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Liver & intrahepatic bile ducts

Biliary tract disease

Primary biliary cholangitis

Author: Raul S. Gonzalez, M.D.

Editor-in-Chief: Debra L. Zynger, M.D.

Last author update: 10 December 2020

Last staff update: 4 August 2022

Copyright: 2002-2024, PathologyOutlines.com, Inc.

PubMed Search: Primary biliary cholangitis liver pathology

Table of Contents

Cite this page: Gonzalez R. Primary biliary cholangitis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/liverPBC.html. Accessed December 22nd, 2024.

Definition / general

Primary biliary cholangitis (PBC) is a chronic, progressive cholestatic liver disease with granulomatous destruction of interlobular bile ducts, leading to fibrosis and ultimately cirrhosis

Essential features

Typically occurs in middle aged women; extremely rare in children
Labs include elevated alkaline phosphatase, elevated IgM and the classic antimitochondrial antibody (AMA)
Histologic changes, including the pathognomonic florid duct lesions, can be patchy

Terminology

Previously called primary biliary cirrhosis; renamed because not all patients progress to cirrhosis (Clin Res Hepatol Gastroenterol 2015;39:e57)

ICD coding

ICD-10: K74.3 - primary biliary cirrhosis

Epidemiology

Reported prevalence of 65.4 women per 100,000 in U.S.; incidence appears to be increasing (Clin Liver Dis 2003;7:795)

Sites

Involves the most proximal portion of biliary tree, namely the interlobular bile ducts and canals of Hering; larger bile ducts are not typically affected (Hum Pathol 2002;33:983)

Etiology

Likely autoimmune; associated with Sjögren syndrome, scleroderma, thyroiditis, rheumatoid arthritis, Raynaud phenomenon, membranous glomerulonephritis, systemic lupus erythematosus, celiac disease

Clinical features

85% are women, usually ages 40 - 60
Symptoms include insidious onset of pruritis, malaise, dark urine, light stools, hepatomegaly, xanthomas, and xanthelasma
Can develop cirrhosis and die from liver failure
Some patients have overlap disease with autoimmune hepatitis; much more rarely, patients may have overlap with primary sclerosing cholangitis (PSC); in overlap, strict criteria for both diseases must be met (ACG Case Rep J 2018;5:e54)
Increased risk of hepatocellular carcinoma once cirrhotic but there does not appear to be significant increased risk of cholangiocarcinoma (unlike in primary sclerosing cholangitis)

Diagnosis

2 out of 3 of the following criteria are required:
- Serum alkaline phosphatase > 1.5 times the upper limit of normal, antimitochondrial antibody, liver sample showing nonsuppurative destructive cholangitis and destruction of interlobular bile ducts (Autoimmun Rev 2014;13:441)
- Other characteristic clinical features include disease-specific antinuclear antibodies (sp100 and gp210), elevated serum IgM, hypercholesterolemia, xanthomas, Sicca syndrome, pruritus, and fatigue (Autoimmun Rev 2014;13:441)
- Patients who appear to have primary biliary cholangitis except for negative antimitochondrial antibody are said to have AMA-negative primary biliary cholangitis, also called autoimmune cholangitis

Laboratory

Elevated serum alkaline phosphatase and IgM, AMA in 95%, elevated conjugated bilirubin (late)
M2 form of AMA, present in 90%, is against E2 subunit of pyruvate dehydrogenase complex

Radiology description

Parenchymal lace-like fibrosis and periportal halo sign on T2-weighted MRI in some patients (Eur J Radiol 2009;69:523)

Case reports

32 year old woman with hypokalemia (Medicine (Baltimore) 2018;97:e13172)
51 year old woman treated with sulfasalazine and abatacept (BMJ Case Rep 2018)
56 year old woman with rheumatoid arthritis (Cureus 2017;9:e1562)
62 year old man with dermatitis herpetiformis (Cureus 2017;9:e1247)
74 year old woman with multiple hepatic malignancies (World J Hepatol 2017;9:1378)

Treatment

Ursodeoxycholic acid and obeticholic acid improve liver function and symptoms but may not halt progression of disease
Liver transplant for advanced / cirrhotic cases; may eventually recur in the graft

Gross description

Hepatomegaly early; cirrhosis late

Gross images

Contributed by Raul Gonzalez, M.D.

