PDF下载 ( 3408 KB)
P-I-R分型和Laennec分级与乙型肝炎肝硬化患者抗病毒治疗后组织学和预后的关系
DOI: 10.3969/j.issn.1001-5256.2023.03.015
伦理学声明：本研究方案于2013年9月13日经由解放军总医院第五医学中心伦理委员会审批，批号：2013145D，所纳入患者均签署知情同意书。
利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。
作者贡献声明：吕采红、宋铮、罗婧参与了研究数据的获取分析解释过程以及论文起草；常秀娟修改文章内容；杨永平设计研究思路。
Association of P-I-R classification and Laennec grading with histology and prognosis after antiviral therapy in patients with hepatitis B cirrhosis
-
摘要:
目的 研究P-I-R分型和Laennec分级评价乙型肝炎肝硬化患者接受抗病毒治疗后的组织学改变，及两种评价系统与临床预后的关系。 方法 连续筛选2013年10月—2014年10月来自14个中心的218例患者，病理(Ishak评分≥5分)诊断肝硬化接受抗病毒治疗72周完成2次肝组织活检，并符合P-I-R分型标准。218例患者分为无肝细胞癌(HCC)组(n=186)和HCC组(n=32)。计数资料组间比较采用χ2检验和Fisher精确检验。比较抗病毒治疗后HCC发生情况时，连续变量采用非参数检验Mann-Whitney U检验；比较P-I-R分型与Laennec分级不同组间差异时，连续变量采用非参数检验Kruskal-Wallis H检验。采用单因素和多因素Cox比例风险回归分析并计算风险比(HR)和95%CI。采用Kaplan-Meier法计算HCC的累积发生率。 结果 抗病毒治疗72周后无HCC组和HCC组间P-I-R分型情况比较差异有统计学意义(P＜0.001)。抗病毒治疗前后Laennec分级和P-I-R分型的分布均有统计学差异(P值均＜0.001)。抗病毒治疗后，按照Laennec分级分为4A组(n=33)、4B组(n=71)、4C组(n=114)，3组间PLT(H=36.429，P＜0.001)、LSM(H=13.983, P=0.004)、Ishak评分(χ2=23.060, P＜0.001)、HAI评分(P＜0.001)比较差异均有统计学意义。抗病毒治疗72周后，按照P-I-R分型分为R组(n=70)、I组(n=52)和P组(n=96)，3组间PLT(H=7.193，P=0.028)、LSM(H=6.238, P=0.045)、Ishak评分(χ2=7.986, P＜0.001)、HAI评分(P=0.002)、HCC发生情况(P＜0.001)比较，差异均有统计学意义。P-I-R分型P组和R组HCC发生率有显著差异(HR=24.21; 95%CI: 0.46~177.99, P=0.002)。经过调整其他混杂因素后，P-I-R分型是预测HCC发生的独立指标(HR=12.69; 95%CI: 4.63~34.80, P=0.002)。 结论 P-I-R分型和Laennec分级均能反应患者抗病毒治疗前后纤维化的特征及改变情况，其中P-I-R分型对抗病毒治疗后纤维化的改变更敏感。P-I-R分型(治疗后)可用于预测抗病毒治疗后患者HCC发生的风险。 Abstract:Objective To investigate the role of P-I-R classification and Laennec grading in evaluating histological changes in patients with hepatitis B cirrhosis after receiving antiviral therapy, as well as the association of these two evaluation systems with clinical prognosis. Methods A total of 218 patients from 14 centers were consecutively screened from October 2013 to October 2014, and these patients were diagnosed with liver cirrhosis based on pathology (Ishak score ≥5), received antiviral therapy for 72 weeks, completed two liver biopsies, and met the P-I-R classification criteria. The 218 patients were divided into non-hepatocellular carcinoma (HCC) group with 186 patients and HCC group with 32 patients. The chi-square test and the Fisher's exact test were used for comparison of categorical data between groups. For the comparison of HCC after antiviral therapy, the non-parametric Mann-Whitney U test was used for continuous variables, and for the comparison of P-I-R classification and Laennec grading, the non-parametric Kruskal-Wallis H test was used for continuous variables. Univariate and multivariate Cox regression analyses were used to calculate hazard ratio (HR) and 95% confidence interval (CI), and the Kaplan-Meier method was