Histological progression of non-alcoholic fatty liver disease: a critical reassessment based on liver sampling variability

Aliment Pharmacol Ther. 2007 Sep 15;26(6):821-30. doi: 10.1111/j.1365-2036.2007.03425.x.


Background: In non-alcoholic fatty liver disease, histological lesions display a significant sampling variability that is ignored when interpreting histological progression during natural history or therapeutic interventions.

Aim: To provide a method taking into account sampling variability when interpreting crude histological data, and to investigate how this alters the conclusions of available studies.

Methods: Natural history studies detailing histological progression and therapeutic trials were compared with the results of a previously published sampling variability study.

Results: Natural history studies showed an improvement in steatosis, which was significantly higher than expected from sampling variability (47% vs. 8%, P < 0.0001). In contrast, no study showed a change in activity grade or ballooning higher than that of sampling variability. There was only a marginal effect on fibrosis with no convincing demonstration of a worsening of fibrosis, a conclusion contrary to what individual studies have claimed. Some insulin sensitizing drugs and anti-obesity surgery significantly improved steatosis, while most did not significantly impact on fibrosis or activity.

Conclusions: Sampling variability of liver biopsy is an overlooked confounding factor that should be considered systematically when interpreting histological progression in patients with non-alcoholic fatty liver disease.

Publication types

  • Comparative Study

MeSH terms

  • Body Mass Index
  • Data Interpretation, Statistical
  • Disease Progression
  • Female
  • Fibrosis
  • Follow-Up Studies
  • Humans
  • Liver Diseases / diagnosis*
  • Liver Diseases / pathology
  • Liver Extracts / analysis*
  • Male


  • Liver Extracts