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Buchman, Alan L.

doi:10.1023/a:1005628121546

Cited by 85 publications

(16 citation statements)

References 176 publications

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“…Today, more than 30,000 US patients are permanently dependent on PN for survival (37). Long term use of PN is associated with many complications, including septicemia and metabolic abnormalities (38). The most serious complication associated with long term PN use is PN-associated liver disease (PNALD).…”

Section: Parenteral Nutrition and Essential Fatty Acid Deficiencymentioning

confidence: 99%

The essentiality of arachidonic acid and docosahexaenoic acid

Meisel

Meijer

et al. 2009

Prostaglandins, Leukotrienes and Essential Fatty Acids

139

119

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Objective The purpose of this review is to correlate the clinical finding that patients receiving parenteral nutrition with a fish oil-based lipid emulsion do not develop essential fatty acid deficiency (EFAD) with an experimental murine model, thus showing that arachidonic acid (AA) and docosahexaenoic acid (DHA) are likely to be the essential fatty acids. Background Conventional belief is that linoleic acid (LA, omega-6) and alpha-linolenic acid (ALA, omega-3) are the essential fatty acids (EFAs). We have shown that a fish oil-based lipid emulsion containing AA (omega-6) and docosahexaenoic acid (DHA, omega-3) and insignificant quantities of LA and ALA is efficacious in the treatment of parenteral nutrition-associated liver disease (PNALD), a major cause of liver-related morbidity and mortality. The prospect of using a fish oil-based lipid emulsion as monotherapy has raised concerns of EFAD development, hindering its adoption into clinical practice. Design Data from patients in our institution who received PN with a fish oil-based lipid emulsion was reviewed for clinical and biochemical evidence of EFAD, defined as an elevated triene-tetraene ratio (Mead acid/AA >0.2). We also investigated the minimum amount of fish oil required to prevent EFAD in a murine model and determined whether DHA and AA alone can prevent EFAD. Results No patients receiving PN with a fish oil-based lipid emulsion in our institution have developed biochemical or clinical evidence of EFAD such as an elevated triene-tetraene ratio, growth retardation or dermatitis. This observation parallels our previously published animal studies, which demonstrated prevention of EFAD when thirteen percent of total calories were from fish oil. Moreover, current work in our laboratory shows that AA and DHA provision alone is sufficient to prevent biochemical and physiologic evidence of EFAD in a murine model. Conclusions When dosed appropriately, fish oil-based lipid emulsions contain sufficient EFAs to prevent EFAD. Furthermore, AA and DHA alone may be the true EFAs.

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Section: Parenteral Nutrition and Essential Fatty Acid Deficiencymentioning

confidence: 99%

The essentiality of arachidonic acid and docosahexaenoic acid

Meisel

Meijer

et al. 2009

Prostaglandins, Leukotrienes and Essential Fatty Acids

139

119

View full text Add to dashboard Cite

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“…10–13 Likewise, pharmacologic interventions such as treatment with metronidazole, ursodeoxycholic acid, or choline, have had moderate success. 14 In refractory hepatic failure in the setting of intestinal failure, liver transplantation (with or without small bowel) remains the only option. Considering modern graft and patient 5 year survival rates for liver small bowel and small bowel alone transplants are in the range of 43–75% and 57–75% respectively, alternative medical and surgical strategies for short bowel syndrome and PNALD are still needed.…”

Section: Introductionmentioning

confidence: 99%

Parenteral Fish Oil Improves Outcomes in Patients With Parenteral Nutrition-Associated Liver Injury

et al. 2009

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OBJECTIVE The objective was to determine the safety and efficacy of a fish oil-based intravenous lipid emulsion (IFE) in the treatment of PNALD. SUMMARY AND BACKGROUND DATA Parenteral nutrition-associated liver disease (PNALD) can be a lethal complication in children with short bowel syndrome (SBS). IFE based on soybean oil administered with parenteral nutrition (PN) may contribute to its etiology. METHODS We performed an open-labeled trial of a fish-oil IFE in 42 infants with SBS who developed cholestasis (serum direct bilirubin > 2 mg/dL) while receiving soybean IFE. Safety and efficacy outcomes were compared with those from a contemporary cohort of 49 infants with SBS and cholestasis whose PN course included soybean IFE only. The primary efficacy end-point was time to reversal of cholestasis (direct bilirubin ≤2 mg/dL). RESULTS Three deaths and 1 liver transplantation occurred in the fish oil cohort, compared to 12 deaths and 6 transplants in the controls (P=0.005). Among survivors not transplanted during PN, cholestasis reversed while receiving PN in 19/38 patients in the fish oil cohort vs. 2/36 patients in the controls. Based on Cox models, subjects receiving fish oil-IFE experienced reversal of cholestasis 6 times faster (95% CI=2.0,37.3) than those receiving soybean IFE. The provision of fish oil IFE was not associated with hypertriglyceridemia, coagulopathy, essential fatty acid deficiency. Moreover, hypertriglyceridemic events and abnormal INR levels were more common among controls. CONCLUSIONS Fish oil IFE is safe, may be effective in treating PNALD, and may reduce mortality and organ transplantation rates in children with SBS.

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“…Unfortunately, up to 65% of these children experience some liver dysfunction, which may manifest histologically as cholestasis or cirrhosis, and/or biochemically as hyperbilirubinemia and elevated serum aminotransferases 2,3 . Parenteral nutrition-associated liver disease (PNALD) progresses to end-stage liver failure in 15% to 50% of patients 4,5 and together with sepsis is the most common cause of death in patients with short-bowel syndrome 6-8 .…”

Section: Introductionmentioning

confidence: 99%

Persistent alanine aminotransferase elevations in children with parenteral nutrition-associated liver disease

Yang

Lee

Valim

et al. 2009

Journal of Pediatric Surgery

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Background Parenteral nutrition associated liver disease (PNALD) is a serious condition affecting many children with short bowel syndrome. The aim of this study was to longitudinally assess serum alanine aminotransferase (ALT), a marker for hepatocyte injury, in enterally fed children with PNALD. Methods Retrospective chart review of 31 patients treated from 1999 to 2006 by the Center for Advanced Intestinal Rehabilitation at Children's Hospital Boston. Inclusion criteria included: PN duration > 3 months with subsequent tolerance of full enteral nutrition, and evidence of PN associated liver injury. Time to normalize ALT and direct bilirubin was estimated using Kaplan-Meier and Cox proportional-hazards methods. Results Mean age PN cessation was 6 months (range 2-14 months). Median PN duration was 18 weeks (IQR = 13, 33 weeks) and median follow-up was 24 weeks (IQR = 14, 48 weeks). After transition to full enteral nutrition, 74% of children normalized direct bilirubin, whereas only 50% normalized ALT. Kaplan-Meier median time to direct bilirubin and ALT normalization were 13 weeks and 35 weeks respectively (P=0.001). Conclusion Children with PNALD who have achieved PN independence have persistent ALT elevation despite normal direct bilirubin levels. This implies that hepatic injury may be ongoing beyond the time of bilirubin normalization in this cohort of patients.

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Cited by 85 publications

References 176 publications

The essentiality of arachidonic acid and docosahexaenoic acid

The essentiality of arachidonic acid and docosahexaenoic acid

Parenteral Fish Oil Improves Outcomes in Patients With Parenteral Nutrition-Associated Liver Injury

Persistent alanine aminotransferase elevations in children with parenteral nutrition-associated liver disease

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