Growth in Infants and Children With Intestinal Failure-associated Liver Disease Treated With Intravenous Fish Oil.

BACKGROUND: Infants with intestinal failure (IF) and IF-associated liver disease (IFALD) are at risk for poor somatic growth because of increased metabolic demands, inadequate intake, intestinal malabsorption, chronic liver disease and other comorbidities. There are limited data on the nutritional adequacy of intravenous fish oil lipid emulsion (FOLE) compared with standard soybean oil lipid emulsion (SOLE) in the setting of intestinal failure. AIMS: To describe growth patterns in a large cohort of infants with IFALD treated with FOLE. METHODS: We compared growth data from infants enrolled in a single-center, prospective FOLE study to published norms, as well as to a multicenter, historical cohort of infants with IF treated with SOLE. RESULTS: One hundred thirty-eight infants with IFALD were treated with FOLE and 108 with SOLE. Compared with normative growth curves from WHO and published preterm data, infants in both groups from 6 to 11 months postmenstrual age exhibited declines in mean weight- and length-for-age z scores. At 24 months postmenstrual age compared with WHO growth data, infants treated with FOLE had a mean (95% confidence interval [CI]) weight-for-age z-score of 0.13 (-0.18 to 0.45) and length-for-age z-score of 0.07 (-0.33 to 0.47). In comparison, at 24 months postmenstrual age, infants treated with SOLE had a mean weight for age z-score of -0.93 (-1.20 to -0.67) and mean length for age z-score of -2.33 (-2.75 to -1.91). Independent predictors of higher weight, length and head circumference z-scores included older postmenstrual age at baseline, fewer central line-associated blood stream infections, resolution of cholestasis, type of intravenous fat emulsion (FOLE vs SOLE) and female sex. CONCLUSIONS: Infants with IFALD treated with FOLE showed comparable somatic growth to those treated with SOLE in early infancy, and improved somatic growth up to 24 months of age, supporting its wider use in this patient population.

Trends of INR and Fecal Excretion of Vitamin K During Cholestasis Reversal: Implications in the Treatment of Neonates With Intestinal Failure-Associated Liver Disease.

BACKGROUND: Vitamin K is a fat-soluble compound that plays important roles in coagulation. In children with intestinal failure-associated liver disease (IFALD), the disrupted enterohepatic circulation can lead to intestinal loss of vitamin K. Fish oil-based lipid emulsion (FOLE) has proven effective in treating IFALD. As biliary excretion is restored during cholestasis reversal, the accelerated vitamin K loss can pose a risk for deficiency. METHODS: Ten neonates with IFALD and receiving FOLE monotherapy were prospectively enrolled in the study from 2016 to 2018. In addition to weekly measurements of international normalized ratio (INR) and direct bilirubin (DB), ostomy output was collected for determination of fecal concentrations of phylloquinone (PK). Trends of DB, INR, and fecal PK concentrations were summarized with locally estimated scatterplot smoothing. RESULTS: The median time (interquartile range) from FOLE initiation to cholestasis reversal was 59 (19-78) days. During cholestasis reversal, INR remained relatively unchanged, whereas the mean (95% confidence interval) daily fecal excretion of PK increased from 25.1 (5.0-158.5) ng at the time of FOLE initiation to 158.5 (31.6-1000.0) ng at complete reversal. Examination of individual trends in fecal PK excretion and INR revealed little correlation between the 2 measurements (r = -0.10; P = 0.50). CONCLUSION: Children with IFALD are at risk for vitamin K deficiency during cholestasis reversal. Close monitoring and quantified supplementation of vitamin K may be warranted during this period. However, this should not be guided by INR alone, as it is a poor indicator of vitamin K status.

Characterization of Fatty Acid Profiles in Infants With Intestinal Failure-Associated Liver Disease.

