While there has been a lot of enthusiasm for the use of fish oil as a potential breakthrough for intestinal failure-associated liver disease, this has been based largely on the use of surrogate markers of liver disease and based on comparisons with the historical use of conventional intravenous lipids. The latter problem has been discussed before on this blog (see links below).
A recent study begins to address the issue of surrogate markers by reinforcing the viewpoint that improvements in bilirubin and aminotransferases may not translate into improvement in liver fibrosis or other clinically-meaningful outcomes (JPGN 2013; 56: 364-69). A previous pediatric study (J Pediatr 2010; 156: 327-31) showed failure of regression of hepatic fibrosis in 2 children receiving FOE therapy.
In this study, the authors sequentially examined 6 children on fish-oil lipid emulsions (FOE) who underwent multiple liver biopsies. In this cohort, 5 of 6 children had gastroschisis and the mean gestational age was 35 weeks. Median intestinal (small bowel) length beyond the ligament of Treitz was 26 cm and most children retained about 2/3rds of their colon. Liver biopsies were obtained at the time of other open abdominal operations (eg. serial transverse enteroplasty, stoma takedown).
- Liver fibrosis persisted in 2 cases, progressed in 3 cases, and regressed in 1 case.
- Histology and biochemistries indicated improvement in cholestasis and inflammation.
- One patient has weaned off parenteral nutrition, two patients underwent isolated small bowel transplantation due to recurrent line infections, and three patients receive 25-40% of their calories parenterally.
The biggest limitation of this study besides the small number of enrolled patients was the relatively short time period that was studied. Only one patient who was studied had data reported for FOE more than 36 weeks. The oldest age of any patient at the time of their last biopsy was 131 weeks old.
- “There is no direct evidence to support any one [proposed theoretical benefit of FOE] as clinically meaningful as yet.”
- “Lipid minimization strategies are also effective in reducing cholestasis.”
- “Many of the biopsies taken right at the time of FOE initiation” showed significant fibrosis which “speaks to how quickly fibrosis can develop.” One child had stage 2 fibrosis at 14 weeks of life.
- “The biochemical resolution of cholestasis is at best a weak surrogate marker ..for…enteral independence and overall survival.” “These findings make a strong case for early referral of children with short bowel syndrome to specialized intestinal rehabilitation centers.”
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