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l -1.677 .445 l -1.136 .445 l -.968 1.47 l -.465 1.603 l -.654 .445 l .076 .445 l 0 0 l f Q q 1 0 0 1 544.635 735.056 cm 0 0 m -.178 0 -.308 .166 -.297 .363 c -.292 .579 -.135 .745 .043 .745 c .216 .745 .352 .585 .341 .388 c .33 .172 .173 0 0 0 c h -.4 -3.684 m -.876 -3.684 l -.362 -.522 l .114 -.522 l -.4 -3.684 l f Q q 1 0 0 1 546.61 734.109 cm 0 0 m -.59 0 -.985 -.776 -.985 -1.571 c -.985 -2.042 -.822 -2.303 -.417 -2.303 c .108 -2.303 .568 -1.642 .568 -.719 c .568 -.255 .389 0 0 0 c h -.498 -2.793 m -1.174 -2.793 -1.482 -2.392 -1.482 -1.667 c -1.482 -.407 -.801 .483 .076 .483 c .784 .483 1.076 .013 1.076 -.655 c 1.076 -1.96 .314 -2.793 -.498 -2.793 c f Q q 1 0 0 1 550.196 731.373 cm 0 0 m -.476 0 l -.146 2.023 l -.065 2.519 -.14 2.736 -.384 2.736 c -.882 2.736 -1.433 1.495 -1.558 .713 c -1.671 0 l -2.147 0 l -1.877 1.654 l -1.807 2.106 -1.709 2.698 -1.639 3.162 c -1.168 3.162 l -1.201 2.952 -1.276 2.589 -1.466 1.915 c -1.455 1.915 l -1.201 2.583 -.773 3.225 -.211 3.225 c .287 3.225 .454 2.812 .352 2.15 c 0 0 l f Q q 1 0 0 1 552.684 734.134 cm 0 0 m -.801 0 -1.114 -.973 -1.114 -1.756 c -1.114 -2.169 -1.006 -2.335 -.838 -2.335 c -.33 -2.335 .222 -1.069 .346 -.312 c .384 -.057 l .276 -.025 .151 0 0 0 c h .427 -2.761 m -.054 -2.761 l -.005 -2.487 .097 -2.068 .26 -1.476 c .249 -1.469 l .054 -1.959 -.352 -2.825 -1.006 -2.825 c -1.396 -2.825 -1.607 -2.532 -1.607 -1.864 c -1.607 -.699 -1.093 .452 .081 .452 c .389 .452 .676 .414 .925 .357 c .638 -1.412 .541 -2.004 .427 -2.761 c f Q q 1 0 0 1 554.479 731.373 cm 0 0 m -.476 0 l .276 4.645 l .752 4.645 l 0 0 l f Q q 1 0 0 1 558.547 733.994 cm 0 0 m -.146 .076 -.303 .121 -.492 .121 c -1.174 .121 -1.493 -.782 -1.493 -1.501 c -1.493 -1.832 -1.401 -2.17 -.931 -2.17 c -.72 -2.17 -.492 -2.112 -.325 -2.017 c -.357 -2.519 l -.546 -2.602 -.795 -2.672 -1.066 -2.672 c -1.764 -2.672 -2.002 -2.227 -2.002 -1.629 c -2.002 -.42 -1.423 .592 -.46 .592 c -.238 .592 -.06 .554 .108 .496 c 0 0 l f Q q 1 0 0 1 560.374 734.134 cm 0 0 m -.801 0 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-2.532 -1.417 -1.819 c -1.417 -.592 -.838 .433 .054 .433 c .628 .433 .844 .089 .844 -.286 c .844 -.967 .254 -1.342 -.898 -1.393 c f Q EMC /Artifact <>BDC q 0 841.89 595.276 -841.89 re 297.66 421.02 m W n .059998 841.98 595.32 -841.92 re W n 1 .89 0 0 k q 1 0 0 1 297.525 609.89 cm 0 0 m 272.013 0 l 273.579 0 274.848 -1.269 274.848 -2.835 c 274.848 -110.059 l 274.848 -111.625 273.579 -112.894 272.013 -112.894 c -272.013 -112.894 l -273.579 -112.894 -274.848 -111.625 -274.848 -110.059 c -274.848 -2.835 l -274.848 -1.269 -273.579 0 -272.013 0 c h f* Q EMC /P <>BDC BT /F1 1 Tf 11 0 0 11 43 583.1817 Tm 0 0 0 0 k 0 Tc -.0409 Tw [(Derangement of liver function tests \(LFT)110.9(s\) is common amongst patients receiving parenteral nutrition \(PN\))]TJ ET EMC /P <>BDC BT 11 0 0 11 43 567.1817 Tm -.0046 Tw [(and is currently more common in the paediatric population. )18.1(There is a broad spectrum of disease ranging)]TJ ET EMC /P <>BDC BT 11 0 0 11 43 551.1817 Tm .0017 Tc .0677 Tw [(from transient elevation in the liver enzymes in those receiving short-term PN, through to cirrhosis and)]TJ ET EMC /P <>BDC BT 11 0 0 11 43 535.1817 Tm -.01 Tc -.0255 Tw [(liver failure in those who require long-term PN. )18(The aetiology of