中文English
ISSN 1001-5256
CN 22-1108/R

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

APRI、FIB-4和GPR对慢性乙型肝炎肝脏炎症程度的诊断价值

周新兰 马鑫 王雁冰 李秀芬 黄丹 陆伟 张占卿 丁荣蓉

周新兰,马鑫,王雁冰,等. APRI、FIB-4和GPR对慢性乙型肝炎肝脏炎症程度的诊断价值[J]. 临床肝胆病杂志, 2021, 37(9): 2066-2070. DOI: 10.3969/j.issn.1001-5256.2021.09.013
引用本文: 周新兰,马鑫,王雁冰,等. APRI、FIB-4和GPR对慢性乙型肝炎肝脏炎症程度的诊断价值[J]. 临床肝胆病杂志, 2021, 37(9): 2066-2070. DOI: 10.3969/j.issn.1001-5256.2021.09.013
ZHOU XL, MA X, WANG YB, et al. Value of aspartate aminotransferase-to-platelet ratio index, fibrosis-4, and gamma-glutamyl transpeptidase-to-platelet ratio in diagnosis of liver inflammation grade in patients with chronic hepatitis B[J]. J Clin Hepatol, 2021, 37(9): 2066-2070. DOI: 10.3969/j.issn.1001-5256.2021.09.013
Citation: ZHOU XL, MA X, WANG YB, et al. Value of aspartate aminotransferase-to-platelet ratio index, fibrosis-4, and gamma-glutamyl transpeptidase-to-platelet ratio in diagnosis of liver inflammation grade in patients with chronic hepatitis B[J]. J Clin Hepatol, 2021, 37(9): 2066-2070. DOI: 10.3969/j.issn.1001-5256.2021.09.013

APRI、FIB-4和GPR对慢性乙型肝炎肝脏炎症程度的诊断价值

DOI: 10.3969/j.issn.1001-5256.2021.09.013
详细信息
    通讯作者:

    丁荣蓉,dingrongrong@shphc.org.cn

    周新兰与马鑫对本文贡献相同,同为第一作者

    周新兰与马鑫对本文贡献相同,同为第一作者

  • 中图分类号: R512.62

Value of aspartate aminotransferase-to-platelet ratio index, fibrosis-4, and gamma-glutamyl transpeptidase-to-platelet ratio in diagnosis of liver inflammation grade in patients with chronic hepatitis B

  • 摘要:   目的  评价AST/PLT指数(APRI)、纤维化指数(FIB-4)、GGT/PLT比值(GPR)对慢性乙型肝炎(CHB)患者肝组织炎症分级的诊断价值。  方法  选取2016年10月—2019年10月在上海市公共卫生临床中心住院期间接受经皮肝组织活检及常规实验室检查的CHB患者545例。依据Scheuer方法进行炎症分级(G),并依据临床指标分别计算APRI、FIB-4、GPR。正态分布计量资料2组间比较采用t检验;非正态分布计量资料2组间比较采用Mann-Whitney U检验。计数资料2组间比较采用χ2检验。两变量间相关性应用Spearman相关分析。血清无创诊断模型对肝组织炎症活动度分级的诊断性能评价采用受试者工作特征曲线法(ROC曲线)。采用Delong检验比较血清无创模型的ROC曲线下面积(AUC)。  结果  545例患者中肝组织炎症分级G0~1级224例,G2级209例,G3级112例。Spearman相关分析结果显示,APRI、FIB-4和GPR值与肝组织炎症分级均呈正相关(r值分别为0.611、0.470、0.563,P值均<0.001)。APRI、FIB-4和GPR诊断肝炎症分级G≥2的AUC分别为0.820、0.719、0.782;临界值分别为0.53、1.48和0.20;GPR诊断G≥2的效能优于FIB-4(P=0.01),但略低于APRI(P=0.048)。基于ALT水平分层分析,在ALT ≤1×ULN组、1~2×ULN组和2~5×ULN组,APRI诊断G≥2的AUC分别为0.847、0.786和0.724,FIB-4分别为0.777、0.729和0.626,GPR分别为0.801、0.781和0.607;亚组结果显示除在2~5×ULN组GPR诊断效能低于APRI(P=0.042), 其余ALT分层组GPR和APRI、FIB-4诊断性能相似。APRI、FIB-4和GPR诊断肝炎症分级G≥3的AUC分别为0.791、0.725、0.801;临界值分别为0.66、1.49和0.25;GPR诊断炎症分级G≥3的效能与APRI相似,但优于FIB-4(P=0.006)。基于ALT水平分层分析,在ALT ≤1×ULN组、1~2×ULN组和2~5×ULN组,APRI诊断G≥3的AUC分别为0.900、0.742和0.693,FIB-4分别为0.874、0.683和0.644,GPR分别为0.890、0.805和0.668。亚组结果显示除在1~2×ULN组GPR诊断效能优于FIB-4(P=0.015),其余ALT分层组GPR和APRI、FIB-4诊断性能相似。  结论  APRI、FIB-4和GPR可较准确地诊断CHB肝脏炎症坏死程度,有助于监测CHB疾病进展,并对抗病毒治疗时机的确定有重要意义。