BACKGROUND: The purpose of this study was to characterize fatty acid profiles (FAPs) in parenteral nutrition (PN)-dependent infants with intestinal failure-associated liver disease (IFALD) receiving soybean oil-based lipid emulsion (SO) doses of ∼3 and ∼1 g/kg/d. METHODS: Prospectively collected data were retrospectively reviewed. Serum FAPs of patients <1 year old who experienced development of IFALD while receiving standard PN with SO were examined before transitioning to a fish oil-based lipid emulsion for IFALD treatment. Time on SO, dose, gestational age, and weight- and length-for-age z scores were also reviewed. RESULTS: Among the 49 patients analyzed, there were no differences in demographics or anthropometrics between patients who received standard SO (SO-S) (n = 14, range of dosage 2.06-3.31 g/kg/d) and reduced SO (SO-R) (n = 35, range of dosage 0.90-1.34 g/kg/d). Patients received SO for a median of 53 days (interquartile range 39, 73) before FAP measurement. Patients who received SO-R had significantly higher Mead acid and lower α-linolenic, eicosapentaenoic, linoleic, stearic, total ω-3, and total ω-6 fatty acid levels than patients who received SO-S (P < .01). Triene:tetraene ratios were higher in patients who received SO-R (P = .0009), and no patients experienced biochemical essential fatty acid deficiency (EFAD). CONCLUSION: PN-dependent infants with IFALD receiving SO-R have different FAPs than patients receiving SO-S. No patients in either group had biochemical EFAD.

Long-Term Fish Oil Lipid Emulsion Use in Children With Intestinal Failure-Associated Liver Disease [Formula: see text].

BACKGROUND: Fish oil lipid emulsion (FOLE) and multidisciplinary care for infants with intestinal failure (IF) have been associated with reduced morbidity and mortality due to IF-associated liver disease (IFALD). With increased survival, a greater proportion of infants with IF are now able to remain on parenteral nutrition (PN) in the long term. The purpose of this study was to examine outcomes in children with IFALD who have required long-term PN and FOLE therapy due to chronic IF. MATERIALS AND METHODS: A review of prospectively collected data was performed for children with IFALD who required at least 3 years of PN and FOLE therapy due to chronic IF. Outcomes examined include the incidence of death, transplantation, and essential fatty acid deficiency (EFAD), as well as growth parameters and the biochemical markers of liver disease. RESULTS: Of 215 patients with IFALD treated from 2004-2015, 30 required PN and FOLE therapy for at least 3 years (median, 4.6 years). To date, no patients have died, required transplantation, or developed EFAD. Biochemical markers of liver disease normalized within the first year of therapy with no recurrent elevations in the long term. Weight-for age and length-for-age z scores improved and PN dependence decreased in the first year of therapy, with a stable rate of growth in the long term. CONCLUSIONS: Children with IFALD who required long-term PN and FOLE for chronic IF had no mortality, need for transplantation, EFAD, or recurrence of liver disease in the long term, allowing for continued intestinal rehabilitation.

Risk of post-procedural bleeding in children on intravenous fish oil.

BACKGROUND: Intestinal failure-associated liver disease (IFALD) can be treated with parenteral fish oil (FO) monotherapy, but practitioners have raised concerns about a potential bleeding risk. This study aims to describe the incidence of clinically significant post-procedural bleeding (CSPPB) in children receiving FO monotherapy. METHODS: A retrospective chart review was performed on patients at our institution treated with intravenous FO for IFALD. CSPPB was defined as bleeding leading to re-operation, transfer to the intensive care unit, re-admission, or death, up to one month after any invasive procedure. RESULTS: From 244 patients reviewed, 183 underwent ≥1 invasive procedure(s) (n = 732). Five (0.68%, 95% CI 0.22-1.59%) procedures resulted in CSPPB. FO therapy was never interrupted. No deaths due to bleeding occurred. CONCLUSIONS: Findings suggest that FO therapy is safe, with a CSPPB risk no greater than that reported in the general population. O3FA should not be held in preparation for procedures or in the event of bleeding.

Predictors of failure of fish-oil therapy for intestinal failure-associated liver disease in children.

