Aberrant Centrizonal Features in Chronic Hepatic Venous Outflow Obstruction

Abstract

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.

The liver in heart failure: a biopsy and explant series of the histopathologic and laboratory findings with a particular focus on pre-cardiac transplant evaluation

“…This change has previously been reported by Krings et al 21 Similar to these authors, we found that this lesion can be a cause of confusion such that the biliary-type epithelium may suggest a portal zone and the ductular proliferation may further suggest a large duct obstruction or sepsis. In fact, we found that most portal tracts lacked a significant ductular reaction.…”

“…The liver architecture was further distorted by centrizonal arterioles and biliary metaplasia of cells adjacent to the central veins as recently reported by Krings et al 21 This change was present in varying degrees in each case and was usually apparent on H&E-stained slides. The metaplastic biliary population was particularly well highlighted by cytokeratin 19 immunohistochemistry (Figure 1d).…”

“…Biopsies are often performed with a request to 'rule out cirrhosis', but chronic passive congestion does not appear to progress to cirrhosis in the same manner as chronic viral hepatitis or alcoholic hepatitis. 2,[19][20][21][22][23] The histologic changes in the setting of heart failure show a unique pattern of progression, with sinusoidal dilation preceding the appearance of fibrosis. Inflammation is minimal to absent.…”

“…The existing staging systems for viral hepatitis do not directly apply as they assume a portal-based origin of fibrosis and while steatohepatitis staging schemes include pericentral fibrosis, fibrosis in chronic passive congestion shows a distinctly different pattern of evolution. 19,21,23 In the current study, we report the histologic findings in explanted livers from patients receiving combined heart-liver transplants and attempt to further describe the evolution of fibrosis in patients with heart disease. We also examine the characteristics of liver biopsies from patients receiving heart transplants without concurrent liver transplant to determine whether a threshold at which patients should no longer be considered candidates for isolated heart transplantation can be established.…”

Altered intrahepatic microcirculation of idiopathic portal hypertension in relation to glutamine synthetase expression

“…The expression of GS is known to be induced in regenerating liver tissues following various types of liver injury . In addition, aberrant GS staining in periportal areas, indicative of reverse zonation, has been observed in chronic venous outflow obstruction . Thus, hepatocyte GS expression is increased in various conditions, and the underlying mechanism may be different in various types of disease.…”