Makindo Medical Notes

Related Subjects: |Chronic liver disease |Cirrhosis |Alkaline phosphatase (ALP) |Liver Function Tests |Ascites Assessment and Management |Budd-Chiari syndrome |Autoimmune Hepatitis |Primary Biliary Cirrhosis |Primary Sclerosing Cholangitis |Wilson disease |Hereditary Haemochromatosis |Alpha-1 Antitrypsin (AAT) deficiency |Non alcoholic steatohepatitis (NASH) |Spontaneous Bacterial Peritonitis |Alcoholism and Alcoholic Liver Disease

Primary Biliary Cholangitis (PBC) (previously called Primary Biliary Cirrhosis but not all develop cirrhosis) is a chronic autoimmune cholestatic liver disease. 💡 Classic triad: middle-aged woman + raised ALP + antimitochondrial antibody (AMA) positive.

📖 About

• Autoimmune destruction of intrahepatic small/medium bile ducts → cholestasis → fibrosis → cirrhosis.
• 90–95% have positive antimitochondrial antibodies (AMA, M2 subtype), specificity ~98%.
• Strong female predominance (9:1), usually diagnosed in women aged 40–60.
• Associated autoimmune conditions: hypothyroidism, Sjögren’s syndrome, rheumatoid arthritis, systemic sclerosis.

🧬 Pathophysiology / Background

• Granulomatous lymphocytic inflammation around bile ducts → progressive ductopenia.
• Cholestasis causes accumulation of toxic bile acids → hepatocyte injury.
• Chronic inflammation leads to periportal fibrosis and eventually cirrhosis.

🩺 Clinical Features

• Often asymptomatic, detected on LFTs (raised ALP, GGT).
• Symptoms: fatigue, pruritus, right upper quadrant discomfort.
• Later signs: skin hyperpigmentation, xanthelasma/xanthomas, hepatosplenomegaly, jaundice.
• Complications: fat-soluble vitamin deficiency (A, D, E, K), osteoporosis, portal hypertension, varices.

🔎 Investigations

• LFTs: ALP often >1000 IU/L; GGT raised; AST/ALT mild elevation.
• Antibodies: AMA (M2 subtype) positive in 95%; ↑ serum IgM.
• Ultrasound: rules out extrahepatic obstruction.
• Liver biopsy: shows granulomas + bile duct destruction; not always required if ALP + AMA are diagnostic.
• Other: lipid abnormalities (hypercholesterolaemia, xanthomas).

⚕️ Management

• First-line: Ursodeoxycholic acid (UDCA) → improves bile acid excretion, slows progression, relieves pruritus.
• Second-line: Obeticholic acid (for UDCA-intolerant or non-responders).
• Pruritus relief: cholestyramine, rifampicin, naltrexone (stepwise).
• Supportive: Fat-soluble vitamin supplementation, manage osteoporosis, nutrition optimisation.
• Liver transplantation: excellent outcomes in advanced disease or refractory pruritus.

📉 Poor Prognostic Indicators

• Jaundice (raised bilirubin).
• Low albumin, prolonged PT/INR.
• Presence of ascites, oedema, encephalopathy.
• Portal hypertension and variceal bleeding.

🧾 Differentials

• Primary Sclerosing Cholangitis (PSC): more common in men, associated with ulcerative colitis, p-ANCA positive, involves extrahepatic ducts (beading on MRCP).
• Drug-induced cholestasis.
• Biliary obstruction from gallstones or malignancy.

🌟 Summary: PBC is an autoimmune cholestatic liver disease of middle-aged women. Diagnosis = raised ALP + positive AMA. Treatment = UDCA (± obeticholic acid), vitamin support, transplant in advanced cases. Complications = cirrhosis, varices, fat-soluble vitamin deficiency.

📊 Comparison: PBC vs PSC vs Autoimmune Hepatitis

💡 Exam tip: - PBC → middle-aged woman + ↑ALP + AMA + pruritus. - PSC → young man + UC + ↑ALP + cholangiogram “beading”. - AIH → young woman + ↑ALT/AST + ANA/SMA + responds to steroids.