Prevalence rate of non-obese fatty liver disease and related influencing factors

Jiang DENG; Zhiyi HAN; Cailan XIAO; Yating SUN; Yajun JI; Li AO; Yonghong ZHANG; Xiaolan LU

doi:10.3969/j.issn.1001-5256.2021.11.022

Volume 37 Issue 11

Nov. 2021

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Article Navigation > Journal of Clinical Hepatology > 2021 > 37(11): 2600-2604

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Prevalence rate of non-obese fatty liver disease and related influencing factors

DOI: 10.3969/j.issn.1001-5256.2021.11.022

Jiang DENG^1a,
Zhiyi HAN^2a,
Cailan XIAO^1b,
Yating SUN^1b,
Yajun JI³,
Li AO³,
Yonghong ZHANG^{2b
,
,},
Xiaolan LU^{1b, 3
,
,}

1a.
Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
1b.
Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
2a.
Department of Gastroenterology, Karamay Central Hospital, Karamay, Xinjiang 834099, China
2b.
Physical Examination Center, Karamay Central Hospital, Karamay, Xinjiang 834099, China
3.
Department of Gastroenterology, Pudong Hospital Affiliated to Fudan University, Shanghai 201399, China

Research funding:

Shanghai Natural Science Foundation of China (20ZR1450100);

Talents Training Program of Pudong Hospital affiliated to Fudan University (YJRCJJ201801);

the Fundamental Research Funds for the Central Universities (xjh012019063);

National Key Research and Development Program of China during the 13th Five-Year Plan Period (2018YFC1311504)

Received Date: 2021-04-05
Accepted Date: 2021-04-28
Published Date: 2021-11-20

Abstract

Abstract

Objective To investigate the prevalence rate of non-obese fatty liver disease and its influencing factors, and to provide a reference for the prevention and treatment of fatty liver disease. Methods A total of 23 545 individuals who underwent physical examination in Karamay Central Hospital from January to December 2015 and had complete data of abdominal ultrasound, body mass index (BMI), age, and sex were screened out to analyze the prevalence rate of fatty liver disease, and 7484 individuals with normal BMI who had complete data of triglyceride (TG), fasting blood glucose, and alanine aminotransferase (ALT) were further screened out to perform a multivariate analysis. The 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 multivariate logistic regression analysis was performed to investigate independent influencing factors for non-obese fatty liver disease. Results In 2015, the prevalence rate of fatty liver disease was 30.2% (7116/23 545) among the individuals who underwent physical examination in Karamay Central Hospital. A stratified analysis based on BMI showed that the individuals with emaciation, normal BMI, overweight, and obesity had a prevalence rate of 0.8% (6/706), 9.3% (919/9899), 38.4% (3404/8870), and 68.5% (2787/4070), respectively (all P < 0.05), and male individuals had a significantly higher prevalence rate of fatty liver disease than female individuals (all P < 0.05). Among the 919 patients with non-obese fatty liver disease, young, middle-aged, and elderly patients accounted for 40.7% (374/919), 46.1% (424/919), and 13.2% (121/919), respectively. For the individuals with normal BMI, there was no significant difference in the prevalence rate of fatty liver disease between middle-aged and elderly individuals (14.5% vs 16.8%, P > 0.05), while both of them had a significantly higher prevalence rate than the young individuals (14.5%/16.8% vs 6.0%, P < 0.05). Young and middle-aged male individuals had a significantly higher prevalence rate of fatty liver disease than their female counterparts (χ²=99.40 and 43.29, both P < 0.001), while the elderly male individuals had a significantly lower prevalence rate than their female counterparts (χ²=9.81, P=0.002). For the individuals with normal BMI, the individuals with normal TG had a prevalence rate of fatty liver disease of 5.0% (311/6273), while those with elevated TG had a prevalence rate of 26.8% (325/1211), with a significant difference between the two groups (χ²=624.90, P < 0.001). The multivariate logistic regression analysis showed that age, BMI, ALT, fasting blood glucose, TG, and serum uric acid level were independent influencing factors for fatty liver disease in individuals with normal BMI (all P < 0.001). Conclusion There is a relatively high prevalence rate of non-obese fatty liver disease among individuals undergoing physical examination in Karamay Central Hospital, and 61.5% of the patients with non-obese fatty liver disease have glucose or lipid metabolic disorders. Serum TG level may be used as a simple and effective screening index for non-obese fatty liver disease.
- Fatty Liver Disease,
- Prevalence,
- Risk Factors