Cirrhotic liver

Microscopic (histologic) description

Dense lymphocytic infiltrate in portal tracts with granulomatous destruction and loss of medium sized interlobular bile ducts, focal and variable within the liver
May involve sinusoids early
Periportal Mallory hyaline late, usually minimal neutrophils, variable portal eosinophils; resembles graft versus host disease and graft rejection; ductules derived from periportal hepatocytes are still present; prominent Ito cells with fat vacuoles
Key finding is the florid duct lesion: interlobular bile ducts (within small portal tracts) are destroyed by poorly formed portal epithelioid granulomas
Dense lymphocytic infiltrate in portal tracts can also be seen, mimicking hepatitis
Ductular reaction and duct injury early; duct loss and lobular cholestasis with feathery degeneration late
Lobules may show macrophage aggregates / small granulomas but typically not much of an inflammatory infiltrate
The above changes are patchy and may not be present in a given biopsy
Nodular regenerative hyperplasia may be seen in early disease (Gastroenterology 1992;102:1319)
Staging:
- Florid duct lesions or portal hepatitis
- Ductular reaction or periportal hepatitis
- Bridging/septal fibrosis or bridging necrosis
- Cirrhosis

Microscopic (histologic) images

Contributed by Raul Gonzalez, M.D.

Portal and duct inflammation

Florid duct lesion

Lobular cholestasis

Lobular macrophages

Ductular reaction

Duct loss

Positive stains

Note: None of these stains are routinely used for diagnosis
S100: highlights dendritic cells in the basement membrane in early stage disease (Am J Pathol 1989;134:741)
CD1a: highlights Langerhans cells in biliary epithelium (Am J Surg Pathol 2012;36:732)
Copper stains: positive within hepatocytes in all chronic cholestatic conditions, including PBC

Sample pathology report

Liver, biopsy:
- Biliary pattern injury with mild chronic portal inflammation, ductular reaction, and focal changes suggestive of florid duct lesion (see comment)
- Comment: The histologic findings, in addition to the patient’s reported history of antimitochondrial antibody, are consistent with primary biliary cholangitis. A trichrome stain shows minimal periportal fibrosis.

Differential diagnosis

Autoimmune cholangitis:
- Essentially the same diagnosis, except AMA is negative
Autoimmune hepatitis:
- More normal alkaline phosphatase, antismooth muscle antibody positive and AMA negative, elevated IgG rather than IgM, lobular inflammation
Secondary biliary cirrhosis:
- Cirrhotic liver in the setting of longstanding large duct injury
- No AMA or florid duct lesions
Primary sclerosing cholangitis:
- Minimal inflammation, classic imaging findings
Large duct obstruction:
- Clinical presentation often acute
- Cholestasis early in the disease process, rather than late
Drug induced liver injury:
- Can mimic; clinical correlation necessary

Additional references

Baillieres Best Pract Res Clin Gastroenterol 2000;14:601

Board review style question #1

Antimitochondrial antibody and florid duct lesions
Antineutrophil cytoplasmic antibody and onion skin fibrosis
Antinuclear antibody and ductular reaction
Antismooth muscle antibody and interface hepatitis

Board review style answer #1

A. Antimitochondrial antibody and florid duct lesions

Comment Here

Reference: Primary biliary cholangitis

Board review style question #2

Liver transplant
Low dose steroids
Sofosbuvir
Ursodeoxycholic acid

Board review style answer #2

D. Ursodeoxycholic acid. This is primary biliary cholangitis.

Comment Here

Reference: Primary biliary cholangitis

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