慢性乙型肝炎患者丙氨酸氨基转移酶正常值上限下调必要性初步探讨  

Necessity of lowering the upper limit of normal of alanine aminotransferase in patients with chronic hepatitis B

作　　者：涂文辉[1] 朱伟君[2] 钱峰[3] 张继明 朱传武[3] Wen-Hui Tu;Wei-Jun Zhu;Feng Qian;Ji-Ming Zhang;Chuan-Wu Zhu(Department of Infectious Diseases,Taizhou MunicipalHospital,Taizhou 318000,Zhejiang Province,China;Department of Pathology,Taizhou Municipal Hospital,Taizhou 318000,Zhejiang Province,Chin;Department of Hepatology,the FifthPeople＇s Hospital of Suzhou,Suzhou 215100,Jiangsu Province,Chin;Department of Infectious Diseases,Huashan Hospital,Fudan University,Shanghai 200040,China)

机构地区：[1]台州市立医院感染科,浙江省台州市318000 [2]台州市立医院病理科,浙江省台州市318000 [3]苏州市第五人民医院肝病科,江苏省苏州市215100 [4]复旦大学附属华山医院感染科,上海市200040

出　　处：《世界华人消化杂志》2018年第30期1765-1771,共7页World Chinese Journal of Digestology

基　　金：浙江省台州市科技计划项目;No.1402ky19;中国肝炎防治基金会-天晴肝病研究基金资助课题;No.TQGB20150031~~

摘　　要：目的初步探讨慢性乙型肝炎(hepatitis B virus, HBV)患者目前采用的丙氨酸氨基转移酶正常值上限(upper limit of normal, ULN)下调的必要性.方法收集非活动性乙肝表面抗原(hepatitisBsurface antigen,HBsAg)携带者及接受抗病毒治疗慢性HBV患者715例,病毒DNA均低于检测值下限,其中非活动性HBsAg携带者组57例(携带组),慢性HBV抗病毒治疗组455例(肝炎组), ALT低于2 ULN经肝穿活检后抗病毒治疗组203例(其中ALT<1 ULN 133例, ALT1-2ULN70例)(肝穿组).收集患者年龄、性别、体重、肝功能、血糖、血脂、血常规、乙肝病毒感染血清学标志物、乙肝病毒DNA定量、甲胎蛋白、肝胆脾B超等相关数据.肝穿组收集肝组织炎症分级、纤维化分期及抗病毒治疗1年后肝功能数据.结果全部患者(n=715)ALT水平中位数为19 IU/L, 95%百分位数为31.2 IU/L(95%CI:30-34 IU/L), 95%百分位数男性为34 IU/L(95%CI:31-35 IU/L),女性为26.2 IU/L(95%CI:25-30IU/L).肝穿组患者抗病毒治疗后ALT值下降显著,中位数由37 IU/L降至23 IU/L,具显著统计学差异(F=111.497, P=0.000).根据4种不同ALT正常值上限,肝脏显著炎症(≥G2)的检出率分别为0,38.78%,63.27%和84.69%.以ROC分析ALT对肝组织学显著炎症的评估价值, AUC值(Az)为0.751,对ALT与肝组织学炎症程度作Logistic回归分析, P值为0.331.结论目前应用的ALT正常值上限对评估慢性HBV是偏高的,似乎存在下调的必要性.AIMTo explore the necessity of lowering the upper limit ofnormal of alanine aminotransferase （ALT） in patientswith chronic hepatitis B （CHB）.METHODSA total of 715 CHB patients with undetectable HBV DNAwere studied. Of them, 57 were inactive HBsAg carriers（carrier group）, 455 were those who previously metantiviral criterion and achieved viral and biochemicalresponse （hepatitis group）, and 203 underwent liverbiopsy due to their baseline ALT less than 2 times theupper limit of normal （ULN） and accepted antiviraltreatment （including 133 cases with ALT 〈 1 x ULN and70 cases with ALT 1-2 x ULN） （biopsy group）. Clinicaldata including age, gender, weight, liver function, bloodglucose, blood lipids, routine blood parameters, HBVmarkers, HBV DNA, alpha fetoprotein, and ultrasoundfindings were collected. Inflammation grade, fibrosisstage and liver function data were also collected for therapy.RESULTSALT median value was 19 IU/L and the 95% percentilewas 31.2 IU/L （95%CI： 30-34 IU/L） in all patients （n =715）. The 95% percentile was 34 IU/L in males （95%CI：31-35 IU/L）, and 26.2 IU/L in females （95%CI： 25-30 IU/L）.ALT value decreased significantly in the biopsy groupafter antiviral treatment, and median ALT decreasedfrom 37 IU/L to 23 IU/L, which showed a significantdifference （F = 111.497, P = 0.000）. Based on four differentALT ULN, the detection rates of significant inflammation（≥G2） were 0, 38.78%, 63.27% and 84.69%, respectively,in the biopsy group. When ROC was used to analyzeALT and significant histological inflammation, the AUCvalue was 0.751. Logistic regression analysis showedthat ALT was not associated with significant histologicalinflammation （P = 0.331）.CONCLUSIONThe current ALT ULN is relatively high for assessment ofliver inflammation in patients with CHB, and there maybe a necessity to lower the threshold.

关 键 词：乙型肝炎 慢性 组织学 炎症 丙氨酸氨基转移酶 正常值上限 下调 

分 类 号：R512.62[医药卫生—内科学]