1. TWH LIVER CENTRE UHN centre of excellence Liver issues for the Rhuematologist David Wong, MD University of Toronto www.torontoliver.ca Disclosures (last 1 year): Research Studies: BMS, Gilead, Johnson & Johnson, Vertex Advisory Boards: Merck, Vertex

2. TWH LIVER CENTRE Objectives To understand the sensitivity and specificity of Fibroscan and Fibrotest for liver monitoring in patients receiving MTX To understand the sensitivity and specificity of Fibroscan and Fibrotest for liver monitoring in patients receiving MTX To understand which patients to refer to a specialist To understand which patients to refer to a specialist To consider which labs to monitor when screening for liver problems with DMARDS To consider which labs to monitor when screening for liver problems with DMARDS

3. TWH LIVER CENTRE Do I have cirrhosis?

4. TWH LIVER CENTRE Liver function The liver is not a filter Liver is a factory for synthesis Liver is a factory for synthesis Food digested/absorbed  portal vein Food digested/absorbed  portal vein Raw materials  proteins, carbohydrates, fats Raw materials  proteins, carbohydrates, fats Disposition Disposition Hepatic vein to heart  circulation Hepatic vein to heart  circulation Waste to bile  stool Waste to bile  stool Liver function tests Liver function tests Delivery: platelet count (down with hypersplenism) Delivery: platelet count (down with hypersplenism) Synthesis: INR, Albumin Synthesis: INR, Albumin Excretion: Bilirubin (conjugated) Excretion: Bilirubin (conjugated)

5. TWH LIVER CENTRE Fibrosis progression to symptoms Cirrhosis Symptoms Platelets INR Albumin Bilirubin Imaging, Biopsy

6. TWH LIVER CENTRE Traditional test: Ultrasound Ultrasound Ultrasound Small, coarse (rough), nodular Small, coarse (rough), nodular Ascites Ascites Lobar redistribution Lobar redistribution Echogenic (fatty) Echogenic (fatty) Limitations Limitations Later cirrhosis Later cirrhosis Tough to do in central obesity Tough to do in central obesity Expertise of Radiologist/Technician Expertise of Radiologist/Technician

7. TWH LIVER CENTRE Liver biopsy Safety 1/5: pain from bleed 1/5,000-1/10,000 BLEED Death Pneumothorax etc. Time Hospital x hours Results in weeks Error Inadequate sample Inadequate Expertise Additional information Additional information Inflammation Inflammation Fat Fat

8. TWH LIVER CENTRE Liver biopsies (H&E)

9. TWH LIVER CENTRE Occult cirrhosis can be uncovered by evaluation of unexplained thrombocytopenia VA New York Harbor Health System 2008-2010 VA New York Harbor Health System 2008-2010 N=497 not known to have cirrhosis/liver disease N=497 not known to have cirrhosis/liver disease N=382 analyzed N=382 analyzed N=112 assessed by GI or Hepatology N=112 assessed by GI or Hepatology 62 finished evaluation, 31 (50%) have cirrhosis 62 finished evaluation, 31 (50%) have cirrhosis 4 developed hepatoma 4 developed hepatoma Hepatitis C, ALD, NAFLD Hepatitis C, ALD, NAFLD APRI 1.41 in cirrhotics, 0.64 in non-cirrhotics APRI 1.41 in cirrhotics, 0.64 in non-cirrhotics E Weiss et al. ACG 2012, P1353

10. TWH LIVER CENTRE Combined Clinical Tests: APRI & FIB-4 Cirrhosis Cirrhosis Older individuals Older individuals Platelets fall Platelets fall AST > ALT (alcohol) AST > ALT (alcohol) Limitations Limitations Must be calculated! Must be calculated! APRI <0.5 is good >1.5 is advanced FIB-4 <1.45 is good >2.35 is advanced ASTxULN x 100 Platelet count Age x AST Platelet x ALT

11. TWH LIVER CENTRE Fibrotest Wikipedia or www.torontoliver.ca Age Age Gender Gender GGT GGT Bilirubin Bilirubin May be indirect May be indirect  2-macroglobulin  2-macroglobulin Haptoglobin Haptoglobin May be down May be down Apo-Lipoprotein A1 Apo-Lipoprotein A1 L Castera et al. Gastroenterology 2005;128:343

12. TWH LIVER CENTRE Fibrotest calculator http://torontoliver.ca

13. TWH LIVER CENTRE Fibrotest T Poynard et al. Comparative Hepatology 2004;3:8

14. TWH LIVER CENTRE Fibroscan Accessing the liver Obesity Rib space Air (lungs, gut) Probe size Small (S1 vs S2) Medium* Large Time 2.5-3 minutes/scan Maintenance Maintenance 6-monthly calibration 6-monthly calibration Probe damage Probe damage Gel, cleaning Gel, cleaning

15. TWH LIVER CENTRE Fibroscan

16. TWH LIVER CENTRE Performance characteristics Laurant Castera et al. Gastroenterology 2005;128:343 APRI ASTxULNx100 Platelet

17. TWH LIVER CENTRE Fibrosis in Psoriatics A: New users MTX (N=24), B: Biologics (N=15), C: Long term MTX (N=10) J Chladek et al. J Eur Acad Dermatol Venerol epub Aug 2012 PIIINP = N-terminal propeptide of collagen type III ; HA = Hyaluronic Acid

18. TWH LIVER CENTRE Recommendations for Methotrexate or Imuran Baseline History Metabolic syndrome Did you ever drink on a regular or daily basis? Other history of liver disease Labs ALT, AST, ALP, CBC Ultrasound if abnormal tests Especially if Plts < 150 HBsAg Monitoring Labs ALT, AST, ALP Look for rising numbers over the first year that continue to go up rather than just fluctuate CBC Look for falling platelet count to < 150 Very concerned if Plts 15% over 2 years

19. TWH LIVER CENTRE What to do for your cirrhotics StageClinicalImplication 1Asymptomatic10 year survival > 85-90% 2Esophageal varicesScreen with gastroscopy 3History of variceal bleedBeta blockers lower risk 4AscitesSynthesis failure: transplant HepatomaAt any stageUltrasound surveillance (not AFP) Plts < 150: suspect cirrhosis Plts < 150: suspect cirrhosis Plts < 100: likely will have varices Plts < 100: likely will have varices Plts < 70: higher risk of renal failure (hepatorenal syndrome) Plts < 70: higher risk of renal failure (hepatorenal syndrome) No NSAIDS (even with PPI) No NSAIDS (even with PPI) Tylenol <3-4g/day is much safer Tylenol <3-4g/day is much safer Coffee may be good Coffee may be good Alcohol in moderation may be good Alcohol in moderation may be good

20. TWH LIVER CENTRE Questions?