Diagnosis guide for clinicians

Primary biliary cholangitis: when to suspect it and what to test

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Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease that, untreated, will culminate in end-stage biliary cirrhosis, according to EASL.Source EASL 2017 guideline

AASLD says to suspect it in chronic cholestasis once other causes are excluded, particularly in a middle-aged woman with an unexplained rise in alkaline phosphatase (ALP).

Source AASLD 2018 guidance

In a study of 4 Spanish hospitals, 100 of 697 patients who met the criteria (14.3%) had no diagnosis, follow-up or treatment on record.

Source Olveira-Martín 2021 lost patients study

2 of 3AASLD criteria: cholestatic ALP, AMA or sp100 or gp210 antibodies, and compatible bile duct histologyAASLD 2018 guidance

95%Share of patients with antimitochondrial antibodies (AMA), per AASLDAASLD 2018 guidance

Up to 1 in 800Prevalence the BSG reports in women over age 45; rates run about 10 times higher in women than in menBSG/UK-PBC 2018 guideline

1 in 6People with AMA and a normal ALP who developed PBC within 5 years in a French studyDahlqvist 2017 AMA study

K74.3ICD-10-CM code, Primary biliary cirrhosis (the code title still uses the older name)NLM ICD-10-CM lookup

Orphanet recordORPHA:186 ↗

Inheritance

Multigenic/multifactorial, Unknown

Age of onset

Adolescent, Adult, Elderly

Prevalence

1 to 5 per 10,000 point prevalence, Worldwide
1 to 9 per 100,000 annual incidence, Worldwide
1 to 9 per 100,000 annual incidence, United States

Also called

Hanot syndrome, PBC, Primary biliary cirrhosis

Live from Orphanet (INSERM) via Orphadata, licensed CC BY 4.0, data version 2026-06-23.

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Patterns to test Red flags Often mistaken for What to test Family screening ICD-10 codes Once confirmed For the patient

Patterns that should prompt a test for Primary biliary cholangitis (PBC)

Each sign below is common on its own, which is why Primary biliary cholangitis (PBC) is missed. Published studies describe these combinations as the picture to act on. Rows are ordered from the highest published figure to the lowest, within each kind of measure.

Where testing finds it

Share of each screened or biopsied group found to have Primary biliary cholangitis (PBC), from the cited studies. A bar spans the lowest to the highest published figure.

1
AMA positive+Alkaline phosphatase above 1.5 times the upper limit of normal+AST under 5 times the upper limit of normal
156 AMA-positive patients with a liver biopsy, drawn from 3198 people tested for AMA in 1999 and 2000
This profile gave a 98.2% positive predictive value for PBC on biopsy, and biopsy established PBC in 131 of 156 overall (Zein 2003).Zein 2003 biopsy study
98.2%
2
AMA or PBC-specific ANA positive+Normal alkaline phosphatase+Liver biopsy performed
67 biopsied patients among 169 consecutive AMA-positive outpatients with normal ALP, and 30 biopsied patients with AMA or PBC-specific ANA and normal ALP in the Swiss PBC Cohort Study
Biopsy was diagnostic of PBC in 55 of 67 (82.1%) (Sun 2019), and typical for, consistent with or suggestive of PBC in 24 of 30 (80%) (Terziroli Beretta-Piccoli 2021).Sun 2019 normal ALP biopsy study
80% to 82.1%
3
AMA titer of 1:80 or higher in the laboratory record
1372 patients with AMA titers of 1:80 or higher in the databases of 4 Spanish reference hospitals, 2010 to 2019
Of the 1372, 697 (50.8%) met criteria for PBC, and 100 of those 697 (14.3%) had no diagnosis, follow-up or treatment on record (Olveira-Martín 2021).Olveira-Martín 2021 lost patients study
50.8%
4
Alkaline phosphatase above the reference range+No liver disease or other cause of cholestasis found+AMA tested
27 primary care patients with suspected PBC among 20,480 adults of 14 general practitioners in Brescia, Italy, of whom 9 had AMA tested
Of the 9 patients tested for AMA, 3 were new PBC cases, which is 33% of those tested; the other 18 suspected patients were not tested (Donato 2024).Donato 2024 primary care study
33%
5
First-degree relative with PBC+AMA positive
463 first-degree relatives in the Mayo Clinic PBC Genetic Epidemiology Registry, 40 of them AMA positive
PBC was diagnosed in 24% of AMA-positive relatives against 0.7% of AMA-negative relatives, and in 3% overall (Gulamhusein 2016).Gulamhusein 2016 relatives study
24%
6
AMA positive+Normal alkaline phosphatase+No cirrhosis
AMA-positive patients without established PBC, 229 in all, found through 63 French immunology laboratories and followed for up to 7 years
Among those with normal ALP and no cirrhosis, the 5-year incidence of PBC was 16%, or about 1 in 6 (Dahlqvist 2017).Dahlqvist 2017 AMA study
16%
7
Primary Sjögren syndrome+Chronic cholestatic liver tests
115 patients with primary Sjögren syndrome and no history of liver disease, followed in an outpatient clinic from 1987 to 2020
PBC was found in 6 of 115 (5.2%), all from the 20 patients with chronic cholestatic liver biochemistry (Santos 2022).Santos 2022 Sjögren cohort
5.2%

