A 62-year-old man comes to the office for the evaluation of jaundice. Medical history is significant for uncontrolled type 2 diabetes mellitus and morbid obesity. He does not use tobacco, alcohol, or illicit drugs. There is no family history of liver disease. Vital signs are within normal limits. BMI is 47 kg/m². Mild scleral icterus is present. Heart and lung sounds are normal. The abdomen is nontender and nondistended. Trace bilateral lower extremity edema is present. Laboratory studies reveal elevated transaminases. A liver biopsy is obtained, and trichrome staining shows the following: Which of the following cells is directly responsible for the histologic finding indicated by the arrow?

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11ec160b_378f_443b_9249_75025b32735c_MD0001_00 This patient with diabetes mellitus and morbid obesity has hepatic cirrhosis, likely due to long-standing nonalcoholic fatty liver disease (NAFLD). Cirrhosis is the end stage of multiple liver diseases and is characterized by replacement of normal lobular architecture with regenerating nodules separated by bridging fibrous septa. Cirrhosis can be visualized histologically as thickened collagenous bands (which stain blue with Masson trichrome stain) separating clusters of hepatocytes. Fat infiltration (ie, hepatic steatosis, visible as clear vacuoles within the parenchyma) is commonly seen in both alcohol-induced fatty liver disease and NAFLD. In response to chronic injury, stellate (Ito) cells are activated and transform into myofibroblasts capable of proliferating, promoting chemotaxis, and producing collagen in large quantities. This leads to progressive scar formation and cirrhosis. Manifestations of cirrhosis include jaundice, scleral icterus, spider angiomas, and elevated liver enzymes. Evidence of abnormal hepatic synthetic function (eg, abnormal coagulation parameters, hypoalbuminemia) and thrombocytopenia are also common. (Choice A) Cholangiocytes are epithelial cells within the bile duct system. They transport ions and solutes into bile as it travels through the canaliculi. (Choice B) Hepatocytes are located in the liver parenchyma and have many functions, including protein synthesis and storage, fatty acid metabolism, gluconeogenesis, cholesterol synthesis, and drug metabolism. (Choice C) Kupffer cells are macrophages that reside within hepatic sinusoids. They are indirectly involved in fibrogenesis because they generate cytokines (ie, TNF-alpha) to assist in the activation of stellate cells; however, their primary function is bacterial phagocytosis and the clearance of red blood cells. (Choice D) Sinusoidal endothelial cells, which line hepatic sinusoids, are fenestrated cells that filter solutes out of the blood and into hepatocytes. They assist in the removal of metabolic waste and other macromolecules from circulation. Educational objective: Stellate (Ito) cells are the primary cells involved in hepatic fibrosis. In response to hepatic injury, the stellate cells are activated and transform into myofibroblasts capable of proliferating, promoting chemotaxis, and producing large quantities of collagen. Collagen stains blue with Masson trichrome stain. __________ References: Molecular pathogenesis of hepatic fibrosis and current therapeutic approaches. (http://www.ncbi.nlm.nih.gov/pubmed/21803030) Physiology of cholangiocytes. (http://www.ncbi.nlm.nih.gov/pubmed/23720296) Structural and functional aspects of the liver and liver sinusoidal cells in relation to colon carcinoma metastasis. (http://www.ncbi.nlm.nih.gov/pubmed/16127736)

A 62-Year-Old Man Comes to the Office for the Evaluation