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人工智能在胰腺癌诊治中的应用现状

马昱 贾峰 刘楷宇 刘亚辉

李小婷, 胡伯斌, 刘宏宇, 等. FIB-4和APRI评估慢性HBV感染者肝纤维化程度的效果比较[J]. 临床肝胆病杂志, 2024, 40(12): 2424-2429. DOI: 10.12449/JCH241212.
引用本文: 李小婷, 胡伯斌, 刘宏宇, 等. FIB-4和APRI评估慢性HBV感染者肝纤维化程度的效果比较[J]. 临床肝胆病杂志, 2024, 40(12): 2424-2429. DOI: 10.12449/JCH241212.
LI XT, HU BB, LIU HY, et al. Effectiveness of fibrosis-4 versus aspartate aminotransferase-to-platelet ratio index in evaluating liver fibrosis degree in patients with chronic HBV infection[J]. J Clin Hepatol, 2024, 40(12): 2424-2429. DOI: 10.12449/JCH241212.
Citation: LI XT, HU BB, LIU HY, et al. Effectiveness of fibrosis-4 versus aspartate aminotransferase-to-platelet ratio index in evaluating liver fibrosis degree in patients with chronic HBV infection[J]. J Clin Hepatol, 2024, 40(12): 2424-2429. DOI: 10.12449/JCH241212.

人工智能在胰腺癌诊治中的应用现状

DOI: 10.12449/JCH241032
利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:马昱负责设计论文框架,起草论文;贾峰负责关键点分析,论文修改;马昱、刘楷宇负责文献查找;刘亚辉负责拟定写作思路,指导撰写文章并最后定稿。
详细信息
    通信作者:

    刘亚辉, yahui@jlu.edu.cn (ORCID: 0000-0002-5431-1440)

Current status of the application of artificial intelligence in the diagnosis and treatment of pancreatic cancer

More Information
    Corresponding author: LIU Yahui, yahui@jlu.edu.cn (ORCID: 0000-0002-5431-1440)
  • 摘要: 胰腺癌是消化系统常见的恶性肿瘤,早期诊断率低,手术病死率高,治愈率低,总体预后差。近年来,随着人工智能在医学领域的不断发展,机器学习、深度学习等人工智能技术被广泛应用于医学研究中。本文综述了近年来人工智能技术在胰腺癌筛查、诊断、治疗、并发症及预后预测等方面的应用,为人工智能在胰腺癌诊治中的应用提供依据和新思路。

     

  • 肝纤维化是慢性肝病进行性发展的结果,其终末阶段是肝硬化、失代偿性肝功能衰竭或肝细胞癌(HCC)。肝活检被认为是评估肝纤维化的金标准1-2,但具有侵袭性和一定的风险,且重复性受限3。近年来,非侵入性方法用于诊断肝纤维化已经取得了一些进展,其目的是在肝硬化发展并出现症状之前无需进行肝活检即可检测肝纤维化,这些方法易于使用、可靠且具有再现性,也可用于监测疾病进展和治疗反应4-5。世界卫生组织推荐使用FIB-4和APRI作为慢性乙型肝炎(CHB)患者肝纤维化的非侵入性诊断方法。美国肝病学会、欧洲肝病学会和日本肝病学会等发布的乙型肝炎临床指南中也推荐使用FIB-4和APRI进行肝纤维化诊断6。基于上述背景,本文研究FIB-4和APRI在评估肝纤维化进展方面的作用。

    纳入2013年2月—2022年12月在本院感染科就诊的479例被诊断为慢性HBV感染的患者,其中404例患者进入回顾性研究,75例患者进入前瞻性研究。纳入标准:(1)乙型肝炎表面抗原阳性;(2)在回顾性研究中患者基线时行肝穿刺病理活检;(3)在前瞻性研究中患者在干扰素治疗48周后行肝穿刺活检。排除合并甲、丙、丁及戊型肝炎病毒感染的患者。

