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

马晓艳; 陈云; 刘嘉城; 李婕; 吴超

doi:10.3969/j.issn.1001-5256.2023.01.010

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

马晓艳¹,
陈云²,
刘嘉城³,
李婕³,
吴超^3, , ,

1.
南京大学医学院, 南京 210008
2.
南京医科大学鼓楼临床学院, 南京 210008
3.
南京大学医学院附属鼓楼医院感染疾病科, 南京 210008

基金项目:

国家自然科学基金面上项目 (81970545);

国家自然科学基金面上项目 (82170609)

伦理学声明：本研究方案于2008年12月29日经由南京大学医学院附属鼓楼医院伦理委员会审批，批号：2008022，所纳入患者均签署知情同意书。

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：马晓艳负责实施研究过程，采集整理数据，设计论文框架，起草论文，修订论文；陈云、刘嘉城参与了研究数据的获取分析解释过程，提供指导性支持；李婕、吴超参与起草或修改文章关键内容，终审论文。

详细信息

通信作者:
吴超，dr.wu@nju.edu.cn (ORCID: 0000-0002-1657-010X)

计量
- 文章访问数: 1674
- HTML全文浏览量: 1276
- PDF下载量: 139
- 被引次数: 0
出版历程
- 收稿日期: 2022-07-04
- 录用日期: 2022-09-16
- 出版日期: 2023-01-20

Clinical features and related risk factors of chronic hepatitis B patients with concomitant minimal hepatic steatosis

Xiaoyan MA¹,
Yun CHEN²,
Jiacheng LIU³,
Jie LI³,
Chao WU^{3
, ,
,}

1.
Nanjing University Medical School, Nanjing 210008, China
2.
Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing 210008, China
3.
Department of Infectious Diseases, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China

Research funding:

National Natural Science Foundation of China General Project (81970545);

National Natural Science Foundation of China General Project (82170609)

More Information

Corresponding author: WU Chao, dr.wu@nju.edu.cn (ORCID: 0000-0002-1657-010X)

摘要

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。
- 乙型肝炎, 慢性 /
- 非酒精性脂肪性肝病 /
- 危险因素
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.
- Hepatitis B, Chronic /
- Non-alcoholic Fatty Liver Disease /
- Risk Factor

HTML全文

图 1 炎症及纤维化等级分布

注：a，炎症等级；b，纤维化等级。

Figure 1. Distribution of inflammation stage and fibrosis stage

下载: 全尺寸图片幻灯片

图 2 不同BMI水平极轻脂肪变性的分布

Figure 2. Distribution of minimal steatosis at different BMI levels

下载: 全尺寸图片幻灯片

图 3 BMI正常组不同UA水平的患者极轻脂肪变性分布

Figure 3. Distribution of minimal steatosis at different UA levels in normal BMI group

下载: 全尺寸图片幻灯片

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。

下载: 导出CSV

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)
指标	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。

下载: 导出CSV

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

下载: 导出CSV

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
变量	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

下载: 导出CSV

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
变量	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

下载: 导出CSV

参考文献(26)

