Hepatobiliary pathology.
Insights provided by molecular biology, immunohistochemistry, and transmission electron microscopy have increased our understanding of the pathogenesis and histopathology of hepatitis C virus (HCV) infection, nonalcoholic steatohepatitis (NASH), and bile ductular proliferative reactions in a number of liver diseases. Human and chimpanzee liver infected with HCV showed viral-like particles (50 to 60 nm in diameter) as well as aggregates of short tubules that represent viral envelope material. Interactions of HCV core protein with apolipoproteins have a role in the pathogenesis of HCV-related steatosis. Pathologists should be aware of the spectrum of liver pathology described with the use of highly active antiretroviral therapy (HAART) agents for the human immunodeficiency virus infection, which includes microvesicular steatosis and more severe hepatic injury with confluent necrosis. Proliferation of bile ductular structures is influenced by specific molecules and proteins (eg, the mucin-associated trefoil proteins and estrogens). The interplay between Notch receptors and Jagged 1 protein, as expressed by many cells of the liver (including bile duct epithelium) varies in primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC). Cholangiocarcinoma does not appear to be a long-term complication of small duct PSC. The fatty liver diseases, both alcoholic and nonalcoholic, are characterized by production of reactive oxygen species that have detrimental effects such as opening mitochondrial permeability transition pores with resultant release of cytochrome c into the cytosol. Hepatocellular carcinoma is now a recognized late complication of NASH. The derivation of hepatic stem cells, the roles of HFE protein and other hepatic and intestinal transport proteins in hemochromatosis, and the histopathologic interpretive challenge of centrilobular lesions in posttransplant liver biopsies are among other recent studies considered in this review.
Lefkowitch
Jay H
JH
College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA. jhl3@columbia.edu