Histopathologic distinction between fibrosing cholestatic hepatitis C and biliary obstruction

The histopathologic distinction between posttransplantation fibrosing cholestatic hepatitis C (FCH-C) and biliary obstruction (BO) is challenging. We sought to identify histopathologic features that could be useful in the differential diagnosis between these 2 entities. A total of 38 cases of hepatitis C virus (HCV)-negative, cholangiography-proven BO (including 16 posttransplant and 22 nontransplant patients) and 13 patients with posttransplantation FCH-C were included. FCH-C patients were characterized by cholestatic disease, high HCV viral load, no evidence of biliary tract obstruction on imaging, and typical histopathologic findings (≥3 of the following: 1, prominent ductular reaction; 2, hepatocyte swelling with lobular disarray; 3, periportal sinusoidal fibrosis, and 4, cholestasis). Biopsies were evaluated with hematoxylin and eosin, Masson trichrome, Victoria blue, and rhodanine stains. Cytokeratin 7 (CK7) immunohistochemistry was used to assess for the presence of CK7+ intermediate hepatobiliary cells. We found that portal edema (63.1% vs. 7.6%; P<0.0001), bile duct dilatation (26.3% vs. 0%; P=0.0003), acute cholangitis (15.7% vs. 0%; P=0.008), bile infarcts (10.5% vs. 0%; P=0.03), periductal fibrosis (23.6% vs. 0%; P=0.0007), and periportal copper deposition (60.5% vs. 15.3%; P=0.0006) are significantly more common in BO, whereas hepatocellular swelling with lobular disarray (84.6% vs. 5.2%; P<0.0001) and periportal sinusoidal fibrosis (34.2% vs. 100%; P<0.0001) are seen more frequently in FCH-C. Furthermore, marked ductular reaction with rare or absent CK7+ intermediate cells is highly suggestive of FCH-C in this context (73.6% vs. 7.6%; P<0.0001). In summary, this study offers a comprehensive characterization of the histologic features discriminating FCH-C from BO.