2019年ESPEN肝病营养指南解读

2019年欧洲临床营养和代谢学会再次发布了肝病临床营养指南,历时2年余进行更新和补充,统一了肠内和肠外营养推荐意见,首次提出了非酒精性脂肪性肝病、肝硬化合并骨病、肝硬化合并肥胖、肝硬化合并肌肉减少症和营养相关肝损伤等方面的推荐意见,对指导肝病患者营养管理有着非常重要的价值。本文对该指南进行解读,重新归类整理推荐意见,增进理解,提高实用性。

含鱼油脂肪乳剂在儿童肠外营养相关性肝病的临床应用进展

肠外营养相关性肝病(PNALD)是长期肠外营养(PN)支持导致的肝损害性疾病。尽早肠道喂养替代PN是有效的防治方法,但对无法脱离PN的肠衰竭病儿,脂肪乳剂剂量及类型的选择是防治的关键之一。近年来,许多研究发现,含鱼油脂肪乳剂(FOLE)具有改善甚至逆转PNALD的作用。现对FOLE在儿童PNALD临床研究进展作一综述。

添加鱼油脂肪乳全合一静脉营养对肝功能的影响

目的:了解添加n-3鱼油脂肪乳全合一静脉营养是否可改善肠外营养引起的肝功能损害和胆汁淤积。方法:将100例需要中长期全合一静脉营养支持的患者随机分为2组:对照组50例,使用普通脂肪乳剂250m L;实验组50例,使用普通脂肪乳剂250m L加鱼油脂肪乳剂100m L。输注肠外营养1w后,比较输注前后2组患者血浆转氨酶、胆红素及血浆蛋白水平。结果:肠外营养治疗前后,实验组患者自身对比,血清平均总胆红素(TBIL)、直接胆红素(DBIL)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)均明显降低(P<0.05)。对照组患者自身对比,血清平均ALT、碱性磷酸酶(ALP)、γ-谷氨酰转移酶(γ-GT)均明显升高(P<0.05)。实验组在肠外营养支持后血清平均TBIL、DBIL、ALT、AST、ALP、γ-GT均明显低于对照组(P<0.01)。结论:添加n-3鱼油脂肪乳可改善患者的肝功能损害和胆汁淤积。

肠外营养相关性肝病研究进展

肠外营养相关性肝病(PNALD)是指接受全肠外营养患者出现的一系列肝病,从肝酶异常到脂肪变性,再到纤维化,直至最终出现肝硬化。PNALD的发病机制是多因素的,目前尚不完全清楚。PNALD没有具体的治疗方法,其预防和治疗的管理策略取决于对危险因素的了解。本文就PNALD的发病机制和治疗进展进行综述。

1例膈疝术后超短肠综合征病人的医学营养治疗

短肠综合征(short bowel syndrome,SBS)是指广泛小肠切除术后,肠道有效吸收面积显著减少,残留的功能性肠管不能维持病人营养需要的吸收不良综合征。临床特征为严重腹泻、体质量减轻、水/电解质/酸碱紊乱、营养物质吸收及代谢障碍。其中,超短肠综合征(extra short bowel syndrome, ESBS)是其最严重的形式[1]。2015年欧洲临床营养与代谢学会(European society of parenteral and enteral nutrition, ESPEN)的肠衰竭指南表明SBS是导致慢性肠衰竭的主要病理表现,严重者可能需终身行肠外营养(parenteral nutrition,PN)治疗,并发生以肠外营养/肠衰竭相关肝病(parenteral nutrition–associated liver disease/intestinalfailure–associatedliver disease,PNALD/IFALD)为代表的严重并发症[2]。

早产儿肠外营养相关性肝病的诊断与治疗

早产儿肠外营养相关性肝病是早产儿长期胃肠外营养最主要的并发症之一，其主要特征是结合胆红素≥34.2 μmol/L，伴或不伴肝酶异常，排除其他疾病。其常见危险因素包括胎龄、低出生体质量、胃肠外营养的持续时间、胃肠外营养成分、感染、胃肠疾病、基因易感性等。这种肝损害大多程度较轻，停止静脉营养会自愈，但也有少数会进展到肝纤维化。尽管熊去氧胆酸和鱼油来源的、富含ω-3 PUFA（n－6∶n－3＝1∶7）的脂肪乳剂可用于治疗肠外营养相关性肝病，但临床实际仍缺乏有效的预防、治疗肠外营养相关性肝病的策略，需不断寻找新的治疗手段。

Hepatic encephalopathy in patients with liver cirrhosis:Is there a role of malnutrition?