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胰十二指肠切除术(pancreaticoduodenectomy，PD)目前是治疗胆胰汇合部周围恶性肿瘤及部分良性疾病的唯一根治性手术方式。但是其手术范围广，创伤较大，故术后并发症多。其中，胃排空延迟(delayed gastric emptying，DGE)患者术后禁食时间延长，恢复慢，并且严重影响了患者术后的生活质量。近年有研究^[1-2]表明，Braun吻合(Braun anastomosis，BE)可降低PD术后DGE的发生率，但尚存在争议^[3-5]。Braun手术始于1892年，Braun对胃切除术后出现严重反流性胃食管炎的患者进行二次手术，在连接残胃的空肠输入段和输出段之间进行了肠肠吻合，以降低术后胆汁性胃炎和胆汁性呕吐的发生，并建议在胃肠吻合术后常规进行该吻合，或可以降低术后吻合口瘘及输入袢梗阻的发生率^[6]。理论上BE可以使胆汁和胰液等消化液通过BE口排出，减少对胃黏膜的刺激。亦可通过该吻合口排出部分胃内容物，减少潴留^[7]。也有学者^[1-2]认为可防止肠道扭转并维持消化道稳定，并通过减少胃肠道压力降低胰瘘发生率，进而减少DGE的发生。因此本研究的目的是进一步明确BE对预防PD术后DGE的影响。

1. 资料及方法

1.1 研究对象

收集2016年12月—2019年12月在兰州大学第一医院行根治性PD的患者资料。根据术中是否行BE将患者分为BE组和非BE组。收集患者的性别、年龄、BMI、病理分型、基础疾病、WBC、RBC、PLT、Hb、ALT、AST、TBil、Alb、手术时间、出血量、术后并发症、止吐及通便药物使用次数、第1次化疗时间(术后)、住院时长及住院花费。

1.2 纳入和排除标准

纳入标准：(1)20~80岁。(2)临床上确诊胆胰汇合部周围恶性肿瘤及部分良性疾病，并经多学科会诊后，建议行PD的患者。(3)DGE诊断标准参考《胰腺术后外科常见并发症诊治及预防的专家共识(2017)》^[9]，术后3 d因仍需要气管插管而留置胃管等其他非胃排空功能减弱的情况，同时上消化道造影证实未见胃蠕动波并伴有胃扩张时，出现以下情况之一者，可诊断为术后DGE：①术后需置胃管时间超过3 d；②拔管后因呕吐等原因再次置管；③术后7 d仍不能进食固体食物。根据其严重程度分为A、B、C 3级。A级：鼻胃管(nasogastric tube，NGT)时间大于术后3 d，或术后7 d不能耐受固体饮食，可伴呕吐，可能需要应用促胃肠动力药物。B级：NGT时间术后8~14 d，或术后7 d后重插NGT或术后14 d仍不能耐受固体饮食；伴呕吐，需要应用促胃肠动力药物。C级：NGT时间大于术后14 d，或术后14 d后重插，或不能耐受固体饮食时间大于术后21 d，伴呕吐，需要应用促胃肠动力药物。(4)胰瘘、胆瘘、出血等并发症诊断标准参考《胰腺术后外科常见并发症诊治及预防的专家共识(2017)》^[9]。

排除标准：(1)幽门及其他消化道梗阻吻合口狭窄、吻合口水肿等；(2)胃癌；(3)既往有消化道改建手术史；(4)保留幽门的PD；(5)伴有严重并发症不能耐受手术者；(6)拒绝签署知情同意书者；(7)资料不全者。

1.3 手术方法

两组患者均行开腹PD，采用标准的术式，切除范围包括胰头(包括钩突部)、肝总管以下胆管(包括胆囊)、远端胃、十二指肠及部分空肠，同时清扫胰头周围、肠系膜血管根部，横结肠系膜根部以及肝总动脉周围和肝十二指肠韧带内淋巴结。重建按照胰腺-空肠吻合、肝总管-空肠吻合和胃-空肠吻合顺序进行^[8]。BE组：于胃肠吻合口10 cm处，将连接残胃空肠的输入端与输出端使用直线切割闭合器行空肠-空肠侧侧吻合，吻合口直径2 cm。两组患者术后均常规于胆肠吻合口、胰肠吻合口各放置1根腹腔引流管，胃肠减压管1根，鼻肠营养管1根。

1.4 伦理学审查

本研究方案经由兰州大学第一医院伦理委员会审批，批号：LDYYLL2021-12，所纳入患者均已签署知情同意书。

1.5 统计学方法

采用SPSS 26.0统计学软件进行分析。符合正态分布的计量资料以x±s表示，两组间比较采用独立样本t检验；非正态分布的计量资料以M(P₂₅~P₇₅)表示，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精确检验。P＜0.05为差异有统计学意义。

2. 结果

2.1 一般资料

共纳入132例患者，胰头恶性肿瘤41例，良性疾病10例，胆管下段胆管癌43恶性肿瘤，良性1例，壶腹部恶性肿瘤12例，十二指肠恶性肿瘤25例。合并高血压者29例，合并糖尿病者26例。两组患者的性别、年龄、BMI、术前WBC、RBC、PLT、Hb、ALT、AST、TBil、Alb，糖尿病高血压病史以及病理分型，差异均无统计学意义(P值均＞0.05)(表 1)。

