Fish Oil Based Lipid Emulsions for the Treatment of Intestinal Failure Associated Liver Disease: Nothing Fishy About it!
Intestinal failure (IF) is a condition in which the gut is unable to provide adequate nutrient and fluid requirements for the maintenance of metabolic functions and growth in children. Long term parenteral nutrition (PN) is the backbone of management, however it is complicated by intestinal failure associated liver disease (IFALD) in ~20% children [1] IFALD is defined as hepatic dysfunction as a consequence of the medical and surgical management strategies for IF. Serum bilirubin is a marker of IFALD, value of >1.2 mg/dl is considered a Bred flag^ and 5.8 mg/dl is suggestive of marked liver injury [1] IFALD varies in severity from biochemical cholestasis to end stage liver disease requiring liver intestinal transplantation. Risk factors for IFALD include prematurity, lack of enteral nutrition, sepsis, longer duration and constituents of PN [1] In this issue, Miura et al. report a premature infant with short bowel syndrome on PN who developed IFALD, which was successfully treated with intravenous administration of omega 3 fatty acids [2] Intravenous lipid emulsion (ILE) based on soybean oil (SO) are implicated in IFALD. The ratio ofo 6:o 3 polyunsaturated fatty acid (PUFA) phytosterol and a tocopherol in the ILE are important determinants of IFALD. SO is high in linoleic acid (o 6 PUFA) This is converted into arachidonic acid (AA) which is a precursor for proinflammatory agents. In comparison, fish oil (FO) is rich in o 3PUFA, a source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) which are anti inflammatory. Hence an increase in EPA/AA ratio, as Miura et al. have demonstrated will be anti inflammatory and hepatoprotective [2] The higher a tocopherol and absent phytosterol in FO adds to its benefits. Several observational studies and one RCT have shown that FO is useful for treating infants with IFALD [3] A meta analysis of 3 studies showed that children treated with FO based ILE had a significant decrease in bilirubin as compared to those treated with SO [4] Miura et al. provide confirmation of the same [2] So, is the use of FO the solution for prevention and treatment of IFALD? The answer is not that simple. Firstly, good quality data for the use of FO for treatment of IFALD is lacking. Just like the present report [2] in the other studies also [3] SO was replaced by FO. Hence, it is unclear whether the improvement in cholestasis was due to stopping SO or adding FO or a combination of both. In perhaps the only RCT comparing FO and SO 1.5 g/kg/d) for the treatment of IFALD, Lam et al. found no difference in reversal of IFALD at 4 mo between the groups but the recovery was faster in the FO group [5] Also, resumption of SO in patients whose cholestasis had responded to FO therapy led to the redevelopment of cholestasis in one fourth of the patients [6] Both these prove the beneficial role and superiority of FO over SO for IFALD. Second, there are concerns with use of long term FO based ILE due to lack of long term safety data. FO is deficient in essential fatty acids and may not provide enough calories for growth [7] In this situation, the best lipid emulsion might be a mixture of soybean, coconut, olive and fish oil (SMOF lipid) with a correct balance between o 6/o 3 PUFA. ESPGHAN recommends that it is prudent to use multicomponent FOcontaining ILE in children who need long term PN, despite absence of quality data backing this recommendation [3] Thirdly, even though FO may reduce cholestasis and inflammation, there is data to suggest that it may still result in persistence or worsening of fibrosis in some patients [8] This is probably because, the pathogenesis of IFALD is multifactorial and the intervention should not be limited only to changing the ILE. Other measures like cyclical PN, increase in Anshu Srivastava avanianshu@yahoo.com
The Indian Journal of Pediatrics