Serum Lipidomic Study Of Patients With Chronic Hepatitis B And Fatty Liver

Objective:Our study aims to explore the lipidomic feature of non-alcoholic fatty liver disease（NAFLD）and chronic hepatitis B（CHB）patients with or without fatty liver,and explore the specific non-invasive biomarkers of non-alcoholic steatohepatitis（NASH）in CHB patients.Methods:Serum lipidomic profiles of healthy controls（n=23）,biopsy-proven NAFLD patients（n=42）,CHB without FL（n=17）and CHB with FL patients（n=22）were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry.Lipidomic signatures were compared by orthogonal partial least squares-discriminant analysis（OPLS-DA）.Significant changed lipids were identified combined with univariate analysis.Correlations between lipids and histologic score were performed by spearman correlation analysis.Diagnostic value was analyzed using receiver operating characteristic（ROC）curve.Results:239 lipid species were identified and quantified.There were distinct serum lipid profiles between the control group,NAFLD group and CHB without FL group(OPLS-DA:NAFLD and control:R2Y=0.907,Q2=0.647,P=3.748e-8;NAFLD and CHB without FL R2Y=0.775,Q2=0.518,P=2.81×10^-4;NAFLD and CHB without FL:R2Y=0.961,Q2=0.587,P=1.238e-4).The subjects of CHB with FL overlapped with the subjects of NAFLD and CHB without FL and the lipid alteration was closer to NAFLD group.Compared to the control group,most of the neutral lipids and ceramide were elevated in the NAFLD group,but decreased in the CHB without FL group.Plasmalogens were decreased both groups.The monounsaturated fatty acids were increased in both groups,and were positively correlated with the CHB inflammation and fibrosis scores（Spearman r=0.527,P=0.036 in activity,r=0.540,P=0.032 in fibrosis）.The NAFLD group was mainly characterized with the increased TAGs of lower carbon numbers and double bonds,while the CHB without FL group was characterized by decreased TAG with higher carbon numbers and double bonds.The monounsaturated TAG was significant predictor of NASH（OR=3.215;95%CI:1.663-6.331,P=0.001）and positively correlated with NASH histological activity（r=0.501,P<0.001）.It showed good predictability for NASH in NAFLD patients（AUROC=0.831;95%CI 0.696-0.966）and validated in CHB patients（AUROC=0.833;95%CI 0.698-0.969）by derived cutoffs,which was superior to that of cytokeratin-18（CK-18）and alanine transaminase（ALT）.Conclusions:There were distinct serum lipidome in patients with NAFLD and CHB without FL,providing evidence for the impact on lipid metabolism of HBV infection.The increase of monounsaturated TAG might be specific non-invasive marker for NASH in NAFLD and CHB patients.