BACKGROUND: Parenteral fish-oil (FO) therapy is a safe and effective treatment for intestinal failure-associated liver disease (IFALD). Patients whose cholestasis does not resolve with FO may progress to end-stage liver disease. OBJECTIVE: We sought to identify factors associated with the failure of FO therapy in treating IFALD to guide prognostication and referral guidelines. DESIGN: Prospectively collected data for patients treated with FO at Boston Children's Hospital from 2004 to 2014 were retrospectively reviewed. Resolution of cholestasis was defined as sustained direct bilirubin (DB) <2 mg/dL, and treatment failure as liver transplantation or death while DB was >2 mg/dL as of July 2015. Demographics, laboratory values, and medical history at FO therapy initiation were compared between patients who achieved resolution of cholestasis and those who failed therapy. RESULTS: Among 182 patients treated with FO, 86% achieved resolution of cholestasis and 14% failed therapy. Patients who failed therapy had median (IQR) lower birth weight [1020 g (737, 1776 g) compared with 1608 g (815, 2438 g); P = 0.03] and were older at FO initiation [20.4 wk (9.9, 38.6 wk) compared with 11.7 wk (7.3, 21.4 wk); P = 0.02] than patients whose cholestasis resolved. Patients who failed therapy had more advanced liver disease at therapy initiation than patients whose cholestasis resolved, as evidenced by lower median (IQR) γ-glutamyltransferase [54 U/L (41, 103 U/L) compared with 112 U/L (76, 168 U/L); P < 0.001], higher DB [10.4 mg/dL (7.5, 14.1 mg/dL) compared with 4.4 mg/dL (3.1, 6.6 mg/dL); P < 0.001], and a higher pediatric end-stage liver disease (PELD) score [22 (14, 25) compared with 12 (7, 15); P < 0.001]. A PELD score of ≥15, history of gastrointestinal bleeding, age at FO initiation ≥16 wk, presence of nongastrointestinal comorbidities, and mechanical ventilation at FO initiation were independent predictors of treatment failure. CONCLUSIONS: Most infants with IFALD responded to FO therapy with resolution of cholestasis, and liver transplantation was rarely required. Early FO initiation once biochemical cholestasis is detected in parenteral nutrition-dependent patients is recommended. This trial was registered at clinicaltrials.gov as NCT00910104.

Preservation of biochemical liver function with low-dose soy-based lipids in children with intestinal failure-associated liver disease.

OBJECTIVES: Intestinal failure-associated liver disease (IFALD) contributes to significant morbidity in pediatric patients with intestinal failure (IF); however, the use of parenteral nutrition (PN) with a fish oil-based intravenous (IV) emulsion (FO) has been associated with biochemical reversal of cholestasis and improved outcomes. Unfortunately, FO increases the complexity of care: because it can be administered only under Food and Drug Administration compassionate use protocols requiring special monitoring, it is not available as a 3-in-1 solution and is more expensive than comparable soy-based IV lipid emulsion (SO). Because of these pragmatic constraints, a series of patient families were switched to low-dose (1 g kg(-1) day(-1)) SO following biochemical resolution of cholestasis. The present study examines whether reversal of cholestasis and somatic growth are maintained following this transition. METHODS: The present study is a chart review of all children with IFALD who switched from FO to SO following resolution of cholestasis. Variables are presented as medians (interquartile ranges). Comparisons were performed using the Wilcoxon signed-rank test. RESULTS: Seven patients ages 25.9 (16.2-43.2) months were transitioned to SO following reversal of cholestasis using FO. At a median follow-up of 13.9 (4.3-50.1) months, there were no significant differences between pretransition and post-transition serum alanine and aspartate aminotransferases, direct bilirubin, and weight-for-age z scores. Because of recurrence of cholestasis, 1 patient was restarted on FO after 4 months on SO. CONCLUSIONS: Biochemical reversal of IFALD and growth were preserved after transition from FO to SO in 6 of 7 (86%) patients. Given the challenges associated with the use of FO, SO may be a viable alternative in select patients with home PN.

The natural history of cirrhosis from parenteral nutrition-associated liver disease after resolution of cholestasis with parenteral fish oil therapy.

OBJECTIVE: To determine the natural history of cirrhosis from parenteral nutrition-associated liver disease (PNALD) after resolution of cholestasis with fish oil (FO) therapy. BACKGROUND: Historically, cirrhosis from PNALD resulted in end-stage liver disease, often requiring transplantation for survival. With FO therapy, most children now experience resolution of cholestasis and rarely progress to end-stage liver disease. However, outcomes for cirrhosis after resolution of cholestasis are unknown and patients continue to be considered for liver/multivisceral transplantation. METHODS: Prospectively collected data were reviewed for children with cirrhosis because of PNALD who had resolution of cholestasis after treatment with FO from 2004 to 2012. Outcomes evaluated included need for liver/multivisceral transplantation, mortality, and the clinical progression of liver disease. RESULTS: Fifty-one patients with cirrhosis from PNALD were identified, with 76% demonstrating resolution of cholestasis after FO therapy. The mean direct bilirubin decreased from 6.4 ± 4 mg/dL to 0.2 ± 0.1 mg/dL (P < 0.001) 12 months after resolution of cholestasis, with a mean time to resolution of 74 days. None of the patients required transplantation or died from end-stage liver disease. Pediatric End-Stage Liver Disease scores decreased from 16 ± 4.6 to -1.2 ± 4.6, 12 months after resolution of cholestasis (P < 0.001). In children who remained PN-dependent, the Pediatric End-Stage Liver Disease score remained normal throughout the follow-up period. CONCLUSIONS: Cirrhosis from PNALD may be stable rather than progressive once cholestasis resolves with FO therapy. Furthermore, these patients may not require transplantation and show no clinical evidence of liver disease progression, even when persistently PN-dependent.

Neonates with short bowel syndrome: an optimistic future for parenteral nutrition independence.

IMPORTANCE: The introduction of hepatoprotective strategies and multidisciplinary management has significantly improved the outcome of neonates with short bowel syndrome (SBS) who require parenteral nutrition (PN). OBJECTIVE: To determine the probability of weaning from PN based on intestinal length in neonates with SBS amidst the new era of hepatoprotective strategies and multidisciplinary management. DESIGN, SETTING, AND PARTICIPANTS: Retrospective medical record review at a single-center academic institution. Neonates with no more than 100 cm of small intestine at a corrected gestational age of no more than 30 days who were diagnosed with a surgical gastrointestinal disease and PN dependent for at least 2 weeks were included. Data were collected from January 1, 2004, through June 1, 2012. EXPOSURE: Neonates with SBS requiring PN. MAIN OUTCOMES AND MEASURES: The probability of wean from PN without reinitiation for at least 1 year, as determined by logistic regression. Predictors of wean were evaluated using exact conditional logistic regression. Predictors of time to wean were determined by Cox proportional hazards regression. RESULTS: Sixty-three patients with a median (25th percentile, 75th percentile [interquartile range (IQR)]) gestational age of 31 (27, 35) weeks, birth weight of 1423 (895, 2445) g, small intestinal length of 41.0 (24.0, 65.0) cm, and predicted length of 29.0% (17.1%, 45.5%) underwent analysis. Fifty-one patients (81%) received a fish oil-based lipid emulsion (1 g/kg/d), 40 (63%) were weaned, 11 (17%) remained PN dependent, 4 (6%) underwent transplant, and 8 (13%) died while on PN. Excluding patients who underwent transplant or died, the median (IQR) small intestinal length was 55.0 (28.0, 75.0) cm in weaned and 26.0 (14.0, 41.0) cm in PN-dependent patients (P = .006), with 40 of 51 (78%) weaned by study end. The cumulative probability of wean for patients with at least 50 cm of small intestine was 88% after 12 and 96% after 24 months. Patients with less than 50 cm of small intestine had a cumulative probability of wean of 23% after 12, 38% after 24, and 71% after 57 months. Small intestinal length was found to be the primary predictor of wean. Notable predictors of time to wean included the amount of small intestine remaining (hazard ratio, 1.94 [95% CI, 1.45-2.58] per 20 cm of intestine; P < .001), entirety of care within our institution (3.27 [1.59-6.72]; P = .001), and intestinal lengthening procedure (0.19 [0.04-0.84]; P = .03). CONCLUSIONS AND RELEVANCE: The majority of patients will wean from PN despite short intestinal length, likely as a result of new management strategies combined with a multidisciplinary team approach.

A comparison of 2 intravenous lipid emulsions: interim analysis of a randomized controlled trial.

OBJECTIVE: To assess the safety and efficacy of a fish oil-based intravenous fat emulsion (FIFE) in reducing the incidence of cholestasis in neonates compared with the traditional soybean oil-based intravenous fat emulsion (SIFE). METHODS: A double-blind randomized controlled trial was conducted. Nineteen neonates were enrolled (10 SIFE; 9 FIFE). Nutrition assessments and laboratory studies were serially obtained for the duration of PN support or until 6 months' corrected gestational age. Neurodevelopmental outcomes were assessed at 6 and 24 months' corrected age. RESULTS: There were no differences between groups in demographic characteristics, with an overall median age of 2 days, gestational age of 36 weeks, and birth weight of 2410 g. There were no differences between groups in baseline laboratory values other than alkaline phosphatase (lower in the FIFE group) or in the duration of parenteral nutrition (PN), amount of enteral intake, or the number of operative procedures. The incidence of cholestasis among enrolled patients was significantly lower than expected, resulting in early study termination and an inability to assess for differences in the incidence of cholestasis. The FIFE was associated with no increased risk of growth impairment, coagulopathy, infectious complications, hypertriglyceridemia, or adverse neurodevelopmental outcomes. No patient developed essential fatty acid deficiency. CONCLUSION: The FIFE at 1 g/kg/d was well tolerated in the neonates recruited for this study. Given the necessary early termination of this study, a follow-up trial with revised eligibility criteria is necessary to determine whether the provision of FIFE decreases the incidence of PN-cholestasis compared with the traditional SIFE.

