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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.
World J Clin Cases. Jul 26, 2026; 14(21): 123291
Published online Jul 26, 2026. doi: 10.12998/wjcc.123291
Fish oil emulsion for reversal of intestinal failure-associated liver disease in preterm infants: Three case reports and review of literature
Hong-Ju Chen, Xiao-Ming Xu, Juan Liang, Li Zhang, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Hong-Ju Chen, Zhuo-Ga Danzeng, Xizang Region Child Development Clinical Medical Research Center, Xizang Hospital of West China Second University Hospital, Sichuan University & Xizang Autonomous Region Women’s and Children’s Hospital, Lhasa 850000, Xizang Autonomous Region, China
Hong-Ju Chen, Peng-Fei Ye, Xiao-Ming Xu, Juan Liang, Li Zhang, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Hong-Ju Chen, Zhuo-Ga Danzeng, Department of Neonatology, Xizang Hospital of West China Second University Hospital, Sichuan University & Xizang Autonomous Region Women’s and Children’s Hospital, Lhasa 850000, Xizang Autonomous Region, China
Peng-Fei Ye, Department of Radiology, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
ORCID number: Hong-Ju Chen (0000-0002-9391-536X); Peng-Fei Ye (0000-0003-2790-124X); Juan Liang (0000-0002-6640-373X); Li Zhang (0000-0001-5233-5708).
Co-corresponding authors: Juan Liang and Li Zhang.
Author contributions: Chen HJ, Liang J, and Zhang L conceptualized and designed this case analysis; Chen HJ, Danzeng ZG, and Xu XM drafted the initial manuscript; Chen HJ was responsible for defining the core issues and analyzing the case data; Danzeng ZG coordinated the writing process; Chen HJ, Danzeng ZG, and Ye PF contributed to the initial collection and organization of the case data; Liang J and Zhang L served as corresponding authors, ensuring the academic rigor and depth of the case analysis, taking primary responsibility for academic supervision, leading responses to reviewer comments, and guiding further improvements to the manuscript, thereby ensuring its academic quality and compliance with publication standards. All authors reviewed and approved the final version.
AI contribution statement: AI tools (specifically ChatGPT) were used solely for linguistic refinement and formatting assistance. No AI tool was involved in the generation of research data, interpretation of results, or formulation of conclusions. All AI-generated outputs were critically reviewed and revised by the authors.
Supported by Clinical Research Funding of West China Second University Hospital, Sichuan University, No. KL073; and National Natural Science Foundation of China, No. 81501304.
Informed consent statement: Informed written consent was obtained from the patients for publication of this report and any accompanying images.
Conflict-of-interest statement: All authors declare that they have no conflict of interest to disclose.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Corresponding author: Juan Liang, PhD, Department of Pediatrics, West China Second University Hospital, Sichuan University, No. 20 Section 3, Renmin South Road, Wuhou District, Chengdu 610041, Sichuan Province, China. liangjuan079@163.com
Received: May 14, 2026
Revised: June 3, 2026
Accepted: June 26, 2026
Published online: July 26, 2026
Processing time: 68 Days and 21.7 Hours

Abstract
BACKGROUND

Prolonged parenteral nutrition (PN) is a major risk factor for intestinal failure-associated liver disease (IFALD), particularly in preterm infants. Plant-derived lipid emulsions, rich in phytosterols and ω-6 fatty acids, are considered key contributors. Fish oil lipid emulsions (FO-ILE) have emerged as a potential therapeutic alternative; however, the optimal dose for balancing efficacy and safety remains uncertain.

CASE SUMMARY

We report three preterm infants (gestational age, 31-36+2 weeks) with severe IFALD who were transitioned from soybean oil-based or multi-oil emulsions to FO-ILE. Fish oil was administered at a dose of 2 g/kg/day, a dosing approach for which limited data are available in this population. Prior to the transition, peak direct bilirubin (DB) levels ranged from 191.9 μmol/L to 356 μmol/L, with one patient exhibiting severe cholestasis and marked hepatosplenomegaly. Following 29-63 days of treatment, DB levels decreased to 30.7-89.9 μmol/L, resulting in a faster DB decline than that observed with the conventional 1 g/kg/day dosage. Full enteral feeding was achieved after 69-105 days of PN. The regimen was well tolerated, with no evidence of essential fatty acid deficiency, growth impairment, or bleeding complications.

CONCLUSION

FO-ILE up to 2 g/kg/day was well tolerated and improved liver function, which supports further investigation in PN-dependent infants.

Key Words: Intestinal failure-associated liver disease; Fish oil lipid emulsion; Parenteral nutrition; Preterm infants; Case report

Core Tip: Prolonged parenteral nutrition in preterm infants can lead to intestinal failure-associated liver disease (IFALD). We describe three preterm infants with severe IFALD who were treated with pure fish oil lipid emulsion (FO-ILE) at 2 g/kg/day—higher than conventional protocols. This approach was associated with a rapid decline in direct bilirubin levels and was well tolerated without evidence of essential fatty acid deficiency, growth impairment, or bleeding complications. To the best of our knowledge, this report is among the first reports of high-dose FO-ILE for severe IFALD in preterm infants, a vulnerable population because of hepatic immaturity.



INTRODUCTION

Parenteral nutrition (PN) is essential for the growth and survival of preterm infants; however, prolonged PN use can lead to intestinal failure-associated liver disease (IFALD), which adversely affects clinical outcomes. IFALD is characterized by cholestasis, hepatic steatosis, and fibrosis and can progress to advanced liver disease, including cirrhosis, potentially requiring liver transplantation or resulting in death[1]. Although no uniform diagnostic criteria currently exist, a typical case in infants is defined by PN use for more than 14 days and a serum direct bilirubin (DB) level of ≥ 2 mg/dL (34.2 μmol/L) on two consecutive measurements obtained at least 1 week apart, after exclusion of other causes of liver injury[2]. Based on DB levels, IFALD severity is classified as mild (2-4.9 mg/dL), moderate (5-9.9 mg/dL), or severe (≥ 10 mg/dL)[3]. In pediatric short bowel syndrome, cholestasis (i.e., DB ≥ 2.5 mg/dL) is the strongest predictor of mortality[4]. The incidence of IFALD is approximately 40%-60% in children receiving long-term PN[1] and up to 50% in neonates[5].

Although the pathogenesis of IFALD is not fully understood, plant-derived lipid emulsions (e.g., soybean oil) have been identified as major contributing factors[6]. These emulsions are associated with impaired bile acid secretion and proinflammatory responses mediated by ω-6 polyunsaturated fatty acids and phytosterols[7]. Therefore, an ideal lipid emulsion should contain minimal phytosterols, possess antioxidant properties, and meet the nutritional requirements of infants.

In recent years, the use of intravenous lipid emulsions in preterm infants has evolved, with a gradual shift from soybean oil-based lipid emulsions (SO-ILE) to fish oil-containing composite lipid emulsions and pure fish oil formulations[8]. However, studies evaluating the optimal dose of fish oil lipid emulsions (FO-ILE) in preterm infants, particularly those with IFALD, remain limited. This report describes three preterm infants with severe IFALD who were treated with fish oil emulsion and explores the potential role of higher-dose therapy in this population (Table 1).