     

  • 表  1  研究对象的临床资料

    指标 所有患者(n=545) 炎症分级 统计值 P
    G0~1(n=224) G2~3(n=321)
    年龄(岁) 37(30~44) 37(31~46) 36(30~44) Z=-1.863 0.062
    男性[例(%)] 454(83.3) 148(66.2) 206(64.2) χ2=0.198 0.656
    HBeAg阳性[例(%)] 284(52.1) 84(37.5) 200(62.4) χ2=20.785 <0.001
    HBV DNA(log10 IU/ml) 6.3(4.1~7.3) 4.9(3.0~7.3) 6.6(5.3~7.4) Z=6.295 <0.001
    ALT(U/L) 63.0(32.0~163.0) 37.0(18.0~71.0) 106.5(48.3~286.0) Z=10.735 <0.001
    AST(U/L) 46.0(26.0~98.0) 28.0(20.0~45.5) 75.5(42.0~170.0) Z=12.814 <0.001
    ALP(U/L) 76.0(63.0~95.0) 70.0(59.0~85.0) 83.0(68.0~103.5) Z=6.052 <0.001
    GGT(U/L) 38.0(19.0~79.5) 22.0(14.5~39.0) 63.0(32.3~112.7) Z=11.479 <0.001
    TBil(μmol/L) 15.1(11.1~20.7) 14.3(11.1~17.9) 15.9(11.3~22.0) Z=3.976 <0.001
    Alb(g/L) 41.5(38.5~44.0) 42.8(40.5~45.6) 40.0(37.0~43.5) Z=-8.173 <0.001
    Glo(g/L) 29.0(26.9~33.0) 29.0(26.0~32.0) 30.0(27.0~33.7) Z=5.282 <0.001
    尿素氮(μmol/L) 4.6(3.8~5.5) 4.8(4.0~5.5) 4.5(3.7~5.5) Z=-2.049 0.040
    肌酐(μmol/L) 64.9(54.6~74.7) 63.6(54.7~73.9) 66.3(54.5~75.6) Z=0.694 0.488
    INR 1.1(1.0~1.1) 1.0(1.0~1.1) 1.1(1.0~1.2) Z=6.477 <0.001
    WBC(×109/L) 5.1(4.1~6.1) 5.4(4.1~6.3) 5.0(4.2~6.0) Z=-3.131 0.002
    RBC(×109/L) 2.7(2.1~3.5) 3.0(2.2~3.8) 2.5(2.0~3.2) Z=-3.852 <0.001
    PLT(×109/L) 157(124~192) 177(148~201) 142(110~177) Z=-7.628 <0.001
    APRI 0.81(0.40~1.65) 0.41(0.27~0.75) 1.34(0.73~2.37) Z=13.991 <0.001
    FIB-4 1.41(0.97~2.39) 1.09(0.80~1.52) 1.81(1.24~3.38) Z=10.142 <0.001
    GPR 0.25(0.12~0.66) 0.13(0.08~0.23) 0.40(0.23~1.10) Z=12.444 <0.001
    下载: 导出CSV