Hepatic encephalopathy(HE) is a common complica-tion in patients with liver cirrhosis but its pathogenesis remains incompletely understood.Malnutrition is com-monly encountered in patients with liver cirrhosis and it has been reported to affect the quality of life of this group of patients.Experimental studies suggest that low energy intake and poor nutritional status may facil-itate the development of HE but there are scarce data on the potential role of malnutrition in HE in patients with liver cirrhosis.Two recently published studies have evaluated the potential role of malnutrition in the development of HE in cirrhotic patients with conflicting results.In this letter to the editor we briefly present the results of the two studies as well as potential rea-sons for the conflicting results reported.

Nutritional recommendations for patients with non-alcoholic fatty liver diseases

Fatty liver is the most common liver disease worldwide.Patients with fatty liver disease die primarily from cardiovascular disease and not from chronic liver diseases.Hyperglycemia and hyperinsulinemia induce lipogenesis,thereby increasing the hepatic pool of fatty acids.This pool is also increased by increased delivery of fatty acids through the diet or lipolysis in adipose tissue.Nutritional consultations and lifestyle modification are important in the treatment of non-alcoholic fatty liver disease(NAFLD).Among the dietary constituents,combination of vitamin D,vitamin E,and omega-3 fatty acids shows promise for the treatment of NAFLD.

Effect of rapamycin on hepatic osteodystrophy in rats with portasystemic shunting

AIM： TO study if T-cell activation related to portasystemic shunting causes osteoclast-mediated bone loss through RANKL-dependent pathways. We also investigated if T-cell inhibition using rapamycin would protect against bone loss in rats. METHODS： Portasystemic shunting was performed in male Sprague-Dawley rats and rapamycin 0.1 mg/kg was administered for 15 wk by gavage. Rats received powderized chow and supplemental feeds to prevent the effects of malnutrition on bone composition. Weight gain and growth was restored after surgery in shunted animals. At termination, biochemical parameters of bone turnover and quantitative bone histology were assessed. Markers of T-cell activation, inflammatory cytokine production, and RANKL-dependent pathways were measured. In addition, the roles of IGF-1 and hypogonadism were investigated. RESULTS： Portasystemic shunting caused low turnover osteoporosis that was RANKL independent. Bone resorbing cytokine levels, including IL-1, IL-6 and TNFα, were not increased in serum and TNFα and RANKL expression were not upregulated in PBMC. Portasystemic shunting increased the circulating CD8＋ T-cell population. Rapamycin decreased the circulating CD8＋ T-cell population, increased CD8＋ CD25＋ T-regulatory cell population and improved all parameters of bone turnover. CONCLUSION： Osteoporosis caused by portasystemic shunting may be partially ameliorated by rapamycin in the rat model of hepatic osteodystrophy.

Effect of nutritional counselling on hepatic,muscle and adipose tissue fat content and distribution in non-alcoholic fatty liver disease

AIM： To assess the effectiveness of the current UK clinical practice in reducing hepatic fat （IHCL）.METHODS： Whole body MRI and IH MRS were obtained, before and after 6 mo nutritional counselling, from liver, soleus and tibialis muscles in 10 subjects with non-alcoholic fatty liver disease （NAFLD）.RESULTS： A 500 Kcal-restricted diet resulted in an average weight loss of 4% （-3.4 kg,） accompanied by significant reductions in most adipose tissue （AT） depots, including subcutaneous （-9.9%）, abdominal subcutaneous （-10.2%） and intra-abdominal- AT （-11.4%）. Intramyocellular lipids （IMCL） were significantly reduced in the tibialis muscle （-28.2%）. Decreases in both IHCL （-39.9%） and soleus IMCL （-12.2%） content were also observed, although these were not significant. Several individuals showed dramatic decreases in IHCL, while others paradoxically showed increases in IHCL content. Changes in body composition were accompanied by improvements in certain liver function tests： serum aspartate aminotransferase （AST） and alanine aminotransferase （ALT）. Significant correlations were found between decreases in IHCL and reductions in both intra-abdominal and abdominal subcutaneous AT. Improvements in liver function tests were associated with reductions in intra-abdominal AT, but not with changes in IHCL. CONCLUSION： This study shows that even a very modest reduction in body weight achieved through lifestyle modification can result in changes in body fat depots and improvements in LETs.

