慢性乙型肝炎患者肝纤维化程度与肾损伤的相关性分析

肖璐; 颜学兵; 费媛媛

doi:10.3969/j.issn.1001-5256.2022.10.008

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

肖璐^{1, 2},
颜学兵^3, , ,,
费媛媛⁴

1.
徐州医科大学研究生院，江苏徐州 221000
2.
中国人民解放军陆军第七十一集团军医院感染科，江苏徐州 221000
3.
徐州医科大学附属医院感染科，江苏徐州 221000
4.
宿迁市第一人民医院感染科，江苏宿迁 223800

伦理学声明：本研究方案于2020年11月2日经由中国人民解放军陆军第七十一集团军医院伦理委员会审批，批号：2020-008。

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：肖璐负责课题设计，资料分析，撰写论文；费媛媛参与数据整理；颜学兵负责拟定写作思路，指导撰写文章并最后定稿。

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通信作者:
颜学兵，yxbxuzhou@126.com

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出版历程
- 收稿日期: 2022-03-09
- 录用日期: 2022-04-17
- 出版日期: 2022-10-20

Correlation analysis of hepatic fibrosis and renal injury in patients with chronic hepatitis B

Lu XIAO^{1, 2},
Xuebing YAN^{3
, ,
,},
Yuanyuan FEI⁴

1.
Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu 221000, China
2.
The 71st Group Army Hospital of CPLA Army, Infectious Department, Xuzhou, Jiangsu 221000, China
3.
The Affiliated Hospital of Xuzhou Medical University, Infectious Department, Xuzhou, Jiangsu 221000, China
4.
The Affiliated Suqian First People's Hospital of Nanjing Medical University, Infectious Department, Suqian, Jiangsu 223800, China

More Information

Corresponding author: YAN Xuebing, yxbxuzhou@126.com(ORCID: 0000-0003-4689-7389)

摘要

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。
- 乙型肝炎, 慢性 /
- 肝硬化 /
- 肾小球滤过率 /
- 肾损伤
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.
- Hepatitis B, Chronic /
- Liver Cirrhosis /
- Glomerular Filtration Rate /
- Renal Injury

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图 1 FIB-4与eGFR相关性

Figure 1. Correlation between FIB4 and eGFR

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图 2 不同FIB-4组的肾损伤发生率

Figure 2. Incidence of renal function injury in different FIB-4 groups

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图 3 FIB-4预测肾损伤的ROC曲线

Figure 3. ROC curve of FIB-4 in predicting 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
指标	Q1组(n=200)	Q2组(n=199)	Q3组(n=200)	Q4组(n=199)	统计值	P值
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

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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

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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
指标	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

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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
项目	Q1	Q2	Q3	Q4	P值	自变量每增加1个标准差
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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