How often diagnosed patients show it

Share of patients already diagnosed who had the finding, in the group named on each row. Groups differ by age and type, so read each row with its group.

1
Itch at some point in the illness+Cholestatic liver tests
2194 patients with PBC in the UK-PBC cohort, surveyed by questionnaire
Itch had been experienced by 1613 of 2194 (73.5%), and 34.5% reported persistent itch (Hegade 2019).UK-PBC pruritus study
73.5%
2
Fatigue+Unexplained raised alkaline phosphatase
Patients with PBC in the studies cited by AASLD's 2018 practice guidance
Fatigue has been found in 50% to 78% of patients with PBC, and AASLD calls it the most common symptom.AASLD 2018 guidance
50% to 78%
3
Dry eyes or dry mouth from Sjögren syndrome+Cholestatic liver tests
Adults with PBC across the 17 studies in a systematic review and meta-analysis
Sjögren syndrome had a pooled prevalence of 35% in PBC, ranging from 3.5% to 73% between studies (Deng 2022).Deng 2022 Sjögren meta-analysis
35%
4
Another autoimmune disease, most often thyroid disease or Sjögren syndrome+Raised alkaline phosphatase
1554 patients with PBC from 20 international centers, and 4351 people in the nationwide Dutch PBC Cohort Study
Extrahepatic autoimmune disease was diagnosed in 28.3% (Efe 2021) and 27.3% (Weijsters 2026), present at baseline in 80.7% of the Dutch cases.Dutch PBC Cohort 2026
27.3% to 28.3%
5
AMA negative+PBC-specific antinuclear antibodies such as sp100 or gp210+Cholestatic liver tests
400 patients with AMA-negative PBC and 6217 controls across 11 studies in a meta-analysis
Antinuclear antibodies were found in 27% of AMA-negative PBC (pooled sensitivity), with 98% specificity (Zhang 2019).Zhang 2019 ANA meta-analysis
27%

Also described, without a comparable figure

Raised alkaline phosphatase + Gallstones on ultrasound + Woman in the typical age range for PBC: No frequency for this combination was found; BSG names over-reading gallstones, without considering PBC, as a potential reason for delayed diagnosis.BSG/UK-PBC 2018 guideline
PBC-related autoantibodies on a panel sent for another autoimmune disease + Liver tests not yet measured: No frequency for this combination was found; BSG says the possibility of undiagnosed PBC must always be considered and liver function tests measured.BSG/UK-PBC 2018 guideline
Cholestasis during pregnancy + Liver tests that fail to normalize after delivery: No frequency for this combination was found; EASL notes pregnancy may be the reason for diagnosis when obstetric cholestasis fails to resolve.EASL 2017 guideline

These figures describe published study groups. They are not the chance that any one patient has Primary biliary cholangitis (PBC), and bars whose ranges overlap are not in a settled order.

Red flags for Primary biliary cholangitis (PBC)

What the cited sources describe, grouped by life stage and organ. Each line links to its source.

Routine blood tests

BSG says PBC should always be considered in patients with an otherwise unexplained, repeated rise in ALP, and also in gamma-glutamyl transferase (GGT).BSG/UK-PBC 2018 guideline
EASL notes that chronic cholestatic liver diseases often run without symptoms for months or years and can be identified by a raised serum ALP.EASL 2017 guideline
EASL counts cholestasis as chronic once it lasts longer than 6 months, and says a raised GGT or conjugated bilirubin supports a liver origin for ALP.EASL 2017 guideline
Most patients also have mild aminotransferase elevations and raised immunoglobulins, mainly IgM, and serum cholesterol is often high, according to AASLD.AASLD 2018 guidance
In an Intercept-funded study of 1335 patients in a US consortium, ALP was elevated for 2 to 5 years before diagnosis in every racial and ethnic group studied.Caines 2025 pre-diagnosis ALP study
In an Italian primary care study of 20,480 adults, 27 patients had a raised ALP with no cause found, and only 9 of them had AMA tested.Donato 2024 primary care study