[1]	LI J, ZOU B, YEO YH, et al. Prevalence, incidence, and outcome of non-alcoholic fatty liver disease in Asia, 1999-2019: a systematic review and meta-analysis[J]. Lancet Gastroenterol Hepatol, 2019, 4(5): 389-398. DOI: 10.1016/S2468-1253(19)30039-1.
[2]	ZHENG Q, ZOU B, WU Y, et al. Systematic review with meta-analysis: prevalence of hepatic steatosis, fibrosis and associated factors in chronic hepatitis B[J]. Aliment Pharmacol Ther, 2021, 54(9): 1100-1109. DOI: 10.1111/apt.16595.
[3]	KLEINER DE, BRUNT EM, VAN NATTA M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease[J]. Hepatology, 2005, 41(6): 1313-1321. DOI: 10.1002/hep.20701.
[4]	WANG MM, WANG GS, SHEN F, et al. Hepatic steatosis is highly prevalent in hepatitis B patients and negatively associated with virological factors[J]. Dig Dis Sci, 2014, 59(10): 2571-2579. DOI: 10.1007/s10620-014-3180-9.
[5]	SCHEUER PJ. Classification of chronic viral hepatitis: a need for reassessment[J]. J Hepatol, 1991, 13(3): 372-374. DOI: 10.1016/0168-8278(91)90084-o.
[6]	LAI CL, RATZIU V, YUEN MF, et al. Viral hepatitis B[J]. The Lancet, 2003, 362(9401): 2089-2094. DOI: 10.1016/S0140-6736(03)15108-2.
[7]	SARIN SK, KUMAR M, LAU GK, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update[J]. Hepatol Int, 2016, 10(1): 1-98. DOI: 10.1007/s12072-015-9675-4.
[8]	LEE MH, YANG HI, LIU J, et al. Prediction models of long-term cirrhosis and hepatocellular carcinoma risk in chronic hepatitis B patients: risk scores integrating host and virus profiles[J]. Hepatology, 2013, 58(2): 546-554. DOI: 10.1002/hep.26385.
[9]	WONG GL, CHAN HL, YU Z, et al. Coincidental metabolic syndrome increases the risk of liver fibrosis progression in patients with chronic hepatitis B-a prospective cohort study with paired transient elastography examinations[J]. Aliment Pharmacol Ther, 2014, 39(8): 883-893. DOI: 10.1111/apt.12658.
[10]	YEN YH, CHANG KC, TSAI MC, et al. Elevated body mass index is a risk factor associated with possible liver cirrhosis across different etiologies of chronic liver disease[J]. J Formos Med Assoc, 2018, 117(4): 268-275. DOI: 10.1016/j.jfma.2017.09.002.
[11]	CHEN YC, HSU CW, JENG WJ, et al. Advanced liver fibrosis is associated with necroinflammatory grade but not hepatic steatosis in chronic hepatitis B patients[J]. Dig Dis Sci, 2021, 66(12): 4492-4500. DOI: 10.1007/s10620-020-06761-x.
[12]	SETO WK, FUNG J, CHEUNG KS, et al. Body-mass index is associated with fibrosis regression during long-term nucleoside analogue therapy in chronic hepatitis B[J]. Aliment Pharmacol Ther, 2016, 44(10): 1071-1079. DOI: 10.1111/apt.13804.
[13]	ZHU L, JIANG J, ZHAI X, et al. Hepatitis B virus infection and risk of non-alcoholic fatty liver disease: A population-based cohort study[J]. Liver Int, 2019, 39(1): 70-80. DOI: 10.1111/liv.13933.
[14]	PAIS R, RUSU E, ZILISTEANU D, et al. Prevalence of steatosis and insulin resistance in patients with chronic hepatitis B compared with chronic hepatitis C and non-alcoholic fatty liver disease[J]. Eur J Intern Med, 2015, 26(1): 30-36. DOI: 10.1016/j.ejim.2014.12.001.
[15]	NAU AL, SOARES JC, SHIOZAWA MB, et al. Clinical and laboratory characteristics associated with dyslipidemia and liver steatosis in chronic HBV carriers[J]. Rev Soc Bras Med Trop, 2014, 47(2): 158-164. DOI: 10.1590/0037-8682-0009-2014.
[16]	YILMAZ B, KOKLU S, BUYUKBAYRAM H, et al. Chronic hepatitis B associated with hepatic steatosis, insulin resistance, necroinflammation and fibrosis[J]. Afr Health Sci, 2015, 15(3): 714-718. DOI: 10.4314/ahs.v15i3.3.
[17]	CHEN Y, CAO D, LI C, et al. A nomogram for discrimination of non- alcoholic fatty liver disease in patients with chronic hepatitis B[J]. Eur J Gastroenterol Hepatol, 2021, 33(1): 69-75. DOI: 10.1097/MEG.0000000000001691.
[18]	YUAN H, YU C, LI X, et al. Serum uric acid levels and risk of metabolic syndrome: a dose-response meta-analysis of prospective studies[J]. J Clin Endocrinol Metab, 2015, 100(11): 4198-4207. DOI: 10.1210/jc.2015-2527.
[19]	HWANG IC, SUH SY, SUH AR, et al. The relationship between normal serum uric acid and nonalcoholic fatty liver disease[J]. J Korean Med Sci, 2011, 26(3): 386-391. DOI: 10.3346/jkms.2011.26.3.386.
[20]	XU CF, YU CH, XU L, et al. High serum uric acid increases the risk for nonalcoholic fatty liver disease: a prospective observational study[J]. PLoS One, 2010, 5(7): e11578. DOI: 10.1371/journal.pone.0011578.
[21]	ZHENG X, GONG L, LUO R, et al. Serum uric acid and non-alcoholic fatty liver disease in non-obesity Chinese adults[J]. Lipids Health Dis, 2017, 16(1): 202. DOI: 10.1186/s12944-017-0531-5.
[22]	ZHOU M, YANG N, XING X, et al. Obesity interacts with hyperuricemia on the severity of non-alcoholic fatty liver disease[J]. BMC Gastroenterol, 2021, 21(1): 43. DOI: 10.1186/s12876-021-01615-w.
[23]	PETTA S, CAMMÀ C, CABIBI D, et al. Hyperuricemia is associated with histological liver damage in patients with non-alcoholic fatty liver disease[J]. Aliment Pharmacol Ther, 2011, 34(7): 757-766. DOI: 10.1111/j.1365-2036.2011.04788.x.
[24]	FERNÁNDEZ RODRÍGUEZ CM, ALLER R, GUTIÉRREZ GARCÍA ML, et al. Higher levels of serum uric acid influences hepatic damage in patients with non-alcoholic fatty liver disease (NAFLD)[J]. Rev Esp Enferm Dig, 2019, 111(4): 264-269. DOI: 10.17235/reed.2019.5965/2018.
[25]	BALLESTRI S, NASCIMBENI F, ROMAGNOLI D, et al. The independent predictors of non-alcoholic steatohepatitis and its individual histological features. : Insulin resistance, serum uric acid, metabolic syndrome, alanine aminotransferase and serum total cholesterol are a clue to pathogenesis and candidate targets for treatment[J]. Hepatol Res, 2016, 46(11): 1074-1087. DOI: 10.1111/hepr.12656.
[26]	DUAN H, ZHANG R, CHEN X, et al. Associations of uric acid with liver steatosis and fibrosis applying vibration controlled transient elastography in the united states: a nationwide cross-section study[J]. Front Endocrinol (Lausanne), 2022, 13: 930224. DOI: 10.3389/fendo.2022.930224.