Primary Biliary Cholangitis - PBC | Choose the Right Test

Medical Experts

Contributors critically edit at least some content for accuracy and integrity, and approve any content they edit for publication.
Authors frame content, identify key sources of information, draft and/or critically edit and revise content to ensure medical accuracy and integrity, and review and approve content for publication.

Contributor

Nandakumar

Vijayalakshmi (Viji) Nandakumar, PhD, MS

Former Medical Director, Immunology, ARUP Laboratories

Contributor

Peterson

Lisa K. Peterson, PhD, D(ABMLI)

Associate Professor of Pathology (Clinical), University of Utah

Medical Director, Immunology, ARUP Laboratories

Primary biliary cholangitis (PBC), previously referred to as primary biliary cirrhosis, is an autoimmune liver disorder characterized by chronic, progressive cholestatic disease. If untreated, PBC leads to cirrhosis, or scarring of the entire liver, which can result in liver failure.¹

Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.

^{2

Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568-1594.}^{3

European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67(1):145-172.} The prevalence of PBC is estimated at 19-402 per million individuals.^{3

European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67(1):145-172.}^{4

Bowlus CL, Gershwin E. The diagnosis of primary biliary cirrhosis. Autoimmun Rev. 2014;13(5-Apr):441-444.} PBC is more common in women than in men,^{1

Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.}^{2

Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568-1594.}^{3

European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67(1):145-172.} and usually arises at 40-50 years of age. Symptoms of PBC may include chronic pruritus (itching), fatigue, sicca symptoms, abdominal pain, jaundice, and arthralgia.^{1

Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.}^{2

Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568-1594.}^{3

European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67(1):145-172.} PBC is thought to develop through a combination of genetic and environmental factors, including urinary tract infections, reproductive hormone replacement, nail polish use, and cigarette smoking.^{1

Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.} Additional risk factors include the presence of another autoimmune disorder (particularly celiac disease, systemic sclerosis, thyroid disease, and Sjögren syndrome^{2

Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568-1594.}^{3

European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67(1):145-172.}) and family history of PBC.^{1

Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.}^{2

Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568-1594.}^{3

European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67(1):145-172.}Laboratory tests in the workup of PBC include liver biochemistry tests (such as alkaline phosphatase [ALP] and aminotransferase tests) and tests for autoantibodies (including antimitochondrial M2 antibodies [AMAs] and antinuclear antibodies [ANAs] such as anti-sp100 and antiglycoprotein 210 [anti-gp210] antibodies). Liver biochemistry tests can be used for prognosis and for monitoring treatment response.^{1

Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.}^{2

Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568-1594.}^{3

European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67(1):145-172.}

Quick Answers for Clinicians

How are primary biliary cholangitis antibody serology results interpreted?

Antimitochondrial M2 antibodies (AMAs) are present in the serum of >90% of patients with primary biliary cholangitis (PBC), and antinuclear antibodies (ANAs) are often present.¹

Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.

Serum antibodies are detected via enzyme-linked immunosorbent assays (ELISAs) or other immunoassays.^{1

Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.} The diagnostic performance characteristics of these assays and results may not be commutable. Positive results for ANAs using solid-phase immunoassays (eg, ELISAs) are generally meaningless, as PBC-relevant ANA patterns (including nuclear dot, nuclear rim, centromere, and cytoplasmic patterns) can only be observed via immunofluorescence (IF) antibody assays. Immunoassays for detecting specific ANAs (eg, anti-sp100 and antiglycoprotein 210 [anti-gp210]) are important for confirmation.

When is it appropriate to perform a liver biopsy for suspected primary biliary cholangitis?

Although liver biopsy is no longer recommended for the majority of patients with primary biliary cholangitis (PBC),¹

Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.

^{2

Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568-1594.} specificity issues may arise with antimitochondrial M2 antibodies (AMAs) and antinuclear antibodies (ANAs). Thus, histology may be needed if liver biochemistry tests, autoantibody tests, and imaging fail to establish a diagnosis of PBC or are equivocal.^{3

European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67(1):145-172.} Histology is also useful to establish diagnosis in overlap syndromes, such as PBC/autoimmune hepatitis (PBC/AIH).^{2

Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568-1594.}

What are indications for liver transplantation in patients with primary biliary cholangitis?

Although earlier detection and intervention have reduced the need for liver transplantation in patients with primary biliary cholangitis (PBC),¹

Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.

the British Society of Gastroenterology (BSG) recommends consideration of liver transplantation in all patients with bilirubin >50 µmol/L or with pruritus that is refractory to all medical therapy.^{2

Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568-1594.}

Should nutritional status be assessed in patients with primary biliary cholangitis?