A.S.P.E.N. clinical guidelines: nutrition support of neonatal patients at risk for metabolic bone disease.

BACKGROUND: Premature infants are at increased risk for metabolic bone disease, with resulting delayed bone growth, osteopenia, and rickets. METHOD: A systematic review of the best available evidence to answer a series of questions regarding neonatal patients at risk of metabolic bone disease receiving parenteral or enteral nutrition was undertaken and evaluated using concepts adopted from the Grading of Recommendations, Assessment, Development and Evaluation working group. A consensus process was used to develop the clinical guideline recommendations prior to external and internal review and approval by the American Society for Parenteral and Enteral Nutrition Board of Directors. QUESTIONS: (1) What maternal risk factors predispose the neonate to metabolic bone disease? (2) What is the optimal type of feeding to promote neonatal bone health? (3) When and how should vitamin D supplements be administered? (4) Does parenteral nutrition (PN) predispose a neonate to metabolic bone disease, and if so, are there PN formulation recommendations to minimize this risk?

Provision of a soy-based intravenous lipid emulsion at 1 g/kg/d does not prevent cholestasis in neonates.

BACKGROUND: One of the most common and severe complications of long-term parenteral nutrition (PN) is PN-associated cholestasis. The soybean oil-based lipid emulsion administered with PN has been associated with cholestasis, leading to an interest in lipid reduction strategies. The purpose of this study was to determine whether the provision of a soybean oil-based lipid emulsion at 1 g/kg/d compared with 2-3 g/kg/d is associated with a reduced incidence of cholestasis. METHODS: Retrospective review of neonates admitted between 2007 and 2011 with a gastrointestinal condition necessitating ≥ 21 days of PN support. Neonates were divided into 2 groups based on the intravenous lipid emulsion dose: 1-g group (1 g/kg/d) and 2- to 3-g group (2-3 g/kg/d). The primary outcome measure was the incidence of cholestasis. RESULTS: Sixty-one patients met inclusion criteria (n = 29, 1-g group; n = 32, 2- to 3-g group). The 2 groups did not differ in any baseline characteristics other than associated comorbidities that were more common in the 2- to 3-g group. The duration of PN, the number of operative procedures and bloodstream infections, and enteral nutrition (EN) were similar between groups. The incidence of cholestasis was not different between groups (51.7%, 1-g group; 43.8%, 2- to 3-g group; P = .61), and there was no difference between groups in the time to cholestasis (32.6 ± 24.1 days, 1-g group; 27.7 ± 10.6 days, 2- to 3-g group; P = .48). Overall, 44.8% of patients with cholestasis were transitioned to full EN, and 55.2% were transitioned to a fish oil-based lipid emulsion after which the direct bilirubin normalized in all patients. CONCLUSION: Lipid reduction to 1 g/kg/d does not prevent or delay the onset of cholestasis in neonates.

A.S.P.E.N. clinical guidelines: nutrition support of neonatal patients at risk for necrotizing enterocolitis.

