代谢相关脂肪性肝病肝纤维化分期与结直肠占位性病变的关联性分析
DOI: 10.12449/JCH260611
Association between liver fibrosis staging and colorectal space-occupying lesions in metabolic associated fatty liver disease
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摘要:
目的 探讨结直肠占位性病变与代谢相关脂肪性肝病(MAFLD)之间的关联,以期为MAFLD人群早期识别结直肠占位性病变提供新思路。 方法 回顾性纳入2018年9月1日—2023年8月31日于山东第一医科大学第一附属医院(山东省千佛山医院)住院,并同期完成结肠镜及腹部影像学(腹部超声、腹部磁共振成像或计算机体层成像之一)检查的12 252例患者。根据结肠镜结果将患者分为结直肠占位组(n=6 545)与结直肠非占位组(n=5 707)。比较两组患者的基线资料,采用单因素及多因素Logistic回归分析筛选结直肠占位性病变的影响因素,并进一步探讨MAFLD及基于肝纤维化4项(FIB-4)、非酒精性脂肪性肝病纤维化评分(NFS)和天冬氨酸氨基转移酶/血小板比值指数(APRI)评分评估的肝纤维化与结直肠占位性病变的关联。符合偏态分布的计量资料两组间比较采用Mann-Whitney U检验;计数资料两组间比较采用χ²检验或Fisher确切概率法。 结果 单因素分析显示,结直肠占位组患者的年龄(Z=-95.628,P<0.001)、男性占比(χ2=406.910,P<0.001)、体重(Z=-24.928,P<0.001)、体重指数(BMI)(Z=-21.367,P<0.001)、舒张压(Z=-15.527,P<0.001)、收缩压(Z=-16.965,P<0.001)、冠心病史(χ2=28.112,P<0.001)、高血压史(χ2=152.993,P<0.001)、糖尿病史(χ2=52.175,P<0.001)、脑梗死史(χ2=14.097,P<0.001)、白细胞(WBC)(Z=-12.801,P<0.001)、血红蛋白(HGB)(Z=-19.258,P<0.001)、天冬氨酸氨基转移酶(Z=-6.673,P=0.001)、丙氨酸氨基转移酶(Z=-10.375,P<0.001)、碱性磷酸酶(Z=-10.496,P<0.001)、γ-谷氨酰转移酶(GGT)(Z=-18.893,P<0.001)、血尿素氮(Z=-13.291,P<0.001)、肌酐(Z=-16.798,P<0.001)、尿酸(Z=-16.822,P<0.001)、甘油三酯(Z=-10.186,P<0.001)和空腹葡萄糖(Z=-15.761,P<0.001)显著高于结直肠非占位组。多因素Logistic回归分析结果显示,年龄[比值比(OR)=1.052,95%置信区间(CI):1.045~1.057,P<0.001]、性别(OR=0.523,95%CI:0.466~0.587,P<0.001)、BMI(OR=1.031,95%CI:1.018~1.046,P<0.001)、高血压史(OR=1.140,95%CI:1.019~1.276,P=0.022)、WBC(OR=1.057,95%CI:1.028~1.087,P<0.001)、GGT(OR=1.001,95%CI:1.000~1.002,P=0.021)、白蛋白(Alb)(OR=0.982,95%CI:0.969~0.995,P=0.008)及HGB(OR=1.004,95%CI:1.001~1.008,P=0.019)是结直肠占位性病变的独立影响因素。在MAFLD人群中,校正年龄、性别、BMI、高血压史、WBC、HGB、GGT及Alb后,经FIB-4与NFS评分评估的中高危进展期肝纤维化仍是结直肠占位性病变的影响因素(FIB-4:OR=1.457,95%CI:1.176~1.810;NFS:OR=1.499,95%CI:1.244~1.809,P值均<0.05)。其中,基于FIB-4评分评估的肝纤维化程度与结直肠占位性病变的病理类型、部位、大小及数量均无显著相关性(P值均>0.05);基于NFS的中高危进展期肝纤维化虽与病理类型、部位及大小无关,但与病变数量可能存在关联(χ2=9.770,P<0.05)。 结论 年龄、性别、BMI、高血压史、WBC、HGB、GGT及Alb是结直肠占位性病变的独立影响因素。经FIB-4或NFS评估的中高危进展期肝纤维化与结直肠占位性病变存在独立关联,其中基于NFS评估的肝纤维化程度可能与占位性病变数量增多相关。 Abstract:Objective To investigate whether there exists an independent association beyond shared risk factors between colorectal space-occupying lesions and metabolic associated fatty liver disease (MAFLD), and to provide new ideas for early identification of colorectal space-occupying lesions in the MAFLD population. Methods A retrospective analysis was performed for 12 252 patients who were hospitalized