In patients with advanced primary biliary cholangitis (PBC), fat and fat-soluble vitamins (A, D, E, and K) may not be well absorbed. Laboratory testing for vitamin deficiency and supplementation should be considered.²

Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568-1594.

Indications for Testing

Laboratory testing for PBC is used to

Diagnose PBC in patients who present with symptoms (chronic pruritus, fatigue, sicca symptoms, and abdominal pain) or with evidence of cholestatic liver disease or jaundice without evidence of other causes
Establish prognosis in patients diagnosed with PBC
Monitor therapeutic response, disease progression, and development of comorbidities in patients diagnosed with PBC

Criteria for Diagnosis

Suspicion of PBC is increased in the setting of chronic cholestasis after exclusion of other liver disease. Guidelines recommend consideration of PBC in patients with otherwise unexplained elevated ALP and/or pruritus or fatigue.²

Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568-1594.

PBC may occur with autoimmune hepatitis (AIH). PBC/AIH overlap syndrome usually refers to AIH in a patient with a diagnosis of PBC.¹

Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.

Diagnosis of PBC or PBC/AIH overlap syndrome is based on cholestatic liver biochemistry, the presence of PBC-specific autoantibodies, and if needed, imaging, liver biopsy, or genetic testing.

Society-Recommended Diagnostic Criteria for PBC and PBC/AIH Overlap Syndrome
AASLD, 2018	BSG, 2018	EASL, 2017
Criteria for Diagnosis of PBC
At least 2 of the following: Biochemical evidence of cholestasis with elevation of ALP activity Presence of AMAs or other PBC-specific antibodies (anti-sp100, anti-gp210, antikelchlike 12, and/or antihexokinase 1) Histopathologic evidence of nonsuppurative cholangitis and destruction of small or medium bile ducts on liver biopsy	1 of the following: Presence of AMAs (titer >1:40) or PBC-specific ANAs in the context of otherwise unexplained cholestatic liver biochemistry (increased ALP or GGT) Histopathologic evidence on liver biopsy	1 of the following, in the appropriate clinical context: Elevated ALP and GGT and/or conjugated bilirubin, in conjunction with history, physical examination, and abdominal findings of focal lesions and dilated bile ducts AMA or PBC-specific ANA positivity in the context of clinical presentation Bile duct abnormalities on MRCP with or without EUS Abnormal findings (parenchymal damage or biliary lesions) on liver biopsy Positive genetic test results
Criteria for Diagnosis of PBC/AIH Overlap Syndrome
Confirmed PBC and at least 2 of the following: ALT activity >5 x ULN IgG ≥2 x ULN and/or SMA positivity Liver biopsy with moderate or severe interface hepatitis	Histopathologic evidence on liver biopsy	At least 2 of the following: ALP >2 x ULN or GGT >5 x ULN AMA titer >1:40 Florid bile duct lesions on liver biopsy And at least 2 of the following: ALT >5 x ULN IgG >2 x ULN or SMA positivity Liver biopsy with moderate or severe interface hepatitis
AASLD, American Association for the Study of Liver Diseases; ALT, alanine transaminase; BSG, British Society of Gastroenterology; EASL, European Association for the Study of the Liver; EUS, endoscopic ultrasound (abdominal); GGT, gamma-glutamyl transferase; IgG, immunoglobulin G; MRCP, magnetic resonance cholangiopancreatography; SMA, smooth muscle antibody; ULN, upper limit of normal Sources: AASLD, 2018¹ Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419. ; BSG, 2018^{2 Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568-1594.}; EASL, 2017^{3 European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67(1):145-172.}

Laboratory Testing

Diagnosis

Liver Biochemistry Tests

The majority of patients with PBC exhibit elevated ALP,¹

Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.

Autoantibody Tests

PBC is characterized by specific autoantibodies for mitochondrial, nuclear, and centromere antigens.¹

Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.

Antimitochondrial M2 Antibodies

AMAs are present in >90% of patients with PBC.¹

Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.

AMA testing is not useful in the absence of symptoms, as the frequency of AMAs in the general population is reported to be high (up to one per 1,000), but the frequency of PBC is much lower (19-402 per million individuals).^{3

European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67(1):145-172.}^{4

Bowlus CL, Gershwin E. The diagnosis of primary biliary cirrhosis. Autoimmun Rev. 2014;13(5-Apr):441-444.} Several methods are available to detect AMAs, including immunofluorescence (IF), immunoblotting, enzyme immunoassays, Luminex bead assays, and enzyme inhibition assays^{1

Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.}; these methods vary in their performance characteristics. AMA positivity is a defining serologic signature of PBC in the setting of chronic intrahepatic cholestasis.^{3

European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67(1):145-172.}

Antinuclear Antibodies and Centromere Antibodies

ANAs, particularly anti-gp210 and/or anti-sp100,¹

Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.

