Liver & intrahepatic bile ducts

Benign / nonneoplastic

Nodular regenerative hyperplasia

Last author update: 1 February 2012
Last staff update: 27 April 2023 (update in progress)

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PubMed Search: Nodular regenerative hyperplasia liver

Deepali Jain, M.D.
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Cite this page: Jain D. Nodular regenerative hyperplasia. website. Accessed September 30th, 2023.
Definition / general
  • Nodular hyperplasia diffusely affecting entire liver but with no / minimal fibrous septa
  • Partial nodular transformation:
    • Very rare, focal form of nodular regenerative hyperplasia, usually perihilar region
    • Portal hypertension usually prominent due to portal venous thrombosis
Clinical features
  • Incidental finding at autopsy in 1 - 3%; present in 5% of elderly
  • Develops at all ages but usually symptomatic at ≥ 40 years old
  • Associated with portal hypertension, connective tissue disease (rheumatoid arthritis, polyarteritis nodosa), myeloproliferative or lymphoproliferative disorders, vascular disorders, chemotherapy or immunosuppressive drugs (Arch Pathol Lab Med 2004;128:49), HIV, CHF, Felty syndrome
  • May be part of the early noncirrhotic stages of primary biliary cirrhosis
  • May be due to moderate to severe sclerosis of small portal veins, portal venous thrombosis or arteriosclerosis causing heterogeneous blood flow, variable ischemia and reactive hepatocyte hyperplasia
  • Mildly elevated alkaline phosphatase, gamma GT, normal alpha fetoprotein
Gross description
  • Heavy liver in patients with myeloproliferative disorders, otherwise normal
  • Finely granular capsule, parenchyma has multiple tan white nodules, 0.1 to 1 cm, separated by congested parenchyma
  • Large nodules may exhibit hemorrhage or necrosis
  • May resemble metastatic carcinoma or cirrhosis
Microscopic (histologic) description
  • Diffuse nodules of hyperplastic hepatocytes with central, single portal tract but with different orientation at low power
  • Regions of internodular hepatocyte atrophy, usually centrilobular, associated with areas of hepatocyte regeneration (plump hepatocytes with pale cytoplasm), sinusoidal congestion / dilation and compression of central veins making them difficult to identify
  • No / minimal fibrosis
  • Hepatocyte plates are usually 2 - 3 cells thick compared to thin plates in atrophic areas
  • Hepatocytes may have clear / vacuolated cytoplasm, cholestasis associated with pseudoglandular spaces, variable large cell change
  • No lipofuscin in atrophic hepatocytes
  • No / rare extramedullary hematopoiesis, no / minimal inflammation
  • On biopsy, apparent lack of central veins and presence of curvilinear areas of congestion are suggestive
  • Partial nodular transformation:
    • Nonfibrotic nodules in liver near porta hepatis
    • Regenerating hepatocytes with thickened cell plates compressing adjacent single cell plates (highlighted with reticulin stain); normal portal tracts
    • Nodules are larger than nodular regenerative hyperplasia
Positive stains
  • Reticulin highlights nodular architecture and hepatocyte atrophy
  • Trichrome highlights compressed central veins
Differential diagnosis
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