Table 1 Clinical characteristics of 3 cases.

Case 1
Case 2
Case 3
SexMaleFemaleMale
Gestational age31 weeks35 weeks36+2 weeks
Birth weight1320 g920 g2750 g
ConditionNecrotizing enterocolitis, septic shock, meconium intestinal obstructionHemodynamically significant patent ductus arteriosus, heart failure, neonatal pneumoniaComplex small bowel atresia, neonatal sepsis
Medications that may cause cholestasisCefoperazone-sulbactam, vancomycinCefoperazone-sulbactam, meropenem, ibuprofenCefoperazone-sulbactam, meropenem
Direct bilirubin (μmol/L)At FO-ILE start229.2191.938.4
Peak value229.2191.9356
At FO-ILE cessation89.919.930.7
Peak total bilirubin (μmol/L)300.9298.3451.9
Duration of PN before FO-ILE69 days22 days42 days
Duration of FO-ILE therapy29 days47 days63 days
Duration of PN after FO-ILE0 days0 days0 days
Duration of PN98 days69 days105 days
Peak triglyceride level (borderline high: 1.7-2.25 mmol/L)2.00 mmol/L2.06 mmol/L3.39 mmol/L
Peak prothrombin time value (9.0-15.0 seconds)14.7 seconds15.7 seconds16.5 seconds
Peak APTT value (18.3-38.3 seconds)45.9 seconds48.3 seconds37.2 seconds
Peak INR value (0.8-1.5)1.431.531.65
Triene:TetraeneNormalNormalNormal
OutcomeResolvedResolvedResolved
CASE PRESENTATION
Chief complaints

Case 1: A preterm infant was admitted 18 minutes after delivery and subsequently developed abdominal distention and poor stooling.

Case 2: Tachypnea for 3 days following preterm birth.

Case 3: Suspected small intestinal atresia or stenosis based on fetal magnetic resonance imaging (MRI) at 30+6 weeks of gestation. The infant was admitted immediately after birth.

History of present illness

Case 1: A male infant born at 31 weeks of gestation with a birth weight of 1320 g presented with abdominal distension and poor stooling shortly after birth due to meconium intestinal obstruction. Following feeding, he developed recurrent bilious vomiting, abdominal distension, and hypoactive bowel sounds, accompanied by hyponatremia, acidosis, and portal venous gas. Neonatal necrotizing enterocolitis with perforation and septic shock were diagnosed. Ileostomy was performed, and cefoperazone-sulbactam and vancomycin were administered.

Intraoperatively, the small intestine measured 140 cm in length; the distal 40 cm showed severe necrosis, whereas the proximal 100 cm was less severely affected. During reintroduction of feeding, the patient received a SO-ILE (maximum 3.5 g/kg/day), amino acids (3-3.5 g/kg/day), and carbohydrates (9-16 g/kg/day). Over time, the skin gradually developed a dull yellow hue.

Case 2: A female infant born at 35 weeks of gestation with a birth weight of 920 g was treated with ibuprofen for hemodynamically significant patent ductus arteriosus and associated heart failure. The patient received cefoperazone-sulbactam followed by meropenem for neonatal pneumonia. As the patient was small for gestational age and presented with generalized edema, hepatomegaly, and ascites, prolonged PN was required.

The patient was started on a lipid emulsion containing soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF), administered at a maximum dose of 3.5 g/kg/day, along with amino acids and carbohydrates, as in Case 1. After 20 days of PN, the patient developed feeding intolerance, worsening jaundice, and progressive hepatomegaly.

Case 3: A male infant born at 36+2 weeks of gestation with a birth weight of 2750 g underwent fetal MRI, which suggested possible small bowel atresia or stenosis. On day 2 of life, the patient underwent resection of the atretic small bowel with jejunal anastomosis and enterostomy.

Intraoperatively, multiple atresias were identified, leading to a diagnosis of complex small bowel atresia (types IIIB and IV). Feeding was resumed after a 10-day postoperative fast, during which he received a SMOF at a maximum dose of 3 g/kg/day. Over time, his stools became pale, and his skin developed a dull yellow hue.

History of past illness

Case 1: No relevant past medical history.

Case 2: After birth, the infant, who was the smaller of twins, received mechanical ventilation and anti-infective treatment at an outside hospital for preterm birth and tachypnea; however, respiratory irregularities persisted.

Case 3: No relevant past medical history.

Personal and family history

Case 1: No relevant personal or medical history.

Case 2: No significant personal or medical history.

Case 3: No relevant personal or medical history.

Physical examination

Case 1: Progressive jaundice and hepatosplenomegaly were observed.

Case 2: Worsening jaundice and hepatomegaly were noted.

Case 3: Dull yellow discoloration of the skin, marked abdominal distension, and hepatosplenomegaly were observed.

Laboratory examinations

Case 1: Baseline DB was 13.5 μmol/L. Peak values included alanine aminotransferase (ALT) 220 U/L, aspartate aminotransferase (AST) 443 U/L, DB 229.2 μmol/L, and total bile acids (TBA) 213.4 μmol/L after 69 days of SO-ILE therapy.

Case 2: Baseline DB was 22.5 μmol/L. DB increased to 191.9 μmol/L, and TBA reached 264.3 μmol/L after 22 days of SMOF therapy.

Case 3: Baseline DB was 16.9 μmol/L. DB increased to 38.4 μmol/L after 42 days of SMOF therapy.

Imaging examinations

Cases 1 and 2: No imaging examinations specific to IFALD were performed.

Case 3: Computed tomography demonstrated marked hepatosplenomegaly (Figure 1).

Figure 1
Figure 1 Computed tomography images of Case 3. A: Axial view: Portal lymphatic stasis (orange arrow) and hepatosplenomegaly; B: Coronal view: Hepatosplenomegaly with splenic extension to the left iliac fossa (orange arrow).
FINAL DIAGNOSIS
Case 1

(1) Very low birth weight (1320 g); (2) Neonatal necrotizing enterocolitis; (3) Postoperative status: Ileostomy, adhesiolysis, and reduction of intestinal volvulus; (4) Septic shock; (5) Meconium intestinal obstruction; (6) Very preterm infant (31 weeks); (7) Functional short bowel syndrome; and (8) IFALD.

Case 2

(1) Extremely low birth weight (920 g); (2) Hemodynamically significant patent ductus arteriosus; (3) IFALD; (4) Ascites; (5) Preterm infant (35 weeks); and (6) Neonatal pneumonia.

Case 3

(1) Complex small intestinal atresia (types IIIB and IV); (2) IFALD; (3) Splenomegaly with hypersplenism; (4) Preterm infant (36+2 weeks); (5) Intestinal adhesions; (6) Ascites; and (7) Neonatal sepsis.

TREATMENT
Case 1

The lipid emulsion was switched to pure fish oil, initiated at 0.5 g/kg/day and gradually increased to a maximum of 2 g/kg/day. L-carnitine and glutathione were administered as adjunctive therapy.

Case 2

Initial treatment with ursodeoxycholic acid and probiotics was ineffective. The patient was subsequently switched to pure fish oil, starting at 0.8 g/kg/day and gradually increasing to 2 g/kg/day.

