碱性磷酸酶阈值标志着乙型肝炎的显着纤维化

StephenW

Infectious Disease Advisor Contributing Writer
February 01, 2019
Alkaline Phosphatase Threshold Marks Significant Fibrosis in Hepatitis B

Patients with chronic HBV infection are recommended to receive antiviral therapy if they have moderate to severe fibrosis, therefore staging of fibrosis in these patients is crucial. Patients with chronic HBV infection are recommended to receive antiviral therapy if they have moderate to severe fibrosis, therefore staging of fibrosis in these patients is crucial.

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(−).


Reference

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

StephenW

传染病顾问特约撰稿人
2019年2月1日
碱性磷酸酶阈值标志着乙型肝炎的显着纤维化

如果慢性HBV感染患者有中度至重度纤维化，建议接受抗病毒治疗，因此这些患者的纤维化分期至关重要。如果慢性HBV感染患者有中度至重度纤维化，建议接受抗病毒治疗，因此这些患者的纤维化分期至关重要。

根据发表在欧洲胃肠病学和肝病学杂志上的一项研究，血清碱性磷酸酶水平高于69.5 IU / L可以区分乙型肝炎e抗原阴性（HBeAg [ - ]）的慢性乙型肝炎患者的显着纤维化。使用该截断值来识别显着的纤维化可以减少所订购的肝脏活组织检查的数量。

这项研究包括191名从未接受过治疗的慢性乙型肝炎患者，104名参与者为HBeAg（+），87名为HBeAg（ - ），以及337名健康对照者。对所有参与者进行经皮肝活检，并使用Scheuer分类系统评估肝纤维化阶段;得分≥2表明显着纤维化。对于具有正态分布的数据，使用学生t检验或单向方差分析来比较连续变量的均值。对于具有非正态分布的数据，使用Mann-Whitney检验。 Fisher精确检验或卡方检验用于分析分类变量。

与健康个体相比，慢性乙型肝炎患者血清碱性磷酸酶水平显着升高。在HBeAg（ - ）的所有参与者中，这些水平随着纤维化的更高阶段而显着增加。 HBeAg（+）慢性HBV感染者的碱性磷酸酶水平变化未发现显着。碱性磷酸酶水平独立预测整组研究参与者中的显着纤维化（接受者操作曲线下的面积[AUROC] = 0.651; 95％CI，0.566-0.736），尽管它分别对HBeAg（ - ）（AUROC）进行了预测。 = 0.717; 95％CI，0.601-0.833）。在鉴定具有显着纤维化评分≥2的HBEAg（ - ）慢性乙型肝炎时，确定最佳阈值> 69.5IU / L）。

该研究的局限性包括样本量小，回顾性研究设计以及缺乏某些可接受的纤维化标志物。

研究人员得出结论，碱性磷酸酶的最佳临界值最好设定为> 69.5 IU / l，以区分HBeAg（ - ）慢性乙型肝炎和显着纤维化患者，并且这种截止可能会减少对肝脏活组织检查的需求。并指导临床治疗尚未接受过治疗的HBeAg慢性乙型肝炎患者（ - ）。


参考

胡杰张昕顾杰等血清碱性磷酸酶水平作为筛查乙型肝炎e抗原阴性慢性乙型肝炎初治患者中显着纤维化的简单而有用的试验[在线发表于2018年12月12日]。 Eur J Gastroenterol Hepatol。 doi：10.1097 / MEG.0000000000001336