currently limited to clinical observation, though our knowledge base is rapidly expanding since recent consensus clinical definition and guidance. Moreover, there are now animal models of ACLF and imaging modalities to better characterize events in the brain that occur with ACLF. However, as yet there has been little in the way of interventional study of this condition which are much needed. In this review we dissect existing clinical and experimental data to better characterise the manifestations of ACLF on the brain and allow for the development of targeted therapy as currently the plethora of existing interventions were designed to treat either the effects of cirrhosis or acute liver injury independently.
    Metabolic Brain Disease 05/2014; 29(4). DOI:10.1007/s11011-014-9553-0 · 2.64 Impact Factor
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