Nodular Regenerative Hyperplasia of the Liver in Rheumatic Disease: Cases and Review of the Literature

Abstract

Nodular regenerative hyperplasia (NRH) is a rare disease that is characterized by benign transformation of the hepatic parenchyma into small nodules with little to no fibrosis. Nodular regenerative hyperplasia is a cause of noncirrhotic portal hypertension. Symptoms can range from asymptomatic disease to more serious complications of portal hypertension such as esophageal varices and ascites. Nodular regenerative hyperplasia has been described in association with a variety of different rheumatologic, hematologic, and oncologic diseases, as well as in immune deficiency states and with exposures to certain toxins. Diagnosis is made by histology, and the treatment involves addressing the underlying disease. The first description of this rare disease was actually described in a patient with rheumatoid arthritis, neutropenia, and splenomegaly (Felty's Syndrome). We describe 2 cases of NRH associated with underlying rheumatic disorders, in one of which NRH was actually the presenting feature of the patient's underlying autoimmune condition. Subsequently, we provide a brief review of the literature of NRH in autoimmune disease with respect to epidemiology, cause, clinical manifestations, diagnosis, and treatment.

Keywords: autoimmune; nodular regenerative hyperplasia; portal hypertension; vasculopathy.

Figure 1.

(a) Liver biopsy slides visualized in low magnification with Masson trichome stain, which stains for collagen, shows that there is vague nodularity present. There is an absence of fibrous septa at the periphery of the nodules, which is an important feature which distinguishes NRH from cirrhosis. (b) Reticulin stain from the same area showing nodules (annotated by circles). The reticulin stain allows for appreciation of 2 populations of hepatocytes that differ in size. The nodules themselves are composed of thickened liver cell plates whereas their boundaries consist of thin, parallele, and compressed cell plates. Abbreviation: NRH, nodular regenerative hyperplasia.

Figure 2.

Mesenteric angiography demonstrating microaneurysms in the ileal branches of the superior mesenteric artery (a) and upper pole of the left kidney (b), as seen in polyarteritis nodosa.