    表  2  血清参数对肝组织炎症分级G≥2级的诊断价值

    指标 ALT分层 AUC(95% CI) P 截断值 敏感度(%) 特异度(%) 准确度(%)
    APRI 所有患者(n=545) 0.820(0.781~0.855) <0.000 1 0.53 80.4 69.4 75.1
    ≤1×ULN (n=208) 0.847(0.785~0.896) <0.000 1 0.34 87.7 73.6 78.1
    1~2×ULN (n=167) 0.786(0.708~0.852) <0.000 1 0.58 80.5 65.5 74.5
    2~5×ULN (n=170) 0.724(0.639~0.799) <0.000 1 0.98 72.2 62.5 69.2
    FIB-4 所有患者(n=545) 0.719(0.675~0.760) <0.000 1 1.48 56.8 77.3 66.7
    ≤1×ULN (n=208) 0.777(0.709~0.836) <0.000 1 1.35 71.9 75.2 74.2
    1~2×ULN (n=167) 0.729(0.647~0.802) <0.000 1 1.41 62.2 72.7 66.4
    2~5×ULN (n=170) 0.626(0.537~0.709) <0.000 1 0.92 84.4 40.0 70.8
    GPR 所有患者(n=545) 0.782(0.741~0.819) <0.000 1 0.20 74.7 71.3 73.1
    ≤1×ULN (n=208) 0.801(0.735~0.857) <0.000 1 0.15 73.7 78.5 77.0
    1~2×ULN (n=167) 0.781(0.702~0.847) <0.000 1 0.25 69.5 80.0 73.7
    2~5×ULN (n=170) 0.607(0.517~0.691) 0.052 7 0.27 66.7 55.0 63.1
    下载: 导出CSV

    表  3  血清参数模型对肝组织炎症分级G≥3级的诊断价值

    指标 ALT分层 AUC(95% CI) P 截断值 敏感度(%) 特异度(%) 准确度(%)
    APRI 所有患者(n=545) 0.791(0.750~0.827) <0.000 1 0.66 89.2 60.1 64.9
    ≤1×ULN (n=208) 0.900(0.846~0.940) <0.000 1 0.53 93.3 83.4 84.3
    1~2×ULN (n=167) 0.742(0.660~0.813) <0.000 1 0.64 86.2 55.6 62.1
    2~5×ULN (n=170) 0.693(0.606~0.771) <0.000 1 1.37 60.0 72.0 69.2
    FIB-4 所有患者(n=545) 0.725(0.681~0.766) <0.000 1 1.49 70.3 66.0 66.7
    ≤1×ULN (n=208) 0.874(0.816~0.919) <0.000 1 1.76 93.3 80.9 82.0
    1~2×ULN (n=167) 0.683(0.598~0.760) <0.000 1 1.41 72.4 58.3 61.3
    2~5×ULN (n=170) 0.644(0.555~0.726) <0.000 1 1.13 83.3 41.0 50.8
    GPR 所有患者(n=545) 0.801(0.761~0.837) <0.000 1 0.25 86.5 65.2 68.8
    ≤1×ULN (n=208) 0.890(0.835~0.932) <0.000 1 0.17 98.0 73.4 74.7
    1~2×ULN (n=167) 0.805(0.729~0.868) <0.000 1 0.28 93.1 67.6 73.0
    2~5×ULN (n=170) 0.668(0.580~0.748) 0.001 8 0.30 76.7 53.0 58.5
    下载: 导出CSV
  • [1] SHIH C, YANG CC, CHOIJILSUREN G, et al. Hepatitis B virus[J]. Trends Microbiol, 2018, 26(4): 386-387. DOI: 10.1016/j.tim.2018.01.009.
    [2] LAMPERTICO P, INVERNIZZI F, VIGANÒ M, et al. The long-term benefits of nucleos(t)ide analogs in compensated HBV cirrhotic patients with no or small esophageal varices: A 12-year prospective cohort study[J]. J Hepatol, 2015, 63(5): 1118-1125. DOI: 10.1016/j.jhep.2015.06.006.
    [3] KIM WR, LOOMBA R, BERG T, et al. Impact of long-term tenofovir disoproxil fumarate on incidence of hepatocellular carcinoma in patients with chronic hepatitis B[J]. Cancer, 2015, 121(20): 3631-3638. DOI: 10.1002/cncr.29537.
    [4] KEW MC. Serum aminotransferase concentration as evidence of hepatocellular damage[J]. Lancet, 2000, 355(9204): 591-592. DOI: 10.1016/S0140-6736(99)00219-6.
    [5] NGUYEN MH, GARCIA RT, TRINH HN, et al. Histological disease in Asian-Americans with chronic hepatitis B, high hepatitis B virus DNA, and normal alanine aminotransferase levels[J]. Am J Gastroenterol, 2009, 104(9): 2206-2213. DOI: 10.1038/ajg.2009.248.
    [6] DONG M, WU J, YU X, et al. Validation and comparison of seventeen noninvasive models for evaluating liver fibrosis in Chinese hepatitis B patients[J]. Liver Int, 2018, 38(9): 1562-1570. DOI: 10.1111/liv.13688.
    [7] LEMOINE M, SHIMAKAWA Y, NAYAGAM S, et al. The gamma-glutamyl transpeptidase to platelet ratio (GPR) predicts significant liver fibrosis and cirrhosis in patients with chronic HBV infection in West Africa[J]. Gut, 2016, 65(8): 1369-1376. DOI: 10.1136/gutjnl-2015-309260.
    [8] WU X, CAI B, SU Z, et al. Aspartate transaminase to platelet ratio index and gamma-glutamyl transpeptidase-to-platelet ratio outweigh fibrosis index based on four factors and red cell distribution width-platelet ratio in diagnosing liver fibrosis and inflammation in chronic hepatitis B[J]. J Clin Lab Anal, 2018, 32(4): e22341. DOI: 10.1002/jcla.22341.
    [9] WANG L, LI J, YANG K, et al. Comparison and evaluation of non-invasive models in predicting liver inflammation and fibrosis of chronic hepatitis B virus-infected patients with high hepatitis B virus DNA and normal or mildly elevated alanine transaminase levels[J]. Medicine (Baltimore), 2020, 99(23): e20548. DOI: 10.1097/MD.0000000000020548.
    [10] Chinese Society of Hepatology and Chinese Society of infectious Diseases, Chinese Medical Association. The guideline of prevention and treatment for chronic hepatitis B: A 2015 update[J]. J Cin Hepatol, 2015, 31(12): 1941-1960. DOI: 10.3969/j.issn.1001-5256.2015.12.002.