Fatigue and itch

AASLD calls fatigue the most common symptom, found in 50% to 78% of patients, and describes it as relatively constant or slowly progressive.AASLD 2018 guidance
Itch may be local or diffuse, is worse in the evening, and is often set off by contact with clothing, heat or pregnancy, per AASLD.AASLD 2018 guidance
In the UK-PBC cohort, 1613 of 2194 patients (73.5%) had experienced itch at some point, and 34.5% reported persistent itch.UK-PBC pruritus study
EASL says many patients never have itch, so its absence should not be considered when diagnosing the disease.EASL 2017 guideline
BSG stresses that the severity of fatigue and itch does not correlate with the stage of liver disease, and itch can improve as disease worsens.BSG/UK-PBC 2018 guideline
Right upper quadrant pain, nonspecific and not progressive, is found in about 17% of patients, according to AASLD.AASLD 2018 guidance
BSG lists cholestasis or itch during an earlier pregnancy as associated with a later diagnosis of PBC.BSG/UK-PBC 2018 guideline

Skin, eyes and mouth

AASLD says the examination is usually normal in early disease, though excoriations, xanthelasma, xanthoma and hepatomegaly may be seen.AASLD 2018 guidance
EASL describes scratch lesions particularly on the arms and legs, and itch triggered or worsened by warmth at night.EASL 2017 guideline
Dry eyes and dry mouth are frequent; BSG says most patients have sicca symptoms without primary Sjögren syndrome and that clinicians should ask about them.BSG/UK-PBC 2018 guideline
Jaundice is a late finding in patients with advanced liver disease, according to AASLD.AASLD 2018 guidance

Other autoimmune disease

A 20-center international study of 1554 patients found extrahepatic autoimmune disease in 28.3%, led by autoimmune thyroid disease (10.6%) and Sjögren disease (8.3%).Efe 2021 autoimmune disease cohort
In a Dutch nationwide cohort of 4351 people with PBC, 27.3% had another autoimmune disease, and it was already present at baseline in 80.7% of them.Dutch PBC Cohort 2026
A meta-analysis of 17 studies put the pooled prevalence of Sjögren syndrome in PBC at 35%, with single studies ranging from 3.5% to 73%.Deng 2022 Sjögren meta-analysis
In a clinic cohort of 115 patients with primary Sjögren syndrome and no known liver disease, 6 (5.2%) had PBC, all among the 20 with chronic cholestatic liver tests.Santos 2022 Sjögren cohort
BSG reports Raynaud phenomenon in up to one quarter of patients and limited scleroderma (CREST syndrome) in about 8%.BSG/UK-PBC 2018 guideline
When PBC-related autoantibodies turn up on a panel sent for another autoimmune disease, BSG says undiagnosed PBC must always be considered and liver tests measured.BSG/UK-PBC 2018 guideline
In a study built from local AMA records, 23 of 148 patients meeting PBC criteria were unknown to hepatology, most followed by specialties other than gastroenterology.Garrido 2021 undiagnosed PBC study

Who is affected, and family

Rates are about 10 times higher in women than in men, and BSG gives the median age at diagnosis as 65 years.BSG/UK-PBC 2018 guideline
EASL says male sex is associated with later diagnosis and more advanced disease at presentation.EASL 2017 guideline
Patients who present before age 45 are often symptomatic and less likely to respond well to ursodeoxycholic acid, per EASL.EASL 2017 guideline
BSG reports a sibling relative risk of 10, rising to 35 for the daughters of mothers with PBC.BSG/UK-PBC 2018 guideline
Case-control studies have confirmed cigarette smoking and recurrent urinary tract infections as strongly associated with PBC, according to BSG.BSG/UK-PBC 2018 guideline

Late presentation

Among US veterans in a Gilead-funded study, 10.7% to 26.4% already had cirrhosis when PBC was diagnosed, depending on the case definition used.Wong 2026 veterans study
BSG notes that occasional patients still present with very advanced disease at the point of needing liver transplantation.BSG/UK-PBC 2018 guideline

Primary biliary cholangitis (PBC) is often mistaken for

Diagnoses patients commonly carry first, and why the sources say they are confused.