used to calculate the cumulative incidence rate of HCC. Results After 72 weeks of antiviral therapy, there was a significant difference in P-I-R classification between the non-HCC group and the HCC group (P < 0.001). There were significant differences in the distribution of Laennec grading and P-I-R classification before and after antiviral therapy (P < 0.001). After antiviral therapy, the 218 patients were divided into 4A group with 33 patients, 4B group with 71 patients, and 4C group with 114 patients according to Laennec grading, and there were significant differences between these three groups in platelet count (PLT) (H=36.429, P < 0.001), liver stiffness measurement (LSM) (H=13.983, P=0.004), Ishak score (χ2=23.060, P < 0.001), and HAI score (P < 0.001). After antiviral therapy, the 218 patients were divided into R group with 70 patients, I group with 52 patients, and P group with 96 patients according to P-I-R classification, and there were significant differences between these three groups in PLT (H=7.193, P=0.028), LSM (H=6.238, P=0.045), Ishak score (χ2=7.986, P < 0.001), HAI score (P=0.002), and HCC (P < 0.001). There was a significant difference in the incidence rate of HCC between the P and R groups based on P-I-R classification (HR=24.21, 95%CI: 0.46-177.99, P=0.002). After adjustment for other confounding factors, P-I-R classification was an independent predictive factor for HCC (HR=12.69, 95%CI: 4.63-34.80, P=0.002). Conclusion Both P-I-R classification and Laennec grading can reflect the features and changes of fibrosis before and after antiviral therapy, and P-I-R classification is more sensitive to fibrosis changes after antiviral therapy. P-I-R classification (after treatment) can be used to assess the risk of HCC in patients after antiviral therapy. -
Key words:
- Hepatitis B /
- Liver Cirrhosis /
- Carcinoma, Hepatocellular /
- P-I-R Typing /
- Laennec Classification
-
图 2 基线和抗病毒治疗72周后患者P-I-R分型和Laennec分级的比较
注：a, 基线和抗病毒治疗72周后P-I-R分型和Laennec分级患者分布; b, 基线时P-I-R分型和Laennec分级各分组的分流; c, 抗病毒治疗72周后P-I-R分型和Laennec分级各分组的分流。
Figure 2. Comparison of P-I-R typing and Laennec grading of patients at baseline and after 72 weeks of antiviral therapy
图 3 抗病毒治疗72周后各指标在P-I-R分型和Laennec分级中的分布差异
Figure 3. Differences in distribution of clinical data between P-I-R typing and Laennec grading after 72 weeks of antiviral treatment
图 4 不同Lannec分级和P-I-R分型患者HCC发生率的差异
Figure 4. Prediction of the incidence of HCC by Lannec grading and P-I-R typing
表 1 无HCC组和HCC组基线资料的比较
Table 1. Comparison of baseline data between the non-HCC group and the HCC group