in The First Affiliated Hospital of Shandong First Medical University (Shandong Provincial Qianfoshan Hospital) and underwent both colonoscopy and abdominal imaging (abdominal ultrasound, magnetic resonance imaging, or computed tomography) from September 1, 2018 to August 31, 2023. According to colonoscopy findings, the patients were divided into colorectal space-occupying lesion group with 6 545 patients and non-colorectal space-occupying lesion group with 5 707 patients. Baseline data were compared between the two groups. The univariate and multivariate Logistic regression analyses were used to identify influencing factors for colorectal space-occupying lesions, and further analysis was performed to investigate the association of MAFLD and liver fibrosis (assessed by fibrosis-4 [FIB-4], nonalcoholic fatty liver disease fibrosis score [NFS], and aspartate aminotransferase-to-platelet ratio index) with colorectal space-occupying lesions. The Mann-Whitney U test was used for comparison of continuous data with skewed distribution between groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. Results The univariate analysis showed that compared with the non-colorectal space-occupying lesion group, the colorectal space-occupying lesion group had significantly higher age (Z=-95.628, P<0.001), proportion of male patients (χ2=406.910, P<0.001), body weight (Z=-24.928, P<0.001), body mass index (BMI) (Z=-21.367, P<0.001), diastolic blood pressure (Z=-15.527, P<0.001), systolic blood pressure (Z=-16.965, P<0.001), proportion of patients with history of coronary heart disease (χ2 =28.112, P<0.001)/hypertension (χ2 =152.993, P<0.001)/diabetes (χ2 =52.175, P<0.001)/cerebral infarction (χ2 =14.097, P<0.001), white blood cell count (WBC) (Z=-12.801, P<0.001), hemoglobin (HGB) (Z=-19.258, P<0.001), aspartate aminotransferase (Z=-6.673, P=0.001), alanine aminotransferase (Z=-10.375, P<0.001), alkaline phosphatase (Z=-10.496, P<0.001), gamma-glutamyl transpeptidase (GGT) (Z=-18.893, P<0.001), blood urea nitrogen (Z=-13.291, P<0.001), creatinine (Z=-16.798, P<0.001), uric acid (Z=-16.822, P<0.001), triglyceride (Z=-10.186, P<0.001), and fasting blood glucose (Z=-15.761, P<0.001). The multivariate Logistic regression analysis showed that age (odds ratio [OR]=1.052, 95% confidence interval [CI]: 1.045 — 1.057, P<0.001), sex (OR=0.523, 95%CI: 0.466 — 0.587, P<0.001), BMI (OR=1.031, 