A 45-year-old woman comes to the office for progressive itchiness and fatigue. She also notes yellowing of the eyes and skin. Physical examination shows scleral icterus, multiple excoriations on both the upper and the lower extremities, and hepatomegaly. Laboratory results are as follows:
| Liver function studies | |
| Total bilirubin | 5.3 mg/dL |
| Alkaline phosphatase | 982 U/L |
| Aspartate aminotransferase (SGOT) | 89 U/L |
| Alanine aminotransferase (SGPT) | 67 U/L |
| Gamma-glutamyl transpeptidase | 450 U/L (normal: 10-60 U/L) |
Liver biopsy reveals dense lymphocytic infiltration of the portal triads, as well as granulomatous destruction of interlobular bile ducts. Which of the following is the most likely diagnosis?
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This patient with fatigue, pruritus, jaundice, and elevated alkaline phosphatase has liver biopsy results consistent with primary biliary cholangitis (PBC), a chronic autoimmune disorder that disproportionately affects middle-aged women. PBC is characterized by T-cell–mediated destruction of the small intralobular bile ducts, which is visualized histologically as a dense lymphocytic inflammation of portal tracts with granulomatous destruction of interlobular bile ducts (ie, florid duct lesions).
PBC typically develops insidiously; fatigue and pruritus are often the presenting symptoms. Cholestasis results in a characteristic pattern of liver injury (ie, elevated alkaline phosphatase, elevated gamma-glutamyl transferase, direct hyperbilirubinemia, normal or mildly elevated aminotransferases) and examination findings (eg, hepatomegaly, jaundice). Hypercholesterolemia is also common due to reduced cholesterol excretion. Elevated antimitochondrial antibodies are highly characteristic.
(Choices A and B) Acute hepatitis B and autoimmune hepatitis (AIH) both result in a hepatocellular, not a cholestatic, pattern of liver injury. Hepatitis B is characterized histologically by lobular mononuclear inflammation, hepatocyte balloon degeneration, and ground-glass hepatocytes, whereas AIH results in portal and periportal lymphoplasmacytic infiltration of the liver (ie, interface hepatitis).
(Choice D) Primary sclerosing cholangitis causes a cholestatic pattern of liver injury but it is identified histologically by fibrous obliteration of bile ducts, as well as concentric periductal deposition of connective tissue in an onion skin–like pattern. It is strongly associated with ulcerative colitis.
(Choice E) Sarcoidosis can cause a cholestatic pattern of liver injury but is characterized by noncaseating granulomas with hepatic fibrosis and a multinucleated giant cell formation. The dense portal lymphocytic infiltration characteristic of PBC is not seen. In addition, most patients have symptoms of systemic sarcoidosis (eg, cough, hilar lymphadenopathy).
Educational objective:
Primary biliary cholangitis is an autoimmune disorder that most commonly affects middle-aged women and is characterized by fatigue, pruritus, jaundice, cholestasis (eg, elevated alkaline phosphatase, elevated gamma-glutamyl transferase, direct hyperbilirubinemia), and antimitochondrial antibodies. Histologic findings include dense lymphocytic portal tract inflammation with granulomatous destruction of interlobular bile ducts.