项目 总体(n=218) 无HCC组(n=186) HCC组(n=32) 统计值 P值 治疗方式[例(%)] χ2=0.476 0.097 ETV+PLC 117(53.7) 95 (51.1) 22(68.8) ETV+BJRG 101(46.3) 91(48.9) 10 (31.3) 年龄(岁) 46.0(19.0~68.0) 46.0(19.0~68.0) 47.0(34.0~63.0) U=2833 0.664 男性[例(%)] 157(72.0) 133(71.5) 24(75.0) χ2=0.837 0.846 饮酒史[例(%)] 39(17.9) 30(16.1) 9(28.1) χ2=2.207 0.166 BMI(kg/m2) 23.6(15.8~36.3) 23.7(15.8~36.3) 23.0(17.7~32.7) U=3070 0.777 Alb(g/L) 41.0(26.9~50.0) 41.0 (26.9~50.0) 42.0(30.4~48.0) U=2935 0.903 TBil(μmol/L) 15.2(5.0~149.0) 14.4(5.0~149.0) 17.4(6.1~47.9) U=2348 0.057 ALT(U/L) 50.5(10.0~1370.0) 49.0(10.0~1370.0) 66.5(13.0~854.0) U=2473 0.128 AST(U/L) 46.0(17.0~836.0) 45.0(17.0~836.0) 55.0(20.0~635.0) U=2415 0.089 PLT(×109/L) 125.0(45.0~277.0) 130.0(45.0~277.0) 116.0(50.0~223.0) U=3652 0.040 AFP(ng/mL) 7.00(0.91~200.00) 7.00(0.91~200.00) 9.90(2.17~185.00) U=2587 0.238 HBV DNA (log10 IU/mL) 5.60(3.40~8.90) 5.70(3.40~8.90) 5.10(3.70~7.80) U=3692 0.030 HBeAg阳性[例(%)] 114 (52.3) 97(52.2) 17(53.1) χ2=1.040 ＞0.05 LSM (kPa) 16.1(4.2~60.4) 15.6(4.2~60.4) 19.1(4.8~41.0) U=2543 0.190 脾脏长度(mm) 113(69~194) 113(69~169) 115(86~194) U=2706 0.414 HAI评分[例(%)]1) 0.519 1~4分 25(11.5) 23(12.4) 2(6.3) 5~8分 118(54.1) 97(52.2) 21(65.6) 9~12分 68(31.2) 60(32.3) 8(25.0) 13~18分 7(3.2) 6(3.2) 1 (3.1) Ishak纤维评分[例(%)] χ2=1.358 0.621 5分 66(30.3) 58(31.2) 8(25.0) 6分 152(69.7) 128(68.8) 24(75.0) P-I-R分型[例(%)]1) 0.167 R 21(9.6) 15(8.1) 6(18.8) I 22(10.1) 19(10.2) 3(9.4) P 175(80.3) 152(81.7) 23(71.9) Laennec分级[例(%)] χ2=1.049 0.592 4A 23(10.6) 18(9.7) 5(15.6) 4B 41(18.8) 35(18.8) 6(18.8) 4C 154(70.6) 133(71.5) 21(65.6) 注：ETV, 恩替卡韦；PLC, 安慰剂; BJRG，鳖甲软肝片；HAI, 组织学活动指数。1)采用Fisher检验。 
下载: 导出CSV
表 2 无HCC组和HCC组治疗后一般资料的比较
Table 2. Comparison of general data after treatment between non-HCC group and HCC group
项目 总体(n=218) 无HCC组(n=186) HCC组(n=32) 统计值 P值 BMI(kg/m2) 23.6(15.8~36.3) 23.6(15.8~36.3) 23.0(17.7~32.7) U=2333 0.773 Alb(g/L) 44.4(21.1~57.3) 44.3(21.1~57.3) 45.3(38.0~52.5) U=2447 0.336 TBil(μmol/L) 15.0(2.0~164.0) 15.1(2.0~164.0) 14.8(6.6~46.0) U=2209 0.661 ALT(U/L) 26.0(8.0~730.0) 26.0(9.0~730.0) 24.0(8.0~85.0) U=2477 0.638 AST(U/L) 33.9(8.0~803.0) 26.0(8.0~803.0) 27.0(13.0~68.0) U=2177 0.275 PLT(×109/L) 147.0(56.0~279.0) 150.0(56.0~279.0) 121.0(62.0~226.0) U=1552 0.061 AFP(ng/mL) 2.9(0.0~27.9) 2.9(0.0~27.9) 3.1(1.0~7.4) U=2420 0.967 HBV DNA(log10 IU/mL) N(N~4.11) N(N~4.11) N(N~3.39) U=2386 0.933 HBeAg阳性[例(%)] 98(45.0) 88(47.3) 10(31.3) χ2=0.508 0.135 LSM(kPa) 9.35(1.00~49.70) 9.50(1.00~49.70) 9.00(1.00~45.00) U=3305 0.318 LSM变化[例(%)]1) 0.867 减少 126(57.8) 106(57.0) 20(62.5) 稳定 80(36.7) 69(37.1) 11(34.4) 增加 12(5.5) 11(5.9) 1(3.1) 脾脏长度(mm) 109(24~183) 110(24~171) 108(80~183) U=3130 0.641 HAI评分[例(%)]1) 0.466 1~4分 0 0 0 5~8分 95(43.6) 84(45.2) 11(34.4) 9~12分 122(56.0) 101(54.3) 21(65.6) 13~18分 1(0.5) 1(0.5) 0 Ishak纤维评分[例(%)] χ2=2.533 0.06 5分 98(45.0) 89(47.8) 9(28.1) 6分 120(55.0) 97(52.2) 23(71.9) P-I-R分型[例(%)]1) ＜0.001 R 70(32.1) 69(37.1) 1(3.1) I 52(23.9) 49(26.3) 3(9.4) P 96(44.0) 68(36.6) 28(87.5) Laennec分级[例(%)] χ2=2.349 0.308 4A 33(15.1) 31(16.7) 2(6.3) 4B 71(32.6) 59(31.7) 12(37.5) 4C 114(52.3) 96(51.6) 18(56.3) 注：N，不可测出；1)采用Fisher检验。