表 1 两组患者一般资料比较

指标	BE组(n=54)	非BE组(n=78)	统计值	P值
男/女(例)	33/21	46/32	χ²=0.061	0.806
年龄(岁)	62.0(53.5~66.0)	56.0(50.0~67.0)	H=-1.565	0.118
BMI(kg/m²)	23.21±2.92	22.62±3.36	t=1.032	0.304
WBC(×10⁹/L)	5.71(4.59~7.55)	5.75(4.46~7.10)	H=-0.429	0.466
RBC(×10¹²/L)	4.38±0.60	4.32±0.66	t=0.559	0.577
PLT(×10⁹/L)	236.76±85.30	218.69±73.30	t=1.301	0.195
Hb(g/L)	133.56±3.06	133.55±2.53	t=0.001	0.999
ALT(U/L)	133.00(43.75~254.00)	115.00(40.50~245.00)	H=-0.206	0.837
AST(U/L)	117.50(35.50~201.25)	79.00(38.50~183.50)	H=-0.818	0.413
TBil(μmol/L)	153.60(22.43~280.40)	134.60(20.35~238.95)	H=-0.727	0.467
Alb(g/L)	41.30(37.68~43.48)	40.60(38.05~43.35)	H=-0.388	0.698
糖尿病(例)	11	15	χ²=0.026	0.871
高血压(例)	12	17	χ²=0.003	0.954
病理分型[例(%)]
胰头恶性肿瘤	16(29.63)	25(32.05)	χ²=0.087	0.768
胰头良性疾病	4(7.41)	6(7.69)	χ²=0	1.000
胆管下段恶性肿瘤	17(31.4)	26(33.33)	χ²=1.643	0.896
胆管下段良性疾病	1(1.85)	0		0.409
壶腹部恶性肿瘤	5(9.26)	7(8.97)	χ²=0.000	1.000
十二指肠恶性肿瘤	11(20.37)	14(17.95)	χ²=0.122	0.727
出血量(ml)	300.00(200.00~400.00)	200.00(187.75~400.00)	H=-0.655	0.512
手术时长(min)	400(300~530)	360(320~430)	H=-0.838	0.402

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2.2 术中出血量及手术时间比较

所有患者均顺利完成手术。两组患者在出血量及手术时长上均无明显差异(P值均＞0.05)(表 1)。

2.3 术后第1天生化指标比较

术后第1天，两组患者常规检验指标中BE组WBC水平高于BE组(H=-2.402，P=0.016)，其他指标两组差异均无统计学意义(P值均＞0.05)(表 2)。

表 2 术后第1天生化指标、并发症及DGE发生率比较

指标	BE组(n=54)	非BE组(n=78)	统计值	P值
WBC(×10⁹/L)	14.29(11.40~18.23)	11.65(9.87~15.98)	H=-2.402	0.016
RBC(×10¹²/L)	3.76(3.38~4.02)	3.75(3.43~4.09)	H=-0.157	0.875
PLT(×10⁹/L)	223.98±81.30	210.21±83.25	t=0.944	0.347
Hb(g/L)	115.00(104.75~125.00)	115.50(103.00~126.00)	H=-0.190	0.849
AST(U/L)	76.50(52.75~120.25)	84.00(58.50~121.00)	H=-0.310	0.756
ALT(U/L)	93.00(49.75~150.50)	91.50(52.00~155.75)	H=-0.245	0.806
TBil(μmol/L)	101.10(25.60~162.45)	76.20(22.70~159.00)	H=-0.461	0.645
Alb(g/L)	30.00±3.88	31.25±3.61	t=-1.907	0.059
并发症[例(%)]
出血	9(16.67)	11(14.10)	χ²=0.163	0.686
DGE	50(92.59)	65(83.33)	χ²=2.438	0.118
胰瘘(B+C级)	6(11.11)	18(23.08)	χ²=3.071	0.081
胆瘘	3(5.56)	6(7.69)	χ²=0.016	0.898
胃肠瘘	1(1.85)	3(3.85)		0.644
伤口感染	4(7.41)	10(12.82)	χ²=0.986	0.321
伤口裂开	0	2(2.56)		0.513
腹腔感染	14(25.93)	17(21.79)	χ²=0.303	0.582
肠梗阻	1(1.85)	4(5.13)		0.648
DGE发生率[例(%)]
A级	27(50.00)	31(39.74)		＞0.05
B级	20(37.04)	19(24.36)		＞0.05
C级	3(5.56)	15(19.23)		＜0.05
总体	50(92.59)	65(83.33)	χ²=2.438	＞0.05