Resting energy expenditure and glucose, protein and fat oxidation in severe chronic virus hepatitis B patients

AIM: To study and determine the resting energy ex- penditure (REE) and oxidation rates of glucose, fat and protein in severe chronic hepatitis B patients. METHODS: A total of 100 patients with liver diseases were categorized into three groups: 16 in the acute hepatitis group, 56 in the severe chronic hepatitis group, and 28 in the cirrhosis group. The REE and the oxidation rates of glucose, fat and protein were as- sessed by indirect heat measurement using the CCM-D nutritive metabolic investigation system. RESULTS: The REE of the severe chronic hepatitis group (20.7 ± 6.1 kcal/d per kg) was significantly lower than that of the acute hepatitis group (P = 0.014). The respiratory quotient (RQ) of the severe chronic hepatitis group (0.84 ± 0.06) was significantly lower than that of the acute hepatitis and cirrhosis groups (P = 0.001). The glucose oxidation rate of the severe hepatitis group (39.2%) was significantly lower than that of the acute hepatitis group and the cirrhosis group (P < 0.05), while the fat oxidation rate (39.8%) in the severe hepatitis group was markedly higher than that of the other two groups (P < 0.05). With improve- ment of liver function, the glucose oxidation rate in- creased from 41.7% to 60.1%, while the fat oxidation rate decreased from 26.3% to 7.6%. CONCLUSION: The glucose oxidation rate is signifi-cantly decreased, and a high proportion of energy is provided by fat in severe chronic hepatitis. These re- sults warrant a large clinical trail to assess the optimal nutritive support therapy for patients with severe liver disease.

Histone modifications and alcohol-induced liver disease:Are altered nutrients the missing link?

Alcoholism is a major health problem in the United States and worldwide,and alcohol remains the single most significant cause of liver-related diseases and deaths.Alcohol is known to influence nutritional status at many levels including nutrient intake,absorption,utilization,and excretion,and can lead to many nutritional disturbances and deficiencies.Nutrients can dramatically affect gene expression and alcohol-induced nutrient imbalance may be a major contributor to pathogenic gene expression in alcohol-induced liver disease(ALD).There is growing interest regarding epigenetic changes,including histone modifications that regulate gene expression during disease pathogenesis.Notably,modifications of core histones in the nucleosome regulate chromatin structure and DNA methylation,and control gene transcription.This review highlights the role of nutrient disturbances brought about during alcohol metabolism and their impact on epigenetic histone modifications that may contribute to ALD.The review is focused on four critical metabolites,namely,acetate,S-adenosylmethionine,nicotinamide adenine dinucleotide and zinc that are particularly relevant to alcohol metabolism and ALD.

Nutritional status in relation to lifestyle in patients with compensated viral cirrhosis

