Deep learning-based quantification of NAFLD/NASH progression in human liver biopsies.

Journal: Scientific reports
PMID:

Abstract

Non-alcoholic fatty liver disease (NAFLD) affects about 24% of the world's population. Progression of early stages of NAFLD can lead to the more advanced form non-alcoholic steatohepatitis (NASH), and ultimately to cirrhosis or liver cancer. The current gold standard for diagnosis and assessment of NAFLD/NASH is liver biopsy followed by microscopic analysis by a pathologist. The Kleiner score is frequently used for a semi-quantitative assessment of disease progression. In this scoring system the features of active injury (steatosis, inflammation, and ballooning) and a separated fibrosis score are quantified. The procedure is time consuming for pathologists, scores have limited resolution and are subject to variation. We developed an automated deep learning method that provides full reproducibility and higher resolution. The system was established with 296 human liver biopsies and tested on 171 human liver biopsies with pathologist ground truth scores. The method is inspired by the way pathologist's analyze liver biopsies. First, the biopsies are analyzed microscopically for the relevant histopathological features. Subsequently, histopathological features are aggregated to a per-biopsy score. Scores are in the identical numeric range as the pathologist's ballooning, inflammation, steatosis, and fibrosis scores, but on a continuous scale. Resulting scores followed a pathologist's ground truth (quadratic weighted Cohen's κ on the test set: for steatosis 0.66, for inflammation 0.24, for ballooning 0.43, for fibrosis 0.62, and for the NAFLD activity score (NAS) 0.52. Mean absolute errors on a test set: for steatosis 0.29, for inflammation 0.53, for ballooning 0.61, for fibrosis 0.78, and for the NAS 0.77).

Authors

  • Fabian Heinemann
    Drug Discovery Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397, Biberach an der Riß, Germany. fabian.heinemann@boehringer-ingelheim.com.
  • Peter Gross
    Drug Discovery Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397, Biberach an der Riß, Germany.
  • Svetlana Zeveleva
    Cardiometabolic Diseases Research, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT, 06877, USA.
  • Hu Sheng Qian
    Cardiometabolic Diseases Research, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT, 06877, USA.
  • Jon Hill
    Global Computational Biology and Digital Sciences, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT, 06877, USA.
  • Anne Höfer
    Institute of Pathology, Hannover Medical School, and the German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), 30625, Hanover, Germany.
  • Danny Jonigk
    Institute of Pathology, Hannover Medical School, and the German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), 30625, Hanover, Germany.
  • Anna Mae Diehl
    Duke Department of Medicine, Gastroenterology, Lasalle Street, GSRB 1, Durham, NC, 27710, USA.
  • Manal Abdelmalek
    Duke Department of Medicine, Gastroenterology, Lasalle Street, GSRB 1, Durham, NC, 27710, USA.
  • Martin C Lenter
    Drug Discovery Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397, Biberach an der Riß, Germany.
  • Steven S Pullen
    Cardiometabolic Diseases Research, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT, 06877, USA.
  • Paolo Guarnieri
    Cardiometabolic Diseases Research, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT, 06877, USA.
  • Birgit Stierstorfer
    Drug Discovery Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397, Biberach an der Riß, Germany.