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.
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.
Authors: Jens-Peter Kühn; Diego Hernando; Birger Mensel; Paul C Krüger; Till Ittermann; Julia Mayerle; Norbert Hosten; Scott B Reeder Journal: J Magn Reson Imaging Date: 2013-10-10 Impact factor: 4.813
Authors: Nathalie C Leite; Cristiane A Villela-Nogueira; Claudia R L Cardoso; Gil F Salles Journal: World J Gastroenterol Date: 2014-07-14 Impact factor: 5.742
Authors: Takeshi Yokoo; Masoud Shiehmorteza; Gavin Hamilton; Tanya Wolfson; Michael E Schroeder; Michael S Middleton; Mark Bydder; Anthony C Gamst; Yuko Kono; Alexander Kuo; Heather M Patton; Santiago Horgan; Joel E Lavine; Jeffrey B Schwimmer; Claude B Sirlin Journal: Radiology Date: 2011-01-06 Impact factor: 11.105