Gilead Sciences

This information is intended for US healthcare professionals.

Gilead Sciences

This information is intended for US healthcare professionals.

  2. Primary Biliary Cholangitis
  3. PBC Diagnosis

Diagnosis of Primary Biliary Cholangitis (PBC)

Diagnosing PBC involves the utilization of appropriate tests including serum markers and histological evidence.1

PBC Diagnostic Criteria1

Per the AASLD guidelines, PBC diagnosis requires 2 of 3 criteria to be met:

Most patients with PBC have abnormal liver tests indicating elevation of ALP, but also mild elevations of ALT and AST activity, and increased levels of immunoglobulins.

In patients without cirrhosis:

  • The degree of elevation in ALP is strongly related to the severity of ductopenia and inflammation
  • The increase in aminotransferase activity and IgG levels reflects the degree of periportal and lobular necrosis and inflammation
  • Hyperbilirubinemia reflects the severity of ductopenia and biliary piecemeal necrosis

AMA is found in 95% of PBC patients. The presence or absence of AMA, rather than the magnitude of antibody level, is most important in diagnosis.

It’s important to note that nearly all AMA-negative PBC patients have PBC-specific antinuclear antibodies, including sp100 and glycoprotein 210, which are present in over 30% of PBC patients negative for AMA by indirect immunofluorescence.

Histologic lesions are divided into 4 stages:

  • Stage 1: Portal inflammation with or without florid bile duct lesions
  • Stage 2: Gradual increase of periportal lesions extending into the hepatic parenchyma, characterized by cellular necrosis/apoptosis, separation of hepatocytes by inflammatory cells, and macrophages
  • Stage 3: Distortion of the hepatic architecture due to fibrosis
  • Stage 4: Cirrhosis with the existence of regenerative nodules

Approaches for Assessing PBC Stage and Fibrosis

Fibrosis surveillance plays an important role for patients at all stages of PBC, and patients should have staging done at baseline.2 In the majority of patients, noninvasive approaches including imaging and serum tests are preferred for assessing PBC and fibrosis stage.1-4

imaging-icon_mob
Imaging
  • LSM by TE/FibroScan2,3,a
  • MRE2,4
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Serum Tests
  • Enhanced Liver Fibrosis (ELF)™ test5
  • AST/platelet ratio index2
  • Bilirubin and ALP2,b,c
  • GLOBE‑PBC score2,6
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Liver Biopsy
  • Liver biopsy is no longer required for staging in most patients1,d

AASLD, American Association for the Study of Liver Diseases; ALP, alkaline phosphatase; AMA, antimitochondrial antibody; AST, aspartate aminotransferase; Ig, immunoglobulin; LSM, liver stiffness measurement; MRE, magnetic resonance elastography; TE, transient elastography; VCTE, vibration-controlled transient elastography.

aImaging to predict clinical outcomes or decompensation includes LSM by TE ≥10 kPa, VCTE ≥10 kPa, and MRE ≥4.3 kPa.2

bBilirubin and ALP are recommended to be monitored at baseline and as a part of routine testing.2

cBilirubin levels ≤0.6x ULN or normal ALP may have important prognostic implications regarding liver transplant and survival at one year.2

dLiver biopsy may be occasionally recommended in AMA-negative patients and to exclude other concomitant diseases such as autoimmune hepatitis and nonalcoholic steatohepatitis.1

References:

  1. Lindor KD, Bowlus CL, Boyer J, Levy C, Mayo M. Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419. doi:10.1002/hep.30145
  2. Kowdley KV, Bowlus CL, Levy C, et al. Application of the latest advances in evidence-based medicine in primary biliary cholangitis. Am J Gastroenterol. 2023;118(2):232-242. doi:10.14309/ajg.0000000000002070
  3. Shen M, Lee A, Lefkowitch JH, Worman HJ. Vibration-controlled transient elastography for assessment of liver fibrosis at a USA academic medical center. J Clin Transl Hepatol. 2022;10(2):197-206. doi:10.14218/JCTH.2021.00188
  4. Venkatesh SK, Wells ML, Miller FH, et al. Magnetic resonance elastography: beyond liver fibrosis-a case-based pictorial review. Abdom Radiol (NY). 2018;43(7):1590-1611. doi:10.1007/s00261-017-1383-1
  5. Petersen JR, Stevenson HL, Kasturi KS, et al. Evaluation of the aspartate aminotransferase/platelet ratio index and enhanced liver fibrosis tests to detect significant fibrosis due to chronic hepatitis C. J Clin Gastroenterol. 2014;48(4):370-376. doi:10.1097/MCG.0b013e3182a87e78
  6. Harms MH, Hirschfield GM, Floreani A, et al. Obeticholic acid is associated with improvements in AST-to-platelet ratio index and GLOBE score in patients with primary biliary cholangitis. JHEP Rep. 2020;3(1):100191. doi:10.1016/j.jhepr.2020.100191