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Serum sphingolipids reflect the severity of chronic HBV infection and predict the mortality of HBV-acute-on-chronic liver failure.

ABSTRACT: Patients with HBV-acute-on-chronic liver failure (HBV-ACLF) have high mortality and frequently require liver transplantation; few reliable prognostic markers are available. As a class of functional lipids, sphingolipids are extensively involved in the process of HBV infection. However, their role in chronic HBV infection remains unknown. The aim of this study was to determine the serum sphingolipid profile in a population of patients with chronic HBV infection, paying special attention to exploring novel prognostic markers in HBV-ACLF. High performance liquid chromatography tandem mass spectrometry was used to examine the levels of 41 sphingolipids in 156 serum samples prospectively collected from two independent cohorts. The training and validation cohorts comprised 20 and 28 healthy controls (CTRL), 29 and 23 patients with chronic hepatitis B (CHB), and 30 and 26 patients with HBV-ACLF, respectively. Biometric analysis was used to evaluate the association between sphingolipid levels and disease stages. Multivariate analysis revealed difference of sphingolipid profiles between CHB and HBV-ACLF was more drastic than that between CTRL and CHB, which indicated that serum sphingolipid levels were more likely to associate with the progression HBV-ACLF rather than CHB. Furthermore, a 3-month mortality evaluation of HBV-ACLF patients showed that dhCer(d18 : 0/24 : 0) was significantly higher in survivors than in non-survivors (including deceased patients and those undergoing liver transplantation, p < 0.05), and showed a prognostic performance similar to that of the MELD score. The serum sphingolipid composition varies between CTRL and chronic HBV infection patients. In addition, dhCer(d18 : 0/24 : 0) may be a useful prognostic indicator for the early prediction of HBV-ACLF.

SUBMITTER: Qu F

PROVIDER: S-EPMC4138167 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Serum sphingolipids reflect the severity of chronic HBV infection and predict the mortality of HBV-acute-on-chronic liver failure.

Qu Feng F Zheng Su-Jun SJ Liu Shuang S Wu Cai-Sheng CS Duan Zhong-Ping ZP Zhang Jin-Lan JL

PloS one 20140819 8

Patients with HBV-acute-on-chronic liver failure (HBV-ACLF) have high mortality and frequently require liver transplantation; few reliable prognostic markers are available. As a class of functional lipids, sphingolipids are extensively involved in the process of HBV infection. However, their role in chronic HBV infection remains unknown. The aim of this study was to determine the serum sphingolipid profile in a population of patients with chronic HBV infection, paying special attention to explor ...[more]

PMID: 25136927

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Project description:BackgroundAlthough the Asian Pacific Association for the Study of the Liver acute-on-chronic liver failure (ACLF) research consortium (AARC) ACLF score is easy to use in patients with hepatitis b virus-related ACLF (HBV-ACLF), serum lactate is not routinely tested in primary hospitals, and its value may be affected by some interference factors. Neutrophil-to-lymphocyte ratio (NLR) is used to assess the status of bacterial infection (BI) or outcomes in patients with various diseases. We developed an NLR-based AARC ACLF score and compared it with the existing model.MethodsA total of 494 HBV-ACLF patients, enrolled in four tertiary academic hospitals in China with 90-day follow-up, were analysed. Prognostic performance of baseline NLR and lactate were compared between cirrhotic and non-cirrhotic subgroups via the receiver operating curve and Kaplan-Meier analyses. A modified AARC ACLF (mAARC ACLF) score using NLR as a replacement for lactate was developed (n = 290) and validated (n = 204).ResultsThere were significantly higher baseline values of NLR in non-survivors, patients with admission BI, and those with higher grades of ACLF compared with the control groups. Compared with lactate, NLR better reflected BI status in the cirrhotic subgroup, and was more significantly correlated with CTP, MELD, MELD-Na, and the AARC score. NLR was an independent predictor of 90-day mortality, and was categorized into three risk grades (< 3.10, 3.10-4.78, and > 4.78) with 90-day cumulative mortalities of 8%, 21.2%, and 77.5% in the derivation cohort, respectively. The mAARC ACLF score, using the three grades of NLR instead of corresponding levels of lactate, was superior to the other four scores in predicting 90-day mortality in the derivation (AUROC 0.906, 95% CI 0.872-0.940, average P < 0.001) and validation cohorts (AUROC 0.913, 95% CI 0.876-0.950, average P < 0.01), with a considerable performance in predicting 28-day mortality in the two cohorts.ConclusionsThe prognostic value of NLR is superior to that of lactate in predicting short-term mortality risk in cirrhotic and non-cirrhotic patients with HBV-ACLF. NLR can be incorporated into the AARC ACLF scoring system for improving its prognostic accuracy and facilitating the management guidance in patients with HBV-ACLF in primary hospitals.

