Abstract

Liver fibrosis is the major determinant of liver related complications in patients with non-alcoholic fatty liver disease (NAFLD). A gut microbiota signature has been explored to predict advanced fibrosis in NAFLD patients. The aim of this study was to validate and compare the diagnostic performance of gut microbiota-based approaches to simple non-invasive tools for the prediction of advanced fibrosis in NAFLD. 16S rRNA gene sequencing was performed in a cohort of 83 biopsy-proven NAFLD patients and 13 patients with non-invasively diagnosed NAFLD-cirrhosis. Random Forest models based on clinical data and sequencing results were compared with transient elastography, the NAFLD fibrosis score (NFS) and FIB-4 index. A Random Forest model containing clinical features and bacterial taxa achieved an area under the curve (AUC) of 0.87 which was only marginally superior to a model without microbiota features (AUC 0.85). The model that aimed to validate a published algorithm achieved an AUC of 0.71. AUC’s for NFS and FIB-4 index were 0.86 and 0.85. Transient elastography performed best with an AUC of 0.93. Gut microbiota signatures might help to predict advanced fibrosis in NAFLD. However, transient elastography achieved the best diagnostic performance for the detection of NAFLD patients at risk for disease progression.

Highlights

  • Liver fibrosis is the major determinant of liver related complications in patients with non-alcoholic fatty liver disease (NAFLD)

  • Several non-invasive tests such as the NAFLD fibrosis score (NFS)[6] and fibrosis-4 index (FIB-4) index[7] have been developed and included into a diagnostic algorithm proposed by the European Association for the Study of the Liver[8]

  • The aim of this study was to validate the diagnostic accuracy of the gut microbiota-based prediction model published by Loomba et al.[15], to compare the results to an own Random Forest model including clinical features and 16S rRNA gene sequencing data and to compare the results to the NFS and FIB-4 index as well as transient elastography as ultrasound-based method for the prediction of advanced fibrosis in 96 NAFLD patients

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Summary

Introduction

Liver fibrosis is the major determinant of liver related complications in patients with non-alcoholic fatty liver disease (NAFLD). Loomba et al were the first, who precisely and non-invasively identified NAFLD patients with advanced fibrosis (F3-F4) by using a machine learning algorithm which combined the abundance of specific gut microbial taxa and clinical features[15] This Random Forest algorithm has not been validated so far. The aim of this study was to validate the diagnostic accuracy of the gut microbiota-based prediction model published by Loomba et al.[15], to compare the results to an own Random Forest model including clinical features and 16S rRNA gene sequencing data and to compare the results to the NFS and FIB-4 index as well as transient elastography as ultrasound-based method for the prediction of advanced fibrosis (fibrosis stage F3-F4) in 96 NAFLD patients

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