liver disease is multifactorial, relating to both)]TJ ET EMC /P <>BDC BT 11 0 0 11 43 519.1817 Tm 0 Tw [(the patient and nutritional factors, and hence the term intestinal failure-associated liver disease \(IF)55.2(ALD\).)]TJ ET EMC /P <>BDC BT /F2 1 Tf 12 0 0 12 22.6771 478.511 Tm 1 .89 0 0 k 0 Tc (Key points)Tj ET EMC /P <>BDC BT /F1 1 Tf 8 0 0 8 22.6771 460.3417 Tm 0 0 0 .8 k (1. )Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 460.3417 Tm [(Identify other causes of abnormal LFT)110.9(s; PN is not the most common )]TJ ET EMC /P <>BDC BT 8 0 0 8 34.0157 447.8417 Tm (cause. Sepsis, drug therapy and pre-existing liver disease, are common )Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 435.3417 Tm (aetiologies)Tj ET EMC /P <>BDC BT 8 0 0 8 22.6771 422.8417 Tm (2.)Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 422.8417 Tm [(Paediatric patients often present with cholestatic LFT)110.9(s)]TJ ET EMC /P <>BDC BT 8 0 0 8 22.6771 410.3417 Tm (3.)Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 410.3417 Tm (An excess of any of the macronutrient components of PN can cause )Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 397.8417 Tm [(abnormal LFT)110.9(s)]TJ ET EMC /P <>BDC BT 8 0 0 8 22.6771 385.3417 Tm (4.)Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 385.3417 Tm [(Continuous PN is more associated with abnormal LFT)110.9(s than cyclical PN)]TJ ET EMC /P <>BDC BT 8 0 0 8 22.6771 372.8417 Tm (5.)Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 372.8417 Tm (First-generation, soya bean-based lipid preparations are associated with )Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 360.3417 Tm [(most LFT)18.1( abnormalities)]TJ ET EMC /P <>BDC BT 8 0 0 8 22.6771 347.8417 Tm -.01 Tc (6.)Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 347.8417 Tm [(An excess of copper)55.2(, manganese, or aluminium can cause abnormal LFT)110.8(s)]TJ ET EMC /P <>BDC BT 8 0 0 8 22.6771 335.3417 Tm 0 Tc (7.)Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 335.3417 Tm (Deficiencies of choline, taurine, carnitine or essential fatty acids can )Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 322.8417 Tm [(cause abnormal LFT)110.9(s)]TJ ET EMC /P <>BDC BT 8 0 0 8 22.6771 310.3417 Tm (8.)Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 310.3417 Tm [(T)37.1(reatment addresses the factors above and consideration is given to )]TJ ET EMC /P <>BDC BT 8 0 0 8 34.0157 297.8417 Tm (maximising oral/enteral feeding, cyclical PN, changing bile composition )Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 285.3417 Tm (\(URSO\) and occasionally antibiotic therapy)Tj ET EMC /P <>BDC BT 8 0 0 8 22.6771 272.8417 Tm (9.)Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 272.8417 Tm [(Severe IF)55.2(ALD-associated liver failure is an indication for small bowel )]TJ ET EMC /P <>BDC BT 8 0 0 8 34.0157 260.3417 Tm (transplantation.)Tj ET EMC /P <>BDC BT /F2 1 Tf 12 0 0 12 22.6771 238.8417 Tm 1 .89 0 0 k (Explanations)Tj ET EMC /P <>BDC BT 8 0 0 8 22.6771 220.1724 Tm 0 0 0 .8 k (A.)Tj ET EMC /P <>BDC BT /F1 1 Tf 8 0 0 8 34.0157 220.1724 Tm [(There are many other contributors to abnormal LFT)18.1( in patients with )]TJ ET EMC /P <>BDC BT 8 0 0 8 34.0157 207.1724 Tm (intestinal failure who require PN. Pre-existing liver disease can be )Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 194.1724 Tm (identified in up to a third of such patients prior to initiation of PN. )Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 181.1724 Tm [(Drug-related causes of elevated LFT)110.9(s should be identified \(e.g. )]TJ ET EMC /P <>BDC BT 8 0 0 8 34.0157 168.1724 Tm (antibiotics, antifungals and proton pump inhibitors\). Sepsis commonly )Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 155.1724 Tm [(causes abnormal LFT)110.9(s in adults on PN and in neonates causes )]TJ ET EMC /P <>BDC BT 8 0 0 8 34.0157 142.1724 Tm (cholestasis. Small bowel bacterial overgrowth can lead to cholestasis )Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 129.1724 Tm (and portal endotoxaemia. Specific to the intestinal failure population, the )Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 116.1724 Tm (residual small bowel length in continuity is important. Small bowel length)Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 103.1724 Tm [(<100 cm may be associated with abnormal LFT)110.9(s, while length <50 cm )]TJ ET EMC /P <>BDC BT 8 0 0 8 34.0157 90.1724 Tm -.02 Tc [(may be associated with cholestasis. Periods of biliary stasis \(due to surgery)74.2(,)]TJ ET EMC /P <>BDC BT 8 0 0 8 34.0157 77.1724 Tm -.01 Tc (nil by mouth or drugs\) predispose to biliary sludge and thus to gallstones.)Tj ET EMC /P <>BDC BT /F2 1 Tf 8 0 0 8 22.6771 64.1724 Tm (B.)Tj ET EMC /P <>BDC BT /F1 1 Tf 8 0 0 8 34.0157 64.1724 Tm (Paediatric patients with intestinal failure used to have a higher prevalence)Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 51.1724 Tm 0 Tc [(of severe IF)55.2(ALD; and a quarter of those advanced to end-stage liver )]TJ ET EMC /P <>BDC BT 8 0 0 8 314.865 481.4231 Tm (failure. Intrahepatic cholestasis and hyperbilirubinaemia are the )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 468.4231 Tm [(hallmark of IF)55.2(ALD in this population, which is uncommon in the adult )]TJ ET EMC /P <>BDC BT 8 0 0 8 314.865 455.4231 Tm (population.)Tj ET EMC /P <>BDC BT /F2 1 Tf 8 0 0 8 303.5263 442.4231 Tm (C.)Tj ET EMC /P <>BDC BT /F1 1 Tf 8 0 0 8 314.865 442.4231 Tm -.01 Tc (An excess of energy in the form of glucose, protein and/or lipid can result )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 429.4231 Tm [(in abnormal LFT)110.8(s. Excessive glucose infusion causes hyperinsulinaemia, )]TJ ET EMC /P <>BDC BT 8 0 0 8 314.865 416.4231 Tm (which inhibits fatty acid oxidation, and so may result in hepatic steatosis. )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 403.4231 Tm (Replacement of a proportion of the glucose energy with lipid reduces )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 390.4231 Tm [(steatosis, but excessive parenteral lipid may also cause abnormal LFT)110.8(s. )]TJ ET EMC /P <>BDC BT 8 0 0 8 314.865 377.4231 Tm 0 Tc (Proposed mechanisms include a limited ability of administered lipid to )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 364.4231 Tm (undergo lipolysis due to a reduced cholesterol content, an accumulation )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 351.4231 Tm (of phytosterols, and an increased production of pro-inflammatory )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 338.4231 Tm (mediators due to a high linoleic acid content. Excessive amino acids )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 325.4231 Tm (may promote cholestasis in neonates.)Tj ET EMC /P <>BDC BT /F2 1 Tf 8 0 0 8 303.5263 312.3331 Tm (D.)Tj ET EMC /P <>BDC BT /F1 1 Tf 8 0 0 8 314.865 312.3331 Tm (First-generation soya bean-based lipid emulsions have been available )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 299.2431 Tm [(for clinical use for over 60 years. )18.1(Thus, the complications of excess lipid )]TJ ET EMC /P <>BDC BT 8 0 0 8 314.865 286.1531 Tm (administration described above have been well documented in those )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 273.0631 Tm [(receiving such preparations, even at modest levels. Comparatively)74.2(, )]TJ ET EMC /P <>BDC BT 8 0 0 8 314.865 259.9731 Tm -.015 Tc (second-generation \(medium-long chain triglycerides and monounsaturated)Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 246.8832 Tm 0 Tc (fatty acids\) and third-generation \(fish oil-based; mixed lipid emulsions\) )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 233.7931 Tm [(preparations may be associated with less hepatotoxicity)74.2(. )55.2(A)18.1(vailable )]TJ ET EMC /P <>BDC BT 8 0 0 8 314.865 220.7032 Tm (comparative literature suggests an improvement in cholestasis and a )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 207.6131 Tm [(reduction in morbidity and mortality)74.2(, although further definitive studies )]TJ ET EMC /P <>BDC BT 8 0 0 8 314.865 194.5232 Tm [(are required. )18.1(There has been much interest in the role of phytosterols )]TJ ET EMC /P <>BDC BT 8 0 0 8 314.865 181.4331 Tm [(\(plant-derived sterols similar to cholesterol\) in the aetiology)74.2(.)]TJ ET EMC /P <>BDC BT /F2 1 Tf 8 0 0 8 303.5263 168.3932 Tm (E.)Tj ET EMC /P <>BDC BT /F1 1 Tf 8 0 0 8 314.865 168.3932 Tm (Copper and manganese are important trace elements in multiple )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 155.3531 Tm (physiologic processes, but accumulation within the liver is hepatotoxic. )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 142.3131 Tm (Both substances are excreted via the biliary route and may accumulate )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 129.2732 Tm [(in the setting of pre-existing cholestasis. )55.2(Aluminium serves no known )]TJ ET EMC /P <>BDC BT 8 0 0 8 314.865 116.2332 Tm (physiologic function in humans and the gut absorbs <1% of the amount )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 103.1932 Tm [(ingested. When present in PN solutions, however)55.2(, this mechanism is )]TJ ET EMC /P <>BDC BT 8 0 0 8 314.865 90.1532 Tm (bypassed, which can allow accumulation and hepatotoxicity \(as well as )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 77.1132 Tm [(neurotoxicity)74.2(, anaemia, and bone disease\). )18.1(The aluminium content of )]TJ ET EMC /P <>BDC BT 8 0 0 8 314.865 64.0732 Tm (PN preparations results from its presence in calcium gluconate and )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 51.0331 Tm (inorganic phosphate additives.)Tj ET EMC /P <>BDC BT /F2 1 Tf 9 0 0 9 22.6772 814.1643 Tm 1 .15 0 0 k [(THE BRITISH INTESTINAL)18.1( F)55.2(AILURE )37.1(ALLIANCE \(BIF)55.2(A\) T)18.1(O)0(P)18.1( TIPS )37.1(ARTICLE SERIES)]TJ ET EMC /Artifact <>BDC 0 0 0 .6 k .059998 806.78 595.32 1.417 re f EMC /P <>BDC BT /F1 1 Tf 8 0 0 