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...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.展开更多
Parenteral nutrition associated liver disease (PNALD) is a significant complication in infants receiving long-term parenteral nutrition (PN). Chronic administration of PN has been associated with its development. Our ...Parenteral nutrition associated liver disease (PNALD) is a significant complication in infants receiving long-term parenteral nutrition (PN). Chronic administration of PN has been associated with its development. Our purpose is to characterize our incidence of PNALD over an extended period and identify risk factors for its development, including administration of soybean-based injectable lipid emulsions (ILEs) as we transit to novel ILEs</span><span style="font-family:Verdana;"> in our practice</span><span style="font-family:Verdana;">. Infants receiving 30 days or more of PN were included. PNALD was defined as a direct bilirubin ≥ 2 mg/dL. Data collected included: patient demographics, clinical and enteral feeding characteristics. Macronutrient intake was recorded using these cut-offs: glucose infusion rate (GIR) of ≤14 mg/kg/min or above, protein doses of ≤3 g/kg/day or above and lipid doses of ≤2 g/kg/day or above.</span><span style="font-family:""> </span><span style="font-family:Verdana;">A total of 349 infants were included, with an annual incidence of PNALD ranging between 34</span><span style="font-family:Verdana;">% </span><span style="font-family:Verdana;">-</span><span style="font-family:""> </span><span style="font-family:Verdana;">54%. Infants with PNALD were younger by gestation (27 vs. 29.5 weeks) and smaller by birthweight (900 vs. 1248 grams). Sepsis, GI disease including necrotizing enterocolitis and bowel resection were significantly associated with an increased risk for development of PNALD. PNALD infants received lower protein doses (3.0 vs 3.3 g/kg/day, p = 0.014) while receiving higher GIR (11.4 vs 10.7 mg/kg/min, p = 0.012) compared to non-PNALD infants. Low birth weight, sepsis and bowel resection remain strong indicators of risk for PNALD. No single macronutrient increased our infants’ risk for PNALD. The use of newer ILEs when available should be evaluated for their impact on PNALD development.展开更多
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...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.展开更多
AIM To determine if packed red blood cell transfusions contribute to the development of parenteral nutrition associated liver disease. METHODS A retrospective chart review of 49 premature infants on parenteral nutriti...AIM To determine if packed red blood cell transfusions contribute to the development of parenteral nutrition associated liver disease. METHODS A retrospective chart review of 49 premature infants on parenteral nutrition for > 30 d who received packed red blood cell(PRBC) transfusions was performed. Parenteral nutrition associated liver disease was primarily defined by direct bilirubin(db) > 2.0 mg/dL. A high transfusion cohort was defined as receiving > 75 mL packed red blood cells(the median value). KaplanMeier plots estimated the median volume of packedred blood cells received in order to develop parenteral nutrition associated liver disease.RESULTS Parenteral nutritional associated liver disease(PNALD) was noted in 21(43%) infants based on db. Among the 27 high transfusion infants, PNALD was present in 17(64%) based on elevated direct bilirubin which was significantly greater than the low transfusion recipients. About 50% of the infants, who were transfused 101-125 mL packed red blood cells, developed PNALD based on elevation of direct bilirubin. All infants who were transfused more than 200 mL of packed red blood cells developed PNALD. Similar results were seen when using elevation of aspartate transaminase or alanine transaminase to define PNALD.CONCLUSION In this retrospective, pilot study there was a statistically significant correlation between the volume of PRBC transfusions received by premature infants and the development of PNALD.展开更多
