Epigenetics, inflammation and postoperative complications: a scoping review.

Abstract

Excessive postoperative inflammation is associated with multisystem complications after surgery, culminating in morbidity, mortality and increased healthcare costs. Epigenetic modifications regulate gene transcription without altering DNA sequences and can augment powerful inflammatory responses. Translational studies have emerged, investigating how epigenetic mechanisms influence perioperative inflammation and complications. This scoping review consolidates studies in this expanding field and provides informed recommendations for future research. The protocol for this scoping review was created using best-practice guidelines and was prospectively registered and published. Searches were conducted using Medline and Embase and included studies published in English between 1946 and 2025. Two reviewers independently screened titles and abstracts, then full texts of studies before data extraction. Included studies investigated postoperative complications alongside epigenetic mechanisms and inflammation. Studies (n=15 451) were assessed for title and abstract screening, and 26 articles were included in the review. Included studies were published between 2016 and 2025. Cardiac surgery was investigated most often, followed by general and colorectal surgery. Several surgical specialities were not represented. Most studies investigated microRNA mechanisms, investigating either a small number of microRNAs (≤8) or using whole transcriptome approaches. DNA methylation and histone modifications were investigated less commonly. Complications were variably defined in the included studies, and most studies focused on a small number of complications. Inflammation was heterogeneously assessed, with most studies using C-reactive protein and interleukin-6 or both, whereas other studies used broader proteomic approaches to quantify inflammation. DNA methylation and histone modifications are less researched epigenetic mechanisms in perioperative inflammation. Future studies should recruit patients with homogeneous surgical insults. Studies should use standard measures of inflammation to enhance generalisability, whereas experimental approaches (including transcriptomics and proteomics) could advance mechanistic understanding in exploratory studies. Future research would benefit from consistent use of validated definitions of postoperative complications to enable comparison between studies.