8 22.6772 14.3571 Tm 0 0 0 0 k [(BIF)55.2(A)55.2( is a Specialist Interest Group of ϳԹ )]TJ ET EMC /P <>BDC BT /F2 1 Tf 8 0 0 8 191.2006 14.3571 Tm [(www)37.1(.bapen.org.uk )]TJ ET EMC /P <>BDC BT /F1 1 Tf 8 0 0 8 22.6772 620.987 Tm 0 0 0 .8 k [(Darren W)18.1(ong and the BIF)55.2(A)55.2( Committee)]TJ ET EMC /P <>BDC BT 6 0 0 6 510.4381 41.029 Tm (Continued over page...)Tj ET EMC Q endstream endobj 84 0 obj <>/ExtGState<>>> endobj 90 0 obj <> endobj 121 0 obj <>stream /Figure <>BDC q 1 i -15.701 718.718 625.343 -710.979 re 297.66 421.02 m W* n 0 841.89 595.276 -841.89 re 297.66 421.02 m W n .059998 841.98 595.32 -841.92 re W n /GS3 gs q 689.024 104.165 87.087 -576.064 -74.627 494.297 cm /Im1 Do Q EMC /Artifact <>BDC Q q 1 i 0 841.89 595.276 -841.89 re 297.66 421.02 m W n .059998 841.98 595.32 -841.92 re W n 1 .1 0 .1 k /GS2 gs .059998 .059998 595.32 31.422 re f EMC /P <>BDC BT /F2 1 Tf 8 0 0 8 22.6771 776.0669 Tm 0 0 0 .8 k -.1109 Tc 0 Tw (F.)Tj ET EMC /P <>BDC BT /F1 1 Tf 8 0 0 8 34.0157 776.0669 Tm 0 Tc (Choline is required for very low-density lipoprotein synthesis within the )Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 763.0669 Tm [(liver)55.2(, and hence the export of hepatocyte triacylglycerol. Deficiency of )]TJ ET EMC /P <>BDC BT 8 0 0 8 34.0157 750.0669 Tm (choline therefore results in hepatic steatosis and has been associated )Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 737.0669 Tm (with elevated aminotransferase levels in those receiving PN. Small )Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 724.0669 Tm (placebo-controlled studies of parenteral choline supplementation have )Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 711.0669 Tm (shown reversal of these abnormalities \(choline is not available in the )Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 698.0669 Tm [(UK\). )18.1(T)110.9(aurine is an important component of bile salt conjugation )]TJ ET EMC /P <>BDC BT 8 0 0 8 34.0157 685.0669 Tm (pathways, and deficiency has been associated with cholestatic liver )Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 672.0669 Tm (disease, particularly in neonates and pre-term infants. Parenteral )Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 659.0669 Tm (supplementation of taurine prevents neonatal liver disease, but to date )Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 646.0669 Tm [(has shown no benefit in adult IF)55.2(ALD. Carnitine aids in the mitochondrial )]TJ ET EMC /P <>BDC BT 8 0 0 8 34.0157 633.0669 Tm (transport of long-chain fatty acids, and severe deficiency can result in )Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 620.0669 Tm (hepatic steatosis.)Tj ET EMC /P <>BDC BT /F2 1 Tf 8 0 0 8 22.6771 607.0669 Tm (G.)Tj ET EMC /P <>BDC BT /F1 1 Tf 8 0 0 8 34.0157 607.0669 Tm (Cyclic PN \(usually PN given during night time only\) is associated with )Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 594.0669 Tm [(less LFT)18.1( abnormalities than continuous PN.)]TJ ET EMC /P <>BDC BT /F2 1 Tf 8 0 0 8 22.6771 581.0669 Tm (H.)Tj ET EMC /P <>BDC BT /F1 1 Tf 8 0 0 8 34.0157 581.0669 Tm (Given the causes of liver dysfunction outlined above, treatment is )Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 568.0669 Tm (aimed at ameliorating identified causative factors. Sepsis must be )Tj ET