慢性乙型肝炎患者肝纤维化程度与肾损伤的相关性分析
DOI: 10.3969/j.issn.1001-5256.2022.10.008
Correlation analysis of hepatic fibrosis and renal injury in patients with chronic hepatitis B
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摘要:
目的 分析慢性乙型肝炎(CHB)患者肝纤维化程度与肾功能损伤的关系。 方法 回顾性分析2010年5月—2019年10月798例CHB患者的肾功能,根据研究对象的肝纤维化4因子指数(FIB-4)水平将患者分为4组,Q1组(FIB-4≤0.74)200例,Q2组(0.74<FIB-4<1.13)199例,Q3组(1.13≤FIB-4<2.0)200例,Q4组(FIB-4≥2.0)199例。非正态分布计量资料多组间比较采用Kruskal-Wallis H检验。计数资料组间比较采用χ2检验。采用一元线性回归分析和Spearman偏相关分析确定FIB-4与估算肾小球滤过率(eGFR)之间的关系。采用多因素Logistic回归模型评估肾损伤的风险因素,计算优势比(OR)和95%CI。采用多分类Logistic回归分析不同分组的FIB-4与肾损伤的关系,计算OR和95%CI。绘制ROC曲线分析FIB-4在肾损伤诊断中的价值。 结果 FIB-4与年龄具有相关性(r值为0.650,P<0.001),因此采用Spearman偏相关分析对年龄、性别进行矫正。结果显示,FIB-4与ALT、AST、ALP、GGT、LDH、TBil、DBil、总蛋白、Alb、球蛋白、TBA、LAP、PLT、HBV DNA、AFP、eGFR仍有明显相关性(r值分别为0.202、0.354、0.292、0.287、0.222、0.377、0.361、-0.085、-0.412、0.168、0.422、0.247、-0.421、0.172、0.318、-0.359,P值均<0.05)。一元线性回归分析显示eGFR与FIB-4呈负相关(R2=0.1949)。多因素Logistic回归分析结果显示,HBV DNA、FIB-4是肾损伤的独立危险因素,(OR值分别为1.227、1.581,95%CI分别为1.038~1.452、1.359~1.839,P值分别为0.017、P<0.001)。多分类Logistic回归分析发现,FIB-4水平与可能的肾损伤发病呈正相关,随着FIB-4四分位数的降低,肾损伤发病率逐渐下降。FIB-4对肾损伤预测的ROC曲线下面积为0.74(95%CI: 0.67~0.82,P<0.001),敏感度为0.47,特异度为0.93,最佳截断值为3.48。 结论 CHB患者肝纤维化程度与肾损伤的风险相关。 Abstract:Objective To analyze the relationship between liver fibrosis and renal injury in patients with chronic hepatitis B (CHB). Methods We retrospectively analyzed the renal function of 798 CHB patients who were enrolled from May 2010 to October 2019. According to the quartile of fibrosis-4 (FIB-4) index, the population was divided into four groups: group Q1 (FIB-4≤0.74), group Q2 (0.74 < FIB-4 < 1.13), Q3 group (1.13≤FIB-4 < 2.0), and Q4 group (FIB-4≥2.0). The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between multiple groups. The chi-square test was used for comparison of categorical data between groups. Spearman partial correlation analysis was used to determine the relationship between FIB-4 and estimated glomerular filtration rate (eGFR). Multivariate Logistic regression model was used to assess the risk factors of renal injury using odds ratio (OR) and 95% confidence intervals (CI). Multiple Logistic regression was used to analyze the relationship between FIB-4 and renal injury in different groups. Results Because FIB-4 was correlated with age (r=0.650, P < 0.001), Spearman partial correlation analysis was used to adjust for age and gender. We found FIB-4 index was significantly associated with ALT, AST, ALP, GGT, LDH, TBil, DBil, TP, Alb, Glo, TBA, LAP, PLT, HBV DNA, AFP and eGFR (r values were 0.202, 0.354, 0.292, 0.287, 0.222, 0.377, 0.361, -0.085, -0.412, 0.168, 0.422, 0.427, 0.247, -0.421, 0.172, 