First diagnosis	Why it is confused
Gallstones	Gallstones are frequent and usually silent in PBC, and BSG names over-reading them in the typical PBC demographic as a potential reason for delayed diagnosis.BSG/UK-PBC 2018 guideline
Fatty liver disease	BSG notes that a rise in ALP alone can also be found in nonalcoholic fatty liver disease, and that biopsy may be needed to identify the dominant injury.BSG/UK-PBC 2018 guideline
Bone disease or vitamin D deficiency	ALP also comes from bone, intestine and placenta, so EASL lists Paget disease, vitamin D deficiency and pregnancy among other causes of a raised level.EASL 2017 guideline
Drug-induced cholestasis	About 30% of drug-induced liver injury shows a cholestatic enzyme pattern, and EASL says the drug history should include herbal preparations and anabolic steroids.EASL 2017 guideline
Hypothyroidism, depression, anemia or a sleep disorder	AASLD says fatigue in PBC may be multifactorial and lists these as other causes to consider.AASLD 2018 guidance
Itch of unknown cause or a primary skin condition	AASLD describes itch that is local or diffuse, and says the physical examination is usually normal in early-stage disease.AASLD 2018 guidance
Intrahepatic cholestasis of pregnancy	EASL notes that pregnancy may be the reason for diagnosis when obstetric cholestasis fails to resolve.EASL 2017 guideline
Autoimmune hepatitis	Antinuclear and anti-smooth muscle antibodies occur in nearly half of patients, and AASLD says mild interface hepatitis is a common feature of PBC itself.AASLD 2018 guidance
Small duct primary sclerosing cholangitis	BSG calls small duct primary sclerosing cholangitis the chief differential diagnosis when autoantibodies are negative.BSG/UK-PBC 2018 guideline
Sarcoidosis	AASLD lists sarcoidosis in the differential diagnosis, alongside a cholestatic drug reaction, biliary obstruction, autoimmune hepatitis and primary sclerosing cholangitis.AASLD 2018 guidance
Sjögren syndrome or thyroid disease alone	Extrahepatic autoimmune disease was already present at baseline in 80.7% of affected patients in the Dutch cohort, whose authors note symptoms may come from either condition.Dutch PBC Cohort 2026
Hyperlipidemia	Serum cholesterol is often elevated in PBC as in other cholestatic diseases, according to AASLD.AASLD 2018 guidance

Codes patients often carry before this diagnosis

For spotting the pattern in a problem list or registry. Descriptions are checked daily against NLM's ICD-10-CM service; this is not coding advice.

Abnormal levels of other serum enzymes, or abnormal results of liver function studies R74.8, R94.5

BSG says PBC should always be considered in otherwise unexplained, repeated elevation of ALP or GGT.BSG/UK-PBC 2018 guideline

Cholestatic pruritus, or pruritus, unspecified L29.81, L29.9

In the UK-PBC cohort, 73.5% of patients had experienced itch at some point in their disease.UK-PBC pruritus study

Other fatigue, or chronic fatigue, unspecified R53.83, R53.82

AASLD calls fatigue the most common symptom of PBC, found in 50% to 78% of patients.AASLD 2018 guidance

Sjogren syndrome M35.00, M35.01

A meta-analysis put the pooled prevalence of Sjögren syndrome in PBC at 35%.Deng 2022 Sjögren meta-analysis

Autoimmune thyroiditis, or hypothyroidism, unspecified E06.3, E03.9

Autoimmune thyroid disease was the most common extrahepatic autoimmune disease in a 1554-patient international cohort.Efe 2021 autoimmune disease cohort

CR(E)ST syndrome, or Raynaud's syndrome without gangrene M34.1, I73.00

BSG reports Raynaud phenomenon in up to one quarter of patients and limited scleroderma in about 8%.BSG/UK-PBC 2018 guideline

Calculus of gallbladder without cholecystitis without obstruction K80.20

BSG names over-reading gallstones in the typical PBC demographic as a potential reason for delayed diagnosis.BSG/UK-PBC 2018 guideline

Fatty (change of) liver, not elsewhere classified K76.0

BSG notes that a rise in ALP alone can also be found in fatty liver disease, alongside incidental AMA.BSG/UK-PBC 2018 guideline

Autoimmune hepatitis K75.4

AASLD says antinuclear antibody and mild interface hepatitis are common features of PBC and should not be labeled overlap.AASLD 2018 guidance

Pure hypercholesterolemia, unspecified, or hyperlipidemia, unspecified E78.00, E78.5

Serum cholesterol is often elevated in PBC, as in other cholestatic diseases.AASLD 2018 guidance

Testing for Primary biliary cholangitis (PBC), step by step

The testing order the cited guidance describes, by who it applies to. It summarizes published guidance and is not a plan for any one patient.

