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血清神经酰胺水平与 HBeAg 阴性乙型肝炎病毒感染患者队列中的病毒学事件和乙型肝炎病毒基因型 D 相关。

Serum sphingolipid levels associate with upcoming virologic events and HBV genotype D in a cohort of patients with HBeAg-negative HBV infection.

机构信息

Universitätsklinikum Frankfurt, Frankfurt am Main, Germany.

Pharmazentrum Frankfurt, Institut für Allgemeine Pharmakologie, Frankfurt am Main, Germany.

出版信息

PLoS One. 2018 Nov 15;13(11):e0207293. doi: 10.1371/journal.pone.0207293. eCollection 2018.

Abstract

OBJECTIVES

Sphingolipids (SLs) have been implicated as potent regulators of the hepatitis B virus (HBV) life cycle. We investigated the SL biomarker potential regarding virologic endpoints in a prospective subgroup of patients with HBeAg-negative chronic HBV infection.

METHODS

From 2009-2016 98 patients with HBeAg-negative HBV infection were prospectively followed over four years. Clinical, laboratory and imaging data were evaluated annually. SLs were assessed in available serum probes via liquid chromatography coupled to tandem mass spectrometry.

RESULTS

Of those 98 patients, 10 (10.2%) showed HBV reactivation, 13 (13.2%) lost HBsAg and 9 (9.1%) gained status of HBsAg-/HBsAb-coexistence, whereas 66 (67.3%) had no events. Within the four-year analysis sphingosine (p = 0.020), sphinganine (p<0.001), dhS1P (p<0.001), C16DHC (p<0.01) and C20Cer (p<0.001) showed a significant upregulation in patients without virologic events, C18Cer significantly decreased (p<0.001). At baseline decreased S1P-, dhS1P- and C16Cer-levels were observed in patients with upcoming status of HBsAg-/HBsAb-coexistence. S1P and dhS1P levels were elevated HBV genotype D infected patients.

CONCLUSIONS

In a prospective cohort of patients with a HBeAg-negative HBV infection, serum SLs associated with the virologic course and HBV genotype D. Further studies are required to elucidate SLs as potential novel predictors of the course of HBeAg-negative HBV infection.

摘要

目的

神经酰胺(SL)已被认为是乙型肝炎病毒(HBV)生命周期的有效调节剂。我们研究了在 HBeAg 阴性慢性 HBV 感染的前瞻性亚组患者中,SL 生物标志物在病毒学终点方面的潜力。

方法

2009 年至 2016 年,我们前瞻性地随访了 98 例 HBeAg 阴性 HBV 感染患者,随访时间为四年。每年评估临床、实验室和影像学数据。通过液相色谱-串联质谱法在可用的血清探针中评估 SL。

结果

在这 98 例患者中,有 10 例(10.2%)发生 HBV 再激活,13 例(13.2%)失去 HBsAg,9 例(9.1%)获得 HBsAg-/HBsAb 共存状态,而 66 例(67.3%)无事件发生。在四年分析中,在无病毒学事件的患者中,神经鞘氨醇(p=0.020)、神经鞘氨醇(p<0.001)、dhS1P(p<0.001)、C16DHC(p<0.01)和 C20Cer(p<0.001)均呈显著上调,C18Cer 则显著下调(p<0.001)。在即将发生 HBsAg-/HBsAb 共存状态的患者中,基线时 S1P、dhS1P 和 C16Cer 水平降低。HBV 基因型 D 感染患者 S1P 和 dhS1P 水平升高。

结论

在 HBeAg 阴性 HBV 感染患者的前瞻性队列中,血清 SL 与病毒学过程和 HBV 基因型 D 相关。需要进一步研究阐明 SL 是否可以作为 HBeAg 阴性 HBV 感染过程的潜在新型预测指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c0/6237377/48e21f859fa9/pone.0207293.g001.jpg

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