PBC and PSC: Back to Basics

[Pages:29]PBC and PSC: Back to Basics

grace.kim@ucsf.edu

Outline

? In chronic cholestatic liver disease, liver biopsy plays a supporting role

? Case-based discussion ? Clinical information, including laboratory

findings and radiographic features, must be integrated for diagnosis

5/27/2016

Disclosure

No financial interest or other relationship with the manufacturer(s) of the product(s) or provider(s) of the service(s) that will be discussed in this presentation.

Case 1 clinical history

? 54 year old woman, asymptomatic, incidentally discovered to have elevated alkaline phosphatase (ALP) and positive antimitochondrial antibodies (AMA)

? Liver biopsy performed

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What finding would you like to see on biopsy so you can diagnosis it as PBC?

A. Portal and lobular inflammation B. Infiltrate with easily identified plasma cells C. Florid duct lesion D. Ductular reaction E. Ductopenia F. Periportal copper deposition G. CK7 positive periportal hepatocytes H. Nodular regenerative hyperplasia I. Biliary pattern of cirrhosis

AASLD and EASL recommendations

? 2 of 3 required criteria for PBC diagnosis

? Presence of antimitochondrial antibodies (AMA) ? Alkaline phosphatase (ALP) at least 1.5 times

upper limit of normal for >24 weeks ? Histologic evidence of PBC, specifically

nonsuppurative cholangitis and duct injury

Bowlus CL, Gershwin ME. The diagnosis of primary biliary cirrhosis. Autoimmun Rev. 2014 Apr-May;13(4-5):441-4. Lindor KD, et al. Primary biliary cirrhosis. Hepatology 2009;50:291?308.

EASL. Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol 2009;51:237?67.

5/27/2016

AASLD and EASL recommendations

? 2 of 3 required criteria for PBC diagnosis

? Presence of antimitochondrial antibodies (AMA) ? Alkaline phosphatase (ALP) at least 1.5 times

upper limit of normal for >24 weeks ? Histologic evidence of PBC, specifically

nonsuppurative cholangitis and duct injury

Bowlus CL, Gershwin ME. The diagnosis of primary biliary cirrhosis. Autoimmun Rev. 2014 Apr-May;13(4-5):441-4. Lindor KD, et al. Primary biliary cirrhosis. Hepatology 2009;50:291?308.

EASL. Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol 2009;51:237?67.

Antimitochondrial antibodies (AMA)

? Major autoantigen target by PBC patient sera

? M2 antigen fraction

? E2 subunits of

? Pyruvate dehydrogenase complex (PDC-E2) ? Branched chain 2-oxo-acid dehydrogenase complex (BCOADC-

E2) ? 2-oxo glutarate dehyrogenase complex (OGDC-E2)

? E1 and E3 binding protein of PDC

Muratori L, et al. Antimitochondrial Antibodies and Other Antibodies in Primary Biliary Cirrhosis: Diagnostic and Prognostic Value. Clin Liver Dis 2008 May;12(2):261-76.

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AMA test methodology

? Indirect immunofluorescence assay (IFA)

? Positive titer is 1:40 ? Sensitivity 70-90%

? Enzyme-linked immunosorbent assay (EIA)

? AMA-M2 antibodies is most frequently used

? First generation utilized PDC-E2

? 10% of PBC pts only react to BCOADC-E2 and/or OGDC-E2

? MIT3 or BPO expresses BCOADC-E2, PDC-E2 and OGDCE2 epitopes

? Sensitivity 94%

D?hnrich C, et al. New ELISA for detecting primary biliary cirrhosis-specific antimitochondrial antibodies. Clin Chem. 2009 May;55(5):978-85. Selmi C, Bowlus CL, Gershwin ME, Coppel RL. Primary biliary cirrhosis. Lancet. 2011 May 7;377(9777):1600-9.

AMA positive also in...

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