Managing Abnormal LFTs
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This document discusses managing abnormal liver function tests (LFTs) in patients on parenteral nutrition. It finds that while short-term parenteral nutrition can elevate LFTs in some patients, long-term use commonly leads to abnormal LFTs. The causes of abnormal LFTs include sepsis, pre-existing liver disease, lipid overload, and intravenous lipid-associated fatty liver disease. The document recommends assessing for other causes, modifying nutrition including limiting lipid intake to less than 1g/kg/day, and considering referral for small bowel transplant for persistently abnormal LFTs with fibrotic liver disease and ultra-short bowel. Fibroscan is preferable to biopsy for evaluating liver disease in these patients.
Managing Abnormal LFTs
- 1. Managing abnormal LFTs Dr Simon Gabe Consultant Gastroenterologist St Mark’s Hospital
- 3. Questions How common are abnormal LFTs in patients on IVN? Is it the parenteral nutrition?
- 4. Abnormal LFTs Author Study % Elevated AST Alk Phos Bil Lindor et al. 1979 2 weeks PN (high glucose & no lipid) 68% 54% 21% Clarke et al. 1991 4 weeks PN (more balanced PN) 27% 32% 31% Short term PN
- 5. Is it the parenteral nutrition? Liver biopsies •93 patients on TPN •35 matched controls Assessment •19 histological grades •27 clinical variables Results: abnormal hepatic histology correlated with • Pre-existing liver disease • Abdominal sepsis • Renal failure • Blood transfusion Histology DID NOT correlate with TPN administration Wolfe et al, Arch Surg 1998;123:1084-1090 Short term PN
- 6. Abnormal LFTs & short term PN Baker & Nightingale, Clin Nutr 2004;23:864 • 60% LFTs worsened on PN • 30% LFTs resolved on PN Abn LFTs before PN started (34% patients) • 46% sepsis • 24% underlying liver disease Abn LFTs while on PN (9% patients) 58 patients receiving PN (M:F 36:22) 48 (83%) fistula, obstruction, ileus, failed EN
- 7. Abnormal LFTs & long term PN Author No. HPN patients Abn LFTs Severe liver disease Luman et al, 2002 107 48% 0% Salvino et al, 2006 162 95% 4% Lloyd et al, 2008 113 24% CC Cavicci et al, 2000 90 65% CC 26% at 2 years 50% at 5 years Chan et al, 1999 42 14% Ito & Shills, 1991 16 19% CC = chronic cholestasis Long term PN
- 8. Questions What are the causes of abnormal liver function? What can to do to change this?
- 9. Abnormal LFTs on PN Sepsis Drugs PNALD Calculus or acalculus cholecystitis Pre-existing liver disease or underlying disease Short-term PN Long-term PN
- 10. What do I do? AssessMedications Sepsis & collections Liver screen Liver USS Calorie requirements Calories delivered Lipid delivered
- 11. Patient dependent causes Enteral nutrition Nutrient deficiency Nutrient toxicity IFALD Pre-existing liver disease Sepsis Intestinal anatomy Prematurity Lack of enteral nutrition Choline Taurine EFA, protein Carnitine, vit E Glucose Lipid Manganese, Cu, Phytosterols Long term PN
- 12. SB length important SB length not important Intestinal anatomy Long term PN Mechanism?
- 13. What is evil ….. More parenteral lipid? More parenteral calories?