Anyone with liver tests that suggest cholestasis

History and examination
EASL recommends a detailed history and examination. It says the drug history should cover prescribed medicines, herbal preparations, anabolic steroids and alcohol.EASL 2017 guideline

Anyone with a raised ALP

Confirm the ALP is from the liver and persistent
EASL says a liver origin is usually supported by a raised GGT or conjugated bilirubin. It treats cholestasis lasting longer than 6 months as chronic.EASL 2017 guideline

Anyone with cholestatic liver tests

Abdominal ultrasound
EASL recommends ultrasound as the first imaging test, to separate intrahepatic from extrahepatic cholestasis. BSG recommends a baseline ultrasound for all patients with suspected PBC.EASL 2017 guideline

Anyone with persistently raised ALP or GGT and no other cause

AMA and antinuclear antibodies
BSG recommends checking antimitochondrial (AMA) and antinuclear (ANA) reactivity in these patients. EASL recommends screening for AMA and PBC-specific ANA in all patients with unexplained cholestasis.BSG/UK-PBC 2018 guideline

Anyone with cholestatic liver tests and autoantibody results

Apply the diagnostic criteria
AASLD says PBC can be diagnosed when 2 of 3 criteria are met. The criteria are ALP elevation, AMA or sp100 or gp210 antibodies if AMA is negative, and histology showing nonsuppurative destructive cholangitis.AASLD 2018 guidance

Adults with cholestasis and no likelihood of systemic disease

The EASL and BSG wording
EASL says the diagnosis can be made on a raised ALP plus AMA at a titer above 1 in 40. BSG calls AMA above 1 in 40, with cholestatic liver tests and no alternative explanation, usually sufficient.BSG/UK-PBC 2018 guideline

AMA-negative patients with cholestasis

PBC-specific antinuclear antibodies
EASL accepts nuclear dot or perinuclear rim immunofluorescence, or sp100 or gp210 results, in the correct context. The 2026 AGA and AASLD guideline includes a recommendation on these antibodies in AMA-negative suspected PBC.EASL 2017 guideline

Patients whose other features are atypical

Immunoglobulins
BSG says a polyclonal rise in IgM is characteristic of PBC. It is not part of standard diagnostic criteria but can help when other features are atypical.BSG/UK-PBC 2018 guideline

Patients with unexplained cholestasis, especially if antibodies are negative

MRCP
EASL recommends magnetic resonance cholangiopancreatography (MRCP) in unexplained cholestasis. BSG says excluding primary sclerosing cholangitis by MRCP is warranted in seronegative patients.EASL 2017 guideline

AMA-positive patients with a cholestatic profile

When liver biopsy is not needed
BSG says biopsy is not recommended when autoantibodies and cholestatic liver tests are clear cut. AASLD questions its role when ALP is at least 1.5 times normal and AST is under 5 times normal.BSG/UK-PBC 2018 guideline
The study behind that threshold
Zein and colleagues studied 156 AMA-positive patients with biopsies. ALP above 1.5 times and AST under 5 times the upper limit gave a 98.2% positive predictive value for PBC.Zein 2003 biopsy study

Patients without PBC-specific antibodies, or with suspected coexisting disease

When liver biopsy is needed
EASL recommends against biopsy unless PBC-specific antibodies are absent, autoimmune hepatitis or steatohepatitis is suspected, or other comorbidities are present. BSG says confirming PBC without diagnostic autoantibodies requires a biopsy.EASL 2017 guideline

PBC patients with ALT more than 5 times the upper limit of normal

Biopsy for possible autoimmune hepatitis
AASLD says biopsy should be considered in these patients to rule out concomitant autoimmune hepatitis or other liver disease. EASL calls biopsy mandatory to confirm autoimmune hepatitis features.AASLD 2018 guidance

PBC patients with features of autoimmune hepatitis

Paris criteria for overlap
AASLD describes the Paris criteria as 2 of 3 features. They are ALT above 5 times the upper limit, IgG at least 2 times the upper limit or anti-smooth muscle antibody, and moderate or severe interface hepatitis.AASLD 2018 guidance

People with AMA but a normal ALP

AMA positive with normal liver tests
EASL says AMA alone is not sufficient to diagnose PBC and recommends annual biochemical reassessment. AASLD suggests liver tests every 2 to 3 years until age 65, noting there are no data.EASL 2017 guideline

Patients newly diagnosed with PBC

Associated autoimmune conditions
BSG suggests it is reasonable to screen all patients at baseline for celiac disease, thyroid disease and Sjögren syndrome. AASLD says thyroid status should be monitored annually.BSG/UK-PBC 2018 guideline

