Ablation of very-long-chain
ceramides (Cers) with consecutive elevations in
sphinganine levels has been shown to cause a severe hepatopathy in a knockout mouse model. We have recently shown that serum
sphingolipids (SLs) are deregulated in patients with chronic
liver disease. However, their role as possible
biomarkers in
liver fibrosis remains to date unexplored. We assessed, using liquid chromatography/tandem mass spectrometry, serum concentrations of various SL metabolites in 406 patients with chronic viral
hepatitis, 203 infected with genotype 1 hepatitis C virus (HCV) and 203 with hepatitis B virus (HBV), respectively. We observed significant variations of serum SLs, with
sphingosine and
sphinganine being, both in univariate (P<0.05) as well as in multivariate analysis, significantly associated to severity of
liver fibrosis in HCV-infected patients (odds ratio [OR]: 1.111; confidence interval [CI]: 1.028-1.202; P=0.007 and OR, 0.634; CI, 0.435-0.925; P=0.018, respectively). Serum SLs correlated significantly with serum
triglyceride and
cholesterol levels as well as with
insulin resistance, defined by the homeostatic model assessment index, in HCV patients. Sustained viral response rates in HCV patients were independently predicted by serum C24Cer (OR, 0.998; CI, 0.997-0.999; P=0.001), its unsaturated derivative C24:1Cer (OR, 1.001; CI, 1.000-1.002; P=0.059), and C18:1Cer (OR, 0.973; CI, 0.947-0.999; P=0.048), together with
ferritin (OR, 1.006; CI, 1.003-1.010; P<0.001),
alkaline phosphatase (OR, 1.020; CI, 1.001-1.039; P=0.032), and interleukin-28B genotype (OR, 9.483; CI, 3.139-28.643; P<0.001).
CONCLUSION: