Benign liver tumours: understanding molecular physiology to adapt clinical management

Nat Rev Gastroenterol Hepatol. 2022 Nov;19(11):703-716. doi: 10.1038/s41575-022-00643-5. Epub 2022 Jul 14.


Improvements in understanding the pathophysiology of the different benign liver nodules have refined their nosological classification. New criteria have been identified using imaging, histology and molecular analyses for a precise diagnosis of these tumours. Improvement in the classification of liver tumours provides a more accurate prediction of disease progression and has modified patient management. Haemangioma and focal nodular hyperplasia, the most common benign liver tumours that develop in the absence of chronic liver disease, are usually easy to diagnose on imaging and do not require specific treatment. However, hepatocellular adenomas and cirrhotic macronodules can be difficult to discriminate from hepatocellular carcinoma. The molecular subtyping of hepatocellular adenomas in five major subgroups defined by HNF1A inactivation, β-catenin mutation in exon 3 or exon 7/8, and activation of inflammatory or Hedgehog pathways helps to identify the tumours at risk of malignant transformation or bleeding. New clinical, biological and molecular tools have gradually been included in diagnostic and treatment algorithms to classify benign liver tumours and improve patient management. This Review aims to explain the main pathogenic mechanisms of benign liver tumours and how this knowledge could influence clinical practice.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma, Liver Cell* / diagnosis
  • Adenoma, Liver Cell* / genetics
  • Adenoma, Liver Cell* / therapy
  • Carcinoma, Hepatocellular* / pathology
  • Focal Nodular Hyperplasia* / diagnosis
  • Focal Nodular Hyperplasia* / pathology
  • Focal Nodular Hyperplasia* / therapy
  • Hedgehog Proteins / genetics
  • Humans
  • Liver / pathology
  • Liver Neoplasms* / diagnosis
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / therapy


  • Hedgehog Proteins