Predicting Postoperative Liver Dysfunction Based on Blood‐Derived MicroRNA Signatures

Abstract

There is an urgent need for an easily assessable preoperative test to predict postoperative liver function recovery and thereby determine the optimal time point of liver resection, specifically as current markers are often expensive, time consuming, and invasive. Emerging evidence suggests that microRNA (miRNA) signatures represent potent diagnostic, prognostic, and treatment‐response biomarkers for several diseases. Using next‐generation sequencing as an unbiased systematic approach, 554 miRNAs were detected in preoperative plasma of 21 patients suffering from postoperative liver dysfunction (LD) after liver resection and 27 matched controls. Subsequently, we identified a miRNA signature—consisting of miRNAs 151a‐5p, 192‐5p, and 122‐5p—that highly correlated with patients developing postoperative LD after liver resection. The predictive potential for postoperative LD was subsequently confirmed using real‐time PCR in an independent validation cohort of 98 patients. Ultimately, a regression model of the two miRNA ratios 151a‐5p to 192‐5p and 122‐5p to 151a‐5p was found to reliably predict postoperative LD, severe morbidity, prolonged intensive care unit and hospital stays, and even mortality before an operation with a remarkable accuracy, thereby outperforming established markers of postoperative LD. Ultimately, we documented that miRNA ratios closely followed liver function recovery after partial hepatectomy. Conclusion: Our data demonstrate the clinical utility of an miRNA‐based biomarker to support the selection of patients undergoing partial hepatectomy. The dynamical changes during liver function recovery indicate a possible role in individualized patient treatment. Thereby, our data might help to tailor surgical strategies to the specific risk profile of patients.

Reply:

“…In addition, more details on the variables of patients' characteristics should be included in this study. Clarification about the omissions we mention would greatly solidify the conclusions of the study by Starlinger et al (1) Haisu Dai, M.D. Kaicheng Shen, M.D.…”

“…Indeed, plasma albumin levels significantly differed between patients with and without liver dysfunction (LD) in our exploration cohort. (1) As mentioned by the authors, it is already known that decreased plasma albumin levels correlate with perioperative outcome. However, we feel quite confident about our results, as we were able to validate the predictive potential of our microRNA (miRNA) signature in an independent validation cohort in whom no significant differences in albumin levels were observed.…”

Letter to the Editor: Predicting Postoperative Liver Dysfunction Based on Blood Derived MicroRNA Signatures

“…The study by Starlinger et al (1) reported that they have found microRNA (miRNA)-based biomarkers, which could reliably predict postoperative liver dysfunction (LD) after liver resection and dynamically monitor liver function recovery and might represent a very useful tool to define the most suitable time point for liver resection to avoid postoperative LD and complications. More importantly, they showed superior prognostic performance when compared to currently used clinical markers for prediction of postoperative LD.…”

“…We read with interest the study of Starlinger et al (1) evaluating the ability of microRNA signatures to predict postoperative liver dysfunction in patients with liver cancer. The results showed that it could effectively predict postoperative liver dysfunction.…”

“…First, their conclusions showed that preoperative microRNA signatures as a single indicator can effectively predict postoperative liver dysfunction. (1) However, there are many factors affecting liver function after hepatectomy, including preoperative, intraoperative, and postoperative factors. (2) A single preoperative indicator may be difficult to fully and effectively project postoperative liver function, especially for patients with cirrhosis.…”