Chronic intestinal failure(CIF)is a rare but feared complication of Crohn’s disease.Depending on the remaining length of the small intestine,the affected intestinal segment,and the residual bowel function,CIF can res...Chronic intestinal failure(CIF)is a rare but feared complication of Crohn’s disease.Depending on the remaining length of the small intestine,the affected intestinal segment,and the residual bowel function,CIF can result in a wide spectrum of symptoms,from single micronutrient malabsorption to complete intestinal failure.Management of CIF has improved significantly in recent years.Advances in home-based parenteral nutrition,in particular,have translated into increased survival and improved quality of life.Nevertheless,60%of patients are permanently reliant on parenteral nutrition.Encouraging results with new drugs such as teduglutide have added a new dimension to CIF therapy.The outcomes of patients with CIF could be greatly improved by more effective prevention,understanding,and treatment.In complex cases,the care of patients with CIF requires a multidisciplinary approach involving not only physicians but also dietitians and nurses to provide optimal intestinal rehabilitation,nutritional support,and an improved quality of life.Here,we summarize current literature on CIF and short bowel syndrome,encompassing epidemiology,pathophysiology,and advances in surgical and medical management,and elucidate advances in the understanding and therapy of CIF-related complications such as catheter-related bloodstream infections and intestinal failure-associated liver disease.展开更多
Parenteral nutrition-associated liver disease(PNALD)is a liver dysfunction caused by various risk factors presented in patients receiving total parenteral nutrition(TPN).Omega-6 rich Intralipid?and omega-3 rich Omegav...Parenteral nutrition-associated liver disease(PNALD)is a liver dysfunction caused by various risk factors presented in patients receiving total parenteral nutrition(TPN).Omega-6 rich Intralipid?and omega-3 rich Omegaven?are two intravenous lipid emulsions used in TPN.TPN could affect the hepatic expression of genes in anti-oxidative stress,but it’s unknown whether TPN affects genes in drug metabolism.In this study,either Intralipid?-or Omegaven?-based TPN was administered to mice and the expression of a cohort of genes involved in anti-oxidative stress or drug metabolism was analyzed,glutathione(GSH)levels were measured,and protein levels for two key drug metabolism geneswere determined.Overall,the expression of most genes was downregulated by Intralipid?-based TPN(Gstpl,Gstml,3,6,Nqol,Ho-1,Mt-1,Gclc,Gclm,Cyp2d9,2f2,2b 10,and 3a11).Omegaven?showed similar results as Intralipid?except for preserving the expression of Gstml and Cyp3a11,and increasing Ho-1.Total GSH levels were decreased by Intralipid?,but increased by Omegaven?.CYP3A11 protein levels were increased by Omegaven?.In conclusion,TPN reduced the expression of many genes involved in anti-oxidative stress and drug metabolism in mice.However,Omegaven?preserved expression of Cyp3a11,suggesting another beneficial effect of Omegaven?in protecting liver functions.展开更多
文摘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.
文摘Parenteral nutrition associated liver disease (PNALD) is a significant complication in infants receiving long-term parenteral nutrition (PN). Chronic administration of PN has been associated with its development. Our purpose is to characterize our incidence of PNALD over an extended period and identify risk factors for its development, including administration of soybean-based injectable lipid emulsions (ILEs) as we transit to novel ILEs</span><span style="font-family:Verdana;"> in our practice</span><span style="font-family:Verdana;">. Infants receiving 30 days or more of PN were included. PNALD was defined as a direct bilirubin ≥ 2 mg/dL. Data collected included: patient demographics, clinical and enteral feeding characteristics. Macronutrient intake was recorded using these cut-offs: glucose infusion rate (GIR) of ≤14 mg/kg/min or above, protein doses of ≤3 g/kg/day or above and lipid doses of ≤2 g/kg/day or above.</span><span style="font-family:""> </span><span style="font-family:Verdana;">A total of 349 infants were included, with an annual incidence of PNALD ranging between 34</span><span style="font-family:Verdana;">% </span><span style="font-family:Verdana;">-</span><span style="font-family:""> </span><span style="font-family:Verdana;">54%. Infants with PNALD were younger by gestation (27 vs. 29.5 weeks) and smaller by birthweight (900 vs. 1248 grams). Sepsis, GI disease including necrotizing enterocolitis and bowel resection were significantly associated with an increased risk for development of PNALD. PNALD infants received lower protein doses (3.0 vs 3.3 g/kg/day, p = 0.014) while receiving higher GIR (11.4 vs 10.7 mg/kg/min, p = 0.012) compared to non-PNALD infants. Low birth weight, sepsis and bowel resection remain strong indicators of risk for PNALD. No single macronutrient increased our infants’ risk for PNALD. The use of newer ILEs when available should be evaluated for their impact on PNALD development.
