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

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.

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.

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

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.

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.