abnormal liver transaminases…to biopsy or not to biopsy? · 2020-03-18 · prednisone 50 mg po q...
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Abnormal Liver Transaminases…To biopsy or
not to biopsy?DR. PHILIP WONG, ASSOCIATE PROFESSOR OF MEDICINE, MCGILL UNIVERSITY
DR. SUSAN GILMOUR, PROFESSOR OF PEDIATRICS, UNIVERSITY OF ALBERTA
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Disclosures
Dr. Gilmour Clinical trials, site PI Abbvie, Mirum
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Biopsy: Completing the picture or just adding to it?
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Case Study
20 year old male referred to your GI practice because of elevated liver transaminases on pre-isotretinoin screening
Labs from family physician: AST 105 u/l [6-35 u/l] ALT 98 u/l [6-45 u/l] ALP 275 u/l [53-128 u/l] GGT 50 u/l [7-50 u/l] Tbili 18 μmol/l [1.7-18.9 u/l]
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Case Study (con’t)
20 year old male previously healthy, no oral antibiotic therapy for acne, no colitis symptoms, no family history of liver disease or IBD
Patient is not sure why he is in a GI office, he states he feels well and he HATES needles
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Further Investigations?
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Further Investigations
ANA 1:80; IgG 18 g/l [7-15 g/l] SMA neg; AMA neg; LKM neg Cu; ceruloplasmin; ferritin, alpha 1 all normal EBV old infection; Hep A, B, C negative and reflect
immunization for HBV Ultrasound: very mild heterogeneity ; no
hepatosplenomegaly; normal portal flow Radiology did an ultrasound shear wave: “mild fibrosis
score”
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Next Steps…
Treat based on biochemistry?Liver biopsy then decide on therapy?
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Histology
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Case Study (con’t)
Prednisone 50 mg po q daily was started, and then azathioprine 100 mg daily was added
Transaminases trend down but do not normalize When the prednisone was weaned the transaminases
increase to more than initial presentation Patient very clear that they are adherent with
medications (and patient is mildly Cushingoid; 6 TGN levels in therapeutic range)
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Next Steps
? Change pharmacotherapy ?Rebiopsy ?MRCP All of the above None of the above
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MRCP: “attenuated intrahepatic ducts”
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Overlap Syndrome: Entity or Evolution
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Dilemma
AIH, PBC, PSC have emerged as distinct clinical entities But none of these have known distinct etiological
agents, or distinctive pathogenic pathways to definitively define them
These are all clinical syndromes with clinical, lab, serological, genetic and histological features that can be shared.
We define by the clustering of the above
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AIH with Secondary Features = Overlap Syndromes
Czaja Dig Dis Sci 2013
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Overlap Syndrome
AIH has been described in overlap with cholangiopathies: AIH and Primary biliary cirrhosis AIH and Primary sclerosing cholangitis
No validated criteria for the diagnosis of AIH/PBC or AIH/PSC
Literature describes the two entities being diagnosed at the same time, AIH first or PBC/PSC first diagnosed
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AIH/PBC
Frequency of overlap AIH/PBC 7 to 13% of AIH patients (adult)
Retrospective studies have found that these patients have: Higher AST/ALT to PBC alone Higher δ-globulin levels Higher prevalence of other autoimmune disorders
Efe et al Eur J Gastroenterol Hepatol 2012
Heurgue et al J Gastroenterol Hepatol 2010
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Paris Criteria
Require the presence of 2/3 clinical hallmarks of each disease, AIH and PBC AIH
ALT 5 X ULN IGg 2 X ULN
+ SMA Histology of interface hepatitis
PBC ALP 2 X ULN GGT 2 X ULN AMA +
Histology of duct lesions
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AIH/PSC
Frequency of overlap is 6 to 11% of AIH patients Less female prevalence vs AIH alone More likely to be associated with IBD than AIH alone Pediatric study found that 31% of AIH patients had histological
evidence of biliary damage Czaja Dig Dis Sci 2013
Gregorio et al Hepatol 2001
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Diagnostic CriteriaAIH/PSC
No specific criteria Clinically these are patients with:
AIH predominantly
Cholestatic labs
Absence of AMA
Histological and/or radiographic findings of bile duct injury or loss
Concurrent IBD (+/-)
Non-responsive to conventional corticosteroid therapy
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Discussion!