慢性乙型肝炎患者合并极轻肝脏脂肪变性的临床特征及危险因素分析
DOI: 10.3969/j.issn.1001-5256.2023.01.010
Clinical features and related risk factors of chronic hepatitis B patients with concomitant minimal hepatic steatosis
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摘要:
目的 观察慢性乙型肝炎(CHB)患者合并极轻肝脏脂肪变性的临床指标的变化,并分析极轻脂肪变性发生的相关影响因素。 方法 纳入2018年7月—2022年3月在南京大学医学院附属鼓楼医院感染疾病科行肝穿刺活检的CHB患者共179例。依据脂肪变性程度分为无脂肪变性组(n=98)、极轻脂肪变性组(n=81)。收集人口学信息、临床资料及肝组织病理学资料,比较各观察指标在两组中的差异。符合正态分布的计量资料两组间比较采用独立样本t检验,不符合正态分布的两组间比较采用Mann-Whitney U检验,计数资料两组间比较采用χ2检验。相关性分析采用Spearman检验。Logistic回归分析极轻脂肪变性发生的危险因素。 结果 极轻脂肪变性组中男性比例(69.1% vs 52.0%)及显著纤维化比例(43.2% vs 25.5%)较无脂肪变性组高(χ2值分别为5.390、6.234,P值均<0.05)。极轻脂肪变性组BMI[(23.61±2.95)kg/m2 vs(22.13±2.67)kg/m2]、尿酸(UA)[333.0(291.0~375.5)μmol/L vs 287.5(244.8~345.3)μmol/L]、TG[0.92(0.66~1.14)μmol/L vs 0.77(0.62~1.02)μmol/L]、肝脏脂肪受控衰减参数(CAP)[234(214~258)dB/m vs 218(201~237)dB/m]水平均高于无脂肪变性组(t=-4.150,Z=-3.620,Z=-2.224,Z=-2.867,P值均<0.05)。正常体质量组,极轻脂肪变性患者UA[(333.0±63.9)μmol/L vs(291.0±72.8)μmol/L]、HBV DNA[4.44(3.51~6.79)log10 IU/mL vs 3.42(3.00~5.03)log10 IU/mL]高于无脂肪变性患者(t=-2.395,Z=-2.474,P值均<0.05)。BMI(OR=1.223,95%CI:1.086~1.378,P=0.001)、UA(OR=1.006,95%CI:1.002~1.010,P=0.008)为CHB合并极轻脂肪变性的危险因素。UA(OR=1.007,95%CI:1.001~1.013,P=0.022)为正常体质量CHB患者合并极轻脂肪变性的危险因素。 结论 合并极轻脂肪变性的CHB患者显著纤维化比例、CAP高于无脂肪变性者。BMI、UA是CHB患者发生极轻脂肪变性的独立危险因素。尤其在正常体质量CHB患者,UA升高与极轻脂肪变性的发生关系密切。 Abstract:Objective To investigate the changes of clinical indices in chronic hepatitis B (CHB) patients with concomitant minimal hepatic steatosis and related factors for minimal hepatic steatosis. Methods A total of 179 CHB patients who underwent liver biopsy in Department of Infectious Diseases, Affiliated Drum Tower Hospital of Nanjing University Medical School, from July 2018 to March 2022 were enrolled, and according to the degree of steatosis, they were divided into non-steatosis group with 98 patients and minimal hepatic steatosis group with 81 patients. Demographic information, clinical data, and liver histopathology data were collected, and related observation indices were compared between the two groups. The independent samples t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between groups. A Spearman correlation analysis was performed, and a Logistic regression analysis was used to investigate the risk factors for minimal hepatic steatosis. Results Compared with the non-steatosis group, the minimal hepatic steatosis group had a significantly higher proportion of male patients (69.1% vs 52.0%, χ2=5.390, P < 0.05) and a significantly higher proportion of patients with significant liver fibrosis (43.2% vs 25.5%, χ2=6.234, P < 0.05). Compared with the non-steatosis group, the minimal hepatic steatosis group had significantly higher levels of body mass index (BMI) (23.61±2.95 kg/m2 vs 22.13±2.67 kg/m2, t=-4.150, P < 0.05), uric acid (UA) [333.0(291.0-375.5) μmol/L vs 287.5(244.8-345.3) μmol/L, Z=-3.620, P < 0.05], triglyceride [0.92 (0.66-1.14) μmol/L vs 0.77 (0.62-1.02) μmol/L, Z=-2.224, P < 0.05], and controlled attenuation parameter (CAP) [234 (214-258) dB/m vs 218 (201-237) dB/m, Z=-2.867, P < 0.05]. In the group with normal body weight, the patients with minimal hepatic steatosis had significantly higher levels of UA (333.0±63.9 μmol/L vs 291.0±72.8 μmol/L, t=-2.395, P < 0.05) a nd HBV DNA [4.44 (3.51-6.79) log10 IU/mL vs 3.42 (3.00-5.03) log10 IU/mL, Z=-2.474, P < 0.05]. BMI (odds ratio [OR]=1.223, 95% confidence interval [CI] : 1.086-1.378, P=0.001) and UA (OR=1.006, 95%CI: 1.002-1.010, P=0.008) were risk factors for minimal hepatic steatosis in CHB patients, and UA (OR=1.007, 95%CI: 1.001-1.013, P=0.022) was a risk factors for minimal hepatic steatosis in CHB patients with normal body weight. Conclusion Compared with the non-steatosis CHB patients, the CHB patients with minimal hepatic steatosis have a significantly higher proportion of patients with significant liver fibrosis and a significantly higher level of CAP. BMI and UA are independent risk factors for minimal hepatic steatosis in CHB patients, and for the CHB patients with normal body weight, elevated UA is closely associated with the onset of minimal hepatic steatosis. -
Key words:
- Hepatitis B, Chronic /
- Non-alcoholic Fatty Liver Disease /
- Risk Factor
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表 1 CHB患者的临床及病理特征
Table 1. Baseline clinical characteristics of the CHB patients
指标 无脂肪变性组(n=98) 极轻脂肪变性组(n=81) 统计值 P值 男[例(%)] 51(52.0) 56(69.1) χ2=5.390 0.020 年龄(岁) 38.0(31.0~48.3) 37.0(31.5~47.0) Z=-0.072 0.942 高血压[例(%)] 2(2.0) 5(6.2) χ2=2.004 0.157 BMI(kg/m2) 22.13±2.67 23.61±2.95 t=-4.150 <0.001 PLT(×109/L) 169.0±47.8 165.5±48.6 t=0.732 0.465 ALT(U/L) 22.25(14.15~34.80) 30.10(18.70~47.85) Z=-2.944 0.003 AST(U/L) 21.25(17.45~26.60) 23.70(19.65~35.20) Z=-2.555 0.011 ALP(U/L) 58.25(46.18~68.05) 60.90(51.20~74.05) Z=-1.616 0.106 GGT(U/L) 15.35(11.68~22.55) 18.10(14.20~28.70) Z=-2.466 0.014 UA(μmol/L) 287.5(244.8~345.3) 333.0(291.0~375.5) Z=-3.620 <0.001 TG(mmol/L) 0.77(0.62~1.02) 0.92(0.66~1.14) Z=-2.224 0.026 TC(mmol/L) 3.96±0.80 3.90±0.77 t=0.876 0.382 FBS(mmol/L) 4.28(4.05~4.58) 4.30(4.06~4.62) Z=-0.430 0.667 HDL(mmol/L) 1.35(1.10~1.56) 1.22(0.99~1.50) Z=-1.759 0.079 LDL(mmol/L) 2.27(1.83~2.65) 2.15(1.83~2.67) Z=-0.032 0.975 HBsAg(log10 IU/mL) 3.00(2.29~3.89) 3.30(2.87~4.06) Z=-1.774 0.076 HBeAg(+)[例(%)] 29(29.6) 29(35.8) χ2=0.781 0.377 HBV DNA(log10 IU/mL) 3.55(3.01~5.03) 4.31(3.01~7.06) Z=-1.692 0.091 CAP(dB/m)1) 218(201~237) 234(214~258) Z=-2.867 0.004 显著炎症[例(%)] 29(29.6) 28(34.6) χ2=0.506 0.477 显著纤维化[例(%)] 25(25.5) 35(43.2) χ2=6.234 0.013 注:FBS,空腹血糖。1)共102例数据参与分析,其中无脂肪变性组59例,极轻脂肪变性组43例。 表 2 不同BMI分组的基线特征
Table 2. Baseline clinical characteristics of the CHB patients, stratified by BMI
