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Primary Biliary Cirrhosis Investigations Complications: Metabolic bone disease (osteoporosis plus malacia). Hypercholesterolaemia and xanthomas. Malabsorption ( due to decreased bile salt secretion. Anaemia.
The target autoantigens (=the M2 antigens) the E2 subunits of the pyruvate dehydrogenase complex, the branched chain 2-oxo-acid dehydrogenase complex, the ketoglutaric acid dehydrogenase complex All take part in oxidative phosphorylation Very homologous Antibody titers do not correlate with disease severity or rate of progression Sensitivity of 95%, spec of 98% No apparent difference in the clinical spectrum or course of patients with PBC who are AMA-positive or AMA-negative
CD8+
CD4+
Foamy degeneration of hepatocytes Toxins (eg bile acid) cause hepatocyte
Laboratory tests Eosinophils- can be elevated early in the disease course. Antimitochondrial antibodies are present in 95 %. AMA is 95 % sensitive and 98 % specific. 13 % of first-degree relatives of PBC positive are AMA positive, suggesting they are susceptible to developing PBC. Antinuclear antibodies are present in 70%. A variety of ANA staining patterns is present. ANA positive is associated with overlap and also signify worse prognosis. PBC patients who are AMA negative and have a positive ANA, a disease called autoimmune cholangitis or AMA negative PBC, have the same outcomes as those who are AMA positive and ANA negative. Hyperlipidemia occurs in 50%. LDL and VLDL mildly elevated. HDL’s are usually very elevated. Patients are not at increased cardiovascular risk. Liver biopsy features:
Mononuclear inflammatory infiltrate.
Formation of lymphoid aggregates
CD4+ and CD8+ cells are present in high concentration in
the portal triads of patients with PBC, often surrounding
and infiltrating necrotic bile ducts- they both target amino
acids 159-167 of PDC-E2.
Epithelioid granulomas.
Bile duct damage.
Foamy degeneration of hepatocytes.
Always have high hepatic alk phos levels The value tends to reach a plateau early in the course of the disease and then usually fluctuates within 20 % of this value. The serum levels of aminotransferases is normal or slightly elevated, rarely increased > 5x normal. Fluctuate within a relatively narrow range, If rise to > 10x normal consider overlap syndrome The serum bilirubin concentration is usually normal early in the course of the disease but becomes elevated in most patients as the disease progresses. Both the direct and indirect fractions are increased. An elevated serum bilirubin is a poor prognostic sign.
Other Increased IgM, ceruloplasmin, bile acids (which are strikingly elevated), and hyaluronate. Rising hyaluronate levels correlate with the serum bilirubin and histologic worsening of the disease. Genetically susceptible host with an inability to suppress T-cell attack on bile duct epithelial cells Age > 21 (?specific hormone profile) Triggering event (bile duct epithelial damage?, drug reaction?, gallstones?, viral infection? Progressive damage to bile duct epithelial cells Increased expression of HLA class I and II antigens Retention of toxic substances eg bile acids Cholestasis
Gradual loss of bile ducts
Progressive portal and periportal scarring Cirrhosis and portal hypertension
Hepatic failure and complications of portal hypertension
Written by Dr Sebastian Zeki
