Histologic changes mimicking biliary disease in liver biopsies with venous outflow impairment

Kakar, Sanjay; Batts, Kenneth P.; Poterucha, John J.; Burgart, Lawrence J.

doi:10.1038/modpathol.3800073

Cited by 46 publications

(25 citation statements)

References 12 publications

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“…But in the study by Isogai M et al, acute cholestasis (65.4%) is noted as the most common change [14]. Kakar S et al, observed extensive fibrosis with portal-portal linking in patients of choledocholithiasis [15], this was shown to be the result of chronic cholestasis in each case. This observation is important because the fibrosis could ultimately leads to irreversible secondary biliary cirrhosis [15].…”

Section: Liver Histopathological Changes With Gallstone Diseasementioning

confidence: 99%

“…Kakar S et al, observed extensive fibrosis with portal-portal linking in patients of choledocholithiasis [15], this was shown to be the result of chronic cholestasis in each case. This observation is important because the fibrosis could ultimately leads to irreversible secondary biliary cirrhosis [15]. If obstruction is relieved; considerable resolution is still possible at chronic cholestasis stages, which emphasize the importance of early surgery.…”

Section: Liver Histopathological Changes With Gallstone Diseasementioning

confidence: 99%

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Impact of Biliary Calculi on the Liver

Rangaswamy

Singh

et al. 2017

JCDR

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Introduction: Gallstone is implicated for hepatocellular injury due to chronic extra hepatic large bile duct obstruction with or without repeated episodes of cholangitis. Aim:To study the liver changes in patients undergoing oper ative procedure for gallstone disease and to determine the relationship between severity of these changes with position of biliary calculus in biliary tree. Materials and Methods:Sixty patients who underwent operative procedure for gallstone disease between October 2013 and September 2015 were evaluated. The Liver Function Test (LFT) was done preoperatively and postoperatively. Intraoperative liver biopsy was taken. The histopathological changes of liver and their severity were noted.

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Section: Liver Histopathological Changes With Gallstone Diseasementioning

confidence: 99%

Section: Liver Histopathological Changes With Gallstone Diseasementioning

confidence: 99%

Impact of Biliary Calculi on the Liver

Rangaswamy

Singh

et al. 2017

JCDR

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“…[1][2][3][5][6][7][8][9] In addition to these welldefined lobular features, several studies have described the presence of periportal changes, including mild portal inflammation, fibrosis, and ductular reaction, in patients with chronic venous outflow obstruction. 10,11 Interestingly, Pai and Hart 10 have also identified cytokeratin (CK) 7 + perivenular hepatocytes of intermediate phenotype in chronic venous outflow obstruction, which correlated with a cholestatic chemistry profile. Indeed, patients with chronic venous outflow obstruction often present with a cholestatic liver profile, including elevated bilirubin and alkaline phosphatase.…”

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confidence: 97%

Aberrant Centrizonal Features in Chronic Hepatic Venous Outflow Obstruction

Krings

Can

Ferrell

2014

American Journal of Surgical Pathology

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Chronic hepatic venous outflow obstruction is characterized by centrizonal scarring but may also display features that can lead to portal tract mimicry and misdiagnosis as biliary disease, especially given elevated cholestatic liver profiles in these patients. However, these histopathologic features have not been systematically described. We graded the numbers of centrizonal arterioles, ductules, keratin 7+ hepatocytes, CD34+ microvessels, and capillarized sinusoids in 61 cases of chronic venous outflow obstruction and assessed changes in metabolic zonation by glutamine synthetase staining. Centrizonal arterioles and ductules were present in 82.0% and 72.1% of cases, respectively, and correlated with fibrosis. Centrizonal CD34+ microvessels and sinusoidal capillarization were closely associated and present in 25 (92.6%) and 26 (96.3%) of 27 cases, respectively. Centrizonal capillarized sinusoids and microvessels, which were present in all cases with advanced fibrosis, were demonstrated in 90% and 80% of the cases without significant fibrosis, respectively. The results suggest that capillarization and/or microvessel formation precede and may contribute to centrizonal scarring, whereas arterialization likely reflects vascular remodeling associated with progressive fibrosis. Centrizonal ductules were often immature, being either keratin 7+/keratin 19- (36.4%) or keratin 7-/keratin 19- (10.0%). Centrizonal keratin 7+ intermediate-phenotype hepatocytes were present in 25 (92.5%) of 27 cases. Lastly, 22 (91.7%) of 24 cases showed loss of metabolic zonation, with reversed zonation in 2 (8.3%) cases. Together, the findings indicate that vascular and lobular reorganization in chronic venous outflow obstruction may result in mimicry of central zones as portal tracts. Recognition of these changes is essential to prevent misdiagnosis of this condition as biliary tract disease.

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“…Kakar et al demonstrate a bile ductular reaction at the periphery of portal tracts. 4 The ductular reaction was quite mild in many cases. We confirmed this finding in our study population as 9 of 22 (41%) either had histological (seven) or immunohistochemical (two) evidence of a ductular reaction.…”

Section: Discussionmentioning

confidence: 99%

“…Kakar et al recently described portal changes in the liver biopsies of patients with hepatic venous outflow obstruction due to right heart failure, Budd-Chiari syndrome, and veno-occlusive disease. 4 They found that nearly half of the patients had evidence of a ductular reaction; however, none of the patients had evidence of biliary tract disease. They argued that such changes could account for the liver chemistry abnormalities.…”

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confidence: 99%

Aberrant expression of cytokeratin 7 in perivenular hepatocytes correlates with a cholestatic chemistry profile in patients with heart failure

Pai

Hart

2010

Modern Pathology

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A cholestatic liver chemistry profile (elevations in alkaline phosphatase and bilirubin) is commonly encountered in patients with hepatic venous outflow obstruction due to right heart failure. Liver biopsies from these patients demonstrate varying degrees of sinusoidal dilatation, red blood cell extravasation and sinusoidal congestion. Recently, a bile ductular reaction mimicking biliary tract disease has been identified in B50% of patients with venous outflow obstruction possibly explaining the cholestatic profile encountered in these patients. In this study, we evaluated the liver biopsies from 22 patients with heart failure. Marked sinusoidal dilatation involving zones 2 and 3 was observed in 15 patients. Similar to a previous study, 7 of 22 patients had histologic evidence of a mild ductular reaction. Cytokeratin 7 immunohistochemistry revealed a mild ductular reaction in an additional two cases. Strikingly, CK7 was aberrantly expressed in perivenular hepatocytes in 20 of 22 cases. Perivenular CK7 immunoreactivity was focal in most cases; however, in five cases it was quite extensive and extended into zone 2. There was no significant association between marked sinusoidal dilatation and extensive perivenular CK7 positivity. Extensive perivenular CK7 positivity was significantly associated with both elevated bilirubin, as well as the presence of fibrosis. However, a ductular reaction was not associated with a cholestatic liver chemistry profile.

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Histologic changes mimicking biliary disease in liver biopsies with venous outflow impairment

Cited by 46 publications

References 12 publications

Impact of Biliary Calculi on the Liver

Impact of Biliary Calculi on the Liver

Aberrant Centrizonal Features in Chronic Hepatic Venous Outflow Obstruction

Aberrant expression of cytokeratin 7 in perivenular hepatocytes correlates with a cholestatic chemistry profile in patients with heart failure

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