0.318, -0.359, respectively, all P < 0.001). eGFR was negatively correlated with FIB-4 (R2=0.192 9). Multivariate logistic regression analysis found that HBV DNA(OR=1.227, 95%CI: 1.038-1.452, P=0.017), FIB-4(OR=1.581, 95%CI: 1.359-1.839, P < 0.001) were independent risk factors for renal injury. The AUC value of FIB-4 in predicting renal injury was 0.74 (95%CI: 0.67-0.82, P < 0.001), with a sensitivity of 0.47, a specificity of 0.93, and an optimal cutoff value of 3.48. Conclusions The degree of liver fibrosis in CHB patients is associated with the risk of renal injury. -
Key words:
- Hepatitis B, Chronic /
- Liver Cirrhosis /
- Glomerular Filtration Rate /
- Renal Injury
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表 1 按FIB-4分层的研究人群特征
Table 1. Characteristics of the study population stratified by the FIB-4 quartiles
指标 FIB-4 统计值 P值 Q1组(n=200) Q2组(n=199) Q3组(n=200) Q4组(n=199) 男性[例(%)] 111(55.5) 122(61.3) 110(55) 131(65.8) χ2=6.587 0.087 年龄(岁) 29(26~33) 35(31~43) 46.5(37~54) 41(52~60) H=329.27 0.001 ALT(U/L) 27.4(21.1~42.7) 25.3(18.4~42.7) 24.6(16.6~40.5) 38.2(21.7~76.7) H=38.37 0.001 AST(U/L) 22.7(20.1~27.4) 23.9(20.0~31.3) 24.2(19.9~32.3) 35.7(25.4~67.2) H=117.32 0.001 ALP(U/L) 61.1(51.0~72.3) 61.2(50.6~74.5) 64.8(53.6~79.3) 76.0(62.6~97.8) H=67.46 0.001 GGT(U/L) 18.2(14.2~25.4) 18.2(13.9~29.5) 18.3(13.4~28.3) 29.5(16.9~58.8) H=55.76 0.001 LDH(U/L) 186(167~209) 193(173~212) 189(171~210) 209(179~238) H=43.20 0.001 TBiL(mmol/L) 10.7(8.4~13.5) 11.7(9.0~15.8) 11.6(9.5~15.0) 14.9(11.3~19.6) H=62.83 0.001 DBiL(mmol/L) 2.7(1.7~3.7) 2.9(2.1~4.3) 2.9(2.3~3.9) 4.4(2.9~6.4) H=81.14 0.001 总蛋白(g/L) 74.6(71.9~77.5) 74.8(71.7~77.7) 74.2(71.3~77.2) 73.3(69.5~77.2) H=11.08 0.011 Alb(g/L) 45.3(44.3~46.9) 45.4(44.3~46.9) 44.7(43.6~46.2) 43.7(41.1~45.7) H=60.64 0.001 球蛋白(g/L) 29.2(26.9~31.7) 29.5(27.3~32.2) 29.7(26.4~32.3) 29.7(26.5~34.3) H=2.79 0.425 TBA(μmol/L) 2.0(1.4~3.0) 1.9(1.2~2.8) 2.3(1.3~4.1) 4.8(2.3~13.0) H=109.26 0.001 LAP(U/L) 51.6(46.5~58.9) 51.5(47.1~58.0) 51.1(46.1~58.1) 55.9(47.2~68.3) H=23.71 0.001 PLT(×109/L) 226.5(203.3~258.8) 190.0(169.0~221.0) 169.0(149.0~197.8) 119.0(86.0~158.0) H=342.03 0.001 BUN(mmol/L) 4.5(3.7~5.4) 4.7(3.9~5.4) 4.9(4.2~5.8) 4.9(4.2~5.8) H=12.65 0.005 甘油三酯(mmol/L) 0.8(0.7~1.1) 0.9(0.6~1.1) 0.9(0.7~1.1) 0.8(0.6~1.1) H=1.93 0.587 TC(mmol/L) 4.1(3.7~4.7) 4.1(3.6~4.7) 4.1(3.6~4.7) 4.1(3.7~4.8) H=0.28 0.963 高密度脂蛋白(mmol/L) 1.3(1.1~1.6) 1.3(1.1~1.5) 1.3(1.1~1.6) 1.4(1.1~1.7) H=2.41 0.493 低密度脂蛋白(mmol/L) 2.3(1.9~2.8) 2.3(1.9~2.9) 2.3(1.9~2.8) 2.3(1.9~2.7) H=1.57 0.667 apoA(g/L) 1.2(1.0~1.3) 1.2(1.0~1.3) 1.2(1.0~1.4) 1.2(0.9~1.4) H=7.65 0.054 apoB(g/L) 0.7(0.6~0.8) 0.7(0.6~0.9) 0.7(0.6~0.8) 0.7(0.6~0.9) H=0.72 0.868 eGFR(mL·min-1·1.73 m-2) 121.4(111.8~138.8) 121.0(108.3~134.5) 116.1(103.0~127.0) 95.6(71.3~118.7) H=117.03 0.001 HBV DNA(拷贝/mL) 3.2(2.7~7.5) 2.8(2.7~4.6) 2.7(2.7~3.9) 3.4(2.7~5.8) H=22.11 0.001 AFP(g/L) 2.0(1.3~3.3) 2.5(1.4~3.8) 2.2(1.3~3.7) 3.5(1.6~8.5) H=45.80 0.001 表 2 年龄和性别矫正后的FIB-4与临床特征的相关性
