Managing abnormal LFTs

Transcription

1 Managing abnormal LFTs Dr Simon Gabe Consultant Gastroenterologist St Mark s Hospital

2 It depends Short Long

3 Questions How common are abnormal LFTs in patients on IVN? Is it the parenteral nutrition?

4 Short Author Lindor et al Clarke et al Abnormal LFTs Study 2 weeks (high glucose & no lipid) 4 weeks (more balanced ) % Elevated AST Alk Phos Bil 68% 54% 21% 27% 32% 31%

5 Short Is it the parenteral nutrition? Liver biopsies 93 patients on T 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 T administration Wolfe et al, Arch Surg 1998;123:

6 Short Abnormal LFTs & short 58 patients receiving (M:F 36:22) 48 (83%) fistula, obstruction, ileus, failed EN Abnormal LFTs before started (34% patients) 60% LFTs worsened on 30% LFTs resolved on Abnormal LFTs while on (9% patients) 46% sepsis 24% underlying liver disease Baker & Nightingale, Clin Nutr 2004;23:864

7 Long Abnormal LFTs & long Author No. H patients Abn LFTs Severe liver disease Luman et al, % 0% Salvino et al, % 4% Lloyd et al, % CC Cavicci et al, % CC 26% at 2 years 50% at 5 years Chan et al, % Ito & Shills, % CC = chronic cholestasis

8 Questions What are the causes of abnormal liver function? What can to do to change this?

9 Abnormal LFTs on parenteral nutrition support Sepsis Medications Short Pre-existing liver disease Underlying disease Acalculus cholecystitis Long Gallstones IFALD

10 What do I do? Sepsis & collections Medications Liver screen Liver USS Assess Calorie requirements Calories delivered Lipid delivered

11 Long Glucose Lipid Manganese, Cu, Phytosterols Nutrient toxicity Choline Taurine EFA, protein Carnitine, vit E Patient dependent causes IFALD Nutrient deficiency Pre-existing liver disease Sepsis Intestinal anatomy Prematurity Enteral nutrition Lack of enteral nutrition

12 Long Intestinal anatomy SB length important SB length not important Mechanism?

13 Ultra-short bowel, alcohol & liver fibrosis 32 patients had a liver biopsy 55 months (9-201) after starting 81% had a short bowel (gut < 200 cm) 37% had an ultra-short bowel (gut < 20 cm) Liver fibrosis associated with Ultra-short bowel (risk ratio 12.4) Alcohol consumption (risk ratio 7.4) Alcohol & ultrashort SB Alcohol or ultrashort SB No alcohol & no ultrashort SB Cazals-Hatem et al, Liver International 2017;1 9

14 What is evil.. More parenteral lipid? More parenteral calories?

15 Short Long Glucose Parenteral glucose Fast or excessive infusion Steatosis Lindor et al, 1979 Large amount of energy supplied as glucose (>GOR) Associated with steatosis

16 Long Soybean oil Free Probability of chronic cholestasis, of being free probability of CC (%) (%) Years on H 0.5 g/kg/day lipid <1 g/kg/day lipid >1 g/kg/day lipid Vega et al. Clin Nutr :865-6 Cavicchi M et al. Ann Intern Med 2000;132:

17 Long Parenteral lipid emulsions Generation Description Lipid types Brands 1 st Conventional lipid 2 nd Lipid emulsions with reduced PUFA 3 rd Lipid emulsions with reduced PUFA & specific ω6/ω3 FA ratio LCT (soybean oil) LCT (soy/safflower oil) Structured lipids (MCT/LCT) Olive oil based emulsion Fish oil Soy/MCT/olive oil/fish oil Intralipid Structolipid Clinoleic Omegaven SMOF

18 Short Long RCT: SMOF v soybean oil Alk Phos ALT AST GGT Bilirubin * * * Change with SMOF after 4 weeks Change with soybean oil after 4 weeks Klek et al, Clin Nutr 2013;32:

19 Fish oil effect: >1 mechanism Antioxidative protection n-3 fatty acids α-tocopherol Inflammatory mediators n-3 fatty acids IFALD Phytosterols None or less

20 Long Reversal of cholestasis Colomb et al. JPEN 2000; 24(6):

21 Oct-02 Feb-03 Jun-03 ALP ALT Bili Oct-03 Feb-04 Jun-04 Oct-04 SB infarction Feb-05 Jun-05 Oct-05 Feb-06 All lipids stopped Jun-06 Oct-06 Feb-07 Jun-07 Oct-07 Feb-08 Lipids reintroduced Jun-08 Oct-08 Feb-09 Jun-09 Oct-09

22 <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

23 Short Long Manage non nutritional causes Fibrotic liver disease Abnormal LFTs on Modify enteral & parenteral nutrition Persistently abnormal LFTs Referral for SB transplant Ultra short bowel (<50cm) Pharmacological treatment

24 Questions Do you give cyclical parenteral nutrition? Fibroscan or liver biopsy?

25 : continuous vs cyclical Continuous Jeopardizes hepatic mitochondrial re-energization Liver glycogen deposition when given for 5 days Circadian pattern May reduce the risk of postischaemic mitochondrial liver dysfunction Liver glygogen after 5 days T Cyclical T Morikawa et al, Hepatology Cont T

26 Which one? Liver biopsy Higher risk procedure More definitive diagnosis Elastography Interpretation difficult Not invasive

27 FibroScan stiffness Significant correlation with bilirubin & histological cholestasis No correlation with histologic fibrosis Fibroscan value and Brunt stage (histological fibrosis score) Fibroscan value and histological cholestasis grade Van Gossum et al. JPEN 2014:DOI: /

28 How can this affect your practice? Chronic IF (Type 2-3) Acute IF (Type 1) 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 2 nd or 3 rd generation lipid but stability issues may mean that the lipid is given separately 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