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Perioperative use of dexamethasoneglucorticosteroids is a major cofounder of transcriptome analysis of surgical biopsies

ABSTRACT: A significant number of liver biopsies originate from surgery or surgical resection, performed under general anaesthesia, where glucocorticoids, often dexamethasone (DEX), are routinely used as prophylaxis against postoperative nausea and vomiting (PONV) and administered perioperatively. DEX is a potent agonist of the ubiquitously expressed glucocorticoid receptor (GR), rapidly regulating transcription of hundreds of metabolic and inflammatory related genes within 0.5–2 hours of administration. Consequently, the timing and dosing of DEX administration during intraoperative liver biopsy has the potential to profoundly influence gene expression across several cell types and, thus, potentially introduce significant bias in transcriptomic analyses and mask or enhance potential biological effects. To investigate how different biopsy procedures (e.g. preoperative and intraoperative) impact transcriptomes, we performed RNA sequencing on paired liver biopsies from donors at risk of MASLD and enrolled for weight-loss surgery. This included a preoperative percutaneous baseline biopsy and an intraoperative laparoscopic biopsy obtained during weight-loss surgery. To specifically test for DEX effects on surgical biopsies, donors were administered DEX either during induction of anaesthesia or following biopsy collection. Collectively, our results indicate a clear effect of DEX on gene expression analysis of surgical liver and adipose biopsies. As exemplified by the expression of anti-inflammatory genes and the correlative analysis of liver fibrosis, we show that this can confound transcriptomic analysis and mask correlations between gene expression and biomarkers.

ORGANISM(S): Homo sapiens

PROVIDER: GSE320593 | GEO | 2026/10/02

REPOSITORIES: GEO

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Project description:Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of histological findings, from simple steatosis to steatohepatitis (NASH), the latter presenting a higher risk of cardiovascular and kidney diseases, type 2 diabetes and end-stage liver disease. NAFLD is seen as the hepatic manifestation of the metabolic syndrome and affects up to 70-80% of obese patients. There are currently no approved pharmacological therapies for NASH, thus the only option is lifestyle intervention or bariatric surgery in order to lose weight and to improve insulin resistance. Although surgical intervention has allowed collections of liver biopsies, transcriptomic data from livers are still scarce and especially follow-up data to evaluate the impact of weight loss intervention on the liver. Therefore we studied hepatic transcriptomic data in a large cohort of obese patients assessed for presence of NASH at baseline and 1 year follow-up. Patients visiting the obesity clinic of the Antwerp University Hospital for a problem of being overweight (BMI above 25 to 29.9 kg/m²) or obese (BMI above 30 kg/m²) were prospectively recruited and underwent a hepatic work-up. Patients were excluded from further analysis in case of significant alcohol consumption (>20 g/day), history of bariatric surgery, diagnosis of another liver disease, pre-existing diabetes. Patients who were, however, diagnosed with de novo diabetes at baseline or at follow-up were not excluded. If NAFLD was suspected, liver biopsy was proposed. For patients undergoing bariatric surgery (BS), a liver biopsy was proposed regardless of the criteria. Patients were reassessed after 1 year. Liver biopsy was performed percutaneously (16G Menghini) or peri-operatively (14G Tru-Cut). The different histological features of NAFLD were assessed using the NASH Clinical Research Network (NASH CRN) Scoring System. The presence of NASH was defined according to Chalasani et al. necessitating the combined presence of steatosis, ballooning and lobular inflammation.

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Perioperative use of dexamethasoneglucorticosteroids is a major cofounder of transcriptome analysis of surgical biopsies

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