95%CI: 1.018 — 1.046, P<0.001), history of hypertension (OR=1.140, 95%CI: 1.019 — 1.276, P=0.022), WBC (OR=1.057, 95%CI: 1.028 — 1.087, P<0.001), GGT (OR=1.001, 95%CI: 1.000 — 1.002, P=0.021), Alb (OR=0.982, 95%CI: 0.969 — 0.995, P=0.008), and HGB (OR=1.004, 95%CI: 1.001 — 1.008, P=0.019) were independent influencing factors for colorectal space-occupying lesions. In the MAFLD population, after adjustment for age, sex, BMI, history of hypertension, WBC, HGB, GGT, and Alb, intermediate-to-high risk of advanced liver fibrosis assessed by FIB-4 and NFS was still an influencing factor for colorectal space-occupying lesions (FIB-4: OR=1.457, 95%CI: 1.176 — 1.810, P<0.05; NFS: OR=1.499, 95%CI: 1.244 — 1.809, P<0.05). Liver fibrosis degree based on FIB-4 was not significantly associated with the pathological type, location, size, or number of colorectal space-occupying lesions (all P>0.05). While intermediate-to-high risk of advanced liver fibrosis based on NFS was not associated with pathological type, location, or size, it might be associated with the number of lesions (χ2=9.770, P<0.05). Conclusion Age, sex, BMI, history of hypertension, WBC, HGB, GGT, and Alb are independent influencing factors for colorectal space-occupying lesions. Intermediate-to-high risk of advanced liver fibrosis assessed by FIB-4 or NFS is independently associated with colorectal space-occupying lesions, and liver fibrosis assessed by NFS might be associated with the increase in the number of lesions. -
表 1 两组患者的一般资料及生化资料比较
Table 1. Comparison of general characteristics and biochemical parameters between the two groups of patients
指标 结直肠占位组(n=6 545) 结直肠非占位组(n=5 707) 统计值 P值 年龄(岁) 54(48~59) 50(43~57) Z=-95.628 <0.001 性别[例(%)] χ2=406.910 <0.001 男 4 132(63.1) 2 565(44.9) 女 2 413(36.9) 3 142(55.1) 体重(kg) 72.0(64.0~80.0) 67.5(60.0~77.0) Z=-24.928 <0.001 BMI(kg/m2) 25.34(23.12~27.68) 24.50(22.21~26.97) Z=-21.367 <0.001 舒张压(mmHg) 80(72~88) 78(70~86) Z=-15.527 <0.001 收缩压(mmHg) 130(120~141) 126(117~138) Z=-16.965 <0.001 冠心病史[例(%)] χ2=28.112 <0.001 是 832(12.7) 552(9.7) 否 5 713(87.3) 5 155(90.3) 高血压史[例(%)] χ2=152.993 <0.001 是 1 796(27.4) 1 026(18.0) 否 4 749(72.6) 4 681(82.0) 糖尿病史[例(%)] χ2=52.175 <0.001 是 972(14.9) 598(10.5) 否 5 573(85.1) 5 109(89.5) 脑梗死史[例(%)] χ2=14.097 <0.001 是 355(5.4) 227(4.0) 否 6 190(94.6) 5 480(96.0) WBC(×109/L) 5.68(4.79~6.74) 5.46(4.59~6.47) Z=-12.801 <0.001 PLT(×109/L) 