Case 3

The patient was switched to pure fish oil, initiated at 1.3 g/kg/day and increased to a maximum of 2 g/kg/day. The patient had concurrent sepsis and received sequential treatment with meropenem and cefoperazone-sulbactam. Peak laboratory values, observed after 30 days of pure fish oil therapy, included TBA 74.9 μmol/L, ALT 363 U/L, AST 261 U/L, total bilirubin 451.9 μmol/L, and DB 356 μmol/L. L-carnitine and glutathione were added. The patient subsequently underwent stoma closure, enterolysis, and peritoneal drainage. Intraoperatively, the liver was markedly enlarged and dark brown. Fish oil therapy was continued for 63 days.

In all three cases, an individualized dose-escalation regimen was used. Due to fluid restrictions from the underlying disease, the starting dose of fish oil was not uniform. Tolerability was assessed every 1-3 days, after which the dose was increased by 0.5 g/kg/day when appropriate. Assessment was based on biochemical tolerance indicators, including regular monitoring of DB, transaminases, and lipid levels, as well as clinical signs of bleeding tendency or lipid overload. No fixed escalation intervals were used, and dose adjustments were individualized. None of the infants experienced adverse reactions requiring dose reduction or treatment interruption during dose titration.

OUTCOME AND FOLLOW-UP
Case 1

DB and TBA decreased to 89.9 μmol/L and 60.4 μmol/L, respectively, representing reductions of 62.9% and 71.7% from peak values. After 98 days of PN, near-full enteral feeding was achieved. Following discharge, oral fish oil supplementation was continued until liver function normalized (Figure 2A).

Figure 2
Figure 2 Changes in bilirubin and total bile acid levels, and the course of lipid emulsions treatment during hospitalization in Cases 1-3. A: Direct bilirubin peaked at 229.2 μmol/L after soybean-based lipid emulsion (SO-ILE) therapy and dropped to 89.9 μmol/L after 29 days of FO-ILE therapy; B: Direct bilirubin peaked at 191.9 μmol/L after lipid emulsion containing soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF) therapy and dropped to 19.9 μmol/L after 47 days of FO-ILE therapy; C: Direct bilirubin (DB) increased slightly after SMOF therapy; after switching to FO-ILE, DB rose to a peak of 356 μmol/L before decreasing to 30.7 μmol/L after a total of 63 days of FO-ILE therapy. SMOF: Lipid emulsion containing soybean oil, medium-chain triglycerides, olive oil, and fish oil; FO-ILE: Fish oil lipid emulsion.
Case 2

After 69 days of PN, the patient successfully transitioned to full enteral feeding. At the time of PN discontinuation, DB and TBA levels had decreased to 19.9 μmol/L and 14.3 μmol/L, respectively (Figure 2B).

Case 3

Liver function improved after reaching peak levels. At cessation of fish oil therapy, DB had decreased to 30.7 μmol/L (91.4% reduction from the peak value of 356 μmol/L), and TBA had decreased to 11.7 μmol/L (84.3% reduction). By discharge, DB had further decreased to 15.3 μmol/L (95.7% reduction), accompanied by normalization of liver enzyme levels. After 105 days of PN, full enteral feeding was achieved, and the patient was discharged (Figure 2C).

In Case 1, antibiotic therapy had been completed before initiation of fish oil treatment. In Case 2, no increase in DB levels was observed during ibuprofen administration. DB levels subsequently increased following initiation of PN and continued to rise despite infection control and completion of antibiotic therapy. Following initiation of fish oil treatment, DB levels gradually declined. In Case 3, DB levels continued to increase despite resolution of infection; however, a decline in DB was observed after initiation of fish oil therapy, even while antibiotic treatment was ongoing.

All three infants tolerated fish oil therapy well. Monitoring of coagulation function, blood glucose, and renal function revealed no abnormalities. No persistent lipid overload was observed. In Case 3, triglyceride levels were only mildly and transiently elevated and normalized shortly after enteral feeding volume increased and the requirement for lipid emulsion decreased. Red blood cell fatty acid analysis demonstrated a normal triene:tetraene (T:T) ratio, indicating the absence of essential fatty acid deficiency. Follow-up assessments demonstrated normal growth and development, with sustained tolerance of full enteral feeding.

Case 1 was followed until 6 years and 3 months of age, Case 2 until 6 years of age, and Case 3 until 1 year and 1 month of age. At the latest follow-up, all three infants had normal liver function with no recurrence of IFALD. All achieved and maintained full enteral feeding, and none required liver transplantation.

Neuromotor developmental assessments demonstrated normal neurological development in all cases. In Case 1, General Movements (GMs) assessment was normal at a corrected age of 4 months, the Gesell Developmental Quotient (DQ) was 96 (normal range, 85-115) at a corrected age of 12 months, and 105 at 6 years of age. In Case 2, GMs assessment was normal at a corrected age of 4 months, and the DQ was 110 at 6 years of age. In Case 3, GMs assessment was normal at a corrected age of 5 months, and the Gesell DQ was 102 at 1 year and 1 month of age. All three infants showed normal development in the domains of gross motor, fine motor, language, and social interaction.

DISCUSSION

IFALD is a serious complication in patients receiving long-term PN, with established risk factors including prematurity, low birth weight, gastrointestinal immaturity, inflammation, and sepsis[2]. Its pathogenesis is multifactorial and involves lipid emulsion composition, intestinal barrier dysfunction, gut microbiota dysbiosis, and activation of hepatic innate immunity[9].

Plant-derived lipid emulsions are considered major contributing factors to IFALD and warrant efforts to minimize PN duration and lipid exposure where possible. Doses exceeding 1 g/kg/day may increase exposure to ω-6 polyunsaturated fatty acids and phytosterols while decreasing α-tocopherol levels[10]. Excess ω-6 fatty acids promote inflammation, whereas phytosterols inhibit hepatic farnesoid X receptor (FXR) signaling and disrupt the FXR/fibroblast growth factor-19 pathway[8]. This disruption impairs bile acid flow and promotes oxidative stress and inflammatory liver injury, ultimately leading to cholestasis[11]. Conversely, α-tocopherol enhances antioxidant capacity and lipid metabolism, whereas ω-3 fatty acids reduce liver inflammation and may improve cholestasis and fibrosis[10].

Based on these mechanisms, fish oil-based lipid emulsions provide a rich source of ω-3 fatty acids, including eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, as well as their precursor α-linolenic acid (ALA) and α-tocopherol[12]. These emulsions contain minimal phytosterols and relatively low levels of ω-6 fatty acids [e.g., linoleic (LA) and arachidonic (ARA) acids] and are commonly incorporated into mixed oil lipid emulsions (MOILEs), such as SMOF, as part of lipid minimization strategies[13].

MOILEs have demonstrated hepatoprotective effects and may improve growth and development in infants receiving long-term PN[14]. However, findings have been inconsistent, with some studies reporting no significant difference between MOILEs and SO-ILE[15,16]. Additionally, certain fish oil-containing preparations have not been associated with significant improvements in liver function parameters despite their anti-inflammatory properties[17]. These findings suggest that even small amounts of soy-based lipids may contribute to liver injury, whereas complete replacement with fish oil may provide greater therapeutic benefit.

