Liver Biopsy in Hepatic Venous Outflow Tract Obstruction: An Important Diagnostic Adjunct with New Morphological Insight

Abstract

Background: Liver biopsy is not being routinely performed these days for diagnosis of hepatic venous outflow tract obstruction (HVOTO) due to advent of advanced non-invasive radiological techniques and therefore, its diagnostic utility is underestimated. Aim: To find out if histological examination in HVOTO can contribute in diagnosis and also to see the specificity of the characteristic histological findings compared to other liver diseases. Methods: Histological features of 143 cases of HVOTO were critically analyzed and compared to 130 heterogeneous controls. Histological findings were also compared with the sites of venous blockade determined radiologically. To determine the best staging system in biopsies of HVOTO, fibrosis scores determined by NASH-CRN and histology activity index scoring (HAI) systems were compared with the amount of fibrosis measured by computer assisted image analysis (IA). To supplement morphological clues, immunohistochemical stains were performed for CK19, Hep Par1, FVIII, SMA and CD34. Results: Presence of zone 3 creeping fibrosis and obliterative venopathy with zone 3 hemorrhagic necrosis, ductal metaplasia, megasinusoids and red blood cell trabeculae are diagnostic for HVOTO, and not seen in other liver diseases. Amongst the available fibrosis staging systems, NASH-CRN staging system can best be adapted in HVOTO; however, the fibrosis pattern is unique in the latter. Conclusion: Liver biopsy may be used as an adjunct to radiological techniques for diagnosing HVOTO, to rule out other associated liver pathologies and to score the fibrosis accurately. Zone 3 bile ductal metaplasia is a unique feature of HVOTO which has not yet been reported in literature.