Primary biliary cholangitis

Autoimmune destruction of small intrahepatic bile ducts leading to chronic cholestasis (bile stasis) and progressive fibrosis of the liver (cirrhosis). Classically affects middle-aged women.

• PBC is a major cause of chronic cholestatic liver disease and can progress to cirrhosis and liver failure if untreated. High-yield due to its unique association with anti-mitochondrial antibodies (AMA) and effective early treatment (UDCA) to slow progression.

• Typically a woman in her 40s-60s with insidious onset of fatigue and pruritus (itching, often worse at night). Early disease may be asymptomatic aside from elevated alkaline phosphatase on labs; later, patients can develop jaundice, hyperpigmented skin, and xanthelasma (cholesterol deposits).
• Strongly associated with other autoimmune conditions (seen in up to 70% of patients) such as Sjögren syndrome (dry eyes/mouth), autoimmune thyroid disease, CREST scleroderma, or rheumatoid arthritis.
• Exam may show hepatomegaly and skin excoriations from scratching. Advanced PBC leads to signs of portal hypertension (splenomegaly, ascites, varices) and complications of cirrhosis.

1. Suspect PBC in a patient (especially a middle-aged woman) with a cholestatic liver enzyme pattern (↑ALP much more than ↑ALT) and compatible symptoms. Confirm diagnosis with AMA serology (anti-mitochondrial antibodies present in ~95%).
2. Perform imaging (e.g., ultrasound or MRCP) to exclude extrahepatic biliary obstruction or primary sclerosing cholangitis. If AMA-negative but suspicion remains, or to assess disease stage, consider a liver biopsy (shows nonsuppurative destructive cholangitis and granulomas).
3. Evaluate for co-existing autoimmune diseases and complications: check thyroid function (autoimmune thyroiditis), bone density (risk of osteoporosis from chronic cholestasis), and fat-soluble vitamin levels (A, D, E, K). Monitor lipid profile (PBC often causes hypercholesterolemia).
4. If ALT or liver biopsy suggests interface hepatitis (hepatocellular injury) along with cholestasis, suspect PBC-AIH overlap syndrome; this requires additional immunosuppressive management.

1. Ursodeoxycholic acid (UDCA) – first-line therapy that slows disease progression (improves cholestasis and survival); start as soon as diagnosis is made (13–15 mg/kg/day).
2. If inadequate response to UDCA (e.g., ALP remains high at 1 year), add obeticholic acid (FXR agonist) as second-line. Fibrates (e.g., bezafibrate) are another off-label option for UDCA non-responders (avoid in decompensated cirrhosis).
3. Manage symptoms and complications: cholestyramine or rifampin can help pruritus; supplement fat-soluble vitamins; use bisphosphonates for PBC-related osteoporosis. Screen for and endoscopically treat varices if portal HTN present.
4. Liver transplant is indicated for end-stage PBC (decompensated cirrhosis or severe symptoms like intractable pruritus); transplant is often curative, though AMA may remain positive.

• Remember M for PBC: Middle-aged Moms (90% female), anti-Mitochondrial antibodies (AMA), and elevated IgM levels. (By contrast, PSC affects Sons (men) and is p-ANCA positive with UC.)
• Old name was "primary biliary cirrhosis" – think PBC when you see a cholestatic pattern in a 50-year-old woman, even if cirrhosis hasn't developed yet.

• Any signs of decompensated cirrhosis (e.g., new-onset ascites, encephalopathy, variceal hemorrhage) in PBC → urgent referral for liver transplant evaluation.
• Concomitant high AST/ALT and positive ANA or SMA in a PBC patient → suspect overlap syndrome (PBC + autoimmune hepatitis) requiring biopsy confirmation and immunosuppressive therapy (corticosteroids).
• Severe pruritus unresponsive to medical therapy is a red flag for poor quality of life – can be an indication for earlier transplant consideration.

1. Unexplained cholestatic LFT pattern (↑ALP) in an at-risk patient (especially middle-aged woman) → test AMA and other antibodies (ANA, etc.).
2. If AMA positive (or sp100/gp210), diagnosis of PBC is likely. Obtain imaging (U/S, MRCP) to rule out extrahepatic obstruction or PSC.
3. If AMA negative and imaging normal, consider liver biopsy to confirm PBC (will show florid duct lesions) or identify alternative diagnoses.
4. Start UDCA once PBC is diagnosed (don't wait for biopsy if clinical picture is clear). Recheck liver tests at 6–12 months; if inadequate response, consider adding second-line therapy (obeticholic acid or fibrate).
5. Monitor for progression (development of cirrhosis, varices) and manage complications. Refer for transplant evaluation if liver failure develops despite medical therapy.

• Middle-aged woman with months of pruritus and fatigue, lab tests show markedly ↑alkaline phosphatase, mild ↑AST/ALT, and positive anti-mitochondrial antibodies → Primary biliary cholangitis.
• Patient with long-standing PBC now presents with ascites, jaundice, and variceal bleeding → indicates decompensated cirrhosis from PBC (requires transplant evaluation).