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Hepatic transcriptome signatures in patients with varying degrees of nonalcoholic fatty liver disease compared with healthy normal-weight individuals

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Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of conditions ranging from simple steatosis (NAFL), over non-alcoholic steatohepatitis (NASH) with or without fibrosis, to cirrhosis with end-stage disease. The hepatic molecular events underlying the development of NAFLD and transition to NASH are poorly understood. The present study aimed to determine hepatic transcriptome dynamics in patients with NAFL or NASH compared to healthy normal-weight and obese individuals. RNA sequencing and quantitative histomorphometry of liver fat, inflammation and fibrosis was performed on liver biopsies obtained from healthy normal weight (n=14) and obese (n=12) individuals, NAFL (n=15) and NASH (n=16) patients. Normal weight and obese subjects showed normal liver histology and comparable gene expression profiles. Liver transcriptome signatures were largely overlapping in NAFL and NASH patients, however, clearly separated from healthy normal-weight and obese controls. Most marked pathway perturbations identified in both NAFL and NASH were associated with markers of lipid metabolism, immunomodulation, extracellular matrix remodeling and cell cycle control. Interestingly, NASH patients with positive Sonic hedgehog hepatocyte staining showed distinct transcriptome and histomorphometric changes compared to NAFL. In conclusion, application of immunohistochemical markers of hepatocyte injury may serve as a more objective tool for distinguishing NASH from NAFL, facilitating improved resolution of hepatic molecular changes associated with progression of NAFLD.

Original languageEnglish
JournalAmerican Journal of Physiology: Gastrointestinal and Liver Physiology
Volume316
Issue number4
Pages (from-to)462-472
ISSN0193-1857
DOIs
Publication statusPublished - 1 Apr 2019

    Research areas

  • Histomorphometry, Nonalcoholic fatty liver disease, Nonalcoholic steatohepatitis, Transcriptomics

ID: 56275008