低碳水化合物饮食和生活方式干预对瘦型非酒精性脂肪性肝病患者的疗效观察

何诗华; 戴璐; 郑洁; 吴创鸿; 胡国信

doi:10.12449/JCH240513

低碳水化合物饮食和生活方式干预对瘦型非酒精性脂肪性肝病患者的疗效观察

DOI: 10.12449/JCH240513

何诗华^{1a, 2, 3},
戴璐^1a,
郑洁^1b,
吴创鸿²,
胡国信^{1a, 3, , ,}

1a.
北京大学深圳医院感染性疾病科，广东深圳 518000
1b.
北京大学深圳医院中医科，广东深圳 518000
2.
深圳市前海蛇口自贸区医院感染科，广东深圳 518000
3.
广州医科大学研究生院，广州 511436

基金项目:

国家自然科学基金 (81473473)

伦理学声明：本研究方案于2023年4月11日经由前海蛇口自贸区医院伦理委员会审批，批号：2023-057（申）-01。所有患者均签署知情同意书。

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：何诗华负责研究设计，数据收集与分析，稿件撰写；戴璐、郑洁负责数据收集与分析；吴创鸿负责研究设计、稿件修改；胡国信负责研究设计与把控，并最终定稿。

详细信息

通信作者:
胡国信， huoguoxin8228@sina.com （ORCID： 0009-0003-6618-7672）

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出版历程
- 收稿日期: 2023-07-30
- 录用日期: 2023-10-16
- 出版日期: 2024-05-25

Therapeutic effect of low-carbohydrate diet and lifestyle intervention on patients with lean nonalcoholic fatty liver disease

Shihua HE^{1a, 2, 3},
Lu DAI^1a,
Jie ZHENG^1b,
Chuanghong WU²,
Guoxin HU^{1a, 3
, ,
,}

1a.
Department of Infectious Diseases,Peking University Shenzhen Hospital shenzhen guangdong 518000
1b.
Department of Traditional Chinese Medicine，Peking University Shenzhen Hospital shenzhen guangdong 518000
2.
Department of Infectious Diseases，Shenzhen Qianhai Shekou Free Trade Zone Hospital，Shenzhen，Guangdong 518000，China
3.
Graduate School，Guangzhou Medical University，Guangdong 511436，China

Research funding:

National Natural Science Foundation of China (81473473)

More Information

Corresponding author: HU Guoxin， huoguoxin8228@sina.com （ORCID： 0009-0003-6618-7672）

摘要

摘要: 目的观察低碳水化合物饮食和线上生活方式干预对痩型非酒精性脂肪性肝病（NAFLD）患者的疗效。方法本研究选取2019年12月—2021年3月在北京大学深圳医院感染性疾病科、深圳市前海蛇口自贸区医院感染性疾病科就诊的痩型NAFLD患者53例，予以限制热量摄入的低碳水化合物饮食［总热量摄入根据基础代谢率（BMR）和活动因子（PAL）计算得来，总能量限制在（BMR×95%×PAL－1 000）kcal～（BMR×95%×PAL－500）kcal］，碳水化合物比例波动在10%～55%和生活方式指导8周，通过线上管理软件进行监督随访并观察患者疗效及安全性。比较患者干预前后的脂肪含量（CAP）及肝硬度（LSM）、人体测量学指标、血生化、尿蛋白和尿酮体等。1年后随访患者体质量和BMI。符合正态分布的计量资料两组间比较采用成组t检验；不符合正态分布的计量资料采用配对样本的Wilcoxon符号秩和检验。计数资料组间比较采用χ²检验。结果经8周干预后，患者CAP从（304.47±31.91）db/m下降至（242.43±26.74）db/m，LSM从（7.43±2.41）kPa下降至（6.36±1.79）kPa，体质量从（64.29±7.37）kg下降至（60.24±7.08），差异均有统计学意义（t值分别为11.25、3.72、14.07，P值均<0.001）。25例患者（47.2%）脂肪肝消失，12例LSM异常者（63.2%）恢复正常。52例患者（98.1%）体质量平均下降（4.05±2.32）kg。CAP下降等级随着体质量下降幅度的增加而增加。经干预后患者BMI、腰围、臀围、ALT、AST、GGT、尿酸、空腹血糖、TG、TC、LDL显著下降，HDL显著升高（t值分别为12.85，13.77，10.28，7.64，6.21，8.35，6.83，6.31，7.4，4.97，5.95，-2.21，P值均<0.05）。ALT、AST、GGT、尿酸、空腹血糖、TG、TC、LDL基线异常者恢复正常的比例分别为75%、100%、81.8%、57.1%、100%、66.7%、73.5%、85.3%。尿素氮、血肌酐、尿蛋白、尿酮体无明显改变（P值均>0.05）。随访1年后患者体质量及BMI无反弹（P值均>0.05）。干预及随访期间患者无胃肠道反应。结论低碳水化合物饮食及生活方式干预，可以改善痩型NAFLD患者肝脂肪含量及肝功能、血脂指标，且安全性良好。
- 非酒精性脂肪性肝病 /
- 膳食，低碳水化合物 /
- 生活方式 /
- 膳食，减重
Abstract: Objective To investigate the therapeutic effect of low-carbohydrate diet and online lifestyle intervention on patients with lean nonalcoholic fatty liver disease （NAFLD）. Methods This study was conducted among 53 patients with lean NAFLD who attended Department of Infectious Diseases in Peking University Shenzhen Hospital and Shenzhen Qianhai Shekou Free Trade Zone Hospital from December 2019 to March 2021， and the patients were given low-carbohydrate diet for calorie restriction ［total calorie intake was calculated based on basal metabolic rate （BMR） and physical activity level （PAL） and was restricted within （BMR×95%×PAL-1 000） kcal to （BMR×95%×PAL-500） kcal， and carbohydrate ratio fluctuated between 10% and 55%］ and lifestyle interventions for 8 weeks. An online software was used for supervision and follow-up， and the patients were observed in terms of treatment outcome and safety. The patients were compared in terms of controlled attenuation parameter （CAP）， liver stiffness measurement （LSM）， Anthropometric parameters， blood biochemistry， urinary protein， and urine ketone body before and after intervention. The patients were followed up after 1 year to measure body weight and body mass index （BMI）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the paired-sample Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous； the chi-square test was used for comparison of categorical data between groups. Results After 8 weeks of intervention， CAP decreased from 304.47±31.91 db/m to 242.43±26.74 db/m， LSM decreased from 7.43±2.41 kPa to 6.36±1.79 kPa， and body weight decreased from 64.29±7.37 kg to 60.24±7.08 kg （t=11.25，3.72， and 14.07， all P<0.001）. Of all patients， 25 （47.2%） had disappearance of fatty liver， and abnormal LSM in 12 patients （63.2%） returned to normal； 52 patients （98.1%） had a mean reduction of 4.05±2.32 kg in body weight. The degree of reduction in CAP increased with the degree of reduction in body weight. After intervention， there were significant reductions in BMI， waist circumference， hip circumference， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， gamma-glutamyl transpeptidase （GGT）， uric acid， fasting blood glucose， triglyceride （TG）， total cholesterol （TC）， and low-density lipoprotein （LDL） and a significant increase in high-density lipoprotein （t=12.85， 13.77， 10.28， 7.64， 6.21， 8.35， 6.83， 6.31， 7.4， 4.97， 5.95， and -2.21， all P<0.05）. The patients with abnormal ALT， AST， GGT， uric acid， fasting blood glucose， TG， TC， and LDL at baseline which returned to normal after intervention accounted for 75%， 100%， 81.8%， 57.1%， 100%， 66.7%， 73.5%， and 85.3%， respectively. There were no significant changes in blood urea nitrogen， serum creatinine， urine protein， and urine ketone body （all P>0.05）. There was no rebound in body weight and BMI after 1 year of follow-up （P>0.05）. There were no gastrointestinal reactions during intervention or follow-up. Conclusion Low-carbohydrate diet and lifestyle intervention can improve liver fat content， liver function， and blood lipid parameters in patients with lean NAFLD， with good safety.
- Non-alcoholic Fatty Liver Disease /
- Diet， Carbohydrate-Restricted /
- Life Style /
- Diet， Reducing

