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UHN centre of excellence

Liver issues for the Rhuematologist

David Wong, MDUniversity of Torontowww.torontoliver.ca

Disclosures (last 1 year):Research Studies: BMS, Gilead, Johnson & Johnson, VertexAdvisory Boards: Merck, Vertex

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Objectives

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 consider which labs to monitor when screening for liver problems with DMARDS

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Do I have cirrhosis?

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Liver functionThe liver is not a filter

Liver is a factory for synthesis Food digested/absorbed portal vein Raw materials proteins, carbohydrates, fats Disposition

Hepatic vein to heart circulation Waste to bile stool

Liver function tests Delivery: platelet count (down with

hypersplenism) Synthesis: INR, Albumin Excretion: Bilirubin (conjugated)

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0

20

40

60

80

100

0 20 40 60 80 100

% Fibrosis

% F

unct

ion

Fibrosis progression to symptoms

Cirrhosis

Symptoms

Platelets

INR

Albumin

Bilirubin

Imaging, Biopsy

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Traditional test: Ultrasound

Ultrasound Small, coarse (rough), nodular Ascites Lobar redistribution Echogenic (fatty)

Limitations Later cirrhosis Tough to do in central obesity Expertise of Radiologist/Technician

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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 Inflammation Fat

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Liver biopsies (H&E)

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Occult cirrhosis can be uncovered by evaluation of unexplained

thrombocytopenia VA New York Harbor Health System 2008-

2010 N=497 not known to have cirrhosis/liver

disease N=382 analyzed N=112 assessed by GI or Hepatology

62 finished evaluation, 31 (50%) have cirrhosis 4 developed hepatoma Hepatitis C, ALD, NAFLD

APRI 1.41 in cirrhotics, 0.64 in non-cirrhotics

E Weiss et al. ACG 2012, P1353

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Combined Clinical Tests: APRI & FIB-4

Cirrhosis Older individuals Platelets fall AST > ALT

(alcohol) Limitations

Must be calculated!

APRI

<0.5 is good >1.5 is advanced

FIB-4

<1.45 is good >2.35 is advanced

ASTxULN x 100Platelet count

Age x ASTPlatelet x ALT

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FibrotestWikipedia or www.torontoliver.ca

Age Gender GGT Bilirubin

May be indirect a2-macroglobulin Haptoglobin

May be down Apo-Lipoprotein A1

L Castera et al. Gastroenterology 2005;128:343

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Fibrotest calculatorhttp://torontoliver.ca

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Fibrotest

T Poynard et al. Comparative Hepatology 2004;3:8

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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 6-monthly

calibration Probe damage

Gel, cleaning

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Fibroscan

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Performance characteristics

Laurant Castera et al. Gastroenterology 2005;128:343

APRIASTxULNx100Platelet

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Fibrosis in PsoriaticsA: 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

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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

< 150 and falling by >15% over 2 years

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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 Ultrasound surveillance (not AFP)

Plts < 150: suspect cirrhosis Plts < 100: likely will have varices Plts < 70: higher risk of renal failure (hepatorenal

syndrome) No NSAIDS (even with PPI) Tylenol <3-4g/day is much safer

Coffee may be good Alcohol in moderation may be good

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Questions?