Patients with ongoing unexplained cholestasis, where clinically appropriate

Genetic tests for inherited cholestasis
EASL recommends considering genetic tests for inherited cholestatic syndromes in such patients. It names ATP8B1, ABCB11 and ABCB4 as the most studied transporter genes.EASL 2017 guideline

Where testing goes wrong

A positive AMA alone does not make the diagnosis; EASL says AMA reactivity is sufficient only when combined with abnormal serum liver tests.EASL 2017 guideline
EASL puts AMA positivity in the population at up to 1 in 1000, above its PBC prevalence of up to 0.4 in 1000, and says testing should be targeted.EASL 2017 guideline
BSG cites blood donor and population studies with low-titer AMA and normal liver tests in about 0.5% of people, a higher figure than EASL gives.BSG/UK-PBC 2018 guideline
In a French study, nearly half of newly detected AMAs did not lead to a PBC diagnosis, while PBC went unrecognized in 13% of the nonestablished group.Dahlqvist 2017 AMA study
BSG warns of false positive low-titer AMA in inflammatory conditions, in particular fatty liver disease, where low-level ALP rises are not infrequent.BSG/UK-PBC 2018 guideline
In 155 patients with PBC-specific antibodies and raised ALP or GGT from other diseases, treating the other cause improved the enzymes in 85.1% of those followed.Zeng 2025 antibody-positive non-PBC study
AMA is absent, or present only in low titer (1 in 80 or less) by immunofluorescence, in about 5% to 10% of patients, according to AASLD.AASLD 2018 guidance
AASLD calls immunofluorescence the least sensitive AMA method; over 15% of sera negative by it react to MIT3, a mix of 3 mitochondrial antigens.AASLD 2018 guidance
In AMA-negative PBC, a meta-analysis of 11 studies found pooled sensitivity of 23% for anti-gp210 and 25% for anti-sp100, with specificity of 99% and 97%.Zhang 2019 ANA meta-analysis
In an Intercept-funded US consortium study, Black patients were less likely to be AMA positive than non-Hispanic white patients (odds ratio 0.50).Caines 2025 pre-diagnosis ALP study
A normal ALP does not rule out bile duct injury: biopsy showed cholangitis diagnostic of PBC in 55 of 67 AMA-positive patients with normal ALP.Sun 2019 normal ALP biopsy study
The Swiss PBC Cohort reported histology typical for, consistent with or suggestive of PBC in 24 of 30 antibody-positive patients with normal ALP.Swiss PBC Cohort 2021
BSG, by contrast, recommends neither biopsy nor ursodeoxycholic acid for patients with AMA and normal liver tests, citing their benign prognosis.BSG/UK-PBC 2018 guideline
Biopsy can mislead; BSG says the yield for diagnostic lesions falls below 50% in early disease and that liver involvement can be highly patchy.BSG/UK-PBC 2018 guideline
AASLD says overlap should not be diagnosed from antinuclear antibody and mild interface hepatitis alone, since these are common features of PBC.AASLD 2018 guidance
Published rates of overlap vary with the definition: Paris criteria were met in 1% to 14.2% of patients per AASLD, while EASL cites features in 8% to 10%.AASLD 2018 guidance
BSG adds that true overlap by robust criteria is uncommon, under 2% of Caucasian patients, and that the IAIHG does not recommend its autoimmune hepatitis score for overlap.BSG/UK-PBC 2018 guideline
AMA titer above the diagnostic threshold carries no prognostic meaning, and BSG does not recommend repeat measurement once the diagnosis is clear.BSG/UK-PBC 2018 guideline
EASL cautions that AMA may have limited specificity in acute hepatic injury, and that some hematological disorders and granulomatous hepatitis show incidental reactivity.EASL 2017 guideline
The 2026 AGA and AASLD guideline rates the certainty of evidence behind its 6 recommendations as moderate to very low.AGA/AASLD 2026 guideline

Where to test

NIH Genetic Testing Registry: primary biliary cholangitis: PBC is diagnosed with liver tests and autoantibodies, not a genetic test, and NCBI E-utilities returned no registered tests for this condition on November 11, 2026. NIH does not independently verify submissions or endorse any laboratory.NIH GTR
AMA and PBC-specific ANA through clinical laboratories: BSG says the choice between immunofluorescence and ELISA rests largely on local experience and availability, with no clear evidence that either is superior.BSG/UK-PBC 2018 guideline
Liver biopsy with expert pathology review: AASLD says at least 10 to 15 portal tracts should be present and multiple sections reviewed to appreciate or rule out cholangitis and ductopenia.AASLD 2018 guidance
NIH's Genetic Testing Registry listed 0 tests for a search of “Primary biliary cholangitis (PBC)” on November 12, 2026. NIH does not endorse or verify the labs it lists.

Family screening and referral

Who else in the family

AASLD says family members are at increased risk, particularly female first-degree relatives, including sisters and daughters.AASLD 2018 guidance
The same guidance says the value of screening relatives is not firmly established, yet screening is usually recommended for female first-degree relatives from age 30.AASLD 2018 guidance
AASLD describes screening as a serum ALP, then AMA if ALP is raised, which could be repeated at 5-year intervals if AMA is negative initially.AASLD 2018 guidance
AMA was found in 13.1% of first-degree relatives against 1% of controls in data AASLD cites, and in 20.7% of sisters.AASLD 2018 guidance
In Iceland's genealogical database, first-degree relatives had a relative risk of 9.13, second-degree 3.61 and third-degree 2.59.Icelandic familial risk study
In a Mayo Clinic registry of 463 first-degree relatives, 3% were diagnosed with PBC: 24% of those with AMA and 0.7% of those without.Gulamhusein 2016 relatives study
None of the AMA-positive relatives with a normal ALP at baseline developed PBC over a median 8.9 years in that registry.Gulamhusein 2016 relatives study
BSG says study of the genetic basis of PBC remains a research tool and has had no impact on clinical practice.BSG/UK-PBC 2018 guideline

Who to refer to

BSG describes care as predominantly led by secondary and tertiary care physicians, who confirm the diagnosis, start therapy and coordinate follow-up.BSG/UK-PBC 2018 guideline
BSG suggests people with AMA and normal liver tests can be followed in primary care and re-referred if the tests become abnormal.BSG/UK-PBC 2018 guideline
When true overlap with autoimmune hepatitis is suspected, BSG says liver biopsy with expert clinicopathological review is needed.BSG/UK-PBC 2018 guideline
EASL recommends referral to an expert center for severe pruritus, which may signal an aggressive ductopenic variant with a poor prognosis.EASL 2017 guideline
EASL says symptoms of limited scleroderma should be sought and, if present, patients referred for rheumatology advice.EASL 2017 guideline
AASLD says moderate to severe dry eyes should be referred to an eye specialist.AASLD 2018 guidance
EASL recommends expert consultation for all pregnant patients with PBC.EASL 2017 guideline
AASLD lists decompensated cirrhosis, a MELD score of at least 15 or total bilirubin above 6mg/dL as triggers for liver transplant evaluation.AASLD 2018 guidance

Find a specialist by state

From the CMS NPI Registry, a public directory of US clinicians by registered specialty. A listing is not an endorsement and says nothing about experience with Primary biliary cholangitis (PBC); patient organizations and academic centers can often name experienced clinicians.

ICD-10-CM codes for Primary biliary cholangitis (PBC)

For orders, referrals and prior authorization. Each code is checked daily against NLM's ICD-10-CM service.

K74.3Primary biliary cirrhosisCurrent in NLM's ICD-10-CM listNLM ICD-10-CM lookup

Once the diagnosis is confirmed

Primary biliary cholangitis (PBC) drugs for prescribersA prescribing guide: Livdelzi. The page also lists 3 other FDA-approved medicines without a guide yet.Open trials: 38Screen a de-identified patient against every recruiting Primary biliary cholangitis (PBC) study on ClinicalTrials.gov.Patient and family pageThe plain-language Primary biliary cholangitis (PBC) page, with trials, treatments and help paying.

For the patient: why your doctor ordered this test

Plain language a patient can read or take home.

Your doctor ordered these tests because a liver blood test called alkaline phosphatase stayed high, or because of symptoms such as tiredness or itching.

One possible cause is primary biliary cholangitis, or PBC. In PBC the immune system slowly damages the small tubes that carry bile out of the liver. Many people feel well when it is found.

A blood test looks for antibodies called AMA, which most people with PBC have. An ultrasound checks for other causes such as a blocked bile duct. Most people do not need a liver biopsy, but your doctors or health care professionals may suggest one if the blood tests are unclear.

A positive antibody test by itself does not mean you have PBC. If PBC is confirmed, it can be treated, and finding it early matters. Tell your doctor if a parent, sister or brother has PBC.

Questions clinicians ask about Primary biliary cholangitis (PBC) testing

Which combinations of findings should prompt testing for primary biliary cholangitis (PBC)?

