基于707例肝穿结果探讨慢性HBV感染者启动抗病毒治疗丙氨酸转氨酶阈值的研究

Exploration on ALT threshold for initiating antiviral therapy in chronic HBV-infected patients based on results of 707 liver puncture cases

目的探讨HBV感染者启动抗病毒治疗的丙氨酸转氨酶(alanine aminotransferase,ALT)阈值,为慢性HBV感染者启动抗病毒治疗提供依据。方法回顾性收集2013年10月—2018年8月在延安大学附属医院感染病科住院并经肝活检的未经治疗的慢性HBV感染者707例。在B超引导下采用美国巴德公司16G一次性穿刺针获取肝组织,采用国际上常用的METAVIR评分系统分为轻度肝组织损伤组和明显肝组织损伤组,分别检测ALT水平,采用Mann-Whitney U检验和受试者工作特征(ROC)曲线评估ALT在不同人口学特征下对明显肝组织损伤的诊断价值。结果707例患者中,292例(41.30%)肝穿证实存在明显肝组织损伤(METAVIR≥A2和/或F2);ALT的ULN在分别以NICE标准(男30 U/L,女19 U/L)、AASLD标准(男35 U/L,女25 U/L)、EASL或APASL标准(男、女均为40 U/L)时,30岁为33 U/L;HBeAg阴性为22 U/L、HBeAg阳性为31 U/L。结论慢性HBV感染者启动抗病毒治疗ALT的阈值应个体化,女性、年龄大、HBeAg阴性者ALT的治疗阈值应下调。

Objective To explore the threshold of ALT for initiating antiviral therapy in HBV infected patients,and to provide a basis for initiating antiviral therapy in chronic HBV-infected patients.Methods This retrospective cohort study recruited 707 consecutive treatment-naïve chronic hepatitis B(CHB)patients undergoing diagnostic liver biopsy in the department of infectious diseases of the Affiliated Hospital of Yan′an University from October 2013 to August 2018.Liver biopsy specimens were obtained under ultrasound guidance using Menghini 16G disposable needles.The METAVIR scoring system,which is commonly used internationally,was used to divide the patients into the group with mild liver tissue injury and the group with significant liver tissue injury,and the alanine aminotransferase(ALT)levels were measured separately.Receiver operating characteristic(ROC)curve and Mann-Whitney U test were used to evaluate the diagnostic value of ALT for significant liver tissue injury under different demographic characteristics.Results Of 707 patients,292(41.30%)had significant liver tissue injury confirmed by liver biopsy(METAVIR≥A2 and/or F2).When the ULN of ALT was set to NICE criteria(30 U/L for males,19 U/L for females),AASLD criteria(35 U/L for males,25 U/L for females)and EASL or APASL criteria(40 U/L for males and females),CHB patients with<ULN accounted for 32.38%,35.03%and 36.07%of significant liver tissue injury,respectively.And significant liver tissue injury in CHB patients with 1-2×ULN accounted for 41.99%,41.85%and 50.30%,respectively.The optimal ALT critical values were 33 U/L for overall patients,25 U/L for females,45 U/L for males,45 U/L for≤30 years olds,33 U/L for>30 years olds,22 U/L for HBeAg negative and 31 U/L for HBeAg positive patients.Conclusions The threshold of ALT for initiating antiviral therapy in chronic HBV patients should be individualized,especially should be down-regulated for the females,olders and HBeAg-negative patients.