Conditions · Gastroenterology and hepatology
Primary biliary cholangitis !
An autoimmune liver disease that slowly destroys the small bile ducts, mostly in middle-aged women. Itching and tiredness are typical; it can end in cirrhosis.
Updated 2026-11-01
Structures involved
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Why it happens
- Chronic inflammation: causes, cells and features
- Fibrosis in organs: TGF-β and the myofibroblast
- Bile and the enterohepatic circulation
- Alkaline phosphatase (ALP) as a lab test
- Gallbladder and bile ducts
- Liver: lobule, acinus, hepatocytes, sinusoids, Kupffer cells
What it is
A chronic autoimmune disease in which the immune system destroys the small bile ducts inside the liver. Bile is retained (cholestasis), and over years this can lead to fibrosis, cirrhosis and liver failure. It was formerly called primary biliary cirrhosis.
Who gets it
Uncommon; about nine of every ten patients are women, usually diagnosed between 40 and 60 years. It is described in Latin America as elsewhere, and many cases are now found on routine blood tests before symptoms appear.
Causes
- Autoimmune attack on the epithelial cells of the small intrahepatic bile ducts
- Genetic susceptibility combined with environmental triggers (infections, chemicals, smoking have been proposed)
- Exact cause unknown
Risk factors
- Female sex and middle age
- First-degree relative with the disease
- Other autoimmune diseases: Sjögren disease, autoimmune thyroid disease, systemic sclerosis (CREST), celiac disease, Raynaud phenomenon
- Smoking
Pathophysiology
T cells and antimitochondrial antibodies target the small interlobular bile ducts, causing a non-suppurative destructive cholangitis. Retained bile acids injure hepatocytes and drive fibrosis that progresses from portal tracts to bridging fibrosis and cirrhosis. Reduced bile in the gut impairs fat and fat-soluble vitamin absorption.
Classification
- Histological stages 1 to 4 (portal inflammation, periportal, bridging fibrosis, cirrhosis)
- Asymptomatic (found on tests) versus symptomatic
- PBC–autoimmune hepatitis overlap
Symptoms and signs
- Often no symptoms; isolated raised alkaline phosphatase on blood tests
- Fatigue, frequently the most disabling symptom
- Itching (pruritus), often worse at night and before jaundice
- Dry eyes and dry mouth (associated sicca syndrome)
- Hepatomegaly, skin hyperpigmentation and xanthelasma or xanthomas from high cholesterol
- Late: jaundice, ascites, easy bruising and fatty stools
Diagnosis
- Clinical
- Typical patient is a middle-aged woman with fatigue and itching, or no symptoms with a cholestatic pattern on blood tests. Examination may show hepatomegaly, excoriations and xanthelasma.
- Tests
- Cholestatic profile: high alkaline phosphatase and GGT, with bilirubin rising later. Antimitochondrial antibodies (AMA, M2) are the hallmark and are positive in about 95%; PBC-specific ANA (anti-gp210, anti-sp100) help when AMA is negative. IgM is often raised, along with cholesterol. Diagnosis rests on raised ALP plus positive AMA; biopsy is reserved for doubtful cases or suspected overlap.
- Imaging
- Ultrasound (or MRCP) to exclude extrahepatic obstruction; ducts look normal. Elastography estimates fibrosis; bone densitometry screens for osteoporosis.
Differential diagnosis
- Primary sclerosing cholangitis
- Extrahepatic biliary obstruction (stones, tumour)
- Drug-induced cholestatic liver injury
- Autoimmune hepatitis or overlap syndrome
- Infiltrative disease such as sarcoidosis
Goal of treatment
Slow progression to cirrhosis with bile acid therapy, relieve itching and fatigue, prevent and treat bone loss and vitamin deficiency, and refer for transplant when liver failure approaches.
Treatment
- Medical
- Ursodeoxycholic acid is the first-line, lifelong treatment and improves survival in responders; response is judged by ALP after about a year. Second-line options for poor responders are mainly PPAR agonists (seladelpar, elafibranor, or fibrates off-label); obeticholic acid has been withdrawn in several markets because of safety concerns.
- Medical
- Itching: bile acid sequestrants first, then rifampicin, opioid antagonists or sertraline in selected cases. Replacement of fat-soluble vitamins (A, D, E, K) and calcium with vitamin D for bone protection.
- Follow-up
- Regular liver tests to assess treatment response, bone densitometry, thyroid function, and, once cirrhosis exists, ultrasound every six months for liver cancer and endoscopic screening for varices.
- Surgical
- Liver transplantation for decompensated cirrhosis or intractable itching; the disease can recur in the graft.
Drugs for this condition
Complications
- Cirrhosis with portal hypertension, varices and ascites
- Osteoporosis (hepatic osteodystrophy)
- Fat-soluble vitamin deficiency and steatorrhoea
- Hypercholesterolaemia with xanthomas
- Hepatocellular carcinoma in advanced disease
Prognosis
With ursodeoxycholic acid, patients who respond biochemically have a life expectancy close to that of the general population. Poor response, high bilirubin and advanced fibrosis predict progression; untreated disease often leads to liver failure within one to two decades.
Test yourself
Think of the answer, then tap the question to see it.
Which antibody is the hallmark of primary biliary cholangitis?
Antimitochondrial antibodies (AMA, anti-M2), positive in about 95% of patients.
What is the classic patient and presenting symptom of PBC?
A middle-aged woman with fatigue and itching, or an isolated raised alkaline phosphatase on routine tests.
What is the first-line drug for PBC?
Ursodeoxycholic acid, taken long term; it slows progression and improves survival in responders.
Which bile ducts are affected in PBC compared with PSC?
PBC destroys the small intrahepatic ducts; PSC scars both intrahepatic and extrahepatic ducts.
Which two complications of chronic cholestasis in PBC occur besides cirrhosis?
Osteoporosis and fat-soluble vitamin (A, D, E, K) deficiency; also hypercholesterolaemia with xanthomas.
Related conditions
- Cirrhosis
- Portal hypertension
- Autoimmune hepatitis
- Primary sclerosing cholangitis
- Hypothyroidism
- Coeliac disease
- Sjögren disease
- Osteoporosis
- Hepatocellular carcinoma
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Primary biliary cholangitis: MedlinePlus Medical Encyclopedia (MedlinePlus (U.S. National Library of Medicine), 2024); Primary Biliary Cholangitis (Primary Biliary Cirrhosis) (National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 2021).
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