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March 2014 E-Journal Club

March e-journal club Photo


We had a great traineeship week in March, with trainees from Rochester, NY and Toronto, Canada.  The weather in C’ville continued to be unusual, and our trainees were “treated” to a late spring snowfall, rather than the blooms and blossoms that we usually have in March.  Our article for journal club is about the potential role of omega-3 lipid emulsions in adults with parenteral nutrition associated liver disease.

February Citation:

Xu Z, Li Y, Wang J, Wu B, Li J.  Effect of omega-3 polyunsaturated fatty acids to reverse biopsy-proven parenteral nutrition-associated liver disease in adults. Clin Nutr 2012; 31: 217-223.


This was an open-label case series of 15 adults with short-bowel syndrome who were TPN-dependent and developed parenteral nutrition-associated liver disease (PNALD).  Patients with biopsy proven PNALD had up to 10 gms of their daily lipid emulsion (0.15-0.2 gm/kg) replaced with parenteral Omega-3 lipid emulsion, so that the final Omega-3/Omega-6 ratio was 1:4.  The primary outcomes of the study were changes in biochemical indicators of PNALD, serum lipids and fatty acids, resting energy expenditure (REE), and histologic changes as determined by liver biopsy after 1 month.

REE was measured weekly by indirect calorimetry, and methods appeared to suggest that non-protein calories matched the REE with a 1:1 ratio of carbohydrate to fat. Protein was provided to give a non-protein calorie to nitrogen ratio of 125:1.

Inclusion and Exclusion Criteria:

Inclusion criteria:

Adults with ≤ 100 cm of small bowel, serum direct bilirubin > 34 mM/L (2 mg/dL) and predicted PN duration > 30 days.

Exclusion criteria:

Patients with liver disease from a source other than PNALD or with obvious evidence of infection.

Major Results:

•   12 of the 15 patients (80%), had normalization of direct bilirubin, with a   mean significant decrease in total bilirubin and ALT.

·   Serum triglyceride was numerically, but not statistically significantly decreased (median TG decreased from 203 mg/dl to 97 mg/dl, not statistically different)

•   11 of the 15 patients were biopsied pre- and post omega-3 treatment. 

·    Liver biopsy post-treatment demonstrated histologic improvement with decreased cholestasis, steatosis and inflammation, but no significant difference in fibrosis.

Author’s Conclusions:

Supplemental omega-3 parenteral lipid emulsion is safe and effective in the treatment of PNALD in adults.


The strengths of this study include the fact that patients were relatively similar, and each served as their own control.  Additionally, liver biopsy with objective scoring was used in addition to lab values, and the pathologist who evaluated the biopsy samples was blinded to the study.  The methods of this study differ from case reports of pediatric and neonatal patients with PNALD who receive omega-3 lipid emulsion, because the current study only provided a portion of the lipids as omega-3.  Previous case reports we have reviewed provided all of the lipids as omega-3.

One limitation of this study is the fact that patients were not randomized into active and placebo groups and all were aware that patients were receiving a possibly beneficial treatment.  There were also a limited number of patients enrolled, for a limited amount of time and not all patients received pre and post liver biopsy (n =11).  It is unclear what the long-term outcome of these patients would be, and if continued or cycled periods of omega-3 lipid emulsion would prevent long term hepatic compromise.

One factor that we did discuss was the fact that although the methods state that patients received a 100% soybean oil lipid emulsion at baseline, a table listed the composition of the standard lipid emulsion (Lipofundin, B. Braun) used by all the patients, which provided a 50/50 mixture of MCT with soybean oil.  It is unclear if these results would translate to our patients, who do receive a soybean based lipid emulsion.  We also discussed the severity of liver disease in patients that had received PN for median of only 2 months, with the longest period on PN of 19 months.  Our experience is that PNALD often occurs after longer periods of PN.  We wondered if these patients had more readily reversible disease due the relatively short time on PN that would explain the rapid changes after 1 month of omega-3 lipid emulsion.

We did learn that there is an ongoing randomized study of omega-3 lipid emulsion in PNALD that is scheduled to be completed later this year. http://clinicaltrials.gov/ct2/show/NCT01284049

Our Take Home Message (s)

1.   Substitution of a portion of lipid calories with omega-3 lipid emulsion in adults with relatively short-duration PNALD is associated with normalization of serum bilirubin and decreased cholestasis, steatosis, and hepatic inflammation. 

2.   Larger and longer term randomized studies will be necessary to establish longer term safety and the effects on patient outcomes such as end-stage hepatic failure and survival.


Other News on the UVAHS GI Nutrition Website: (www.ginutrition.virginia.edu):

Upcoming Webinars 2014:

--April 29:  Micronutrient Issues in Gastric Bypass--Kelly O'Donnell, MS, RD, CNSC

--May 20:  Peri-op Nutrition, CHO Loading Prior, and Earlier Post-op Feeding--Kate Willcutts, MS, RD, CNSC

--June 24:  Managing Absorption in the Adult Short Bowel Patient--Carol Rees Parrish, MS, RD

Check out What’s New

--"Nutrition Support Blog”  

--" Resources for the Nutrition Support Clinician

Latest Practical Gastroenterology article  

--Hasemann  A. Yogurt: Nutritious Food or Sugary Treat?  Practical Gastroenterology 2014;XXXVIII(2):37.


Joe Krenitsky MS, RD

Carol Rees Parrish MS, RD