| Backgrounds & Aims: The relationship between non-cholestatic liver disease and bile acids(BAs)remains obscure.This study aimed to verify the relationship between serum TBA and liver injury in patients with non-cholestatic chronic hepatitis B virus(HBV)infection,and to evaluate the value of TBA-to-total cholesterol ratio(TBA/TC)in the diagnosis of cirrhosis and significant liver fibrosis.Methods: In the study of the relationship between TBA and liver injury,nine hundred twenty-two non-cholestatic chronic HBV infected patients with ALP ? 1.5 upper limit of normal(ULN)and GGT ? 3 ULN were rigorously included.Liver biopsy was performed in fifty-three patients.Inflammation grades greater than 2(G3/G4)assessed by Scheuer scoring system and Child-Pugh B/C were considered to be significant liver injury.While in the study of the relationship between TBA/TC and liver fibrosis,six hundred sixty-seven non-cholestatic chronic HBV infected patients with ALP ? 1.5 upper limit of normal(ULN)and GGT ? 3 ULN were rigorously included.Liver biopsy was performed in thirty-two patients and METAVIR scoring system was used to evaluate liver fibrosis stage.Liver ultrasound elastography was performed in one hundred and forty patients,and significant fibrosis was defined as fibrosis ? F2.Serum haematological and biochemical variables were tested.Univariable,multivariable and receiver operating characteristic(ROC)curves analyses were performed.Results: In the study of the relationship between TBA and liver injury,Compared to patients with Child-Pugh A,TBA,total bilirubin(TBIL),ALP,aspartate aminotransferase(AST)and alanine aminotransferase(ALT)were significantly higher in Child-Pugh B/C and were significantly related to Child-Pugh score,while the TBIL/TBA ratio was significantly lower(All P<0.001).In multivariate analysis,AST,ALT and TBA were independently correlated with Child-Pugh B/C [odds ratio(OR)=1.02,P<0.001;OR=0.99,P<0.001;OR=1.04,P<0.001,respectively].The area under the curve(AUC)of TBA(AUC=0.82)was significantly higher than that of AST(AUC=0.73,P<0.001)and ALT(AUC=0.63,P<0.001).Furthermore,in patients performed liver biopsy,TBA,ALP and GGT were significantly increased in G3/G4 while the TBIL/TBA ratio was significantly decreased.TBIL/TBA was independently associated with G3/G4(OR=18.33,P<0.001).The AUC of TBIL/TBA was 0.77 and approached that of TBA(AUC=0.75),however,the sensitivity of TBIL/TBA(81.08%)was higher than TBA(75.68%).While in distinguishing liver fibrosis and cirrhosis,Compared to patients with non-cirrhosis,TBA and TBA/TC were significantly higher in cirrhosis while TC was significantly lower(all P<0.001),and TBA/TC was independently associated with cirrhosis [odds ratio(OR)=1.13,95% confidence interval(CI): 1.09-1.17].The area under the curve(AUC)of TBA/TC was 0.87,which was almost equivalent to APRI(AUC=0.84)and Fib-4(AUC=0.80).But the specificity and positive predictive value of TBA/TC(83.33%,91.10%)were higher than those of APRI(73.61%,87.20%,respectively).Among the patients performed liver biopsy,TBA/TC were significantly higher both in significant fibrosis and cirrhosis as well as significantly correlated with fibrosis stage(all P<0.001;r=0.62,P<0.001).Furthermore,For identifying significant fibrosis in patients performed liver ultrasound elastography,after adjusting other factors,the OR of TBA/TC reached 0.97(95% CI: 0.95-1.00)and the AUC of TBA/TC was 0.67(P<0.001).Conclusion: Serum TBA show a close relationship with significant liver injury in chronic HBV infected patients without cholestasis.Assessment of TBA,especially TBIL/TBA,may be serve as non-invasive markers to diagnose non-cholestatic hepatic damage.Moreover,evaluation of TBA/TC could serve as an additional marker to distinguish significant liver fibrosis and cirrhosis in non-cholestatic chronic HBV infection. |
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