Intravenous lipids may cause parenteral nutrition associated cholestasis (PNAC), parenteral nutrition associated liver disease (PNALD), or intestinal failure associated cholestasis (IFAC) (J Pediatr 2012; 160: 421-7 & editorial 361-2).  PNAC refers to cholestasis due to parenteral nutrition and PNALD refers to PNAC that has progressed to liver dysfunction or permanent liver injury.

In a previous blog (Four advances for intestinal failure), one of the advances for intestinal failure that was noted was the reduction of lipid infusions with parenteral nutrition which reduces IFAC.  This study adds additional information to this area.  In this prospective study, 31 patients were enrolled in a reduced IV fat emulsion group and compared with a matched historical control group.  The reduced fat group received 1gm/kg of a standard soybean-based lipid emulsion (liposyn 20%) twice weekly.  Patients were eligible if they received PN for >2 weeks and had a direct bilirubin >2.5 mg/dL.

Outcomes:

• Total bilirubins dropped 0.73 mg/dL each week in the reduced fat group; in the control group, the bilirubin increased 0.29 mg/dL each week
• Growth was similar in both groups
• Essential fatty acid deficiency (biochemical not clinical features) was identified in 13 of 31 infants among the restricted IV fat emulsion group.

Essential fatty acid deficiency was defined as having a triene: tetraene ratio >0.05 (mild), >0.2 (moderate) or >0.4 (severe).

Limitations:

• Historical control group & small study population
• Fat-restricted group received enteral antibiotics which may have helped reduce cholestasis
• Majority of patients with relatively short duration of TPN: 18 of 31 for less than one month

The reasons why lipids may contribute to PNAC/PNALD/IFAC include the presence of phytosterols.  This in turn may damage hepatocytes via the farnesoid X receptor.  One other aspect of the study was that the fat-restricted cohort had a higher mortality.  This was thought to be related to the cohort being sicker rather than to any nutritional effect.  Specific causes of death included respiratory failure in a patient with an abdominal wall defect, chylothorax/sepsis in a patient with a congenital diaphragmatic hernia, and cardiopulmonary failure in a patient with pulmonary hypoplasia.

The article does throw into question whether the use of a fish oil lipid preparation is needed to improve cholestasis.  In studies supporting fish oil preparations, a confounder was that the total lipid administered was reduced to 1 gm/kg/day in comparison to soybean lipids which were administered at 2-3 gm/kg/day.  This study suggests that reducing the total amount of lipid infusion is the more important factor.

The accompanying editorial makes a couple of useful points:

• Increasing enteral feeds (>50%) is as effective as using less intravenous lipids
• Use of standard lipids at 1gm/kg/day decreased IFAC from 15% to 4% in their intestinal failure patient population
• Drastic reductions in lipids lead to essential fatty acid deficiency and should be avoided.
• Use of Omegaven has not been shown to prevent liver fibrosis even with resolution of cholestasis; similarly, these studies do not inform fully on the long-term liver effects of reducing standard lipids
• Neurologic followup will be important
• Explains “Morton’s fork.”  John Morton was a 16th century Archbishop who wanted to increase taxes on people who were living lavishly.  In addition, he wanted to increase taxes on those living modestly (must be hiding wealth).

Additional references:

• -NEJM 2010; 362: 181.  Letter to editor describes use of fish oil in (n=125) Boston pediatric patients.
• -JPGN 2009; 48: 209. n=12. SBS.  9/12 improved with Omegaven. 3 had transplant (L-ITx). No controls.
• -Pediatrics 2008; 121: e678-86. n=18.  Use of fish oil improved cholestasis compared to historical controls.
• -Pediatrics 2006; 118: e197-e201.  Reversal of TPN-AC c IV omega-3 fatty acids (fish oil-derived) instead of intralipids