下载: 导出CSV
表 3 抗病毒治疗72周后的临床数据在Laennec分级中的分布差异
Table 3. Differences in the distribution of clinical data in Laennec grading after 72 weeks of antiviral therapy
项目 4A组(n=33) 4B组(n=71) 4C组(n=114) 统计值 P值 ALT(U/L) 28.0(9.0~83.0) 24.0(9.0~210.0) 27.0(8.0~121.0) H=0.569 0.481 AST(U/L) 26.0(18.0~49.0) 25.0(8.0~107.0) 27.4(13.0~177.0) H=4.119 0.635 PLT(×109/L) 161.0(56.0~258.0) 166.0(60.0~277.0) 129.0(69.0~279.0) H=36.429 ＜0.001 LSM(kPa) 6.7(3.1~28.9) 8.8(1.0~32.1) 11.8(1.0~49.7) H=13.983 0.004 LSM变化[例(%)]1) 0.848 减少 19(57.6) 42(59.2) 65(57.0) 稳定 14(42.4) 25(35.2) 41(36.0) 增加 0 4(5.6) 8(7.0) Ishak纤维化评分[例(%)] χ2=23.060 ＜0.001 5分 18(54.5) 46(64.8) 34(29.8) 6分 15(45.5) 25(35.2) 80(70.2) HAI评分[例(%)]1) ＜0.001 1~4分 21(63.6) 39(54.9) 35(30.7) 5~8分 12(36.4) 32(45.1) 78(68.4) 9~12分 0 0 1(0.9) 发生HCC[例(%)] χ2=2.349 0.512 是 2(6.1) 12(16.9) 18(15.8) 否 31(93.9) 59(83.1) 96(84.2) 注：1)采用Fisher检验。
下载: 导出CSV
表 4 抗病毒治疗72周后的临床数据在P-I-R分型中的分布差异
Table 4. Differences of the distribution of clinical data of P-I-R types after 72 weeks of antiviral treatment
项目 R组(n=70) I组(n=52) P组(n=96) 统计值 P值 ALT(U/L) 27(9~210) 26(9~108) 25(8~85) H=0.618 0.892 AST(U/L) 25.5(14.0~107.0) 26.0(8.0~76.0) 27.0(13.0~177.0) H=0.770 0.857 PLT(×109/L) 163(56~264) 146(66~260) 129(69~279) H=7.193 0.028 LSM(kPa) 8.65(3.10~28.90) 8.80(3.10~32.10) 10.60(1.00~49.70) H=6.238 0.045 LSM变化[例(%)]1) 0.995 减少 39(55.7) 31(59.6) 56(58.3) 稳定 28(40.0) 18(34.6) 34(35.4) 增加 3(4.3) 3(5.8) 6(6.3) Ishak纤维化评分[例(%)] χ2=7.986 ＜0.001 5分 36(51.4) 29(55.8) 33(34.4) 6分 34(48.6) 23(44.2) 63(65.6) HAI评分[例(%)]1) 0.002 1~4分 40(57.1) 26(50.0) 29(30.2) 5~8分 30(42.9) 26(50.0) 66(68.8) 9~12分 0 0 1(1.0) 发生HCC[例(%)]1) ＜0.001 是 1(1.4) 3(5.8) 28(29.2) 否 69(98.6) 49(94.2) 68(70.8) 注：1)采用Fisher检验。
下载: 导出CSV
表 5 单因素分析HCC发生的影响因素
Table 5. Predictors of HCC occurrence by univariate analysis
变量 HR(95%CI) P值 P-I-R分型 ＜0.001 R 1.00 I 4.40(0.46~177.99) 0.199 P 24.21(0.46~177.99) 0.002 Ishak纤维化评分(6 vs 5) 2.18(1.01~4.72) 0.047 PLT(＞146.5 vs ≤146.5)×109 /L 0.59(0.29~1.21) 0.153 Ishak纤维化评分改变 0.411 好转 1.00 无变化 2.02(0.70~5.81) 0.191 进展 2.15(0.48~9.60) 0.317 治疗方式(ETV+PLC vs ETV+BJRG) 0.50(0.24~1.05) 0.068 Laennec组织学病理分级 0.327 4A 1.00 4B 3.11(0.70~12.15) 0.138 4C 2.82(0.70~12.15) 0.165 年龄(≥43岁vs＜43岁) 1.01(0.97~1.05) 0.674 饮酒史(是vs否) 1.91(0.88~4.13) 0.100 性别(男vs女) 0.81(0.37~1.81) 0.615 HBV DNA(检测到vs未检测到) 1.06(0.32~3.49) 0.921 TBil(＞15 mmol/L vs ≤15 mmol/L) 0.85(0.42~1.70) 0.644 BMI(＞23.55 kg/m2 vs ≤23.55 kg/m2) 0.75(0.37~1.51) 0.418 AST(＞26 U/L vs ≤26 U/L) 1.51(0.75~3.03) 0.249 AFP(＞2.94 ng/mL vs ≤2.94 ng/mL) 1.57(0.77~3.17) 0.212 ALT(＞26 U/L vs ≤26 U/L) 0.81(0.40~1.63) 0.561 LSM变化(kPa) 0.789 稳定 1.00 减少 1.25(0.61~2.55) 0.548
