TWH LIVER CENTRE UHN centre of excellence Liver

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

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

Do I have cirrhosis? TWH LIVER CENTRE

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

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

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

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

Liver biopsies (H&E) TWH LIVER CENTRE

Occult cirrhosis can be uncovered by evaluation of unexplained thrombocytopenia n VA New York Harbor Health System 2008 -2010 n N=497 not known to have cirrhosis/liver disease n n N=382 analyzed N=112 assessed by GI or Hepatology n n 62 finished evaluation, 31 (50%) have cirrhosis n 4 developed hepatoma n Hepatitis C, ALD, NAFLD APRI 1. 41 in cirrhotics, 0. 64 in non-cirrhotics TWH LIVER CENTRE E Weiss et al. ACG 2012, P 1353

Combined Clinical Tests: APRI & FIB-4 n Cirrhosis n Older individuals n Platelets fall n AST > ALT (alcohol) ASTx. ULN x 100 Platelet count n n Limitations n APRI n n n FIB-4 Age x AST Platelet x ALT Must be calculated! n n TWH LIVER CENTRE <0. 5 is good >1. 5 is advanced <1. 45 is good >2. 35 is advanced

Fibrotest Wikipedia or www. torontoliver. ca n n Age Gender GGT Bilirubin n a 2 -macroglobulin Haptoglobin n n May be indirect May be down Apo-Lipoprotein A 1 TWH LIVER CENTRE L Castera et al. Gastroenterology 2005; 128: 343

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

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

Fibroscan n Accessing the liver n n Probe size n n n Maintenance n 6 -monthly calibration Probe damage n Gel, cleaning TWH LIVER CENTRE n n n Obesity Rib space Air (lungs, gut) Small (S 1 vs S 2) Medium* Large Time n 2. 5 -3 minutes/scan

Fibroscan TWH LIVER CENTRE

Performance characteristics APRI ASTx. ULNx 100 Platelet TWH LIVER CENTRE Laurant Castera et al. Gastroenterology 2005; 128: 343

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

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

What to do for your cirrhotics Stage Clinical Implication 1 Asymptomatic 10 year survival > 85 -90% 2 Esophageal varices Screen with gastroscopy 3 History of variceal bleed Beta blockers lower risk 4 Ascites Synthesis failure: transplant Hepatoma At any stage n n n Ultrasound surveillance (not AFP) Plts < 150: suspect cirrhosis Plts < 100: likely will have varices Plts < 70: higher risk of renal failure (hepatorenal syndrome) n n No NSAIDS (even with PPI) Tylenol <3 -4 g/day is much safer Coffee may be good n Alcohol in moderation may be good TWH n LIVER CENTRE

Questions? TWH LIVER CENTRE