## 2 Provision of Energy and Macronutrients in Pediatric Patients on PN
### Effects on Cholesterasis/Liver Function  
In hospitalized newborn infants, infants/toddlers, children, and/or adolescents receiving PN with SMOFlipid administered at doses of up to 3 g lipids/kg BW/day for periods of 1 to 9 weeks, studies report significantly lower incidences of cholestasis and IFALD, as reflected by significantly lower plasma-conjugated bilirubin (CBil), total bilirubin (TBil), and direct bilirubin (DBil) levels compared to controls receiving SO-ILE [88; 91; 98; 99; 100; 101]. Moreover, the administration of SMOFlipid resulted in significantly lower levels of liver enzyme and DBil compared to SO/MCT-ILE [100; 107; 110].  
In 2010, a double-blind RCT investigated the effects of SMOFlipid (lipid dose 1.4 g/kg BW/day), compared to the same dose of SO-ILE, on RBC fatty acid profiles and liver status in children receiving HPN over a period of 4 weeks. Total bilirubin decreased significantly with SMOFlipid, whereas it increased with SO-ILE over the observation period, with the change being significant between the treatment groups [48]. [PERSON] et al. [112] published a cohort comparing serum bilirubin for a duration of 6 months in children with PN-associated jaundice who changed from SO-based ILe Intralipid (n = 9) to SMOFlipid (n = 8). After 6 months, 5 of 8 children in the SMOFlipid group and 2 of 9 children in the Intralipid group had total resolution of jaundice. The median bilirubin fell by 99 umol/L in the SMOFlipid group but increased by 79 umol/L in the Intralipid group (\(p=0.02\)). In a retrospective study on infants, [PERSON] et al. found that SMOFlipid administered at doses between 2 and 3 g lipid/kg BW/day resulted in a lower incidence and decreased severity of IFALD over the first 12 months of administration compared with a historical cohort who received SO-ILE. Infants receiving SMOFlipid were less likely to reach critical CBil levels, and no infant receiving SMOFlipid required \"rescue treatment\" with pure FO-ILE for the salvage of liver function [99]. In a large cross-sectional study including 578 pediatric patients enrolled in HPN centers in France between 2014 and 2019, it was reported that the use of SMOFlipid for these patients significantly increased within this period from 67.4% to 88.3%. Overall, the prevalence of cholestasis was low and remained stable between 4.1 and 5.9% during the study period [9]. In a recent prospective cross-sectional study including 46 children on HPN who were highly dependent upon PN, as indicated by the PNDI (median 120%), these investigators evaluated the clinical safety of SMOFlipid long-term administration (average duration 2.4 years) at doses between 1.5 and 2.0 g/kg BW/day [15]. Liver function tests (ALAT, ASAT, GGT, alkaline phosphatase) and indicators of cholestasis, especially CBil, were close to the normal range in the group receiving SMOFlipid. These results provide further evidence that PN with SMOFlipid reduces the risk of cholestasis and IFALD in the long term [15].  
Overall, studies investigating effects of HPN with SMOFlipid (doses up to 3 g lipids/kg BW/day) for varying durations ranging from 4 weeks to 6.6 years consistently report benefits in terms of the correction or prevention of liver disease following SMOFlipid administration [48; 90; 94; 112].