BACKGROUND: Necrotizing enterocolitis (NEC) is one of the most devastating diseases in the neonatal population, with extremely low birth weight and extremely preterm infants at greatest risk. METHOD: A systematic review of the best available evidence to answer a series of questions regarding nutrition support of neonates at risk of NEC was undertaken and evaluated using concepts adopted from the Grading of Recommendations, Assessment, Development and Evaluation working group. A consensus process was used to develop the clinical guideline recommendations prior to external and internal review and approval by the A.S.P.E.N. Board of Directors. RESULTS/ CONCLUSIONS: (1) When and how should feeds be started in infants at high risk for NEC? We suggest that minimal enteral nutrition be initiated within the first 2 days of life and advanced by 30 mL/kg/d in infants ≥ 1, 000 g. (Weak) (2) Does the provision of mother's milk reduce the risk of developing NEC? We suggest the exclusive use of mother's milk rather than bovine-based products or formula in infants at risk for NEC. (Weak) (3) Do probiotics reduce the risk of developing NEC? There are insufficient data to recommend the use of probiotics in infants at risk for NEC. (Further research needed.) (4) Do nutrients either prevent or predispose to the development of NEC? We do not recommend glutamine supplementation for infants at risk for NEC (Strong). There is insufficient evidence to recommend arginine and/or long chain polyunsaturated fatty acid supplementation for infants at risk for NEC. (Further research needed.) (5) When should feeds be reintroduced to infants with NEC? There are insufficient data to make a recommendation regarding time to reintroduce feedings to infants after NEC. (Further research needed.).

Parenteral fish-oil-based lipid emulsion improves fatty acid profiles and lipids in parenteral nutrition-dependent children.

BACKGROUND: Total parenteral nutrition (PN), including fat administered as a soybean oil-based lipid emulsion (SOLE), is a life-saving therapy but may be complicated by PN-induced cholestasis and dyslipidemia. A fish-oil-based lipid emulsion (FOLE) as a component of PN can reverse PN-cholestasis and has been shown to improve lipid profiles. OBJECTIVE: The objective was to describe changes in the fatty acid and lipid profiles of children with PN-cholestasis who were treated with a FOLE. DESIGN: Lipid and fatty acid profiles of 79 pediatric patients who developed PN-cholestasis while receiving standard PN with a SOLE were examined before and after the switch to a FOLE. All patients received PN with the FOLE at a dose of 1 g · kg(-1) · d(-1) for ≥1 mo. RESULTS: The median (interquartile range) age at the start of the FOLE treatment was 91 (56-188) d. After a median (interquartile range) of 18.3 (9.4-41.4) wk of receiving the FOLE, the subjects' median total and direct bilirubin improved from 7.9 and 5.4 mg/dL to 0.5 and 0.2 mg/dL, respectively (P < 0.0001). Serum triglyceride, total cholesterol, LDL, and VLDL concentrations significantly decreased by 51.7%, 17.4%, 23.7%, and 47.9%, respectively. CONCLUSIONS: The switch from a SOLE to a FOLE in PN-dependent children with cholestasis and dyslipidemia was associated with a dramatic improvement in serum triglyceride and VLDL concentrations, a significant increase in serum omega-3 (n-3) fatty acids (EPA and DHA), and a decrease in serum omega-6 fatty acids (arachidonic acid). A FOLE may be the preferred lipid emulsion in patients with PN-cholestasis, dyslipidemia, or both. This trial is registered at clinicaltrials.gov as NCT00910104.

Surgical intervention in the setting of parenteral nutrition-associated cholestasis may exacerbate liver injury.

PURPOSE: This study compares postoperative markers of liver injury in patients receiving intravenous fish oil (IFO) with parenteral nutrition (PN)-associated cholestasis (PNAC) to patients with resolved PNAC. METHODS: A retrospective review of all cholestatic-IFO patients undergoing abdominal laparotomy between March 1, 2007, and July 1, 2009, led to inclusion of 23 patients who collectively underwent 27 abdominal operations (13 pre-PNAC resolution and 14 post-PNAC resolution). Direct bilirubin (DB), total bilirubin, and alanine aminotransferase levels were examined over time in relation to operations. The time to resume presurgical trend of decreasing DB was calculated. RESULTS: Sixty-nine percent (9/13) of pre-PNAC resolution procedures were associated with postoperative increase in DB compared with 7% (1/14) of post-PNAC resolution procedures associated with a recurrence of cholestasis (P = .02; odds ratio, 29.3; 95% confidence interval, 2.79-306.8). The median time to return to the preoperative downward trend of DB was 21 days. CONCLUSIONS: Operations before PNAC resolution may be associated with an increased postoperative DB, possibly reflecting an exacerbation of liver injury. Operations post-PNAC resolution on IFO had a comparatively low incidence of postoperative cholestasis recurrence. Excepting clinical indication otherwise, it may be advisable to delay surgical intervention in the setting of PNAC in certain cases.