Accordingly, the United States Food and Drug Administration approved the fish oil-based emulsion Omegaven for the treatment of IFALD in 2018[1]. Clinical studies have reported improved outcomes with fish oil compared to SMOF (56% vs 38%) in patients with newly diagnosed IFALD[18]. In neonates and one young infant who developed cholestasis while receiving MOILEs[19,20] or SO-ILEs[21], switching to 100% fish oil has been associated with reductions in bilirubin levels. A dose of 1 g/kg/day has been associated with resolution of cholestasis and improvement in biochemical markers of IFALD in many infants[22], potentially reducing the need for liver transplantation[23]. Omegaven has been associated with more rapid resolution of cholestasis and lower mortality than SO-ILE in previous studies[24]. In our three patients, DB and TBA levels decreased following the transition from SO-ILE or SMOF to fish oil therapy, further supporting its therapeutic potential[25].

Fish oil exerts multiple biochemical and cellular hepatoprotective effects[26]. Its ω-3 fatty acids possess anti-inflammatory properties and promote the generation of specialized pro-resolving mediators, such as resolvins and protectins. ω-3 fatty acids also inhibit nuclear factor κB signaling, reduce leukocyte chemotaxis[27], and suppress cytokine release[1]. Additionally, ω-3 fatty acids modulate innate and adaptive immune responses and inhibit the secretion of profibrotic mediators, including transforming growth factor-beta 1 (TGF-β1) and matrix metalloproteinase-9[28]. These effects may be partially attributable to reduced phytosterol exposure[29].

Although fish oil is rich in polyunsaturated fatty acids (PUFAs) and high PUFA intake may theoretically increase the risk of lipid peroxidation, available evidence suggests that fish oil enhances antioxidant capacity. Animal studies have shown that fish oil reduces DNA damage[30], enhances antioxidant defenses in the brain[31], and alleviates hepatic oxidative stress[32]. Similarly, a study of adolescents with depression found that ω-3 PUFAs reduced lipid peroxidation and enhanced membrane antioxidant capacity[33]. Mechanistically, ω-3 fatty acids increase total antioxidant capacity and the activity of glutathione peroxidase (GPx), superoxide dismutase (SOD), and heme oxygenase-1, while reducing malondialdehyde (MDA) levels. These effects may result from alterations in membrane structure and lipid composition, inhibition of cyclooxygenase-2, and activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, a key regulator of antioxidant responses. Consistent with these findings, fish oil supplementation reduced hepatic F2-isoprostane levels, a recognized marker of lipid peroxidation, while increasing Nrf2, GPx, SOD, and catalase levels in animal models[34].

Moreover, ω-3 fatty acids may directly neutralize reactive oxygen species and modulate endogenous antioxidant systems, including glutathione. In patients receiving home-based PN, higher fish oil doses have been associated with normalization of SOD1 activity without significant cholestasis[35]. Omegaven has been reported to modulate cytokine levels and increase paraoxonase 1 activity, thereby reducing oxidative stress[26]. Beyond their antioxidant effects, ω-3 fatty acids modulate Toll-like receptor 4 signaling and influence hepatic β-oxidation through peroxisome proliferator-activated receptor-α[36], contributing to reduced inflammation. DHA and EPA promote an anti-inflammatory microenvironment and may provide protection against sepsis and viral replication[37], potentially through modulation of immune responses, reduction of C-reactive protein levels, and lower infection rates following hepatectomy[38]. Furthermore, the unique fatty acid composition of fish oil may inhibit the progression of liver fibrosis in IFALD[23]. Fish oil can partially counteract TGF-β1-mediated activation of hepatic stellate cells, thereby contributing to its anti-fibrotic effects[39]. By optimizing the ω-6/ω-3 ratio, fish oil may modulate sterol regulatory element-binding protein-1, reducing hepatic fatty acid synthase activity[36], decreasing hepatic fat accumulation, and improving triglyceride clearance[40].

At the molecular level, fish oil modulates multiple signaling pathways, including the TGF-β-mediated Mothers Against Decapentaplegic Homolog-2/3 pathway, which has been implicated in inflammatory processes[41]. It affects the miR-122/FXR axis, which regulates oxidative stress, inflammation, and metabolic pathways[36]. These mechanisms may contribute to the anti-inflammatory, antioxidant, and anti-fibrotic effects of fish oil in IFALD.

Safety concerns regarding fish oil include essential fatty acid deficiency (EFAD), insufficient caloric intake, and bleeding risk. However, existing evidence generally supports its safety. Although fish oil contains relatively low levels of LA and ALA, studies suggest that EFAD is uncommon, even with long-term use of up to 10 years[42-46]. A dose of 1 g/kg/day may be sufficient to prevent or even treat EFAD[22]. Fish oil contains small amounts of EFAs, and its ARA content is higher than that of SO-ILE; In addition, ARA and DHA can be retroconverted to upstream fatty acids. As ARA, EPA, and DHA serve as precursors for bioactive eicosanoids involved in numerous physiological processes[8], the high EPA and DHA content of fish oil may reduce dependence on ω-6 fatty acids, while still meeting EFA requirements.

With respect to growth and development, some studies suggest that fish oil administered at 1 g/kg/day may provide insufficient caloric intake, necessitating adjustments in carbohydrate provision[18]. However, other studies have reported comparable or improved growth outcomes relative to soybean oil, accompanied by fewer metabolic abnormalities[22,47].

Although ω-3 fatty acids may theoretically increase bleeding risk through effects on platelet function, clinical evidence does not support a significant increase in bleeding events[37]. Improved liver function and platelet counts in patients receiving fish oil may reduce bleeding risk compared with SO-ILE[37]. Consistent with these findings, none of the infants in the present study developed EFAD, growth impairment, or bleeding complications[40].

Optimization of fish oil dosing remains an area of ongoing investigation. Most studies have focused on doses ≤ 1 g/kg/day; however, higher doses may provide additional benefits in selected patients. For example, increasing the dose to 1.5 g/kg/day has been associated with improved weight gain and maintenance of EFA status[48]. Additionally, normal T:T ratios and Mead acid levels have been reported, indicating adequate EFA reserves[49]. Nevertheless, in patients with poor weight gain and elevated glucose infusion rates, increasing the fish oil dose to 1.5 g/kg/day has been shown to improve weight Z-scores, although only a modest reduction in glucose infusion rates (GIRs) was observed, suggesting that higher doses may be required to reduce carbohydrate dependence[49]. Moreover, resolution of cholestasis may be slow, potentially prolonging hospital stays and increasing infection risk and healthcare costs.

All three infants in the present study had impaired glucose tolerance associated with liver dysfunction and required high GIRs. However, IFALD limited the use of conventional lipid emulsions. Increasing glucose delivery alone was insufficient to meet growth requirements, and persistent hyperglycemia is associated with adverse outcomes. Increasing the fish oil dose to 2 g/kg/day reduced glucose infusion requirements while providing additional non-protein calories to support growth. Prior to dose escalation, hypertriglyceridemia (baseline TG > 2.25 mmol/L) and bleeding tendency were excluded. Therefore, fish oil was administered at doses up to 2 g/kg/day to balance efficacy and safety. This approach was associated with improved weight gain and reductions in DB levels, without evidence of EFAD or coagulation abnormalities.