^{3

European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67(1):145-172.} but also antikelchlike 12 and antihexokinase 1,^{1

Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.} are present in approximately 30% of patients with PBC^{2

Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568-1594.}^{3

European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67(1):145-172.}; their presence may correlate with prognosis.^{1

Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.} Centromere antibodies are found in varying percentages in patients with PBC, with significant frequency in PBC/systemic sclerosis (PBC/SSc) overlap syndrome.^{5

Liberal R, Grant CR, Sakkas L, et al. Diagnostic and clinical significance of anti-centromere antibodies in primary biliary cirrhosis. Clin Res Hepatol Gastroenterol. 2013;37(6):572-585.} While ANAs may be detected by enzyme-linked immunosorbent assays (ELISAs) or other immunoassays, the IF method is the most suitable technique, as only specific ANA patterns (nuclear dot, nuclear rim, and cytoplasmic) are relevant to the diagnosis of PBC.^{2

Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568-1594.} Testing for anti-sp100 and anti-gp210 is useful for diagnostic confirmation.

Immunoglobulin Tests

Immunoglobulins are often increased in PBC, particularly IgM and IgG.²

Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568-1594.

^{3

European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67(1):145-172.} Serum bilirubin, globulin, and hyaluronic acid elevation in the context of a decreased serum albumin level and platelet count may indicate the development of cirrhosis and portal hypertension.^{1

Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.}

Other Serologic Tests

Serum cholesterol may be elevated in PBC.¹

Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.

^{3

European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67(1):145-172.} SMA is often elevated in AIH. If SMA is positive (>1:80) in conjunction with PBC, consider PBC/AIH overlap syndrome. Liver-kidney microsome-1 antibody testing can also be used in combination with SMA and ANA testing to diagnose AIH.^{6

Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries. Am J Gastroenterol. 2017;112(1):18-35.} In addition, hepatitis serologies may be useful to assess whether there is a viral cause of liver damage.^{6

Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries. Am J Gastroenterol. 2017;112(1):18-35.}

Genetic Tests

In cases in which a diagnosis of PBC cannot be established via serologic testing, imaging, or liver biopsy, but clinical suspicion persists, genetic testing may be performed for inherited cholestatic disorders. Variants occur most commonly in ATP8B1, ABCB11, and ABCB4 genes, although many others are being identified.³

European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67(1):145-172.

Other Tests

Imaging is largely used to exclude diagnoses of other biliary and infiltrative diseases in patients who present with symptoms suggestive of PBC.²

Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568-1594.

^{3

European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67(1):145-172.} Liver biopsy is not required for diagnosis in the majority of patients.^{1

Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.}^{2

Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568-1594.} However, biopsy may be required to diagnose genuinely antibody-negative disease or disease that cannot be detected via imaging,^{1

Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.}^{2

Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568-1594.}^{3

European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67(1):145-172.} or in patients with suspected concurrent AIH, nonalcoholic steatohepatitis, or other comorbidities.^{3

European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67(1):145-172.}

Prognosis

Several prognostic models exist to assess patients with PBC in terms of treatment response, survival, and the need for transplantation.¹

Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.

Recent Prognostic Models in PBC
	GLOBE	UK-PBC
Laboratory tests	Serum bilirubin Albumin ALP Platelet count (after 1 yr of therapy)	ALP Aminotransferases Serum bilirubin (after 1 yr of therapy) Albumin (baseline) Platelets (baseline)
Other factors	Age at start of therapy	None
Predictions	Transplantation-free survival	Risk of liver transplantation or liver-related death within 5, 10, or 15 yrs
Source: AASLD, 2018^{1 Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.}

Serum bilirubin level is the most heavily weighted factor in all PBC prognostic models and is the best predictor of survival.¹

Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.

^{3

European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67(1):145-172.} ALP is also an important parameter; in multiple models, elevated serum ALP contributes to a prediction of treatment failure.^{1

Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.}^{3

European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67(1):145-172.} In conjunction with baseline serum albumin, serum bilirubin measurements can be used to stratify patients into risk groups, depending on whether baseline and follow-up bilirubin measurements are both normal (low risk), both abnormal (high risk), or one is normal and the other abnormal (medium risk).^{3

European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67(1):145-172.}

The presence of ANAs may be predictive of poor prognosis.³

European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67(1):145-172.