Project description:To validate prognostic scores for acute decompensation of cirrhosis and acute-on-chronic liver failure in Brazilian patients.This is a prospective cohort study designed to assess the prognostic performance of the chronic liver failure-consortium (CLIF-C) acute decompensation score (CLIF-C AD) and CLIF-C acute-on-chronic liver failure score (CLIF-C ACLF), regarding 28-d and 90-d mortality, as well as to compare them to other prognostic models, such as Model for End-Stage Liver Disease (MELD), MELD Sodium (MELD-Na), Child-Pugh (CP) score, and the CLIF-C Organ Failure score (CLIF-C OF). All participants were adults with acute decompensation of cirrhosis admitted to the Emergency Department of a tertiary hospital in southern Brazil. Prognostic performances were evaluated by means of the receiver operating characteristic (ROC) curves, area under the curves (AUC) and 95%CI.One hundred and thirteen cirrhotic patients were included. At admission, 18 patients had acute-on-chronic liver failure (ACLF) and 95 individuals had acute decompensation (AD) without ACLF, of which 24 eventually developed ACLF during the course of hospitalization (AD evolving to ACLF group). The AD group had significantly lower 28-d (9.0%) and 90-d (18.3%) mortality as compared to the AD evolving to ACLF group and to the ACLF group (both P < 0.001). On the other hand, 28-d and 90-d mortalities were not significantly different between AD evolving to ACLF group and ACLF group (P = 0.542 and P = 0.708, respectively). Among patients with ACLF, at 28 d from the diagnosis, CLIF-C ACLF was the only score able to predict mortality significantly better than the reference line, with an AUC (95%CI) of 0.71 (95%CI: 0.54-0.88, P = 0.021). Among patients with AD, all prognostic scores performed significantly better than the reference line regarding 28-d mortality, presenting with similar AUCs: CLIF-C AD score 0.75 (95%CI: 0.63-0.88), CP score 0.72 (95%CI: 0.59-0.85), MELD score 0.75 (95%CI: 0.61-0.90), MELD-Na score 0.76 (95%CI: 0.61-0.90), and CLIF-C OF score 0.74 (95%CI: 0.60-0.88). The same occurred concerning AUCs for 90-d mortality: CLIF-C AD score 0.70 (95%CI: 0.57-0.82), CP score 0.73 (95%CI: 0.62-0.84), MELD score 0.71 (95%CI: 0.59-0.83), MELD-Na score 0.73 (95%CI: 0.62-0.84), and CLIF-C OF score 0.65 (95%CI: 0.52-0.78).This study demonstrated that CLIF-C ACLF is the best available score for the prediction of 28-d mortality among patients with ACLF. CLIF-C AD score is also useful for the prediction of mortality among cirrhotic patients with AD not fulfilling diagnostic criteria for ACLF, but it was not superior to other well-established prognostic scores.

Project description:BACKGROUNDHBV-related acute-on-chronic liver failure (HBV-ACLF) is hallmarked by high short-term mortality rates, calling for accurate prognostic biomarkers for initial risk stratification.METHODSThree tandem mass tag-labeled (TMT-labeled) quantitative proteomic studies were performed on 10 patients with HBV-related acute hepatic decompensation and on 20 patients with HBV-ACLF. Candidate biomarkers were preliminarily verified in a cross-sectional cohort (n = 144) and further confirmed in 2 prospective cohorts (n = 207 and n = 148).RESULTSPlasminogen, a potential prognostic biomarker for HBV-ACLF, was identified by TMT quantitative proteomics and preliminarily verified in the cross-sectional cohort. Further validation with a prospective cohort (n = 207) showed that plasminogen levels at admission were significantly lower (P < 0.001) in HBV-ACLF nonsurvivors than in survivors. The cumulative survival duration of patients with high plasminogen levels was significantly longer (P < 0.001) than that of patients with low plasminogen levels. During hospitalization, plasminogen levels significantly decreased (P = 0.008) in the deterioration group but significantly increased (P < 0.001) in the improvement group. Additionally, plasminogen levels gradually increased in survivors but gradually decreased in nonsurvivors. The P5 score, a prognostic panel incorporating plasminogen levels, hepatic encephalopathy occurrence, age, international normalized ratio (INR), and total bilirubin, was significantly superior to the Child-Pugh, Model for End-stage Liver Disease (MELD), Chronic Liver Failure Consortium ACLF (CLIF-C ACLF), Chinese Group on the Study of Severe Hepatitis B (COSSH), and HINT (a prognostic score based on hepatic encephalopathy occurrence, INR, neutrophil count, and thyroid-stimulating hormone) scores (all P < 0.05). The performances of the plasminogen level and P5 score were validated in a second multicenter, prospective cohort (n = 148).CONCLUSIONSPlasminogen is a promising prognostic biomarker for HBV-ACLF, and sequential plasminogen measurements could profile the clinical course of HBV-ACLF. P5 is a high-performance prognostic score for HBV-ACLF.FUNDINGThe National Key Research and Development Program (2017YFC1200204); the National Natural Science Foundation of China (81400589, 81600497); the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (81121002); the Chinese High-Tech Research and Development Programs (2012AA020204); the National S&T Major Project (2012ZX10002004); and the Zhejiang Provincial Medicine and Health Science and Technology Project (2016147735).

Dataset Information

Serum sphingolipids reflect the severity of chronic HBV infection and predict the mortality of HBV-acute-on-chronic liver failure.

Publications

Serum sphingolipids reflect the severity of chronic HBV infection and predict the mortality of HBV-acute-on-chronic liver failure.

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