The predictive role of autonomic neuropathy in pre- and post-liver transplantation outcomes: a systematic review and meta-analysis

Background: Autonomic neuropathy (AN) in cirrhotic patients has been linked to a higher risk of cirrhosis-related complications and worse outcomes before, during or after liver transplantation (LT). However, only a few studies exist with inconsistent results. Methods: We searched for all articles published until September 2023 that described a diagnosis of AN based on cardiovascular autonomic reflex tests (CARTs), assessment of the rate-corrected QT interval (QTc), heart rate variability (HRV), and baroreflex sensitivity (BRS) tests, in order to evaluate the predictive role of AN in cirrhosis and/or peri-/post-LT prognosis. Results: Twenty-five studies were included: 5, 12, 9, and 1 study, respectively, assessed the predictive role of CARTs, prolonged QTc, HRV indices, and BRS in cirrhosis or peri-/post-LT prognosis. In CARTs-based analysis, the pre-LT pooled mortality rate was significantly higher in cirrhotics with AN compared to those without AN (20% vs. 6%; P=0.01). However, no difference was found between patients with and without pre-LT prolonged QTc in the pre-LT pooled mortality rates (41% vs. 18%; P=0.08), pooled peri-transplant risk of major complications (29% vs. 17%; P=0.08) or post-LT pooled mortality rates (15% vs. 12%; P=0.36). In HRV-based analysis, the standard deviation of normal-to-normal intervals was significantly lower in non-survivors, compared to survivors with cirrhosis: standardized mean difference -2.59, 95% confidence interval -4.75 to -0.43; P=0.04. Conclusions: The presence of CARTs- and HRV-based AN was a good predictor of mortality in the pre-LT setting. Preoperative prolonged QTc did not seem to be associated with the outcome before or after LT.