Pathogenesis and treatment of parenteral nutrition-associated liver disease

BACKGROUND: Parenteral nutrition-associated liver disease (PNALD) has been common in patients who require long-term parenteral nutrition. PNALD develops in 40%-60% of infants on long-term parenteral nutrition compared with 15%-40% of adults on home parenteral nutrition for intestinal failure. The pathogenesis of PNALD is multifactorial and remains unclear There is no specific treatment. Management strategies for its prevention and treatment depend on an understanding of many risk factors. This review aims to provide an update on the pathogenesis and treatment of this disease. DATA SOURCES: A literature search was performed on the MEDLINE and Web of Science databases for articles published up to October 2011, using the keywords: parenteral nutrition associated liver disease, intestinal failure associated liver disease lipid emulsions and fish oil. The available data reported in the relevant literatures were analyzed. RESULTS: The literature search provided a huge amount of evidence about the pathogenesis and management strategies on PNALD. Currently, lack of enteral feeding, extended duration of parenteral nutrition, recurrent sepsis, and nutrient deficiency or excess may play important roles in the pathogenesis of PNALD. Recent studies found that phytosterols present as contaminants in soy-based lipid emulsions, are also an important factor in the pathogenesis. Moreover, the treatment of PNALD is discussed. CONCLUSIONS: The use of lipid emulsions, phytosterols in particular, is associated with PNALD. Management strategies for the prevention and treatment of PNALD include consideration of early enteral feeding, the use of specialized lipid emulsions such as fish oil emulsions, and isolated small bowel or combined liver and small bowel transplantation. A greater understanding of the pathogenesis of PNALD has led to promising interventions to prevent and treat this condition. Future work should aim to better understand the mechanisms of PNALD and the long-term outcomes of its treatment.

Fish oil-based lipid emulsion:current updates on a promising novel therapy for the management of parenteral nutrition-associated liver disease

Intestinal failure is characterized by loss of enteral function to absorb necessary nutrients and water to sustain life.Parenteral nutrition(PN)is a lifesaving therapeutic modality for patients with intestinal failure.Lifelong PN is also needed for patients who have short bowel syndrome due to extensive resection or a dysmotility disorder with malabsorption.However,prolonged PN is associated with short-term and long-term complications.Parenteral nutrition-associated liver disease(PNALD)is one of the long-termcomplications associated with the use of an intravenous lipid emulsion to prevent essential fatty acid deficiency in these patients.PNALD affects 30–60%of the adult population on long-term PN.Further,PNALD is one of the indications for isolated liver or combined liver and intestinal transplantation.There is no consensus on how to manage PNALD,but fish oil-based lipid emulsion(FOBLE)has been suggested to play an important role both in its prevention and reversal.There is significant improvement in liver function in those who received FOBLE as lipid supplement compared with those who received soy-based lipid emulsion.Studies have also demonstrated that FOBLE reverses hepatic steatosis and reduces markers of inflammation in patients on long-term PN.Future prospective studies with larger sample sizes are needed to further strengthen the positive role of FOBLE in PNALD.

临床药师参与肠外营养相关性肝损害患者治疗的药学监护

目的:探讨临床药师在肠外营养相关性肝损害(PNALD)患者的临床营养治疗中的作用,促进临床营养药物的合理应用。方法:临床药师参与1例PNALD患者的治疗过程,建议将原有的"全合一"营养液配方中的5%葡萄糖氯化钠注射液500 m L调整为0.9%氯化钠注射液500 m L,30%长链脂肪乳剂250 m L调整为20%中/长链脂肪乳剂250 m L,8.5%复方氨基酸注射液(18AA)1 000 m L调整为8%复方氨基酸注射液(15AA)750 m L,并加用20%丙氨酰谷氨酰胺注射液100 m L和10%ω-3鱼油脂肪乳注射液100 m L,其余配方不变。另加用保肝药物还原型谷胱甘肽、S-腺苷蛋氨酸进行保肝退黄治疗,并逐渐减少肠外营养(PN)的量,过渡到肠内营养(EN)。结果:医师采纳临床药师的调整建议,该患者的肝功能逐渐恢复正常。结论:PN使用时间,PN中脂质种类、摄入量,营养物过剩等是造成PNALD的主要因素。临床药师在患者的临床营养治疗中开展药学监护可确保营养药物安全、有效地利用,减少并发症及药物不良反应的发生。

全肠外营养所致的肝脏损害─附5例报告

以光镜观察了５例胃肠瘘行全肠外营养（ｔｏｔａｌ ｐａｒｅｎｔｅｒａｌｎｕｔｒｉｔｉｏｎ，ＴＰＮ）支持治疗之肝活检标本。肝之基本病变为淤胆，最先见于胞浆，继而毛细胆管和小胆管；其他病变，如肝细胞变性、枯氏细胞增生、汇管区扩大和纤维及小胆管增生，以及小胆管周围炎等，均为长期淤胆之结果。临床有些酶异常先于病理改变；发病与ＴＰＮ用量、使用时间及营养配方有关。

