A 42-year-old man comes to the office due to progressive fatigue, nausea, and itchiness. On review of systems, the patient admits that he occasionally has bloody stools. Medical history is unremarkable. Examination shows scleral icterus. Percutaneous liver biopsy is performed, and histologic analysis of the tissue sample reveals fibrous obliteration of intrahepatic small bile ducts with concentric replacement by connective tissue. Which of the following is the most likely diagnosis?

Question

A 42-year-old man comes to the office due to progressive fatigue, nausea, and itchiness.  On review of systems, the patient admits that he occasionally has bloody stools.  Medical history is unremarkable.  Examination shows scleral icterus.  Percutaneous liver biopsy is performed, and histologic analysis of the tissue sample reveals fibrous obliteration of intrahepatic small bile ducts with concentric replacement by connective tissue.  Which of the following is the most likely diagnosis?

Quizplus · Accepted Answer

11ec160b_395e_acf1_9249_8f14d1ca4c16_MD0001_00 This patient with fatigue, nausea, pruritus, and scleral icterus has characteristic biopsy findings associated with primary sclerosing cholangitis (PSC), a chronic disorder characterized by inflammation, fibrosis, and stricture of the intrahepatic and extrahepatic bile ducts. Histologic features include fibrous obliteration of the bile ducts as well as concentric periductal connective tissue deposition, which resembles an onion skin-like pattern. PSC affects men disproportionately and has a strong association with ulcerative colitis, likely explaining this patient's bloody stools. Manifestations of PSC are related to cholestasis and include pruritus, jaundice, and fatigue. Laboratory findings also reflect a cholestatic pattern of liver injury and include elevated alkaline phosphatase levels, direct hyperbilirubinemia, and normal to mildly elevated aminotransferases. The diagnosis is typically confirmed with cholangiography (eg, MR or endoscopic retrograde cholangiopancreatography) demonstrating multifocal bile duct stricture with segmental dilations. (Choice A) Autoimmune hepatitis can cause fatigue, pruritus, and jaundice but is characterized histologically by portal and periportal lymphoplasmacytic infiltration. It is usually diagnosed in women with other autoimmune conditions (eg, celiac disease). (Choice B) Cytomegalovirus infection can cause hepatitis; however, microscopy typically reveals large cells with basophilic intracytoplasmic and intranuclear inclusions (eg, owl's eye appearance). In addition, it typically occurs in immunocompromised individuals (eg, transplant patients). (Choice C) Hemochromatosis leads to excessive hepatic iron storage, which results in visible iron deposits within hepatocytes. It is typically associated with diabetes, skin hyperpigmentation, arthralgias, and cardiomyopathy. (Choice D) Primary biliary cholangitis also causes cholestasis with jaundice and pruritus; however, it is characterized histologically by inflammation and granulomatous destruction of the small bile ducts (eg, florid duct lesions). In addition, it is much more common in women and is not usually associated with inflammatory bowel disease. Educational objective: Primary sclerosing cholangitis is characterized by inflammation, fibrosis, and stricture of intrahepatic and extrahepatic bile ducts. Histologic findings include fibrous obliteration of bile ducts and concentric periductal connective tissue deposition (eg, onion skin-like pattern). Manifestations reflect cholestasis and include jaundice, pruritus, fatigue, and a cholestatic injury pattern (ie, elevated alkaline phosphatase, direct hyperbilirubinemia).

A 42-Year-Old Man Comes to the Office Due to Progressive