The Predictive Value Of Serum Total Bile Acid For The Indication Of Antiviral Therapy In Chronic Hepatitis B Patients With High HBV DNA And Normal Or Mildly Elevated ALT Levels

Aim: To evaluate the predictive value of serum total bile acid(TBA)levels for the indication of antiviral therapy in chronic hepatitis B(CHB)patients with high HBV DNA and normal or mild elevation of alanine transaminase(ALT).Methods: A total of 370 patients with CHB admitted to The Second Affiliated Hospital of Anhui Medical University were collected,including 273 patients with hepatitis B virus e antigen(HBeAg)-positive and 97 HBeAg-negative patients.The criteria for determining high HBV-DNA load were based on the Guidelines for the Prevention and Treatment of Chronic Hepatitis B(2015 edition): HBeAg-positive ≥ 20,000 IU/m L;HBeAg-negative ≥ 2,000 IU/m L;mildly elevated ALT was defined as ≤ 2 times the upper-limit of normal(ULN).Case information was collected from patients before liver biopsy,and the Scheuer scoring system was used to grade liver inflammation(G)and fibrosis stage(S).Patients were divided into two groups,G < 2 and S < 2(< G/S2 group)and G ≥ 2 or/and S ≥ 2(≥ G/S2 group).The correlation between TBA and inflammation or fibrosis was analyzed using Spearman’s correlation test with commonly used laboratory indicators of liver function as controls.The ROC and area under the curve(AUC)were used to compare and evaluate the predictive value of TBA with other non-invasive models such as APRI,FIB-4 and RPR for significant histological lesions of the liver(≥ G/S2)and indications for antiviral therapy.Finally,the corresponding best cut-off values,sensitivity,specificity,positive predictive value(PPV)and negative predictive value(NPV)were calculated.Statistical significance was defined as P < 0.05.RESULTS: The differences in TBA levels and APRI,FIB-4 and RPR scores between the HBeAg-positive and negative groups and between the HBeAg-positive < G/S2 and≥ G/S2 groups were statistically significant(P < 0.05),but only the differences in TBA levels between the < G/S2 and ≥ G/S2 groups in HBeAg-negativewere statistically significant(P < 0.05).Serum TBA levels were correlated with the grade of liver inflammation or fibrosis in both HBeAg-positive and negative groups.In HBeAg-positive group,the AUC(95% CI)for serum TBA to discriminate < G/S2 from≥G/S2 was 0.61(0.55-0.67),lower than APRI [0.74(0.69-0.79)],FIB-4 [0.70(0.64-0.75)] and RPR [0.68(0.62-0.73)] with a cut-off value of 8.00 μmol/L and sensitivity,specificity,PPV and NPV of 60.98%,57.86%,41.46% and 75.19%,respectively.While in HBeAg-negative group,the AUC(95% CI)for TBA to discriminate < G/S2 from≥G/S2 was 0.72(0.61-0.81),higher than APRI [0.60(0.50-0.70)],FIB-4 [0.57(0.46-0.67)] and RPR [0.54(0.43-0.67)] with a sensitivity of 67.35%,specificity of 71.05%,PPV and NPV of 75.99% and 61.54%,respectively,and optimal cut-off value of5.40μmol/L.CONCLUTION: Serum TBA has some predictive value in the indication for antiviral therapy in HBeAg-negative CHB patients with high HBV DNA and normal or mildly elevated ALT levels.