下载: 导出CSV
-
[1] D'AMICO G, MORABITO A, D'AMICO M, et al. Clinical states of cirrhosis and competing risks[J]. J Hepatol, 2018, 68(3): 563-576. DOI: 10.1016/j.jhep.2017.10.020. [2] HYTIROGLOU P, THEISE ND. Regression of human cirrhosis: an update, 18 years after the pioneering article by Wanless et al[J]. Virchows Arch, 2018, 473(1): 15-22. DOI: 10.1007/s00428-018-2340-2. [3] CHANG TT, LIAW YF, WU SS, et al. Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B[J]. Hepatology, 2010, 52(3): 886-893. DOI: 10.1002/hep.23785. [4] SCHIFF ER, LEE SS, CHAO YC, et al. Long-term treatment with entecavir induces reversal of advanced fibrosis or cirrhosis in patients with chronic hepatitis B[J]. Clin Gastroenterol Hepatol, 2011, 9(3): 274-276. DOI: 10.1016/j.cgh.2010.11.040. [5] RAMACHANDRAN P, IREDALE JP, FALLOWFIELD JA. Resolution of liver fibrosis: basic mechanisms and clinical relevance[J]. Semin Liver Dis, 2015, 35(2): 119-131. DOI: 10.1055/s-0035-1550057. [6] SINGAL AG, LIM JK, KANWAL F. AGA clinical practice update on interaction between oral direct-acting antivirals for chronic hepatitis C infection and hepatocellular carcinoma: Expert review[J]. Gastroenterology, 2019, 156(8): 2149-2157. DOI: 10.1053/j.gastro.2019.02.046. [7] ROCKEY DC, CALDWELL SH, GOODMAN ZD, et al. Liver biopsy[J]. Hepatology, 2009, 49(3): 1017-1044. DOI: 10.1002/hep.22742. [8] KNODELL RG, ISHAK KG, BLACK WC, et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis[J]. Hepatology, 1981, 1(5): 431-435. DOI: 10.1002/hep.1840010511. [9] BATTS KP. Acute and chronic hepatic allograft rejection: pathology and classification[J]. Liver Transpl Surg, 1999, 5(4 Suppl 1): S21-S29. DOI: 10.1053/JTLS005s00021. [10] SCHEUER PJ. Classification of chronic viral hepatitis: a need for reassessment[J]. J Hepatol, 1991, 13(3): 372-374. DOI: 10.1016/0168-8278(91)90084-o. [11] LUDWIG J. The nomenclature of chronic active hepatitis: an obituary[J]. Gastroenterology, 1993, 105(1): 274-278. DOI: 10.1016/0016-5085(93)90037-d. [12] WANG W, LI J, PAN R, et al. Association of the Laennec staging system with degree of cirrhosis, clinical stage and liver function[J]. Hepatol Int, 2015, 9(4): 621-626. DOI: 10.1007/s12072-015-9648-7. [13] KIM MY, CHO MY, BAIK SK, et al. Histological subclassification of cirrhosis using the Laennec fibrosis scoring system correlates with clinical stage and grade of portal hypertension[J]. J Hepatol, 2011, 55(5): 1004-1009. DOI: 10.1016/j.jhep.2011.02.012. [14] KIM SU, OH HJ, WANLESS IR, et al. The Laennec staging system for histological sub-classification of cirrhosis is useful for stratification of prognosis in patients with liver