    在回顾性研究中,404例慢性HBV感染的患者根据基线时肝穿刺病理结果,分别诊断为乙型肝炎表面抗原携带(ASC)(n=19)、CHB (n=246)、乙型肝炎肝硬化(LC)(n=25)、HCC (n=114)。在前瞻性研究中,75例患者经干扰素治疗48周后停药,在停药时接受肝穿刺病理活检。根据METAVIR评分将患者按肝纤维化程度分为F0、F1、F2、F3和F4期。收集患者基线人口统计学特征(性别、年龄)、生化指标(ALT、AST)、血小板计数等。APRI和FIB-4计算公式及其范围参照既往文献4,APRI=(AST/ULN)×100/血小板计数(109/L);FIB-4=年龄(岁)×AST(U/L)/[血小板计数(109/L)×ALT(U/L)](高值:≥2.67,低值:≤1.30,中间值:1.30~2.67)。具体研究方案详见图1

    图  1  研究方案流程
    Figure  1.  Research proposal process diagram

    使用SPSS 26.0软件进行统计分析。使用单样本Shapiro-Wilk检验对计量资料进行正态分布检验;非正态分布的计量资料采用MP25P75)表示,两组间比较采用Mann-Whitney U检验,多组间数据比较采用Kruskal-Wallis H检验;计数资料组间比较采用χ2检验。采用受试者工作特征曲线(ROC曲线)下面积(AUC)分析评估APRI和FIB-4预测慢性HBV感染者肝纤维化程度差异和疾病进展的能力。P<0.05为差异有统计学意义。

    2.1.1   一般资料

    404例患者平均年龄42(35~51)岁,ALT和AST分别为34(22~54)U/L和31(22~45)U/L。不同纤维化程度(F0~F4)患者的血小板计数(H=25.83,P<0.001)和白蛋白水平(H=20.70,P=0.001)差异均有统计学意义(表1)。

    表  1  基线时AST、ALT、血小板及白蛋白水平
    Table  1.  Levels of AST, ALT, platelets, and albumin at baseline
    指标 数值
    ALT(U/L) 34(22~54)
    AST(U/L) 31(22~45)
    血小板计数(×109/L)
    F0期 204.6(175.6~246.0)
    F1期 203.5(173.6~241.0)
    F2期 198.2(150.0~235.0)
    F3期 192.9(153.5~243.0)
    F4期 168.0(121.5~202.0)
    白蛋白(g/L)
    F0期 43.2(38.9~45.9)
    F1期 42.3(38.9~45.0)
    F2期 41.3(38.6~44.0)
    F3期 41.5(36.9~43.4)
    F4期 39.8(37.0~42.8)
    下载: 导出CSV 
    | 显示表格
    2.1.2   FIB-4和APRI在不同诊断分组中的差异

    FIB-4和APRI在不同疾病分组中的分布情况见图2。诊断为LC和HCC患者的FIB-4显著高于诊断为ASC和CHB患者,差异有统计学意义(P<0.001);诊断为LC和HCC患者的APRI显著高于诊断为ASC和CHB患者,差异有统计学意义(P<0.001)(表2)。

    图  2  FIB-4和APRI在不同疾病分组中的分布
    Figure  2.  Distribution of FIB-4 index and APRI in patients with different diagnostic degrees
    表  2  不同疾病分组的FIB-4和APRI比较
    Table  2.  FIB-4 and APRI indexes of different disease groups were compared
    组别 FIB-4 APRI
    ASC和CHB 1.0(0.7~1.6) 0.4(0.2~0.6)
    LC和HCC 1.7(1.1~2.8) 1.2(0.8~1.9)
    Z 6.79 3.49
    P <0.001 <0.001
    下载: 导出CSV 
    | 显示表格

    FIB-4在高值范围(≥2.67)的患者共139例(34.4%,139/404),其中诊断为LC和HCC患者占66.19%(92/139),诊断为ASC和CHB的患者占33.81%(47/139)。与FIB-4<2.67相比,FIB-4≥2.67时,患者被诊断为LC和HCC的概率升高(66.19% vs 47.54%,χ2=12.75,P<0.001)。

