Nodular regenerative hyperplasia

Nodular regenerative hyperplasia of the liver is the histopathological entity characterized by transformation of normal hepatic parenchyma into small nodules of hyperplastic hepatocytes without intervening fibrosis. It falls within the spectrum of porto-sinusoidal vascular disease and is one of the morphological lesions that can be seen with the clinical diagnosis of idiopathic/noncirrhotic portal hypertension ¹.

Epidemiology

The prevalence among liver biopsies is about 4% ². Among those referred for unexplained liver enzyme abnormalities, the prevalence is higher at 15% ².

Associations

Nodular regenerative hyperplasia has been associated with a wide variety of systemic diseases including rheumatologic disorders (eg, systemic lupus erythematosus), myeloproliferative disorders, solid organ transplantation, chemotherapy, celiac disease, and inflammatory bowel disease ^3,5.

Clinical presentation

The lesion present with liver enzyme/function test abnormalities with or without clinical evidence of portal hypertension ¹. Only about one-third of patients have portal hypertension at the time of diagnosis ².

Pathology

The pathogenesis is not well understood. In many but not all cases ², obstructive/obliterative portal venopathy causes irregular perfusion of the parenchyma, resulting in a hyperproliferative remodeling that is vaguely nodular ^3,4.

Location

Nodular regenerative hyperplasia occurs throughout the liver preferentially around portal tracts ¹.

Macroscopic appearance

Nodular regenerative hyperplasia is characterized by micronodular transformation of liver parenchyma, with the nodules usually 1-3 mm in size but can be larger if confluent ¹. The liver surface can be smooth or irregular ¹.

Note that larger (grossly visible) nodules in the perihilar region that have similar histological features are sometimes referred to as partial nodular transformation ⁴. Large regenerative nodules associated with Budd-Chiari syndrome have previously been described as "focal" nodular regenerative hyperplasia ⁵, but such usage is a misnomer and these entities are now considered separate ⁶.

Microscopic appearance

The nodules are composed of hyperplastic hepatocytes centrally and rimmed by atrophic cell plates ¹. Reticulin stain highlights a condensed reticulin network but not the dense septa of cirrhosis ³. The nodules are ill-defined as they are not limited by fibrosis. They can compress central veins and cause sinusoidal dilatation.

Radiographic features

Imaging findings of nodular regenerative hyperplasia can be subtle across modalities as the nodules are ill-defined and not hyperenhancing compared to normal parenchyma ^5,6. The liver surface is often nodular, mimicking cirrhosis. In addition, there may be features of portal hypertension and the portal vein may show wall thickening and dilatation ^4,5. However, elastography shows lower liver stiffness than in advanced fibrosis/cirrhosis ^4,7.

Ultrasound

The appearance of small isoechoic nodules with a thin hyperechoic rim has been termed coral atoll-like lesions ⁸.

Differential diagnosis

The main alternative consideration for liver surface nodularity is regenerative nodules in cirrhosis. Multiple nodules can also be seen with large regenerative nodules in Budd-Chiari syndrome, but these are hypervascular ⁶. Liver biopsy is required for establishing the diagnosis, but interobserver agreement is low ⁹.