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

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


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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Chromatography, Liquid
  • Female
  • Genotype*
  • Hepatitis B e Antigens
  • Hepatitis B virus* / genetics
  • Hepatitis B virus* / metabolism
  • Hepatitis B, Chronic / blood*
  • Hepatitis B, Chronic / genetics*
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Sphingolipids / blood*
  • Tandem Mass Spectrometry


  • Hepatitis B e Antigens
  • Sphingolipids