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图 1 纳入和排除受试对象的流程图

Figure 1. NAFLD screening process

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表 1 世界卫生组织预测BMR公式

Table 1. Formula for predicting basal metabolic rate by WHO

年龄	男性（kcal/d）	女性（kcal/d）
18～30岁	15.057×体质量+692.200	14.818×体质量+486.600
30～60岁	11.472×体质量+873.100	8.126×体质量+845.600

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表 2 根据生活方式及习惯性体力活动进行PAL分级

Table 2. PAL classification based on lifestyle and habitual physical activity

分类	PAL
静态、轻体力活动生活方式	1.40～1.69
活跃、中度体力活动生活方式	1.70～1.99
剧烈、重体力活动生活方式	2.00～2.40
注：PAL为日常活动评分。

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表 3 干预前后患者人体测量血指标及血生化变化情况

Table 3. Anthropometric measurement of blood indicators and blood biochemical changes

指标	干预前	干预后	t值	P值
体质量（kg）	64.29±7.37	60.24±7.08	14.07	<0.001
BMI（kg/m²）	22.56±0.98	21.16±1.07	12.85	<0.001
WC（cm）	86.57±5.75	82.91±4.82	13.77	<0.001
HC（cm）	94.36±5.04	91.79±4.40	10.28	<0.001
LSM（kPa）	7.43±2.41	6.36±1.79	3.72	<0.001
CAP（db/m）	304.47±31.91	242.43±26.74	11.25	<0.001
ALT（U/L）	63.11±27.34	35.28±13.01	7.64	<0.001
AST（U/L）	43.34±19.41	27.51±6.16	6.21	<0.001
GGT（U/L）	49.53±19.69	31.79±13.11	8.35	<0.001
UA（μmol/L）	475.40±99.17	394.70±79.13	6.83	<0.001
FBG（mmol/L）	5.65±0.86	5.00±0.61	6.31	<0.001
TG（mmol/L）	2.61±1.25	1.57±0.65	7.40	<0.001
TC（mmol/L）	5.83±0.97	5.16±0.66	4.97	<0.001
HDL（mmol/L	1.27±0.58	1.46±0.38	-2.21	0.032
LDL（mmol/L）	3.94±1.00	3.11±0.57	5.95	<0.001
BUN（mmol/L）	4.86±1.02	4.92±0.96	-0.30	0.766
Cr（μmol/L）	69.34±16.34	70.11±18.12	-0.23	0.823

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表 4 患者体质量下降情况

Table 4. The degree of weight loss

体质量下降比例	<3%	3%～5%	5%～7%	7%～10%	>10%
例（%）	5（9.4）	18（34.0）	10（18.9）	13（24.5）	6（11.3）

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表 5 体质量下降和CAP下降的关系

Table 5. Relationship between percent weight loss and percent CAP loss

组别	例数	CAP下降<15%［例（%）］	CAP下降15%～30%［例（%）］	CAP下降>30%［例（%）］
体质量下降<5%	23	19（35.8）	10（18.9）	0（0.0）
体质量下降5%～10%	24	4（7.5）	11（20.8）	0（0.0）
体质量下降>10%	6	1（1.9）	5（9.4）	3（5.7）

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