In published screening and biopsy studies, the highest yields came from AMA positive plus alkaline phosphatase above 1.5 times the upper limit of normal (98.2% of 156 AMA-positive patients with a liver biopsy, drawn from 3198 people tested for AMA in 1999 and 2000), and from AMA or PBC-specific ANA positive plus normal alkaline phosphatase (80% to 82.1% of 67 biopsied patients among 169 consecutive AMA-positive outpatients with normal ALP, and 30 biopsied patients with AMA or PBC-specific ANA and normal ALP in the Swiss PBC Cohort Study). Among patients already diagnosed, the most common combination began with itch at some point in the illness, seen in 73.5% of 2194 patients with PBC in the UK-PBC cohort, surveyed by questionnaire. These figures describe study groups, not any one patient's chance of having primary biliary cholangitis (PBC).

What are the diagnostic criteria for primary biliary cholangitis?

PBC can be diagnosed when 2 of 3 criteria are met, according to AASLD's 2018 guidance. The criteria are biochemical cholestasis based on ALP elevation, AMA or other PBC-specific autoantibodies such as sp100 or gp210, and histology showing nonsuppurative destructive cholangitis. EASL's 2017 guideline says the diagnosis can be made in adults with cholestasis on elevated ALP plus AMA at a titer above 1 in 40. BSG's 2018 guideline treats AMA above 1 in 40 with cholestatic liver tests as usually sufficient.

Is a liver biopsy needed to diagnose PBC?

Usually not; in 156 AMA-positive patients, ALP above 1.5 times and AST under 5 times the upper limit of normal predicted PBC on biopsy 98.2% of the time (Zein 2003). EASL recommends against biopsy unless PBC-specific antibodies are absent, autoimmune hepatitis or steatohepatitis is suspected, or other comorbidities are present. AASLD says biopsy should be considered when ALT is more than 5 times the upper limit of normal.

How is AMA-negative PBC diagnosed?

About 5% to 10% of patients lack AMA or have only a low titer by immunofluorescence, according to AASLD. AASLD says these patients do not require a biopsy if cholestatic liver tests and PBC-specific antibodies such as sp100 or gp210 are present. A meta-analysis of 11 studies found these antinuclear antibodies 98% specific but only 27% sensitive in AMA-negative PBC (Zhang 2019). AASLD and BSG both say true seronegative PBC needs a biopsy.

What does a positive AMA with a normal alkaline phosphatase mean?

Only about 1 in 6 such patients developed PBC within 5 years in a French study of 229 AMA-positive people without established PBC (Dahlqvist 2017). EASL says AMA alone is not sufficient for diagnosis and recommends annual biochemical reassessment. Biopsy series from 2 groups found PBC histology in 80% to 82% of biopsied antibody-positive patients with normal ALP (Sun 2019, Terziroli Beretta-Piccoli 2021). BSG recommends neither biopsy nor treatment in this group.

How often does PBC go undiagnosed?

In a study of 4 Spanish hospitals, 14.3% of 697 patients who met PBC criteria had no diagnosis, follow-up or treatment recorded (Olveira-Martín 2021). In an Italian primary care study, 27 patients had an unexplained raised ALP, 9 were tested for AMA and 3 proved to have PBC (Donato 2024). An Intercept-funded US consortium study found ALP elevated for 2 to 5 years before diagnosis (Caines 2025).

How is overlap between PBC and autoimmune hepatitis identified?

The Paris criteria require 2 of 3 features, as AASLD describes them. They are ALT above 5 times the upper limit of normal, IgG at least 2 times the upper limit or anti-smooth muscle antibody, and moderate or severe interface hepatitis. AASLD reports these were met in 1% to 14.2% of PBC patients. EASL calls liver biopsy mandatory to confirm autoimmune hepatitis features, and BSG says true overlap is probably rare.

Which autoimmune conditions travel with PBC?

About 27% to 28% of patients had another autoimmune disease in 2 large cohorts, most often thyroid disease and Sjögren syndrome (Efe 2021, Weijsters 2026). BSG also reports Raynaud phenomenon in up to one quarter and limited scleroderma in about 8%. BSG suggests screening at baseline for celiac disease, thyroid disease and Sjögren syndrome.

What is the ICD-10 code for primary biliary cholangitis?

The ICD-10-CM code is K74.3, Primary biliary cirrhosis, per the National Library of Medicine's ICD-10-CM lookup checked November 11, 2026. The code title still uses the disease's former name.

Sources

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A reference for licensed professionals, checked against its sources on November 11, 2026. It summarizes what the cited guidance says and does not tell anyone how to diagnose or treat a specific patient. Guidelines change; the current guideline and the treating clinician's judgment govern. Trial Friend is an independent information service, not a medical provider.