The decline in DB appeared more rapid than that reported in historical studies using fish oil at 1 g/kg/day[20,50,51], suggesting that higher doses may provide additional benefit when standard dosing is insufficient. To explore this observation, DB reduction rates were compared with those reported in 20 previously published cases with comparable baseline characteristics treated with 1 g/kg/day fish oil. Among these historical cases, DB reduction rates ranged from 0.13 μmol/L/day to 2.64 μmol/L/day, whereas those in Cases 1 and 2 of the present study were 3.66 μmol/L/day and 4.80 μmol/L/day, respectively (Table 2). Case 3 was excluded from this comparison because fish oil therapy was initiated when DB was only slightly above 2 mg/dL. Instead, the rate of DB decline was assessed from the peak DB value. Peak DB decline rates were 3.66 μmol/L/day, 4.80 μmol/L/day, and 9.86 μmol/L/day in Cases 1-3, respectively. In contrast, peak DB decline rates reported in studies using 1 g/kg/day fish oil ranged from 0.93 μmol/L/day to 2.06 μmol/L/day (Table 3).

Table 2 Comparison of direct bilirubin reduction rates from start to end of fish oil therapy at 1 g/kg/day vs 2 g/kg/day.
Cases
DB at fish oil initiation (μmol/L)
DB at fish oil cessation (μmol/L)
Duration of fish oil therapy
DB reduction rates (μmol/L/day)
This Case 1229.289.929 days4.80
This Case 2191.919.947 days3.66
Case 2[20]44.523.927 days0.76
Case 4[20]51.322.239 days0.75
Case 5[20]70.141.033 days0.88
Case 7[20]148.822.254 days2.34
Case 8[20]162.512.057 days2.64
Case 9[20]160.725.782 days1.65
Case 10[20]109.417.159 days1.56
Case 11[20]90.685.526 days0.20
Case 12[20]198.4112.9112 days0.76
Case 13[20]212.0159.038 days1.39
Case 1[50]58.123.990 days0.38
Case 2[50]99.232.521 weeks0.45
Case 1[51]186.41.741 weeks0.64
Case 2[51]59.922.25 weeks1.08
Case 3[51]70.11.712 weeks0.81
Case 4[51]46.21.717 weeks0.31
Case 6[51]42.81.716 weeks0.37
Case 7[51]42.85.140 weeks0.13
Case 8[51]145.441.032 weeks0.47
Case 10[51]167.695.813 weeks0.79
Table 3 Comparison of the direct bilirubin reduction rates from peak direct bilirubin values to end of treatment at fish oil doses of 1 g/kg/day vs 2 g/kg/day.
Cases
Peak DB (μmol/L)
DB at fish oil cessation (μmol/L)
Duration of fish oil therapy from peak
DB reduction rate (μmol/L/day)
This Case 1229.289.929 days4.80
This Case 2191.919.947 days3.66
This Case 335630.733 days9.86
Case 1[50]109.423.990 days0.95
Case 2[50]136.832.516 weeks0.93
Case 5[51]212.010.314 weeks2.06

To the best of our knowledge, this case series is among the first reports describing fish oil administration at 2 g/kg/day in preterm infants with severe IFALD, with favorable outcomes and no apparent safety concerns.

The route, timing, and duration of administration are important considerations. Oral fish oil has limited absorption in patients with intestinal failure, whereas parenteral administration may produce more rapid effects[26]. One infant with IFALD did not respond to oral therapy but experienced a 69.9% reduction in DB within 7 days of switching to intravenous administration[52], highlighting the importance of the intravenous route. Higher DB levels, elevated pediatric end-stage liver disease scores at the time of fish oil initiation, and older age have been reported as predictors of outcome; thus, early initiation of fish oil based on biochemical evidence of cholestasis has been recommended[53].

DB levels may initially increase after treatment initiation before subsequently declining[54]. Additionally, ω-6 fatty acid levels decrease during the first few weeks of treatment and typically stabilize after approximately 8 weeks. These observations support continued therapy until cholestasis resolves[45]. In the present study, fish oil was initiated progressively earlier across the three cases. In Case 3, treatment was started when DB exceeded 2 mg/dL. Although DB initially increased, sustained therapy was associated with a subsequent decline in DB and eventual resolution of cholestasis, supporting the importance of early and continued treatment.

Limitations

This study has limitations, including a small sample size, the absence of a control group, and the potential for residual confounding. Oxidative stress markers (e.g., MDA, SOD, and F2-isoprostane) were not directly measured because these assays are not routinely performed at our center and require specialized sample collection. However, liver function and coagulation parameters remained stable or improved during treatment in all three infants, erythrocyte fatty acid profiles demonstrated normal T:T ratios, and no clinical signs of hemolysis or lipid peroxidation (e.g., worsening jaundice or thrombocytopenia) were observed. These findings provide indirect evidence supporting the safety of high-dose fish oil therapy. Future studies should include direct measurement of oxidative stress markers to further evaluate the safety of high-dose fish oil in preterm infants.

CONCLUSION

This case series describes three preterm infants with IFALD secondary to long-term PN, in whom plant-derived lipid emulsions were a major contributing factor. FO-ILE demonstrated therapeutic potential and was associated with improvements in biochemical markers of IFALD, likely through its anti-inflammatory, antioxidant, lipid-modulating, and anti-fibrotic properties. Compared with SMOF or SO-ILE, fish oil monotherapy may be associated with a more rapid decline in DB levels and resolution of cholestasis. Determining the optimal fish oil dose remains important for improving treatment outcomes.

In this case series, administration of fish oil at doses up to 2 g/kg/day was well tolerated and was not associated with evidence of EFAD, growth impairment, or coagulation abnormalities. Long-term follow-up demonstrated normal growth and development and no recurrence of IFALD. To the best of our knowledge, this case series is among the first reports describing the use of pure fish oil emulsion at 2 g/kg/day in preterm infants (gestational age, 31-36+2 weeks) with severe IFALD. Although the long-term outcomes were favorable, larger prospective studies are needed to establish optimal dosing strategies and further evaluate the efficacy and safety of fish oil in improving outcomes in PN-dependent infants.

ACKNOWLEDGEMENTS

We would like to thank Sang Ba for collecting data.