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2.4 术后并发症比较

与非BE组相比，BE组C级DGE发生率较低(P＜0.05)。其他并发症如出血、胰瘘(B+C级)、胃肠瘘、切口感染、伤口裂开、腹腔感染、肠梗阻及A级、B级、总体DGE生率均无明显差异(P值均＞0.05)(表 2)。

2.5 术后其他治疗指标比较

与非BE组患者相比，BE组患者止吐药物使用次数少，术后住院时间短，化疗开始时间早，差异均有统计学意义(P值均＜0.05)。在胃管持续时间、恢复饮食时间、住院费用方面两组差异均无统计学意义(P值均＞0.05)(表 3)。

表 3 术后其他治疗指标

指标	BE组(n=54)	非BE组(n=78)	H值	P值
胃管持续时间(d)	7.00(5.75~9.00)	7.00(5.00~11.25)	-0.081	0.935
恢复饮食时间(d)	9.00(7.00~12.00)	11.00(8.00~17.25)	-1.709	0.087
止吐药物使用次数(次)	1.00(0~0.25)	1.00(1.00~4.00)	-2.347	0.019
第1次化疗时间(d)	45.00(38.00~49.75)	53.00(44.00~65.00)	-2.495	0.013
术后住院时长(d)	15.00(12.75~19.25)	18.00(15.00~25.50)	-3.358	0.004
住院费用(元)	70 303.90(56 620.84~94 435.69)	78 455.30(67 485.51~97 124.42)	-1.911	0.056

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3. 讨论

目前研究认为PD术后DGE的具体病因尚未明确，多数研究支持可能与以下多种因素有关：促胃动素分泌的减少^[10-11]、胃节律的破坏^[12]、胃黏膜受反流性胆汁的刺激^[13]、鸭爪神经损毁以及幽门切除丧失了对胃排出功能的约束，减少了胆汁反流入胃的阻碍^[14-15]、吻合口狭窄或水肿^[16]、术前合并糖尿病^[17]、术后并发症如：胰瘘、胆瘘、腹腔内感染^[18]、精神心理因素^[19]等诸多因素的影响。

而BE在理论上可能降低PD术后DGE的发生，故近些年部分研究者^{[1-4, 7]}将BE引入PD中。有研究^{[1-2, 7, 20]}发现，BE方式可以降低PD术后DGE、碱性反流性胃炎或边缘性溃疡的发生。部分研究^{[7, 21]}甚至报道其降低了胰瘘的发生率。在Hochwald等^[7]的研究中，BE组在DGE总体发生率、尽早拔除胃管、尽早进食、尽早出院等方面与非BE组有统计学差异，而临床相关的DGE(B级+C级)差异更加明显(7% vs 31%，P＜0.01)。Xu等^[2]研究发现，BE组DGE发生率显著降低(6.7% vs 26.87%，P＜0.001)，且多因素分析显示BE是唯一的独立危险因素；同时BE组有着更低的临床胰瘘发生率(P＜0.001)。Meng等^[1]研究显示，胰腺残端连续缝合加BE能显著降低DGE(P＜0.01)及临床相关PF发生率(P＜0.05)，但是该实验未能明确BE在结果中的具体作用，亦有可能是连续缝合降低了胰瘘的发生进而降低DGE的发生。部分循证学研究^[22]同样支持BE可降低DGE发生率的观点。但是不同研究之间在重建消化道距离(BE口与胃肠吻合口)和BE吻合口径上不一致，并在术后治疗和护理方案上均存在差^{[1-4, 7]}，部分研究^[3-4]结果并不支持BE可以降低DGE发生率的观点。

本研究中，BE减少了C级DGE的发生，与Xu等^[2]的研究结果不同。本研究两组患者在DGE总体发病率上未表现出明显差异，这可能与本中心拔除胃管时间较晚，导致A级DGE占比(50.43%)较大有关。在目前PD手术加速康复外科理念的实施中，常规术后第2天拔除胃管^[23]，而本回顾性研究未施行加速康复外科理念治疗策略，术后胃管持续时间大多超过3 d，故按照本研究采用的诊断标准，总体DGE发生率明显高于同期国内水平^[24]。在临床上C级DGE患者术后呕吐症状较明显，止吐药物使用次数较多，故在本研究中，BE在降低了C级DGE的发生率的同时，亦降低了术后止吐药物的使用次数。除此之外，BE组患者术后住院时间较短，这可能与C级DGE患者住院时间较长，而BE组C级DGE患者明显较少有关。

由于本回顾性研究在单一机构的局限性，未来还需更大样本的前瞻性研究，统一手术步骤及术后治疗护理方案，并在BE口径以及与胃肠吻合的距离上进行更进一步的探索。

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Prevalence rate of non-obese fatty liver disease and related influencing factors

DOI: 10.3969/j.issn.1001-5256.2021.11.022