Hyaluronic acid is also associated with outcomes.^{3

European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67(1):145-172.}

Monitoring

Various criteria may be used to assess the biochemical response to ursodeoxycholic acid (UDCA) therapy.¹

Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.

Noninvasive tests, including bilirubin, ALP, AST, albumin, and platelet count tests, can be used at baseline and for ongoing monitoring.^{3

European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67(1):145-172.} Transient elastography may also be used to assess response to treatment.^{3

European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67(1):145-172.} In patients with cirrhosis complications, persistent markers of severe disease, and/or severe medically resistant pruritus, consider evaluation for liver transplant.^{2

Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568-1594.}^{3

European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67(1):145-172.} Evaluation of biochemical response to UDCA is recommended 12 months after treatment initiation to determine whether second-line therapy (obeticholic acid) should be considered.^{1

Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.}^{2

Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568-1594.} Guidelines also recommend periodic monitoring of liver biochemistry and monitoring for related complications, per the table below.^{1

Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.}^{2

Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568-1594.}^{3

European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67(1):145-172.} Lifelong follow-up is recommended.^{2

Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568-1594.}

Recommended Laboratory Tests for Monitoring in PBC
Test^a	Patient Population	Recommended Frequency
Liver tests	All patients with PBC	Every 3-6 mos^{1 Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.}; annually^{2 Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568-1594.}
Thyroid stimulating hormone	All patients with PBC	Annually^{1 Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.}
Vitamins A, D, E, and prothrombin time	Patients with bilirubin >2.0 mg/dL	Annually^{1 Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.}
Repeated risk assessment	All patients with PBC	Every 3 yrs^{2 Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568-1594.}
^aBone mineral densitometry, upper endoscopy for varices, and abdominal ultrasound are also recommended¹ Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419. Sources: AASLD, 2018¹ Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419. ; BSG, 2018^{2 Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568-1594.}

ARUP Laboratory Tests

Liver Biochemistry Tests

0020416

Hepatic Function Panel 0020416

Method

Quantitative Enzymatic Assay/Quantitative Spectrophotometry

Components: albumin, ALP, AST, ALT, and bilirubin, protein

0020005

Alkaline Phosphatase, Serum or Plasma 0020005

Method

Quantitative Enzymatic Assay

0021020

Alkaline Phosphatase Isoenzymes, Serum or Plasma 0021020

Method

Quantitative Heat Inactivation/Enzymatic Assay

0020008

Alanine Aminotransferase, Serum or Plasma 0020008

Method

Quantitative Enzymatic Assay

0020007

Aspartate Aminotransferase, Serum or Plasma 0020007

Method

Quantitative Enzymatic Assay

0020009

Gamma Glutamyl Transferase, Serum or Plasma 0020009

Method

Quantitative Enzymatic Assay

0020426

Bilirubin, Direct and Total, Serum or Plasma 0020426

Method

Quantitative Spectrophotometry

0050024

Albumin, Body Fluid 0050024

Method

Quantitative Immunoturbidimetry/Quantitative Spectrophotometry

0030224

Prothrombin Time/International Normalized Ratio 0030224

Method

Electromagnetic Mechanical Clot Detection

Autoantibody Tests

3002479

Autoimmune Liver Disease Reflexive Panel 3002479

Method

Semi-Quantitative Enzyme-Linked Immunosorbent Assay (ELISA)/Semi-Quantitative Indirect Fluorescent Antibody (IFA)

Components: AMA, IgG; liver-kidney microsome-1 antibody, IgG; F-actin (smooth muscle) antibody, IgG; SMA, IgG titer; soluble liver antigen antibody, IgG; ANA with HEp-2 substrate, IgG

3002480

Primary Biliary Cholangitis Panel 3002480

Method

Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody

Components: AMA, IgG; ANA, IgG; anti-gp210 antibody, IgG; anti-sp100 antibody, IgG

0050065

Mitochondrial M2 Antibody, IgG (ELISA) 0050065

Method

Semi-Quantitative Enzyme-Linked Immunosorbent Assay (ELISA)

3000601

Antinuclear Antibody (ANA) with HEp-2 Substrate, IgG by IFA with Reflex by Pattern 3000601

Method

Semi-Quantitative Indirect Fluorescent Antibody/Qualitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Multiplex Bead Assay/Qualitative Immunoblot

0050714

Centromere Antibody, IgG 0050714

Method

Semi-Quantitative Multiplex Bead Assay

3002482

Anti-sp100 and anti-gp210 Antibodies, IgG 3002482

Method

Semi-Quantitative Enzyme-Linked Immunosorbent Assay

3002477

Anti-gp210 Antibody, IgG 3002477

Method

Semi-Quantitative Enzyme-Linked Immunosorbent Assay