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LIVER
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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
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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 function
The liver is not a filter
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Liver is a factory for synthesis
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Food digested/absorbed  portal vein
Raw materials  proteins, carbohydrates, fats
Disposition
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Hepatic vein to heart  circulation
Waste to bile  stool
Liver function tests
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Delivery: platelet count (down with hypersplenism)
Synthesis: INR, Albumin
Excretion: Bilirubin (conjugated)
Fibrosis progression to
symptoms
Cirrhosis
100
% Function
80
INR
Bilirubin
60
Platelets
Albumin
40
Symptoms
20
Imaging, Biopsy
0
0
20
40
60
% Fibrosis
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80
100
Traditional test: Ultrasound
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Ultrasound
Small, coarse (rough), nodular
 Ascites
 Lobar redistribution
 Echogenic (fatty)
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Limitations
Later cirrhosis
 Tough to do in central obesity
 Expertise of Radiologist/Technician
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Liver biopsy
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Safety
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1/5: pain from bleed
1/5,000-1/10,000
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Time
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Additional information
 Inflammation
 Fat
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BLEED
Death
Pneumothorax etc.
Hospital x hours
Results in weeks
Error
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Inadequate sample
Inadequate Expertise
Liver biopsies (H&E)
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Occult cirrhosis can be uncovered by
evaluation of unexplained thrombocytopenia
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VA New York Harbor Health System 2008-2010
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N=497 not known to have cirrhosis/liver disease
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N=382 analyzed
N=112 assessed by GI or Hepatology
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62 finished evaluation, 31 (50%) have cirrhosis
 4 developed hepatoma
 Hepatitis C, ALD, NAFLD
APRI 1.41 in cirrhotics, 0.64 in non-cirrhotics
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E Weiss et al. ACG 2012, P1353
Combined Clinical Tests:
APRI & FIB-4
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Cirrhosis
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ASTxULN x 100
Platelet count
Older individuals
 Platelets fall
 AST > ALT
(alcohol)
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Limitations
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APRI
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FIB-4
Age x AST
Platelet x ALT
Must be calculated!
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<0.5 is good
>1.5 is advanced
<1.45 is good
>2.35 is advanced
Fibrotest
Wikipedia or www.torontoliver.ca
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Age
Gender
GGT
Bilirubin
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a2-macroglobulin
Haptoglobin
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May be indirect
May be down
Apo-Lipoprotein A1
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L Castera et al. Gastroenterology 2005;128:343
Fibrotest calculator
http://torontoliver.ca
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Fibrotest
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T Poynard et al. Comparative Hepatology 2004;3:8
Fibroscan
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Accessing the liver
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Probe size
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Maintenance
 6-monthly calibration
Probe damage
 Gel, cleaning
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Obesity
Rib space
Air (lungs, gut)
Small (S1 vs S2)
Medium*
Large
Time
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2.5-3 minutes/scan
Fibroscan
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Performance characteristics
APRI
ASTxULNx100
Platelet
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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
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J Chladek et al. J Eur Acad Dermatol Venerol epub Aug 2012
Recommendations for
Methotrexate or Imuran
Baseline
 History
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Monitoring
 Labs
Metabolic syndrome
Did you ever drink on a
regular or daily basis?
Other history of liver
disease
Labs
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LIVER
CENTRE
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Ultrasound if abnormal
tests
HBsAg
Especially if Plts < 150
Look for rising numbers
over the first year that
continue to go up rather
than just fluctuate
CBC
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ALT, AST, ALP
ALT, AST, ALP, CBC
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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
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Ultrasound surveillance (not AFP)
Plts < 150: suspect cirrhosis
Plts < 100: likely will have varices
Plts < 70: higher risk of renal failure (hepatorenal syndrome)
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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?
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