Meta-Analysis
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Sep 27, 2023; 15(9): 1060-1083
Published online Sep 27, 2023. doi: 10.4254/wjh.v15.i9.1060
Corrected QT interval in cirrhosis: A systematic review and meta-analysis
Vasileios Periklis Papadopoulos, Konstantinos Mimidis
Vasileios Periklis Papadopoulos, Dialysis, AKESIOS Dialysis Center, Xanthi 67150, Greece
Konstantinos Mimidis, First Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis 68100, Greece
Author contributions: Papadopoulos VP contributed to design of the study; Papadopoulos VP and Mimidis K contributed to conception of the study, acquisition, analysis and interpretation of the data, and drafting of the manuscript; and all authors gave final approval of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Vasileios Periklis Papadopoulos, MD, MSc, PhD, Consultant Physician-Scientist, Research Fellow, Dialysis, AKESIOS Dialysis Center, Vaniano, Xanthi 67150, Greece. vaspapmd@gmail.com
Received: July 16, 2023
Peer-review started: July 16, 2023
First decision: August 4, 2023
Revised: August 13, 2023
Accepted: August 29, 2023
Article in press: August 29, 2023
Published online: September 27, 2023
Processing time: 67 Days and 15.7 Hours
Abstract
BACKGROUND

Corrected QT (QTc) interval is prolonged in patients with liver cirrhosis and has been proposed to correlate with the severity of the disease. However, the effects of sex, age, severity, and etiology of cirrhosis on QTc have not been elucidated. At the same time, the role of treatment, acute illness, and liver transplantation (Tx) remains largely unknown.

AIM

To determine the mean QTc in patients with cirrhosis, assess whether QTc is prolonged in patients with cirrhosis, and investigate whether QTc is affected by factors such as sex, age, severity, etiology, treatment, acute illness, and liver Tx.

METHODS

In the present systematic review and meta-analysis, the searching protocol “{[QTc] OR [QT interval] OR [QT-interval] OR [Q-T syndrome]} AND {[cirrhosis] OR [Child-Pugh] OR [MELD]}” was applied in PubMed, EMBASE, and Google Scholar databases to identify studies that reported QTc in patients with cirrhosis and published after 1998. Seventy-three studies were considered eligible. Data concerning first author, year of publication, type of study, method used, sample size, mean age, female ratio, alcoholic etiology of cirrhosis ratio, Child-Pugh A/B/C ratio, mean model for end-stage liver disease (MELD) score, treatment with β-blockers, episode of acute gastrointestinal bleeding, formula for QT correction, mean pulse rate, QTc in patients with cirrhosis and controls, and QTc according to etiology of cirrhosis, sex, Child-Pugh stage, MELD score, and liver Tx status (pre-Tx/post-Tx) were retrieved. The Newcastle-Ottawa quality assessment scale appraised the quality of the eligible studies. Effect estimates, expressed as proportions or standardized mean differences, were combined using the random-effects, generic inverse variance method of DerSimonian and Laird. Subgroup, sensitivity analysis, and meta-regressions were applied to assess heterogeneity. The study has been registered in the PROSPERO database (CRD42023416595).

RESULTS

QTc combined mean in patients with cirrhosis was 444.8 ms [95% confidence interval (CI): 440.4-449.2; P < 0.001 when compared with the upper normal limit of 440 ms], presenting high heterogeneity (I2 = 97.5%; 95%CI: 97.2%-97.8%); both Egger’s and Begg’s tests showed non-significance. QTc was elongated in patients with cirrhosis compared with controls (P < 0.001). QTc was longer in patients with Child-Pugh C cirrhosis when compared with Child-Pugh B and A (P < 0.001); Child-Pugh B patients presented longer QTc when compared with Child-Pugh A patients (P = 0.003). The MELD score was higher in patients with cirrhosis with QTc > 440 ms when compared with QTc ≤ 440 ms (P < 0.001). No correlation of QTc with age (P = 0.693), sex (P = 0.753), or etiology (P = 0.418) was detected. β-blockers shortened QTc (P< 0.001). QTc was prolonged during acute gastrointestinal bleeding (P = 0.020). Tx tended to improve QTc (P < 0.001). No other sources of QTc heterogeneity were revealed.

CONCLUSION

QTc is prolonged in cirrhosis independently of sex, age, and etiology but is correlated with severity and affected by β-blockers and acute gastrointestinal bleeding. QTc is improved after liver Tx.

Keywords: Liver cirrhosis; Corrected QT interval; Child-Pugh stage; Model for end-stage liver disease score; Liver transplantation; Meta-analysis

Core Tip: Corrected QT (QTc) interval is prolonged in patients with liver cirrhosis and has been proposed to correlate with the severity of the disease. The QTc upper normal limit in cirrhosis is widely debated. Moreover, the effects of sex, age, Child-Pugh stage, model for end-stage liver disease score, and etiology of cirrhosis have not been elucidated, while the role of liver transplantation has been largely unknown. The present study is the first systematic review and meta-analysis focusing on the topics mentioned above, thus aiming to determine whether QTc interval is a useful, easy, and inexpensive tool in the assessment of liver cirrhosis by clinicians.