EMC /P <>BDC BT 8 0 0 8 34.0157 555.0669 Tm [(treated expediently)74.2(, and ef)18.1(forts made to reduce its occurrence, )]TJ ET EMC /P <>BDC BT 8 0 0 8 34.0157 542.0669 Tm (particularly in relation to central venous catheter infections. )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 776.0669 Tm (Culprit)Tj ET EMC /P <>BDC BT 8 0 0 8 339.5263 776.0669 Tm (medications should be identified and stopped if possible. )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 763.0669 Tm (Review and optimisation of the composition of PN solutions should )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 750.0669 Tm (be performed at regular intervals to adjust for individual patient )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 737.0669 Tm (requirements. Maximising oral and/or enteral nutrition will improve gut )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 724.0669 Tm (function and gut hormone release, and reduce bacterial overgrowth )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 711.0669 Tm (and biliary stasis. Changing the lipid preparation to second or third-)Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 698.0669 Tm (generation formulations can be considered. Cyclical, rather than )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 685.0669 Tm [(continuous, PN infusion should be the rule to minimise the ef)18.1(fects of )]TJ ET EMC /P <>BDC BT 8 0 0 8 314.865 672.0669 Tm [(prolonged hyperinsulinaemia. )55.2(Altering bile composition with )]TJ ET EMC /P <>BDC BT 8 0 0 8 314.865 659.0669 Tm [(ursodeoxycholic acid has shown benefit in neonatal IF)55.2(ALD, but there is )]TJ ET EMC /P <>BDC BT 8 0 0 8 314.865 646.0669 Tm [(no evidence of long-term benefit in adult disease. )55.2(Antibiotics to treat )]TJ ET EMC /P <>BDC BT 8 0 0 8 314.865 633.0669 Tm [(bacterial overgrowth may reverse some LFT)18.1( derangement.)]TJ ET EMC /P <>BDC BT /F2 1 Tf 8 0 0 8 303.5263 620.0669 Tm (I.)Tj ET EMC /P <>BDC BT /F1 1 Tf 8 0 0 8 314.865 620.0669 Tm (Referral for small bowel transplantation should be considered in )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 607.0669 Tm [(impending or overt liver failure due to IF)55.2(ALD. It is one of the commonest )]TJ ET EMC /P <>BDC BT 8 0 0 8 314.865 594.0669 Tm (reasons for performing intestinal transplantation. In end-stage liver )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 581.0669 Tm (disease, combined liver and small intestinal transplantation can be )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 568.0669 Tm [(performed. In neonatal IF)55.2(ALD, intestinal adaptation may allow for )]TJ ET EMC /P <>BDC BT 8 0 0 8 314.865 555.0669 Tm (complete weaning of PN with time, and therefore single-organ liver )Tj ET EMC /P <>BDC BT 8 0 0 8 314.865 542.0669 Tm (transplantation may be considered.)Tj ET EMC /P <>BDC BT /F2 1 Tf 9 0 0 9 22.6772 814.1656 Tm 1 .15 0 0 k [(THE BRITISH INTESTINAL)18.1( F)55.2(AILURE )37.1(ALLIANCE \(BIF)55.2(A\) T)18.1(O)0(P)18.1( TIPS )37.1(ARTICLE SERIES)]TJ ET EMC /Artifact <>BDC 0 0 0 .6 k .059998 806.781 595.32 1.4171 re f EMC /P <>BDC BT /F1 1 Tf 8 0 0 8 22.6772 14.3583 Tm 0 0 0 0 k [(BIF)55.2(A)55.2( is a Specialist Interest Group of ϳԹ )]TJ ET EMC /P <>BDC BT /F2 1 Tf 8 0 0 8 191.2007 14.3583 Tm [(www)37.1(.bapen.org.uk )]TJ ET EMC /Artifact <>BDC 0 0 0 .08 k 23.677 358.542 549.698 164.586 re f EMC /P <>BDC BT 9 0 0 9 37.4136 505.5508 Tm 1 .89 0 0 k (Suggested reading)Tj ET EMC /P <>BDC BT 8 0 0 8 37.4136 492.5508 Tm ()Tj ET EMC /P <>BDC BT /F1 1 Tf 8 0 0 8 45.9174 492.5508 Tm 0 0 0 .8 k [(Nightingale JMD. Hepatobiliary)74.2(, renal and bone complications of intestinal failure. Best Practice and Research Clinical Gastroe)]TJ 55.8427 0 TD (nterology 2003; )Tj ET EMC /P <>BDC BT 8 0 0 8 45.9174 479.5508 Tm (17: 907-929.)Tj ET EMC /P <>BDC BT /F2 1 Tf 8 0 0 8 37.4136 466.5508 Tm 1 .89 0 0 k ()Tj ET EMC /P <>BDC BT /F1 1 Tf 8 0 0 8 45.9174 466.5508 Tm 0 0 0 .8 k [(Gabe SM, Culkin )55.2(A. )55.2(Abnormal liver function tests in the parenteral nutrition fed patient. Frontline Gastroenterology 2010;1:98-)]TJ 55.253 0 TD (104.)Tj ET EMC /P <>BDC BT /F2 1 Tf 8 0 0 8 37.4136 453.5508 Tm 1 .89 0 0 k ()Tj ET EMC /P <>BDC BT /F1 1 Tf 8 0 0 8 45.9174 453.5508 Tm 0 0 0 .8 k -.01 Tc [(Buchman )55.2(AL, Naini BV)91.8(, Spilker B. )18.1(The Dif)18.1(ferentiation of Intestinal-Failure-Associated Liver Disease from Nonalcoholic Fatty Liv)]TJ 54.6835 0 TD (er and Nonalcoholic)Tj ET EMC /P <>BDC BT 8 0 0 8 45.9174 440.5508 Tm 0 Tc (Steatohepatitis. Semin Liver Dis. 2017; 37\(1\): 33-44. )Tj ET EMC /P <>BDC BT /F2 1 Tf 8 0 0 8 37.4136 427.5508 Tm 1 .89 0 0 k ()Tj ET EMC /P <>BDC BT /F1 1 Tf 8 0 0 8 45.9174 427.5508 Tm 0 0 0 .8 k [(Norsa L, et al. Prevention and )18.1(T)37.1(reatment of Intestinal Failure-Associated Liver Disease in Children. www)55.2(.ncbi.nlm.nih.gov/pmc/a)]TJ 56.5268 0 TD (rticles/ )Tj ET EMC /P <>BDC BT 8 0 0 8 45.9174 414.5508 Tm (PMC6024802/ Nutrients 2018; 10\(6\): 664.)Tj ET EMC /P <>BDC BT /F2 1 Tf 8 0 0 8 37.4136 401.5508 Tm 1 .89 0 0 k ()Tj ET EMC /P <>BDC BT /F1 1 Tf 8 0 0 8 45.9174 401.5508 Tm 0 0 0 .8 k [(Lal S, et al. Clinical )55.2(Approach to the Management of Intestinal Failure )55.2(Associated Liver Disease \(IF)55.2(ALD\) in adults: a position)]TJ 54.9179 0 TD ( paper from the )Tj ET EMC /P <>BDC BT 8 0 0 8 45.9174 388.5508 Tm [(Home )55.2(Artificial Nutrition and Chronic Intestinal Failure Special Interest Group of ESPEN. Clin Nutr 2018, Jul 9. Pii: S0261-561)]TJ 55.4155 0 TD (4\(18\)31208-1.)Tj ET EMC /P <>BDC BT 8 0 0 8 45.9174 375.5508 Tm (Doi:10.1016/j.clnu.2018.07.006 [Epub ahead of print].)Tj ET EMC Q endstream endobj 122 0 obj <>/XObject<>/ExtGState<>>> endobj 6 0 obj <> endobj 5 0 obj <> endobj 123 0 obj <>stream Adobed         #"""#''''''''''     !! !!''''''''''""  s!1AQa"q2B#R3b$r%C4Scs5D'6Tdt& EFVU(eufv7GWgw8HXhx)9IYiy*:JZjzm!1AQa"q2#BRbr3$4CS%cs5DT &6E'dtU7()󄔤euFVfvGWgw8HXhx9IYiy*:JZjz?lٳ_ |6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6lٳf]6l,/5>j_UѲ+*wnNi{mIH+v_VHIl.vѴ]3t:Nlvăvcՙw9{'Fn095l?קx]9akҘ ʞR|1M3o,RI[?p퇹g(`ǎ"0G ch e͛6lj6lٳf͊6lٳf͊6lٳf͊6loڵmhjG_VA0[^;; ="ɜr7̢QӼ,뷊ެ*}>M|.z(|sސkr 7hGGO3Ⴔƃ2kِLlٳ~lٳf͛vlٳf͛vlٳf͛vlٳafi^e&5u6X}،3͐ɏXKXFp1d8(`vb+6xV&jZz8eGp { =Nk B^A*FS؃d[ڽ懻j:]!Gx[6M ,]W<|,KS"rU`CO=]e >9eɐa) ٳeNH$ƀ3@ߑ$:ߞ#nݟ?w\_[0*V x|iO==9Dr(iXa9y}>kٲƳƐ‹ϨH@ձ*͞66´͛6ٰ͛6–4f՝َ5|i6}ގo*9B<<5\YY8#(tI}ىP5&fo6lٳf͊6lٰ5cs޸'yj]0NqO7~jՈu~#5x3u:|-"ٳc\Lu2kچu_Vf58D~ 7ZFi7 )6+6|=FYg:Lg^!<\^Us6lvZG֬mIVy}vpɷ|py??cvEvjõ{/MSP?46>%+;6ٳ͛6ٳ͛6յ-kmKd,'6.v*0i<ߤEz,MA$R9E*+fusg\9ee[qÿ%ܮ͔I,lٳ1]6lDWlثf͜G+2T2^L-o^}.!~'nl{kJvejo-|zGmI U|A?oi3vH AKӇ)$~G˚+rviӝL1׏b}悻68)8;? 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