指标 正常体质量组(n=112) 超重组(n=57) 无脂肪变性组(n=69) 极轻脂肪变性组(n=43) 统计值 P值 无脂肪变性组(n=19) 极轻脂肪变性组(n=38) 统计值 P值 男[例(%)] 33(47.8) 28(65.1) χ2=3.193 0.074 11(57.9) 28(73.7) χ2=1.462 < 0.001 年龄(岁) 39.0(32.0~48.5) 37.0(29.0~47.0) Z=0.832 0.405 39.0(31.0~50.0) 36.0(32.8~48.5) Z=-0.356 0.722 高血压[例(%)] 1(1.4) 4(9.3) χ2=3.796 0.051 1(5.3) 1(2.6) χ2=0.255 0.614 PLT(×109/L) 161.0±44.7 164.0±48.5 t=-1.767 0.080 199.0±48.4 167.0±49.1 t=2.112 0.039 ALT(U/L) 22.1(14.1~31.5) 26.9(18.8~45.3) Z=-1.849 0.065 24.8(16.2~55.7) 34.2(18.6~55.9) Z=-1.10 0.271 AST(U/L) 21.3(17.4~26.0) 23.7(18.5~29.8) Z=-1.268 0.205 22.5(20.0~28.5) 23.9(19.9~41.2) Z=-1.067 0.286 ALP(U/L) 58.2(45.6~66.9) 60.9(51.6~69.2) Z=-1.161 0.246 60.8±19.7 62.3±19.5 t=0.285 0.776 GGT(U/L) 15.2(11.8~23.5) 16.4(14.1~21.1) Z=-1.182 0.237 18.5(12.8~23.3) 21.6(15.4~37.2) Z=-0.906 0.365 UA(μmol/L) 291.0±72.8 333.0±63.9 t=-2.395 0.018 340.0(254.0~397.0) 340.5(297.8~394.0) Z=-0.635 0.526 TG(mmol/L) 0.78(0.65~0.96) 0.87(0.62~1.13) Z=-1.364 0.172 1.04(0.69~1.34) 0.93(0.71~1.15) Z=-0.279 0.780 TC(mmol/L) 3.98(3.41~4.45) 3.25(3.19~4.36) Z=0.879 0.379 4.01±0.71 4.03±0.78 t=0.901 0.371 FBS(mmol/L) 4.22±0.39 4.29±0.44 t=-0.216 0.829 4.49(4.22~4.90) 4.33(4.03~4.66) Z=-1.168 0.243 HDL(mmol/L) 1.40±0.36 1.24±0.32 t=1.165 0.247 1.20(1.10~1.35) 1.21(0.93~1.48) Z=-0.330 0.741 LDL(mmol/L) 2.27(1.76~2.53) 2.06(1.73~2.54) Z=-0.835 0.404 2.61±0.61 2.30±0.49 t=1.106 0.314 HBsAg(log10 IU/mL) 2.99±1.17 3.30±1.04 t=-1.677 0.096 3.27±1.38 3.27±1.21 t=0.369 0.714 HBeAg(+)[例(%)] 19(27.5) 14(32.6) χ2=0.321 0.571 7(36.8) 15(39.5) χ2=0.037 0.847 HBV DNA(log10 IU/mL) 3.42(3.00~5.03) 4.44(3.51~6.79) Z=-2.474 0.013 3.74(3.26~7.53) 4.24(2.70~7.29) Z=-0.623 0.533 CAP(dB/m)1) 218.0(201.0~234.5) 217.0(206.0~243.5) Z=-0.570 0.569 237.0(218.0~246.0) 250.0(231.5~268.5) Z=-1.390 0.165 显著炎症[例(%)] 18(26.1) 12(27.9) χ2=0.045 0.832 6(31.6) 16(42.1) χ2=0.592 0.442 显著纤维化[例(%)] 20(29.0) 16(37.2) χ2=0.821 0.365 4(21.1) 19(50.0) χ2=4.410 0.036 注:1)4组对应的例数分别为41、22、11、21。 表 3 UA与肝组织学特征相关性分析
Table 3. Correlation between UA and liver histological features
组别 组织学特征 r值 P值 全部 炎症分级 0.004 0.969 纤维化分级 0.063 0.575 正常体质量组 炎症分级 -0.088 0.573 纤维化分级 0.136 0.384 超重组 炎症分级 0.024 0.884 纤维化分级 -0.055 0.744 表 4 CHB合并极轻脂肪变性危险因素的Logistic回归分析
Table 4. Univariate and multivariate analysis of risk factors for CHB complicated with minimal steatosis
变量 单因素 多因素 OR (95% CI) P值 OR (95% CI) P值 男性 2.431(1.313~4.500) 0.005 BMI 1.257(1.116~1.415) <0.001 1.223(1.086~1.378) 0.001 UA 1.007(1.003~1.011) 0.001 1.006(1.002~1.010) 0.008 TG 2.491(1.100~5.641) 0.029 HDL 0.426(0.176~1.032) 0.059 HBsAg 1.260(0.974~1.630) 0.078 HBV DNA < 3 log10 IU/mL 3~5 log10 IU/mL 0.650(0.302~1.400) 0.271 ≥5 log10 IU/mL 1.318(0.586~2.964) 0.504 表 5 正常体质量组CHB合并极轻脂肪变性危险因素的Logistic回归分析
Table 5. Univariate and multivariate analysis of risk factors for CHB complicated with minimal steatosis in normal BMI group
变量 单因素 多因素 OR(95%CI) P值 OR(95%CI) P值 男性 2.036(0.929~4.465) 0.076 UA 1.007(1.001~1.013) 0.022 1.007(1.001~1.013) 0.022 HBsAg 1.363(0.942~1.972) 0.100 HBV DNA <3 log10 IU/mL 3~5 log10 IU/mL 1.583(0.534~4.695) 0.407 ≥5 log10 IU/mL 2.833(0.909~8.834) 0.073 -
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