AIM:To assess the nourishment status and lifestyle of non-hospitalized patients with compensated cirrhosis by using noninvasive methods.METHODS:The subjects for this study consisted of 27 healthy volunteers,59 patients with chronic viral hepatitis,and 74 patients with viral cirrhosis,from urban areas.We assessed the biochemical blood tests,anthropometric parameters,diet,lifestyle and physical activity of the patients.A homeostasis model assessment-insulin resistance(HOMA-IR) value of ≥ 2.5 was considered to indicate insulin resistance.We measured height,weight,waist circumference,arm circumference,triceps skin-fold thickness,and handgrip strength,and calculated body mass index,arm muscle circumference(AMC),and arm muscle area(AMA).We interviewed the subjects about their dietary habits and lifestyle using health assessment computer software.We surveyed daily physical activity using a pedometer.Univariate and multivariate logistic regression modeling were used to identify the relevant factors for insulin resistance.RESULTS:The rate of patients with HOMA-IR ≥ 2.5(which was considered to indicate insulin resistance) was 14(35.9%) in the chronic hepatitis and 17(37.8%) in the cirrhotic patients.AMC(%)(control vs chronic hepatitis,111.9% ± 10.5% vs 104.9% ± 10.7%,P = 0.021;control vs cirrhosis,111.9% ± 10.5% vs 102.7% ± 10.8%,P = 0.001) and AMA(%)(control vs chronic hepatitis,128.2% ± 25.1% vs 112.2% ± 22.9%,P = 0.013;control vs cirrhosis,128.2% ± 25.1% vs 107.5% ± 22.5%,P = 0.001) in patients with chronic hepatitis and liver cirrhosis were significantly lower than in the control subjects.Handgrip strength(%) in the cirrhosis group was significantly lower than in the controls(control vs cirrhosis,92.1% ± 16.2% vs 66.9% ± 17.6%,P < 0.001).The results might reflect a decrease in muscle mass.The total nutrition intake and amounts of carbohydrates,protein and fat were not significantly different amongst the groups.Physical activity levels(kcal/d)(control vs cirrhosis,210 ± 113 kcal/d vs 125 ± 74 kcal/d,P = 0.001),number of steps(step/d)(control vs cirrhosis,8070 ±3027 step/d vs 5789 ± 3368 step/d,P = 0.011),and exercise(Ex)(Ex/wk)(control vs cirrhosis,12.4 ± 9.3 Ex/wk vs 7.0 ± 7.7 Ex/wk,P = 0.013) in the cirrhosis group was significantly lower than the control group.The results indicate that the physical activity level of the chronic hepatitis and cirrhosis groups were low.Univariate and multivariate logistic regression modeling suggested that Ex was associated with insulin resistance(odds ratio,6.809;95% CI,1.288-36.001;P = 0.024).The results seem to point towards decreased physical activity being a relevant factor for insulin resistance.CONCLUSION:Non-hospitalized cirrhotic patients may need to maintain an adequate dietary intake and receive lifestyle guidance to increase their physical activity levels.

肠外营养致严重肝功能损伤1例

肠外营养（parenteral nutrition,PN）是指通过静脉途径为无法经胃肠道摄取和利用营养物质的患者提供完全和充足的营养素,以达到维持机体代谢所需的目的。但长期使用PN可能引起严重的不良反应,包括脓毒血症、代谢失衡、肝功能损伤等。PN引起的肝功能异常称为肠外营养相关肝病（parenteral nutrition-associated liver disease,PNALD）,或者肠衰竭相关肝损害（intestinal failure-associated liver disease,IFALD）。PNALD的病因尚不明确.

Interventions to improve physical function and prevent adverse events in cirrhosis

Cirrhosis is associated with debilitating complications that significantly impact on a patient’s physical function and reduce quality of life.Owing to highly prevalent sarcopenia,malnutrition and hepatic encephalopathy,functional impairment or frailty is a common complication of cirrhosis.Frailty in turn increases the patient’s risk of hospitalization,accidental falls and fractures,and death.The management of frailty and its associated adverse effects is imperative in improving the overall prognosis of patients with advanced liver disease.The cornerstone of therapy revolves around optimizing physical function with appropriate nutrition and exercise.Nutritional therapy with protein supplementation has shown significant benefit,while studies on exercise have been controversial.However,newly emerging studies trend towards a beneficial effect of physical exercise with improvement in quality of life.The implementation of technology in liver disease management shows future promise.Fitbits and other wearable devices can be used to help monitor a patient’s personal progress in physical exercise and nutritional optimization.Additionally,the progressive development of new smartphone applications to help aid in the diagnosis and monitoring of complications of cirrhosis provides a sophisticated avenue for improving care of patients with cirrhosis.