    2.1.3   FIB-4和APRI对肝纤维化程度诊断的准确性
    2.1.3.1   评估APRI和FIB-4与纤维化程度的关系

    FIB-4在F0~F4期的中位值分别为0.91、0.96、1.16、1.35、1.81,其差异有统计学意义(H=42.50,P<0.001)。APRI在F0~F4期的中位值分别为0.32、0.33、0.42、0.56、0.63,其差异有统计学意义(H=35.90,P<0.001)。此外,在F0~F4各纤维化分期中,相同分期的FIB-4中位值均高于APRI(H=59.71,P<0.001)(图3)。

    图  3  APRI和FIB-4与肝纤维化分期的关系
    Figure  3.  APRI and FIB-4 in relation to histological fibrosis staging
    2.1.3.2   APRI和FIB-4对肝纤维化F3期和F4期诊断的准确性

    采用ROC曲线分析FIB-4和APRI对F3、F4期诊断的准确性(图4),其临界值、敏感度及特异度见表3。对于F3期,FIB-4的AUC为0.67(95%CI:0.62~0.72),APRI的AUC为0.65(95%CI:0.60~0.70),其差异无统计学意义(Z=0.71,P=0.480)。对于F4期,FIB-4的AUC为0.72(95%CI:0.67~0.78),APRI的AUC为0.64(95%CI:0.58~0.70),FIB-4对肝纤维化F4期的预测效能高于APRI(Z=10.50,P<0.001)。

    图  4  FIB-4和APRI诊断肝纤维化F3和F4期的ROC曲线
    Figure  4.  ROC curves of FIB-4 and APRI in diagnosing liver fibrosis F3 and F4
    表  3  FIB-4和APRI诊断准确性对比
    Table  3.  Comparison of diagnostic accuracy between FIB-4 and APRI scores
    项目 APRI FIB-4
    F3 F4 F3 F4
    AUC 0.65 0.64 0.67 0.72
    临界值 0.249 0.264 0.329 0.357
    敏感度 0.632 0.653 0.781 0.602
    特异度 0.468 0.611 0.696 0.756
    下载: 导出CSV 
    | 显示表格
    2.2.1   一般资料

    前瞻性研究队列共75例,把停药后肝穿刺时间点作为基线。患者肝纤维化分期为F0~F3,中位年龄42岁。随访观察1~10年,中位随访时间2(1~5)年。ALT和AST分别为44 U/L和36 U/L。不同肝纤维化程度(F0~F4)患者的血小板计数(H=6.33,P=0.09)及白蛋白含量(H=3.04,P=0.39)差异均无统计学意义(表4)。

    表  4  前瞻性研究队列基线时AST、ALT、血小板及白蛋白水平
    Table  4.  Levels of AST, ALT, platelets and albumin at baseline in a prospective study cohort
    指标 数值
    ALT(U/L) 44(26~85)
    AST(U/L) 36(26~60)
    血小板计数(×109/L)
    F0期 204.5(161.0~254.8)
    F1期 186.5(160.6~221.2)
    F2期 187.0(146.3~238.3)
    F3期 148.9(128.5~178.0)
    白蛋白(g/L)
    F0期 41.9(39.7~48.1)
    F1期 42.6(39.4~45.2)
    F2期 43.7(40.1~46.9)
    F3期 41.3(34.3~44.8)
    下载: 导出CSV 
    | 显示表格
    2.2.2   观察期间病情进展与FIB-4和APRI之间的关系

    前瞻性研究队列随访观察1~10年。计算FIB-4和APRI每年增长率[(指标值n+1-指标值n)/n],FIB-4指数10年间平均年增长率为0.008,FIB-4每年增长率在不同观察年限中的分布差异具有统计学意义(H=87.231,P<0.001),而APRI未观察到随时间增长的趋势。此外,根据患者病情进展情况分为CHB-CHB、CHB-LC、LC-LC三组,每组分别为47例、21例和7例。观察发现,FIB-4和APRI在出现病情进展(CHB-LC)的患者中有增加趋势,而在未出现病情进展(CHB-CHB或LC-LC)的患者中没有观察到增加趋势(图5)。

    图  5  观察期间患者病情进展与FIB-4和APRI之间的关系
    Figure  5.  Relationship between the progression of the patient’s condition and FIB-4 and APRI during the observation period
    2.2.3   FIB-4和APRI预测慢性HBV感染者疾病进展的能力