文摘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.
文摘AIM To determine if packed red blood cell transfusions contribute to the development of parenteral nutrition associated liver disease. METHODS A retrospective chart review of 49 premature infants on parenteral nutrition for > 30 d who received packed red blood cell(PRBC) transfusions was performed. Parenteral nutrition associated liver disease was primarily defined by direct bilirubin(db) > 2.0 mg/dL. A high transfusion cohort was defined as receiving > 75 mL packed red blood cells(the median value). KaplanMeier plots estimated the median volume of packedred blood cells received in order to develop parenteral nutrition associated liver disease.RESULTS Parenteral nutritional associated liver disease(PNALD) was noted in 21(43%) infants based on db. Among the 27 high transfusion infants, PNALD was present in 17(64%) based on elevated direct bilirubin which was significantly greater than the low transfusion recipients. About 50% of the infants, who were transfused 101-125 mL packed red blood cells, developed PNALD based on elevation of direct bilirubin. All infants who were transfused more than 200 mL of packed red blood cells developed PNALD. Similar results were seen when using elevation of aspartate transaminase or alanine transaminase to define PNALD.CONCLUSION In this retrospective, pilot study there was a statistically significant correlation between the volume of PRBC transfusions received by premature infants and the development of PNALD.
文摘Chronic intestinal failure(CIF)is a rare but feared complication of Crohn’s disease.Depending on the remaining length of the small intestine,the affected intestinal segment,and the residual bowel function,CIF can result in a wide spectrum of symptoms,from single micronutrient malabsorption to complete intestinal failure.Management of CIF has improved significantly in recent years.Advances in home-based parenteral nutrition,in particular,have translated into increased survival and improved quality of life.Nevertheless,60%of patients are permanently reliant on parenteral nutrition.Encouraging results with new drugs such as teduglutide have added a new dimension to CIF therapy.The outcomes of patients with CIF could be greatly improved by more effective prevention,understanding,and treatment.In complex cases,the care of patients with CIF requires a multidisciplinary approach involving not only physicians but also dietitians and nurses to provide optimal intestinal rehabilitation,nutritional support,and an improved quality of life.Here,we summarize current literature on CIF and short bowel syndrome,encompassing epidemiology,pathophysiology,and advances in surgical and medical management,and elucidate advances in the understanding and therapy of CIF-related complications such as catheter-related bloodstream infections and intestinal failure-associated liver disease.
基金supported by grants from the National Institutes of Health(R01GM104037,R21ES029258,T32ES007148,and P3-ES005022,USA)Department of Veterans Affairs(BX002741,USA).
文摘Parenteral nutrition-associated liver disease(PNALD)is a liver dysfunction caused by various risk factors presented in patients receiving total parenteral nutrition(TPN).Omega-6 rich Intralipid?and omega-3 rich Omegaven?are two intravenous lipid emulsions used in TPN.TPN could affect the hepatic expression of genes in anti-oxidative stress,but it’s unknown whether TPN affects genes in drug metabolism.In this study,either Intralipid?-or Omegaven?-based TPN was administered to mice and the expression of a cohort of genes involved in anti-oxidative stress or drug metabolism was analyzed,glutathione(GSH)levels were measured,and protein levels for two key drug metabolism geneswere determined.Overall,the expression of most genes was downregulated by Intralipid?-based TPN(Gstpl,Gstml,3,6,Nqol,Ho-1,Mt-1,Gclc,Gclm,Cyp2d9,2f2,2b 10,and 3a11).Omegaven?showed similar results as Intralipid?except for preserving the expression of Gstml and Cyp3a11,and increasing Ho-1.Total GSH levels were decreased by Intralipid?,but increased by Omegaven?.CYP3A11 protein levels were increased by Omegaven?.In conclusion,TPN reduced the expression of many genes involved in anti-oxidative stress and drug metabolism in mice.However,Omegaven?preserved expression of Cyp3a11,suggesting another beneficial effect of Omegaven?in protecting liver functions.
