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Plasma and urine biomarkers in acute viral hepatitis E.

ABSTRACT: BACKGROUND:Hepatitis E, caused by the hepatitis E virus (HEV), is endemic to developing countries where it manifests as waterborne outbreaks and sporadic cases. Though generally self-limited with a low mortality rate, some cases progress to fulminant hepatic failure (FHF) with high mortality. With no identified predictive or diagnostic markers, the events leading to disease exacerbation are not known. Our aim is to use proteomic tools to identify biomarkers of acute and fulminant hepatitis E. RESULTS:We analyzed proteins in the plasma and urine of hepatitis E patients and healthy controls by two-dimensional Differential Imaging Gel Electrophoresis (DIGE) and mass spectrometry, and identified over 30 proteins to be differentially expressed during acute hepatitis E. The levels of one plasma protein, transthyretin, and one urine protein, alpha-1-microglobulin (alpha1m), were then quantitated by enzyme immunoassay (EIA) in clinical samples from a larger group of patients and controls. The results showed decreased plasma transthyretin levels (p < 0.005) and increased urine alpha1m levels (p < 0.001) in acute hepatitis E patients, compared to healthy controls. Preliminary results also showed lower urine zinc alpha glycoprotein levels in fulminant hepatitis E compared to acute disease; this remains to be confirmed with more fulminant cases. CONCLUSION:Our results demonstrate the utility of characterizing plasma and urine proteomes for signatures of the host response to HEV infection. We predict that plasma transthyretin and urine alpha1m could be reliable biomarkers of acute hepatitis E. Besides the utility of this approach to biomarker discovery, proteome-level changes in human biofluids would also guide towards a better understanding of host-virus interaction and disease.

SUBMITTER: Taneja S

PROVIDER: S-EPMC2773234 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Plasma and urine biomarkers in acute viral hepatitis E.

Taneja Shikha S Sen Somdutta S Gupta Vijay K VK Aggarwal Rakesh R Jameel Shahid S

Proteome science 20091027

<h4>Background</h4>Hepatitis E, caused by the hepatitis E virus (HEV), is endemic to developing countries where it manifests as waterborne outbreaks and sporadic cases. Though generally self-limited with a low mortality rate, some cases progress to fulminant hepatic failure (FHF) with high mortality. With no identified predictive or diagnostic markers, the events leading to disease exacerbation are not known. Our aim is to use proteomic tools to identify biomarkers of acute and fulminant hepatit ...[more]

PMID: 19860894

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Project description:BackgroundThe study of novel urinary biomarkers of acute kidney injury has expanded exponentially. Effective interpretation of data and meaningful comparisons between studies require awareness of factors that can adversely affect measurement. We examined how variations in short-term storage and processing might affect the measurement of urine biomarkers.Study designCross-sectional prospective.Setting & participantsHospitalized patients from 2 sites: Yale New Haven Hospital (n=50) and University of California, San Francisco Medical Center (n=36).PredictorsWe tested the impact of 3 urine processing conditions on these biomarkers: (1) centrifugation and storage at 4°C for 48 hours before freezing at -80°C, (2) centrifugation and storage at 25°C for 48 hours before freezing at -80°C, and (3) uncentrifuged samples immediately frozen at -80°C.OutcomesUrine concentrations of 5 biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), kidney injury molecule 1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), and cystatin C.MeasurementsWe measured urine biomarkers by established enzyme-linked immunosorbent assay methods. Biomarker values were log-transformed, and agreement with a reference standard of immediate centrifugation and storage at -80°C was compared using concordance correlation coefficients (CCCs).ResultsNeither storing samples at 4°C for 48 hours nor centrifugation had a significant effect on measured levels, with CCCs higher than 0.9 for all biomarkers tested. For samples stored at 25°C for 48 hours, excellent CCC values (>0.9) also were noted between the test sample and the reference standard for NGAL, cystatin C, L-FABP and KIM-1. However, the CCC for IL-18 between samples stored at 25°C for 48 hours and the reference standard was 0.81 (95% CI, 0.66-0.96).LimitationsNo comparisons to fresh, unfrozen samples; no evaluation of the effect of protease inhibitors.ConclusionsAll candidate markers tested using the specified assays showed high stability with both short-term storage at 4°C and without centrifugation prior to freezing. For optimal fidelity, urine for IL-18 measurement should not be stored at 25°C before long-term storage or analysis.

Project description:BackgroundNew renal biomarkers measured in urine promise to increase specificity for risk stratification and early diagnosis of acute kidney injury (AKI) but concomitantly may be altered by urine concentration effects and chronic renal insufficiency. This study therefore directly compared the performance of AKI biomarkers in urine and plasma.MethodsThis single-center, prospective cohort study included 110 unselected adults undergoing cardiac surgery with cardiopulmonary bypass between 2009 and 2010. Plasma and/or urine concentrations of creatinine, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), liver fatty acid-binding protein (L-FABP), kidney injury molecule 1 (KIM1), and albumin as well as 15 additional biomarkers in plasma and urine were measured during the perioperative period. The primary outcome was AKI defined by AKIN serum creatinine criteria within 72 hours after surgery.ResultsBiomarkers in plasma showed markedly better discriminative performance for preoperative risk stratification and early postoperative (within 24h after surgery) detection of AKI than urine biomarkers. Discriminative power of urine biomarkers improved when concentrations were normalized to urinary creatinine, but urine biomarkers had still lower AUC values than plasma biomarkers. Best diagnostic performance 4h after surgery had plasma NGAL (AUC 0.83), cystatin C (0.76), MIG (0.74), and L-FAPB (0.73). Combinations of multiple biomarkers did not improve their diagnostic power. Preoperative clinical scoring systems (EuroSCORE and Cleveland Clinic Foundation Score) predicted the risk for AKI (AUC 0.76 and 0.71) and were not inferior to biomarkers. Preexisting chronic kidney disease limited the diagnostic performance of both plasma and urine biomarkers.ConclusionsIn our cohort plasma biomarkers had higher discriminative power for risk stratification and early diagnosis of AKI than urine biomarkers. For preoperative risk stratification of AKI clinical models showed similar discriminative performance to biomarkers. The discriminative performance of both plasma and urine biomarkers was reduced by preexisting chronic kidney disease.

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Plasma and urine biomarkers in acute viral hepatitis E.

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Plasma and urine biomarkers in acute viral hepatitis E.

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