References
1.  Abi-Aad SJ, Lovell M, Khalaf RT, Sokol RJ. Pathogenesis and Management of Intestinal Failure-Associated Liver Disease. Semin Liver Dis. 2025;45:66-80.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Full Text (PDF)]  [Cited by in Crossref: 6]  [Cited by in RCA: 5]  [Article Influence: 5.0]  [Reference Citation Analysis (0)]
2.  Cimadamore E, Palazzo M, Fioroni MC, Cerverizzo M, Correani A, Burattini I, Biagetti C. Enteral Nutrition in Neonatal Cholestasis: An Up-to-Date Overview. Nutrients. 2025;17:1794.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Full Text (PDF)]  [Cited by in RCA: 2]  [Reference Citation Analysis (0)]
3.  Shakeel F, Newkirk M, Sellers A, Shores DR. Postoperative Feeding Guidelines Improve Outcomes in Surgical Infants. JPEN J Parenter Enteral Nutr. 2020;44:1047-1056.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 9]  [Cited by in RCA: 20]  [Article Influence: 2.9]  [Reference Citation Analysis (0)]
4.  Spencer AU, Neaga A, West B, Safran J, Brown P, Btaiche I, Kuzma-O'Reilly B, Teitelbaum DH. Pediatric short bowel syndrome: redefining predictors of success. Ann Surg. 2005;242:403-9; discussion 409.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 250]  [Cited by in RCA: 238]  [Article Influence: 11.3]  [Reference Citation Analysis (0)]
5.  Huff KA, Cruse W, Vanderpool C. Lipid strategies to prevent intestinal failure-associated liver disease in neonates: A pilot trial. JPEN J Parenter Enteral Nutr. 2023;47:482-493.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in RCA: 7]  [Reference Citation Analysis (0)]
6.  Mercer DF. Fish oil emulsions in the management of intestinal failure-associated liver disease. J Clin Gastroenterol. 2012;46:823-827.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 5]  [Cited by in RCA: 3]  [Article Influence: 0.2]  [Reference Citation Analysis (0)]
7.  Goulet OJ. Intestinal failure-associated liver disease and the use of fish oil-based lipid emulsions. World Rev Nutr Diet. 2015;112:90-114.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 31]  [Cited by in RCA: 18]  [Article Influence: 1.5]  [Reference Citation Analysis (0)]
8.  Chan AP, Rostas S, Rogers S, Martin CR, Calkins KL. Parenteral Nutrition in the Neonatal Intensive Care Unit: Intravenous Lipid Emulsions. Clin Perinatol. 2023;50:575-589.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in RCA: 17]  [Reference Citation Analysis (0)]
9.  Zhao Y, Wang Y, Jiang L, Cai W, Yan J. Impaired intestinal FXR signaling is involved in aberrant stem cell function leading to intestinal failure-associated liver disease in pediatric patients with short bowel syndrome. FASEB J. 2024;38:e23847.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 4]  [Cited by in RCA: 4]  [Article Influence: 2.0]  [Reference Citation Analysis (0)]
10.  Goulet OJ, Cai W, Seo JM. Lipid Emulsion Use in Pediatric Patients Requiring Long-Term Parenteral Nutrition. JPEN J Parenter Enteral Nutr. 2020;44 Suppl 1:S55-S67.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 11]  [Cited by in RCA: 19]  [Article Influence: 3.8]  [Reference Citation Analysis (0)]
11.  Jagadisan B, Dhawan A. Depletion of phytosterols from intravenous lipid emulsions: to be or not to be. Pediatr Res. 2025;97:2179-2181.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Full Text (PDF)]  [Cited by in RCA: 1]  [Reference Citation Analysis (0)]
12.  Rostas SE, McPherson C. Intravenous Lipid Emulsions in Infants: Is Balanced Better? Neonatal Netw. 2019;38:39-45.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 2]  [Cited by in RCA: 4]  [Article Influence: 0.6]  [Reference Citation Analysis (0)]
13.  Huff KA, Nayak SP, Ahmad I, DiGeronimo R, Hair A, Kim JH, Markel T, Piazza A, Reber K, Roberts J, Sharma J, Sullivan K, Ahmad KA, Yanowitz T, Premkumar MH. Patterns of lipid-injectable emulsion use in neonatal intensive care units across the United States: A multi-institution survey. JPEN J Parenter Enteral Nutr. 2023;47:51-58.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in RCA: 5]  [Reference Citation Analysis (0)]
14.  Lee LJ, Kim ES, Romero T, Calkins KL. Association between multioil intravenous lipid emulsion and cholestasis in infants with gastrointestinal disorders: A retrospective cohort study. JPEN J Parenter Enteral Nutr. 2025;49:707-716.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Full Text (PDF)]  [Cited by in RCA: 1]  [Reference Citation Analysis (0)]
15.  Greenberg J, Naik M, Chapman J, Davidson A, Imseis E. Comparison of Two Lipid Emulsions on the Incidence of Parenteral Nutrition Associated Cholestasis in Neonates. J Pediatr Pharmacol Ther. 2023;28:129-135.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in RCA: 4]  [Reference Citation Analysis (0)]
16.  Xie T, Mei H, Chen M, Xu Y, Ma X, Shi L, Chen Z. Association between mixed fatty acid emulsion and parenteral nutrition-associated cholestasis in extremely low-birth-weight infants: A retrospective cohort study. JPEN J Parenter Enteral Nutr. 2025;49:975-982.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Full Text (PDF)]  [Cited by in RCA: 3]  [Reference Citation Analysis (0)]
17.  Weylandt KH, Karber M, Xiao Y, Zhang IW, Pevny S, Blüthner E, von Schacky C, Rothe M, Schunck WH, Pape UF. Impact of intravenous fish oil on omega-3 fatty acids and their derived lipid metabolites in patients with parenteral nutrition. JPEN J Parenter Enteral Nutr. 2023;47:287-300.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 2]  [Cited by in RCA: 11]  [Article Influence: 3.7]  [Reference Citation Analysis (0)]
18.  Raghu VK, Sevilla WMA, King DE, Alissa F, Rothenberger S, Smith KJ, Horslen SP, Rudolph JA. Current practices in lipid emulsion utilization in the prevention and treatment of intestinal failure-associated liver disease: A survey of pediatric intestinal rehabilitation and transplant centers. JPEN J Parenter Enteral Nutr. 2022;46:1585-1592.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in RCA: 8]  [Reference Citation Analysis (0)]
19.  Ramiro-Cortijo D, Del Pozo Arribas S, Inisterra Viu L, Vázquez NG, Saenz de Pipaon M. Exclusive Fish Oil Lipid Emulsion Rescue Strategy Improves Cholestasis in Neonates on Partially Fish Oil-Based Lipid Emulsion: A Pilot Study. Nutrients. 2023;15:509.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in RCA: 2]  [Reference Citation Analysis (0)]
20.  Lee S, Sung SI, Park HJ, Chang YS, Park WS, Seo JM. Fish Oil Monotherapy for Intestinal Failure-Associated Liver Disease on SMOFlipid in the Neonatal Intensive Care Unit. J Clin Med. 2020;9:3393.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Full Text (PDF)]  [Cited by in Crossref: 5]  [Cited by in RCA: 8]  [Article Influence: 1.3]  [Reference Citation Analysis (0)]