230(198~268) 235(201~274) Z=-0.231 0.817 HGB(g/L) 144(133~154) 139(127~151) Z=-19.258 <0.001 AST(U/L) 17.90(15.10~22.00) 17.60(14.90~21.30) Z=-6.673 0.001 ALT(U/L) 17.30(12.40~24.40) 16.00(11.60~23.50) Z=-10.375 <0.001 ALP(U/L) 67(56~80) 66(55~79) Z=-10.496 <0.001 GGT(U/L) 23.00(15.30~38.05) 19.00(13.00~39.00) Z=-18.893 <0.001 Alb(g/L) 45.30(42.60~47.60) 45.60(42.90~47.90) Z=-0.168 0.867 BUN(mmol/L) 4.90(4.10~5.70) 4.70(3.90~5.90) Z=-13.291 <0.001 Cr(μmol/L) 68(59~78) 64(56~75) Z=-16.798 <0.001 UA(μmol/L) 319(264~380) 296(243~362) Z=-16.822 <0.001 TC(mmol/L) 4.77(4.25~5.30) 4.77(4.28~5.27) Z=-0.224 0.822 TG(mmol/L) 1.24(0.98~1.81) 1.24(0.87~1.64) Z=-10.186 <0.001 LDL(mmol/L) 2.77(2.38~3.19) 2.77(2.38~3.16) Z=-1.054 0.291 FBG(mmol/L) 5.14(4.70~5.75) 5.00(4.60~5.50) Z=-15.761 <0.001 注:BMI,体重指数;WBC,白细胞;PLT,血小板计数;HGB,血红蛋白;AST,天冬氨酸氨基转移酶;ALT,丙氨酸氨基转移酶;ALP,碱性磷酸酶;GGT,γ-谷氨酰转移酶;Alb,白蛋白;BUN,血尿素氮;Cr,肌酐;UA,尿酸;TC,总胆固醇;TG,甘油三酯;LDL,低密度脂蛋白;FBG,空腹血糖。
表 2 结直肠占位性病变影响因素的多因素Logistic回归分析
Table 2. Multivariate Logistic regression analysis of influencing factors for colorectal space-occupying lesions
影响因素 β值 Wald OR(95%CI) P值 年龄(岁) 0.050 324.674 1.052(1.045~1.057) <0.001 女性 -0.648 122.073 0.523(0.466~0.587) <0.001 BMI(kg/m2) 0.031 19.965 1.031(1.018~1.046) <0.001 收缩压(mmHg) 0.003 3.231 1.003(0.999~1.006) 0.072 高血压史 0.131 5.241 1.140(1.019~1.276) 0.022 WBC(×109/L) 0.055 15.229 1.057(1.028~1.087) <0.001 GGT(U/L) 0.001 5.362 1.001(1.000~1.002) 0.021 Alb(g/L) -0.018 7.122 0.982(0.969~0.995) 0.008 HGB(g/L) 0.004 5.539 1.004(1.001~1.008) 0.019 注:BMI,体重指数;WBC,白细胞;HGB,血红蛋白;GGT,γ-谷氨酰转移酶;Alb,白蛋白;OR,比值比;CI,置信区间。
表 3 MAFLD与结直肠占位性病变的关系
Table 3. Association of MAFLD with colorectal space-occupying lesions
项目 例数 结直肠占位组 结直肠非占位组 χ2值 P值 MAFLD[例(%)] 5.440 0.020 否 9 189 4 853(52.8) 4 336(47.2) 是 3 063 1 692(55.2) 1 371(44.8) FIB-4[例(%)]1) 14.912 <0.001 <1.3 2 485 1 328(53.4) 1 157(46.6) ≥1.3 469 296(63.1) 173(36.9) APRI[例(%)]2) 0.004 0.950 <0.5 2 842 1 563(55.0) 1 279(45.0) ≥0.5 117 64(54.7) 53(45.3) NFS[例(%)]3) 19.807 <0.001 <-1.455 2 185 1 152(52.7) 1 033(47.3) ≥-1.455 650 407(62.6) 243(37.4) 注:MAFLD,代谢相关脂肪性肝病;FIB-4,肝纤维化4项;APRI,天冬氨酸氨基转移酶/血小板比值指数;NFS,非酒精性脂肪性肝病纤维化评分。1)指标缺失,排除109例;2)指标缺失,排除104例;3)指标缺失,排除228例。
表 4 MAFLD与结直肠占位性病变关系的Logistic回归分析
Table 4. Association of MAFLD with colorectal space-occupying lesions: A Logistic regression analysis
