Infection and the progression of hepatic encephalopathy in acute liver failure
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.
SourceAvailable from: Afaf Saleh
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ABSTRACT: Hepatic encephalopathy (HE) is a neuropsychiatric disorder seen in patients with advanced liver disease or porto-systemic shunts. Based on etiology and severity of HE, the World Congress of Gastroenterology has divided HE into categories and sub-categories. Many user-friendly computer-based neuropsychiatric tests are being validated for diagnosing covert HE. Currently, emphasis is being given to view HE deficits as a continuous spectrum rather than distinct stages. Ammonia is believed to play crucial role in pathogenesis of HE via astrocyte swelling and cerebral edema. However, evidence has been building up which supports the synergistic role of oxidative stress, inflammation and neurosteroids in pathogenesis of HE. At present, treatment of HE aims at decreasing the production and intestinal absorption of ammonia. But as the role of new pathogenetic mechanisms becomes clear, many potential new treatment strategies may become available for clinician.09/2011; 1(2):77-86. DOI:10.1016/S0973-6883(11)60126-6
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ABSTRACT: Systemic inflammation may affect the brain by aggravating the stage of encephalopathy and increasing intracranial pressure (ICP) especially if liver insufficiency with hyperammonemia is present. The aim of this study was to determine if the influence of concomitant hyperammonemia and lipopolysaccharide (LPS) on the brain can be prevented by dexamethasone and cyclooxygenase (COX) inhibitors. Fifty-four male Wistar rats, 6 in each group, were divided into the following groups: Saline+saline; LPS (2mg/kg)+saline; LPS+indomethacin (10mg/kg); LPS+diclofenac (10mg/kg); LPS+dexamethasone (2mg/kg) in experiment A. Experiment-B included the following groups: LPS+NH3 (140μmol/kg/min)+saline; LPS+NH3+indomethacin; LPS+NH3+diclofenac and LPS+NH3+dexamethasone. ICP was monitored via a catheter placed in cisterna magna and changes in CBF were recorded by laser Doppler flowmetry. LPS with and without NH3 induced a similar increase in plasma 6-keto-prostaglandin-F1α (6-keto-PGF1α) concentration together with a concomitant rise in CBF and ICP. Indomethacin and diclofenac prevented the increase in ICP by LPS alone, and with the addition of NH3 the increase in both CBF and ICP, which was associated with a decrease in 6-keto-PGF1α. Dexamethasone only reduced the LPS induced increase in ICP but not CBF, and partly the 6-keto-PGF1α plasma concentration in the combined setup. These data indicate that activation of cycloooxygenases is of central importance for development of cerebral hyperemia and high ICP during concomitant systemic inflammation and hyperammonemia.PLoS ONE 02/2015; 10(2):e0117416. DOI:10.1371/journal.pone.0117416 · 3.53 Impact Factor