21.  Fessatou S, Kourti A, Zavras N, Zouganeli S, Kouna N, Stefos E, Kanavaki I. Improvement in Intestinal-Failure-Associated Liver Disease by Using Parenteral Fish Oil as Monotherapy: Case-Based Review of the Literature. Reports (MDPI). 2023;6:28.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Full Text (PDF)]  [Cited by in RCA: 1]  [Reference Citation Analysis (0)]
22.  Gura K, Premkumar MH, Calkins KL, Puder M. Intravenous Fish Oil Monotherapy as a Source of Calories and Fatty Acids Promotes Age-Appropriate Growth in Pediatric Patients with Intestinal Failure-Associated Liver Disease. J Pediatr. 2020;219:98-105.e4.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 12]  [Cited by in RCA: 22]  [Article Influence: 3.7]  [Reference Citation Analysis (0)]
23.  Gura KM, Premkumar MH, Calkins KL, Puder M. Fish Oil Emulsion Reduces Liver Injury and Liver Transplantation in Children with Intestinal Failure-Associated Liver Disease: A Multicenter Integrated Study. J Pediatr. 2021;230:46-54.e2.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 16]  [Cited by in RCA: 37]  [Article Influence: 7.4]  [Reference Citation Analysis (0)]
24.  Puder M, Valim C, Meisel JA, Le HD, de Meijer VE, Robinson EM, Zhou J, Duggan C, Gura KM. Parenteral fish oil improves outcomes in patients with parenteral nutrition-associated liver injury. Ann Surg. 2009;250:395-402.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 310]  [Cited by in RCA: 257]  [Article Influence: 15.1]  [Reference Citation Analysis (1)]
25.  Frost B, Martin CR, Calkins KL. Dilemmas in the delivery of intravenous lipid emulsions and approach to hypertriglyceridemia in very preterm and low birth weight infants. J Perinatol. 2023;43:1189-1193.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in RCA: 7]  [Reference Citation Analysis (0)]
26.  Flores-López A, Guevara-Cruz M, Avila-Nava A, González-Garay AG, González-Salazar LE, Reyes-Ramírez AL, Pedraza-Chaverri J, Medina-Campos ON, Medina-Vera I, Reyes-García JG, Tovar AR, Serralde-Zúñiga AE. n-3 Polyunsaturated Fatty Acid Supplementation Affects Oxidative Stress Marker Levels in Patients with Type II Intestinal Failure: A Randomized Double Blind Trial. Antioxidants (Basel). 2023;12:1493.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in RCA: 4]  [Reference Citation Analysis (0)]
27.  Thérien A, Cieślak A, Verreault M, Perreault M, Trottier J, Gobeil S, Vohl MC, Barbier O. Omega-3 Polyunsaturated Fatty Acid: A Pharmaco-Nutraceutical Approach to Improve the Responsiveness to Ursodeoxycholic Acid. Nutrients. 2021;13:2617.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Full Text (PDF)]  [Cited by in Crossref: 13]  [Cited by in RCA: 12]  [Article Influence: 2.4]  [Reference Citation Analysis (0)]
28.  Rochling FA. Intravenous Lipid Emulsions in the Prevention and Treatment of Liver Disease in Intestinal Failure. Nutrients. 2021;13:895.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Full Text (PDF)]  [Cited by in Crossref: 14]  [Cited by in RCA: 16]  [Article Influence: 3.2]  [Reference Citation Analysis (0)]
29.  Isaac DM, Alzaben AS, Mazurak VC, Yap J, Wizzard PR, Nation PN, Zhao YY, Curtis JM, Sergi C, Wales PW, Mager DR, Turner JM. Mixed Lipid, Fish Oil, and Soybean Oil Parenteral Lipids Impact Cholestasis, Hepatic Phytosterol, and Lipid Composition. J Pediatr Gastroenterol Nutr. 2019;68:861-867.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 14]  [Cited by in RCA: 13]  [Article Influence: 1.9]  [Reference Citation Analysis (0)]
30.  Pellegrino FJ, Risso A, Corrada Y, Gambaro RC, Seoane AI. Influence of dietary fish oil supplementation on DNA damage in peripheral blood lymphocytes of nine healthy dogs. Vet Rec Open. 2021;8:e12.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Full Text (PDF)]  [Cited by in Crossref: 4]  [Cited by in RCA: 6]  [Article Influence: 1.2]  [Reference Citation Analysis (0)]
31.  Moreno F, Méndez L, Fernández I, Miralles-Pérez B, Giralt M, Romeu M, Ramos-Romero S, Torres JL, Medina I. Influence of the Degree of Unsaturation in Fish Oil Supplements on Oxidative Stress and Protein Carbonylation in the Cerebral Cortex and Cerebellum of Healthy Rats. Antioxidants (Basel). 2024;13:1408.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in RCA: 3]  [Reference Citation Analysis (0)]
32.  Lopes IQP, Monteiro BL, Ferreira AVM, de Moura RF, de Sales Guilarducci J, Leão ER, do Carmo Rodrigues Virote B, Konig I, Murgas LDS, de Castro IC, Pimenta LCJP. Maternal fish oil supplementation improves metabolic and inflammatory markers in mice overfed during the postnatal period. Front Nutr. 2025;12:1685437.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Full Text (PDF)]  [Cited by in RCA: 2]  [Reference Citation Analysis (0)]
33.  Wang J, Li S, Wang D, Gao Y, Wang Q, Wang T, Wang G, Peng D, Qiao Y, Zhou J, Feng L, Hu X, Wan C. Effects of Omega-3 PUFAs on lipid profiles and antioxidant response in depressed adolescents: A metabolomic and lipidomic study. Redox Biol. 2025;82:103617.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Full Text (PDF)]  [Cited by in Crossref: 6]  [Cited by in RCA: 7]  [Article Influence: 7.0]  [Reference Citation Analysis (0)]
34.  Oliveira-Filho RS, Torrinhas RS, Tesser A, Sampaio GR, Torres E, Garla PC, Waitzberg DL. Effect of a parenteral fish-oil-containing lipid emulsion on liver lipid perioxidation and antioxidative defenses in Lewis rats. JPEN J Parenter Enteral Nutr. 2023;47:572-579.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in RCA: 2]  [Reference Citation Analysis (0)]
35.  Sevela S, Meisnerova E, Vecka M, Vavrova L, Rychlikova J, Lenicek M, Vitek L, Novakova O, Novak F. High Dose Fish Oil Added to Various Lipid Emulsions Normalizes Superoxide Dismutase 1 Activity in Home Parenteral Nutrition Patients. Nutrients. 2024;16:485.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in RCA: 2]  [Reference Citation Analysis (0)]
36.  Calkins KL, Thamotharan S, Ghosh S, Dai Y, Devaskar SU. MicroRNA 122 Reflects Liver Injury in Children with Intestinal Failure-Associated Liver Disease Treated with Intravenous Fish Oil. J Nutr. 2020;150:1144-1150.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Full Text (PDF)]  [Cited by in Crossref: 6]  [Cited by in RCA: 7]  [Article Influence: 1.2]  [Reference Citation Analysis (0)]
37.  Gura KM, Calkins KL, Premkumar MH, Puder M. Use of Intravenous Soybean and Fish Oil Emulsions in Pediatric Intestinal Failure-Associated Liver Disease: A Multicenter Integrated Analysis Report on Extrahepatic Adverse Events. J Pediatr. 2022;241:173-180.e1.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 3]  [Cited by in RCA: 11]  [Article Influence: 2.8]  [Reference Citation Analysis (0)]
38.  Liao L, Lei Y, He Q, Liang H, Zhou J, Wang K, Li C. Effects of fat emulsion-based early parenteral nutrition for patients after hemihepatectomy. Br J Nutr. 2025;133:1047-1056.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in RCA: 1]  [Reference Citation Analysis (0)]