Table 2. Age-and gender-adjusted correlations between FIB-4 index and clinical characteristics
指标 r值 P值 ALT(U/L) 0.202 0.001 AST(U/L) 0.354 0.001 ALP(U/L) 0.292 0.001 GGT(U/L) 0.287 0.001 LDH(U/L) 0.222 0.001 TBiL(mmol/L) 0.377 0.001 DBiL(mmol/L) 0.361 0.001 总蛋白(g/L) -0.085 0.016 Alb(g/L) -0.412 0.001 球蛋白(g/L) 0.168 0.001 TBA(μmol/L) 0.422 0.001 LAP(U/L) 0.247 0.001 PLT(×109/L) -0.421 0.001 BUN(mmol/L) -0.046 0.192 甘油三酯(mmol/L) -0.060 0.090 TC(mmol/L) -0.056 0.113 高密度脂蛋白(mmol/L) 0.004 0.905 低密度脂蛋白(mmol/L) -0.068 0.054 apoA(g/L) -0.028 0.438 apoB(g/L) -0.035 0.328 eGFR(mL·min-1·1.73 m-2) -0.359 0.001 HBV DNA(拷贝/mL) 0.172 0.001 AFP(g/L) 0.318 0.001 表 3 肾损伤危险因素的Logistic回归分析
Table 3. Logistic regression analysis of risk factors of renal injury
指标 单变量 多变量 OR (95%CI) P值 OR (95%CI) P值 男性[例(%)] 0.714(0.409~1.245) 0.235 - - 年龄(岁) 1.032(1.011~1.053) 0.002 - - ALT(U/L) 1.001(1.000~1.002) 0.024 - - AST(U/L) 1.004(1.002~1.007) 0.001 - - ALP(U/L) 1.020(1.011~1.029) 0.001 - - GGT(U/L) 1.006(1.002~1.010) 0.004 - - LDH(U/L) 1.007(1.002~1.012) 0.003 - - TBiL(mmol/L) 1.027(1.011~1.043) 0.001 - - DBiL(mmol/L) 1.038(1.013~1.063) 0.003 - - 总蛋白(g/L) 0.976(0.926~1.028) 0.355 - - Alb(g/L) 0.826(0.774~0.881) 0.000 - - 球蛋白(g/L) 1.085(1.032~1.142) 0.002 - - TBA(μmol/L) 1.024(1.012~1.036) 0.001 - - LAP(U/L) 1.022(1.008~1.036) 0.002 - - PLT(×109/L) 0.987(0.982~0.991) 0.001 - - BUN(mmol/L) 0.539(0.887~1.258) 0.539 - - 甘油三酯(mmol/L) 0.951(0.553~1.637) 0.857 - - TC(mmol/L) 0.561(0.668~1.244) 0.561 - - 高密度脂蛋白(mmol/L) 0.774(0.379~1.580) 0.482 - - 低密度脂蛋白(mmol/L) 0.904(0.615~1.328) 0.606 - - apoA(g/L) 0.791(0.308~2.030) 0.626 - - apoB(g/L) 1.018(0.288~3.594) 0.978 - - HBV DNA(拷贝/mL) 1.217(1.078~1.374) 0.001 1.227(1.038~1.452) 0.017 AFP(g/L) 1.003(1.001~1.004) 0.004 - - FIB-4 1.428(1.303~1.565) 0.001 1.581(1.359~1.839) 0.001 表 4 FIB-4与肾损伤风险的相关性
Table 4. Association of FIB-4 with the risk of renal function injury
项目 FIB-4 P值 自变量每增加1个标准差 Q1 Q2 Q3 Q4 模型1 0.111(0.038~0.320) 0.287(0.136~0.632) 0.439(0.229~0.842) 1 0.001 2.720(2.104~3.517) 模型2 0.113(0.039~0.328) 0.289(0.138~0.608) 0.450(0.234~0.866) 1 0.001 2.713(2.094~3.514) 模型3 0.162(0.054~0.488) 0.417(0.189~0.918) 0.621(0.310~1.243) 1 0.006 2.847(2.081~3.894) 注:模型1,未进行协变量矫正;模型2,进行性别矫正后;模型3,进行性别、ALP、GGT、TBil、DBil、TBA、LAP及AFP矫正后。由于在FIB-4的计算中包含了年龄、ALT、AST和PLT等因素,因此模型未进行调整。 -
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