变量 模型1 模型2 模型3 OR 95%CI P值 OR 95%CI P值 OR 95%CI P值 MAFLD 否 1.000 1.000 1.000 是 1.103 1.016~1.197 0.020 1.022 0.933~1.120 0.633 0.988 0.899~1.085 0.798 FIB-4 <1.3 1.000 1.000 1.000 ≥1.3 1.491 1.218~1.830 <0.001 1.493 1.214~1.842 <0.001 1.457 1.176~1.810 0.001 APRI <0.5 1.000 1.000 1.000 ≥0.5 0.988 0.682~1.437 0.950 0.856 0.577~1.272 0.439 0.779 0.515~1.180 0.237 NFS <-1.455 1.000 1.000 1.000 ≥-1.455 1.502 1.256~1.799 <0.001 1.525 1.274~1.829 <0.001 1.499 1.244~1.809 <0.001 注:模型1未校正因素,模型2在模型1的基础上校正年龄、性别、BMI,模型3在模型2的基础上校正高血压史、WBC、HGB、GGT、Alb;因FIB-4评分中包含年龄,NFS评分中包含年龄、BMI、Alb,在进行各个评分的回归分析时未对包含的指标进行校正。MAFLD,代谢相关脂肪性肝病;FIB-4,肝纤维化4项;NFS,非酒精性脂肪性肝病纤维化评分;APRI,天冬氨酸氨基转移酶/血小板比值指数;OR,比值比;CI,置信区间。
表 5 经FIB-4分组肝纤维化分期与结直肠占位性病变特点的关系
Table 5. Association of liver fibrosis stages with characteristics of colorectal space-occupying lesions according to FIB-4 stratification
因素 FIB-4<1.3(n=1 328) FIB-4≥1.3(n=296) χ2值 P值 病理类型[例(%)]1) 0.954 恶性病变 21(1.6) 5(1.7) 良性病变 腺瘤性息肉 912(68.7) 206(69.6) 锯齿状病变 142(10.7) 27(9.1) 炎性息肉 176(13.3) 40(13.5) 单纯脂肪瘤、平滑肌瘤 9(0.7) 1(0.3) 其他类型 2(0.2) 1(0.3) 占位性病变位置[例(%)]2) 2.920 0.404 回盲肠+升结肠 156(11.7) 34(11.5) 结肠肝曲+横结肠+结肠脾曲 211(15.9) 45(15.2) 降结肠+乙状结肠+直肠 461(34.7) 89(30.1) 全结肠 475(35.8) 119(40.2) 占位性病变大小[例(%)]3) 2.060 0.358 ≤5 mm 620(46.7) 123(41.6) >5 mm~≤10 mm 561(42.2) 133(44.9) >10 mm 91(6.9) 23(7.8) 占位性病变数量[例(%)]4) 4.050 0.257 1个 603(45.4) 129(43.6) 2个 321(24.2) 60(20.3) 3~9个 361(27.2) 93(31.4) ≥10个 18(1.4) 6(2.0) 注:FIB-4,肝纤维化4项。1)在FIB-4<1.3组及FIB-4≥1.3组的缺失例数分别为66例、16例;2)两组缺失例数分别为25例、9例;3)两组缺失例数分别为56例、17例;4)两组缺失例数分别为25例、8例。
表 6 经NFS分组肝纤维化分期与结直肠占位性病变特点的关系
Table 6. Association of liver fibrosis stages with characteristics of colorectal space-occupying lesions according to NFS stratification
因素 NFS<-1.455(n=1 152) NFS≥-1.455(n=407) χ2值 P值 病理类型[例(%)]1) 0.801 恶性病变 16(1.4) 8(2.0) 良性病变 腺瘤性息肉 799(69.4) 278(68.3) 锯齿状病变 125(10.9) 38(9.3) 炎性息肉 151(13.1) 57(14.0) 单纯脂肪瘤、平滑肌瘤 6(0.5) 3(0.7) 其他类型 2(0.2) 0(0.0) 占位性病变位置[例(%)]2) 5.370 0.147 回盲肠+升结肠 137(11.9) 44(10.8) 结肠肝曲+横结肠+结肠脾曲 182(15.8) 63(15.5) 降结肠+乙状结肠+直肠 407(35.3) 122(30.0) 全结肠 406(35.2) 166(40.8) 占位性病变大小[例(%)]3) 4.450 0.108 ≤5 mm 542(47.0) 167(41.0) >5 mm~≤10 mm 479(41.6) 191(46.9) >10 mm 81(7.0) 30(7.4) 占位性病变数量[例(%)]4) 9.770 0.021 1个 533(46.3) 169(41.5) 2个 287(24.9) 86(21.1) 3~9个 297(25.8) 132(32.4) ≥10个 15(1.3) 9(2.2) 注:NFS,非酒精性脂肪性肝病纤维化评分。1)在NFS<-1.455组及NFS≥-1.455组的缺失例数分别为53例、23例;2)两组缺失例数分别为20例、12例;3)两组缺失例数分别为50例、19例;4)两组缺失例数分别为20例、11例。
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