Parenteral fish oil improves outcomes in patients with parenteral nutrition-associated liver injury

Abstract

Objective: The objective was to determine the safety and efficacy of a fish oil-based intravenous lipid emulsion (ILE) in the treatment of parenteral nutrition-associated liver disease (PNALD).

Summary and background data: PNALD can be a lethal complication in children with short bowel syndrome (SBS). ILE 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-based ILE in 42 infants with SBS who developed cholestasis (serum direct bilirubin >2 mg/dL) while receiving soybean oil-based ILE. Safety and efficacy outcomes were compared with those from a contemporary cohort of 49 infants with SBS and cholestasis whose PN course included soybean ILE 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 with 12 deaths and 6 transplants in the soybean oil cohort (P = 0.005). Among survivors not transplanted during PN, cholestasis reversed while receiving PN in 19 of 38 patients in the fish oil cohort versus 2 of 36 patients in the soybean oil cohort. Based on Cox models, subjects receiving fish oil-based ILE experienced reversal of cholestasis 6 times faster (95% CI: 2.0-37.3) than those receiving soybean oil-based ILE. The provision of fish oil-based ILE was not associated with hypertriglyceridemia, coagulopathy, or essential fatty acid deficiency. Moreover, hypertriglyceridemic events and abnormal international normalized ratio levels were more common among controls.

Conclusions: Fish oil-based ILE is safe, may be effective in treating PNALD, and may reduce mortality and organ transplantation rates in children with SBS.

Figures

Figure 1. Trends over time of markers of liver dysfunction in the fish oil (solid line) and in the soybean oil control cohorts (dashed line), from baseline in week 0 (starting admnistration of fish oil emulsion in the fish oil cohort and reaching the second direct bilirubin > 2 mg/dL in the soybean oil control cohort) until the end of follow-up of the majority of subjects

Points represent medians (equivalent to the geometric mean) and vertical bars represent interquartile ranges. P represent p-values testing differences between the two study groups of linear trends over time in the natural logarithm of the corresponding test and were estimated based on a longitudinal model with a generalized estimating equation approach.

Figure 1. Trends over time of markers of liver dysfunction in the fish oil (solid line) and in the soybean oil control cohorts (dashed line), from baseline in week 0 (starting admnistration of fish oil emulsion in the fish oil cohort and reaching the second direct bilirubin > 2 mg/dL in the soybean oil control cohort) until the end of follow-up of the majority of subjects

Points represent medians (equivalent to the geometric mean) and vertical bars represent interquartile ranges. P represent p-values testing differences between the two study groups of linear trends over time in the natural logarithm of the corresponding test and were estimated based on a longitudinal model with a generalized estimating equation approach.

Figure 2. Trends over time of markers of essential fatty acid deficiency and coagulopathy in the fish oil (solid line) and in the soybean oil control cohorts (dashed line), from baseline in week 0 (starting admnistration of fish oil emulsion in the fish oil cohort and reaching the second direct bilirubin > 2 mg/dL in the control cohort) until the end of follow-up of the majority of subjects

Points represent medians (equivalent to the geometric mean) and vertical bars represent interquartile ranges. P represent p-values testing differences between the two study groups of linear trends over time in the natural logarithm of the corresponding test and were estimated based on a longitudinal model with a generalized estimating equation approach.

Figure 2. Trends over time of markers of essential fatty acid deficiency and coagulopathy in the fish oil (solid line) and in the soybean oil control cohorts (dashed line), from baseline in week 0 (starting admnistration of fish oil emulsion in the fish oil cohort and reaching the second direct bilirubin > 2 mg/dL in the control cohort) until the end of follow-up of the majority of subjects

Points represent medians (equivalent to the geometric mean) and vertical bars represent interquartile ranges. P represent p-values testing differences between the two study groups of linear trends over time in the natural logarithm of the corresponding test and were estimated based on a longitudinal model with a generalized estimating equation approach.

Figure 2. Trends over time of markers of essential fatty acid deficiency and coagulopathy in the fish oil (solid line) and in the soybean oil control cohorts (dashed line), from baseline in week 0 (starting admnistration of fish oil emulsion in the fish oil cohort and reaching the second direct bilirubin > 2 mg/dL in the control cohort) until the end of follow-up of the majority of subjects

Points represent medians (equivalent to the geometric mean) and vertical bars represent interquartile ranges. P represent p-values testing differences between the two study groups of linear trends over time in the natural logarithm of the corresponding test and were estimated based on a longitudinal model with a generalized estimating equation approach.