39.  Watanabe R, Morii M, Yamagata K, Ebihara T, Sasaki T, Mezaki Y, Mizuno M. 100% Fish oil-based lipid emulsion inhibits hepatic stellate cell activation via suppression of the TGF-β1 autocrine signaling. Hum Cell. 2025;38:153.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 2]  [Cited by in RCA: 3]  [Article Influence: 3.0]  [Reference Citation Analysis (0)]
40.  Secor JD, Yu L, Tsikis S, Fligor S, Puder M, Gura KM. Current strategies for managing intestinal failure-associated liver disease. Expert Opin Drug Saf. 2021;20:307-320.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 2]  [Cited by in RCA: 23]  [Article Influence: 3.8]  [Reference Citation Analysis (0)]
41.  Czerniel J, Gostyńska-Stawna A, Urbaniak N, Sommerfeld-Klatta K, Stawny M. Harnessing algae oil as a sustainable DHA source for parenteral nutrition in vegan patients. Sci Rep. 2025;15:18548.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Full Text (PDF)]  [Cited by in RCA: 4]  [Reference Citation Analysis (0)]
42.  Machigashira S, Kaji T, Onishi S, Yano K, Harumatsu T, Yamada K, Yamada W, Matsukubo M, Muto M, Ieiri S. What is the optimal lipid emulsion for preventing intestinal failure-associated liver disease following parenteral feeding in a rat model of short-bowel syndrome? Pediatr Surg Int. 2021;37:247-256.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Full Text (PDF)]  [Cited by in Crossref: 2]  [Cited by in RCA: 5]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]
43.  Ong ML, Venick RS, Shew SB, Dunn JCY, Reyen L, Grogan T, Calkins KL. Intravenous Fish Oil and Serum Fatty Acid Profiles in Pediatric Patients With Intestinal Failure-Associated Liver Disease. JPEN J Parenter Enteral Nutr. 2019;43:717-725.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 9]  [Cited by in RCA: 12]  [Article Influence: 1.7]  [Reference Citation Analysis (0)]
44.  Hakimian D, Wall E, Herlitz J, Lozano ES, McDonald E, Semrad C, Micic D. Parenteral fish oil lipid emulsion use in adults: a case series and review from an intestinal failure referral center. Eur J Clin Nutr. 2024;78:796-800.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in RCA: 3]  [Reference Citation Analysis (0)]
45.  Gura KM, Premkumar MH, Calkins KL, Puder M. Essential fatty acid deficiency in children treated with long-term 100% fish-oil lipid injectable emulsion: A longitudinal descriptive cohort study. JPEN J Parenter Enteral Nutr. 2025;49:732-740.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in RCA: 3]  [Reference Citation Analysis (0)]
46.  Johnson P, Phillips VL, Lamb N, Guo K, Zhao L, Brennan KM, Prozialeck JD, Cohran VC. Effect of parenteral lipids on essential fatty acid deficiency in pediatric intestinal failure: A retrospective cohort study. JPEN J Parenter Enteral Nutr. 2024;48:793-801.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in RCA: 3]  [Reference Citation Analysis (0)]
47.  Raphael BP, Mitchell PD, Gura KM, Potemkin AK, Squires RH, Puder M, Duggan CP. Growth in Infants and Children With Intestinal Failure-associated Liver Disease Treated With Intravenous Fish Oil. J Pediatr Gastroenterol Nutr. 2020;70:261-268.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 7]  [Cited by in RCA: 12]  [Article Influence: 2.0]  [Reference Citation Analysis (0)]
48.  Riedy M, DePaula B, Puder M, Gura KM, Sztam KA. Higher Doses of Fish Oil-Based Lipid Emulsions Used to Treat Inadequate Weight Gain and Rising Triene:Tetraene Ratio in a Severely Malnourished Infant With Intestinal Failure-Associated Liver Disease. JPEN J Parenter Enteral Nutr. 2017;41:667-671.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 11]  [Cited by in RCA: 9]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]
49.  Bashir A, Karel L, Begany M, Blandine A, Palpant C, Paul E, McCoy T, Maqbool A, Panganiban J. Treatment outcomes of pediatric patients on high dose pure fish oil-based fat emulsion: A retrospective study. Nutr Clin Pract. 2026;41:640-646.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in RCA: 1]  [Reference Citation Analysis (0)]
50.  Lee S, Park HJ, Yoon J, Hong SH, Oh CY, Lee SK, Seo JM. Reversal of Intestinal Failure-Associated Liver Disease by Switching From a Combination Lipid Emulsion Containing Fish Oil to Fish Oil Monotherapy. JPEN J Parenter Enteral Nutr. 2016;40:437-440.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 41]  [Cited by in RCA: 34]  [Article Influence: 3.4]  [Reference Citation Analysis (0)]
51.  Le HD, de Meijer VE, Zurakowski D, Meisel JA, Gura KM, Puder M. Parenteral fish oil as monotherapy improves lipid profiles in children with parenteral nutrition-associated liver disease. JPEN J Parenter Enteral Nutr. 2010;34:477-484.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 38]  [Cited by in RCA: 33]  [Article Influence: 2.1]  [Reference Citation Analysis (0)]
52.  Miura W, Nagano N, Kato R, Okahashi A, Yoshikawa K, Ohashi K, Koshinaga T, Morioka I. Intestinal Failure-Associated Liver Disease and Eicosapentaenoic Acid/Arachidonic Acid Ratio. Indian J Pediatr. 2019;86:548-550.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 1]  [Cited by in RCA: 2]  [Article Influence: 0.3]  [Reference Citation Analysis (0)]
53.  Nandivada P, Baker MA, Mitchell PD, O'Loughlin AA, Potemkin AK, Anez-Bustillos L, Carlson SJ, Dao DT, Fell GL, Gura KM, Puder M. Predictors of failure of fish-oil therapy for intestinal failure-associated liver disease in children. Am J Clin Nutr. 2016;104:663-670.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 29]  [Cited by in RCA: 32]  [Article Influence: 3.2]  [Reference Citation Analysis (0)]
54.  Premkumar MH, Carter BA, Hawthorne KM, King K, Abrams SA. Fish oil-based lipid emulsions in the treatment of parenteral nutrition-associated liver disease: an ongoing positive experience. Adv Nutr. 2014;5:65-70.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 45]  [Cited by in RCA: 49]  [Article Influence: 4.1]  [Reference Citation Analysis (0)]
Footnotes

Peer review: Externally peer reviewed.

Peer-review model: Single blind

Corresponding Author's Membership in Professional Societies: Branch of Neonatologists, Chinese Medical Doctor Association, Member of the Fourth Nutrition Specialty Committee; Tenth Committee of the Perinatal Medicine Branch, Chinese Medical Association, Member of the Nutrition and Metabolism Group.

Specialty type: Pediatrics

Country of origin: China

Peer-review report’s classification

Scientific quality: Grade B, Grade B, Grade C

Novelty: Grade B, Grade B, Grade C

Creativity or innovation: Grade B, Grade B, Grade D

Scientific significance: Grade B, Grade B, Grade D

P-Reviewer: Guo C, Academic Fellow, China; Liu YY, Chief Physician, China S-Editor: Liu JH L-Editor: A P-Editor: Wang WB

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