cirrhosis[J]. J Hepatol, 2012, 57(3): 556-563. DOI: 10.1016/j.jhep.2012.04.029. [15] SUN Y, ZHOU J, WANG L, et al. New classification of liver biopsy assessment for fibrosis in chronic hepatitis B patients before and after treatment[J]. Hepatology, 2017, 65(5): 1438-1450. DOI: 10.1002/hep.29009. [16] RONG G, CHEN Y, YU Z, et al. Synergistic effect of biejia-ruangan on fibrosis regression in patients with chronic hepatitis B treated with entecavir: A multicenter, randomized, double-blind, placebo-controlled trial[J]. J Infect Dis, 2022, 225(6): 1091-1099. DOI: 10.1093/infdis/jiaa266. [17] JI D, CHEN Y, BI J, et al. Entecavir plus Biejia-Ruangan compound reduces the risk of hepatocellular carcinoma in Chinese patients with chronic hepatitis B[J]. J Hepatol, 2022, 77(6): 1515-1524. DOI: 10.1016/j.jhep.2022.07.018. [18] FATTOVICH G, STROFFOLINI T, ZAGNI I, et al. Hepatocellular carcinoma in cirrhosis: incidence and risk factors[J]. Gastroenterology, 2004, 127(5 Suppl 1): S35-S50. DOI: 10.1053/j.gastro.2004.09.014. [19] NAGULA S, JAIN D, GROSZMANN RJ, et al. Histological-hemodynamic correlation in cirrhosis-a histological classification of the severity of cirrhosis[J]. J Hepatol, 2006, 44(1): 111-117. DOI: 10.1016/j.jhep.2005.07.036. [20] SETHASINE S, JAIN D, GROSZMANN RJ, et al. Quantitative histological-hemodynamic correlations in cirrhosis[J]. Hepatology, 2012, 55(4): 1146-1153. DOI: 10.1002/hep.24805. [21] ZIPPRICH A, GARCIA-TSAO G, ROGOWSKI S, et al. Prognostic indicators of survival in patients with compensated and decompensated cirrhosis[J]. Liver Int, 2012, 32(9): 1407-1414. DOI: 10.1111/j.1478-3231.2012.02830.x. [22] RIPOLL C, BAÑARES R, RINCÓN D, et al. Influence of hepatic venous pressure gradient on the prediction of survival of patients with cirrhosis in the MELD Era[J]. Hepatology, 2005, 42(4): 793-801. DOI: 10.1002/hep.20871. [23] JAIN D, SREENIVASAN P, INAYAT I, et al. Thick fibrous septa on liver biopsy specimens predict the development of decompensation in patients with compensated cirrhosis[J]. Am J Clin Pathol, 2021, 156(5): 802-809. DOI: 10.1093/ajcp/aqab024. [24] WANLESS IR, NAKASHIMA E, SHERMAN M. Regression of human cirrhosis. Morphologic features and the genesis of incomplete septal cirrhosis[J]. Arch Pathol Lab Med, 2000, 124(11): 1599-1607. DOI: 10.5858/2000-124-1599-ROHC. [25] HE ZY, WANG BQ, YOU H. Clinical application of quantitative assessment of liver fibrosis based on pathology and imaging technology[J]. J Clin Hepatol, 2018, 35(1): 20-23. DOI: 10.3969/j.issn.1001-5256.2018.01.003.何志颖, 王冰琼, 尤红. 基于病理和影像学的肝纤维化量化评估技术的临床应用[J]. 临床肝胆病杂志, 2018, 34(1): 20-23. DOI: 10.3969/j.issn.1001-5256.2018.01.003. -
本文二维码
图(4) / 表(5)
计量
- 文章访问数: 437
- HTML全文浏览量: 325
- PDF下载量: 73
- 被引次数: 0
