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


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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Available from: Javier Vaquero,
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    • "There is increasing evidence suggesting that the predominant mechanism responsible for the development of cerebral edema/multiorgan failure in ALF is activation of the systemic immune response, through release of proinflammatory cytokines and damage-associated molecular patterns (DAMPs) as a result of massive hepatocyte necrosis, which in turn plays a pivotal role in the clinical course and outcome in ALF patients [4]. Large studies have demonstrated that the presence of the systemic inflammatory response syndrome (SIRS) in ALF is associated with a worsening of HE and poor prognosis [5]. Traditionally, support of the ALF patient, particularly in acetaminophen-ALF, has been based on hemodynamic , neuroprotective, and renal replacement therapy, with the goal of either bridging to hepatic recovery or to liver transplantation (LT). "

    Journal of Hepatology 09/2015; DOI:10.1016/j.jhep.2015.09.010 · 11.34 Impact Factor
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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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