- 14. Parenteral glucose Glucose Fast or excessive infusion Steatosis Lindor et al, 1979 Large amount of energy supplied as glucose (>GOR) Associated with steatosis Long term PN Short term PN
- 15. 0 10 20 30 40 50 60 70 80 90 100 0 1 2 3 4 5 6 7 8 9 10 Years on HPN ProbabilityofbeingfreeofCC(%) 0 10 20 30 40 50 60 70 80 90 100 0 1 2 3 4 5 6 7 8 9 10 Years on HPN Freeofchroniccholestasis,probability(%) Vega et al. Clin Nutr 2004 23:865-6 0.5 g/kg/day lipid <1 g/kg/day lipid >1 g/kg/day lipid Cavicchi M et al. Ann Intern Med 2000;132: 525-32 Soybean oil Long term PN
- 16. Parenteral lipid emulsions Generation Description Lipid types Brands 1st Conventional lipid LCT (soybean oil) LCT (soy/safflower oil) Intralipid 2nd Lipid emulsions with reduced PUFA Structured lipids (MCT/LCT) Olive oil based emulsion Structolipid Clinoleic 3rd Lipid emulsions with reduced PUFA & specific ω6/ω3 FA ratio Fish oil Soy/MCT/olive oil/fish oil Omegaven SMOF Long term PN
- 17. RCT: SMOF v soybean oil -25 -20 -15 -10 -5 0 5 Alk Phos ALT AST GGT Bilirubin Change with SMOF Change with soybean oil Klek et al, Clin Nutr 2013;32:224-231 * * * after 4 weeks after 4 weeks Long term PN Short term PN
- 18. Fish oil effect: >1 mechanism IFALD Antioxidative protection • n-3 fatty acids • α-tocopherol Inflammatory mediators • n-3 fatty acids Phytosterols • None or less
- 19. Colomb et al. JPEN 2000; 24(6): 345-50 Reversal of cholestasis Long term PN
- 20. 0 50 100 150 200 250 300 350 400 450 Oct-02 Feb-03 Jun-03 Oct-03 Feb-04 Jun-04 Oct-04 Feb-05 Jun-05 Oct-05 Feb-06 Jun-06 Oct-06 Feb-07 Jun-07 Oct-07 Feb-08 Jun-08 Oct-08 Feb-09 Jun-09 Oct-09 ALP ALT Bili All lipids stopped SB infarction Lipids reintroduced
- 21. <1g/kg/day (60kg patient) <60g 0.11g/kg/h (60kg patient & 12h infusion) 80g 500ml 20% lipid emulsion 100g Best way to achieve <1g/kg/day is NO DAILY LIPIDS Could use 10% lipid emulsion Less 20% lipid but bag is less stable
- 22. Abnormal LFTs on PN Manage non nutritional causes Modify enteral & parenteral nutrition Persistently abnormal LFTs Fibrotic liver disease Ultra short bowel (<50cm) Referral for SB transplant Pharmacological treatment Long term PN Short term PN
- 23. Questions Do you give cyclical parenteral nutrition? Fibroscan or liver biopsy?
- 24. PN: continuous vs cyclical Continuous PN Jeopardizes hepatic mitochondrial re-energization Liver glycogen deposition when given PN for 5 days Circadian PN pattern May reduce the risk of post- ischaemic mitochondrial liver dysfunction Morikawa et al, Hepatology Liver glygogen after 5 days TPN Cyclical TPN Cont TPN
- 25. Which one? Liver biopsy Elastography Not invasive Interpretation difficult More definitive diagnosis Higher risk procedure
- 26. FibroScan stiffness Significant correlation with bilirubin & histological cholestasis No correlation with histologic fibrosis Van Gossum et al. JPEN 2014:DOI: 10.1177/0148607114538057 Fibroscan value and Brunt stage (histological fibrosis score) Fibroscan value and histological cholestasis grade
- 27. How can this affect your practice? Acute IF (Type 1) • Look for causes other than the IV nutrition • Reasonable to give daily lipid • Do not overfeed • Best type of lipid? • Need more comparative studies • Anti-inflammatory & anti-oxidative properties of fish oil is attractive Chronic IF (Type 2-3) • Key message is to give lipid according to EFA requirements (<1g/kg/day) • Do not increase glucose calories as a result • IFALD patients • Decrease further/stop lipid • Use 2nd or 3rd generation lipid but stability issues may mean that the lipid is given separately