Alkaline Phosphatase Threshold Marks Significant Fibrosis in Hepatitis B

Levels of serum alkaline phosphatase above 69.5 IU/L can distinguish significant fibrosis in individuals with chronic HBV who are e-antigen-negative.

Levels of serum alkaline phosphatase above 69.5 IU/L can distinguish significant fibrosis in individuals with chronic hepatitis B who are hepatitis B e-antigen-negative (HBeAg[-]), according to a study published in the European Journal of Gastroenterology & Hepatology. Using this cutoff value to identify significant fibrosis could decrease the number of liver biopsies ordered.

This study included 191 participants with chronic hepatitis B who had never received treatment, 104 participants were HBeAg(+) and 87 were HBeAg(−), as well as 337 healthy controls. A percutaneous liver biopsy was performed on all participants, and the Scheuer classification system was used to score liver fibrosis stages; scores ≥2 were indicative of significant fibrosis. For data with a normal distribution, a Student’s t-test or one-way variance analysis was used to compare means for continuous variables. For data with a non-normal distribution, the Mann-Whitney test was used. The Fisher’s exact test or chi-square test were used to analyze categorical variables.

Levels of serum alkaline phosphatase were significantly higher among those with chronic hepatitis B compared with healthy individuals. These levels increased significantly with higher stages of fibrosis in all participants who were HBeAg(–). Changes in alkaline phosphatase levels in participants with chronic HBV infection who were HBeAg(+) were not found to be significant. Alkaline phosphatase level independently predicted significant fibrosis in the entire set of study participants (area under receiver operator curve [AUROC]=0.651; 95% CI, 0.566-0.736), although it did so separately for those who were HBeAg(–) (AUROC=0.717; 95% CI, 0.601-0.833). In identifying HBEAg(–) chronic hepatitis B with significant fibrosis score ≥2, the optimal threshold value was determined to be >69.5 IU/L).

Limitations of this study included its small sample size, a retrospective study design, and a lack of certain accepted markers of fibrosis.

The study researchers concluded that the optimal cut-off value of alkaline phosphatase  may best be set at >69.5 IU/l for distinguishing patients with HBeAg(−) chronic hepatitis B and significant fibrosis and that this cutoff may potentially reduce the need for liver biopsies and help to guide the clinical management of treatment-naïve patients  with chronic hepatitis B who were HBeAg(−).

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Hu J, Zhang X, Gu J, et al. Serum alkaline phosphatase levels as a simple and useful test in screening for significant fibrosis in treatment-naive patients with hepatitis B e-antigen negative chronic hepatitis B [published online December 12, 2018]. Eur J Gastroenterol Hepatol. doi: 10.1097/MEG.0000000000001336