    中华医学会肝病学分会, 中华医学会感染病学分会. 慢性乙型肝炎防治指南(2015年更新版)[J]. 临床肝胆病杂志, 2015, 31(12): 1941-1960. DOI: 10.3969/j.issn.1001-5256.2015.12.002.
    [11] SCHEUER PJ. The nomenclature of chronic hepatitis: Time for a change[J]. J Hepatol, 1995, 22(1): 112-114. DOI: 10.1016/0168-8278(95)80269-x.
    [12] KOYAMA Y, BRENNER DA. Liver inflammation and fibrosis[J]. J Clin Invest, 2017, 127(1): 55-64. DOI: 10.1172/JCI88881.
    [13] HUANG H, SUN Z, PAN H, et al. Serum metabolomic signatures discriminate early liver inflammation and fibrosis stages in patients with chronic hepatitis B[J]. Sci Rep, 2016, 6: 30853. DOI: 10.1038/srep30853.
    [14] LAI M, HYATT BJ, NASSER I, et al. The clinical significance of persistently normal ALT in chronic hepatitis B infection[J]. J Hepatol, 2007, 47(6): 760-767. DOI: 10.1016/j.jhep.2007.07.022.
    [15] World Health Organization. Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection[R]. Geneva: WHO, 2015.
    [16] LIU DP, LU W, ZHANG ZQ, et al. Comparative evaluation of GPR versus APRI and FIB-4 in predicting different levels of liver fibrosis of chronic hepatitis B[J]. J Viral Hepat, 2018, 25(5): 581-589. DOI: 10.1111/jvh.12842.
    [17] LI Q, LI W, HUANG Y, et al. The gamma-glutamyl transpeptidase-to-platelet ratio predicts liver fibrosis and cirrhosis in HBeAg-positive chronic HBV infection patients with high HBV DNA and normal or mildly elevated alanine transaminase levels in China[J]. J Viral Hepat, 2016, 23(11): 912-919. DOI: 10.1111/jvh.12563.
    [18] WANG J, XIA J, YAN X, et al. The gamma-glutamyl transpeptidase to platelet ratio predicts liver inflammation in chronic hepatitis B with normal or mildly elevated alanine transaminase[J]. Clin Res Hepatol Gastroenterol, 2020, 44(6): 913-922. DOI: 10.1016/j.clinre.2020.01.011.
  • 加载中
表(3)
计量
  • 文章访问数:  59
  • HTML全文浏览量:  27
  • PDF下载量:  29
  • 被引次数: 0
出版历程
  • 收稿日期:  2021-01-25
  • 修回日期:  2021-03-03
  • 分享
  • 用微信扫码二维码

    分享至好友和朋友圈

目录

    /

    返回文章
    返回