    28.0%(21/75)的患者疾病进展为LC。针对出现疾病进展的患者(CHB-LC),采用ROC曲线评估FIB-4和APRI预测疾病进展的能力。ROC曲线分析结果显示,FIB-4的AUC为0.718(95%CI:0.476~0.760),APRI的AUC为0.555(95%CI:0.408~0.703),二者差异有统计学意义(Z=2.03,P=0.02)。同时根据ROC曲线结果,采用最大约登指数及其所对应的敏感度和特异度进一步计算准确性,结果发现,FIB-4和APRI的临界值分别为0.217和0.185,准确率分别为77.6%和54.7%,FIB-4预测CHB进展为LC的准确率高于APRI(χ2=12.44,P<0.001)。

    近年来,研究发现很多非侵入性检查可用于肝纤维化的诊断,FIB-4和APRI也在其中,可根据患者的年龄、AST和ALT以及血小板计数计算。这些指标在常规临床检查中经常检测,具有简单性和可重复性等优点7-8。然而,目前对FIB-4和APRI的适用性及其随时间变化的可用性评估尚未有明确定论。本研究回顾性分析404例、前瞻性研究75例HBV感染者的FIB-4和APRI在肝纤维化进展中的变化情况。

    本研究回顾性数据分析发现,FIB-4和APRI可以在一定程度上反映出患者纤维化进展的程度,特别是在晚期肝纤维化中,这与既往研究9-10结果一致。本研究还发现,FIB-4分布在较高数值(≥2.67)时,患者被诊断为LC和HCC的可能性更大。此外,在本研究的前瞻性观察队列中,出现疾病进展的患者(CHB-LC)FIB-4呈现增加趋势。与既往Gordon等11提出的FIB-4的增加与HCC发生风险相关这一结果相符。此外,FIB-4和APRI均可作为评估肝纤维化阶段的指标,FIB-4诊断纤维化F4期的准确性高于APRI,并且FIB-4和APRI在肝纤维化F4期诊断中的AUC分别为0.72和0.64,其中FIB-4预测晚期肝纤维化的AUC与既往报道12-14的AUC为0.7~0.8接近。也有研究12-14强调,在所有未经治疗的患者中,尽管病毒载量大致稳定,但FIB-4随着时间的推移,仍表现出明显增加的趋势,每年增加率约11%。既往有研究者6报道,FIB-4和APRI都表现出随时间进展的趋势,并且FIB-4的每年增加率大于APRI,FIB-4表现出了更佳的优势。此外,在出现病情进展的患者中,FIB-4和APRI也都表现出了随时间增加的趋势15-16。在本研究中,出现疾病进展的患者FIB-4和APRI也表现出了随观察时间增加的趋势。以上表明FIB-4和APRI可作为筛查肝纤维化的依据,并且FIB-4优于APRI17

    然而,也有研究1418认为,FIB-4和APRI在预测晚期肝纤维化方面的效果有限。有研究者19-21报道,FIB-4或APRI的假阴性和假阳性比例显著,二者中任何一种筛查难免会有错过需要转诊的患者,并且有过度诊断和无效转诊的风险。FIB-4和APRI可作为评估肝纤维化的指标,但应该谨慎使用。总之,FIB-4和APRI可能具备预测晚期肝纤维化的能力,并且表现出了随时间推移而增加的趋势。因此,监测FIB-4和APRI等非侵入性标志物,对于预测HBV感染者的疾病转归有重要意义。然而,本研究也存在一定的局限性,前瞻性研究队列中的患者已经接受过干扰素治疗并且样本量较少,应该设立治疗组和未治疗组进行比较,排除治疗因素干扰研究结果的可能。尽管如此,本文结果显示FIB-4和APRI具备一定预测晚期肝纤维化及疾病进展的能力,并且FIB-4均优于APRI。

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    梁智星, 叶林森, 杨扬. 人工智能在肝移植中的应用[J]. 临床肝胆病杂志, 2022, 38( 1): 30- 34. DOI: 10.3969/j.issn.1001-5256.2022.01.005.
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