还原型谷胱甘肽预防全肠外营养所致肝损害的临床观察

目的:探讨还原型谷胱甘肽(GSH)预防全肠外营养(TPN)肝损害的临床价值。方法:将82例接受TPN的病人随机分为两组,即对照组(n=42)给予TPN;试验组(n=40),在TPN的同时给予GSH治疗。观察治疗后第7和第14天时静脉血总胆红素(TBIL)、总胆汁酸(TBA)、谷丙转氨酶(ALT)、碱性磷酸酶(AKP)、谷胺酰转肽酶(γ-GT)等的变化。结果:试验组病人TPN第7和第14天时,静脉血TBIL、TBA、ALT、AKP和γ-GT均明显低于对照组,差异有显著性意义(P<0.05)。结论:GSH有助于预防短期TPN所致的肝损害。

左卡尼汀预防肠外营养相关肝损害临床观察

目的探讨左卡尼汀在预防肠外营养相关肝损害方面的作用。方法将69例接受肠外营养(PN)的患者随机分为两组,治疗组(n=34)在接受PN的支持外同时给予左卡尼汀治疗,对照组(n=35)只给予PN治疗。观察治疗前、治疗后第5天和治疗后第10天时静脉血谷丙转氨酶(ALT)、谷草转氨酶(AST)、谷氨酰转移酶(GGT)、总胆红素(TBIL)等指标变化。结果治疗组患者PN治疗后第5天和治疗后第10天ALT、AST、GCT、TBIL均明显低于对照组,差异有统计学意义(P<0.05)。结论适当加入左卡尼汀对于有效预防肠外营养相关肝损害具有重要意义。

鱼油脂肪乳对全肠外营养大鼠肝功能的影响

目的:比较还原型谷胱甘肽、丙氨酰谷氨酰胺、鱼油脂肪乳对全肠外营养大鼠肝功能的影响。方法:取24只SD雄性大鼠,随机分为TPN组、观察组1(TPN+还原型谷胱甘肽)、观察组2(TPN+丙氨酰谷氨酰胺)、鱼油(FOLE)组,每组6只。分别在给药第1、3、7、14天后取血清检测ALT、AKP、γ-GT、TBIL、TBA。第14天取血后处理肝组织,在光镜下观察肝组织的病理改变。结果:FOLE组ALT、AKP、γ-GT、TBIL、TBA水平均显著低于TPN组(P<0.01),AKP、γ-GT、TBIL水平与TPN+还原型谷胱甘肽组相比,有显著区别(P<0.05)。结论:鱼油脂肪乳可有效减少肠外营养相关肝损害的发生。

早产儿营养支持难点与对策

宫外生长发育迟缓(EUGR)在我国还相当普遍,如何对早产儿进行合理营养支持是新生儿科医生需关注的问题之一。该文介绍了早产儿肠外营养支持的途径选择和脂肪乳剂的选择、肠外营养应用时间及肠外营养相关的肝损害等并发症等问题。肠外营养相关的肝损害其机制仍不清,目前主要预防措施是尽早口服喂养、总热卡控制、积极抗感染等。

极低出生体质量儿胃肠外营养相关性胆汁淤积临床分析

目的:对60例极低出生体质量儿胃肠外营养相关性胆汁淤积(PNAC)的临床资料进行回顾性分析,探讨极低出生体质量儿PNAC肝损害的相关因素和近期预后。方法:对我院新生儿监护室2014年7月至2018年6月60例接受≥14 d胃肠外营养的体质量≤1500 g且胎龄≤32周的胆汁淤积患儿进行分析,肝功能损害38例为观察组,剩余22例为对照组。分析PNAC肝损害的相关因素,检测两组患儿胆汁淤积发生时间、持续时间、胆汁淤积程度及肝功能等情况,分析近期预后。结果:PNAC肝损害相关因素包括患儿到达全胃肠内营养的时间(P<0.01)、母孕期糖尿病(P=0.048)和高血压(P=0.036)。观察组胆汁淤积持续时间比对照组长[(88.79±7.57)d vs(35.09±1.30)d,P<0.01],肝功能损害出现在胆汁淤积后约3周,胆汁淤积消退后4周肝功能恢复正常。观察组直接胆红素峰值为(101.30±7.38)μmol/L,明显高于对照组(22.88±0.46)μmol/L(P<0.01)。结论:全胃肠内营养是极低出生体质量儿PNAC肝损害的保护因素,母孕期糖尿病和高血压是危险因素。PNAC肝损害患儿胆汁淤积程度重,持续时间长。PNAC近期预后良好。

多脏器功能障碍综合征中肠外营养相关肝损害的研究进展

多脏器功能障碍综合征(multiple organ dysfunction syndrome,MODS)患者或因感染等因素发生肠衰竭,肠道功能损害无法完成营养物质、电解质的吸收,重症患者进行性营养不良通常发展迅速,尽早肠外营养可以明显改善MODS患者的预后,现在肠外营养广泛应用于各类重症患者,然而肠外营养所引起的肠外营养相关肝损害(parenteral nutrition-associated liver disease,PNALD)在此类患者中普遍存在。PNALD的出现增加了对患者疾病的治愈难度。许多研究发现营养液中添加ω-3鱼油脂肪乳剂是预防与改善PNALD的有效手段。