Nodular regenerative hyperplasia - An under-recognized vascular disorder of liver

Introduction: Nodular regenerative hyperplasia (NRH) is a rare hepatic vascular disorder which is often associated with wide variety of systemic diseases. Intrahepatic microvascular injury and subsequent altered perfusion state leads to development of non-cirrhotic portal hypertension in many of these patients. Diagnosis of NRH often remains unsuspected clinically and liver biopsy is essential for the diagnosis and exclusion of fibrosis. We herein, present clinicopathological features of 22 NRH cases. In addition we assessed CK7 and CD34 expression in hepatocytes and sinusoidal endothelial cells respectively. Results: Most of the cases were associated with systemic disorders, predominantly immunological, inflammatory and drug-related injuries. Signs and symptoms of portal hypertension were found in 86.4 % patients. Majority of the patients showed a predominant mild cholestatic pattern of liver function tests. Nearly all the (21/22) cases showed CK7 positivity in centrizonal hepatocytes which ranged from < 10 % cells to diffuse perivenular positivity extending into the midzonal areas. CD34 positivity in sinusoidal endothelial cells was seen in all the cases, which was prominent in periportal areas in all cases; while perivenular (n = 20) and midzonal (n = 14) areas also showed CD34 positive sinusoidal endothelial cells. Conclusion: This study highlights the role of pathologist in the diagnosis of NRH and stresses upon the need for awareness of NRH as a cause of unexplained portal hypertension in patients with underlying systemic diseases. The altered perfusion state in NRH leads to phenotypic shift in centrizonal atrophic hepatocytes and sinusoidal endothelial cells (as depicted by IHC) which may be responsible for development of portal hypertension.