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

Antonia Neonakia, Vasileios Lekakisa, Evangelos Cholongitasa,b

Medical School of National and Kapodistrian University of Athens, “Laiko” General Hospital of Athens, Athens, Greece

aAcademic Department of Gastroenterology (Antonia Neonaki, Vasileios Lekakis, Evangelos Cholongitas); bFirst Department of Internal Medicine (Evangelos Cholongitas), Medical School of National and Kapodistrian University, “Laiko” General Hospital of Athens, Athens

Correspondence to: Evangelos Cholongitas, MD, PhD, Professor in Medicine-Hepatology, First Department of Internal Medicine, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Agiou Thoma 17, 11527 Athens, Greece, e-mail: cholongitas@yahoo.gr
Received 10 April 2024; accepted 29 May 2024; published online 12 July 2024
DOI: https://doi.org/10.20524/aog.2024.0905
© 2024 Hellenic Society of Gastroenterology

Abstract

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.

Keywords Cirrhosis, liver transplantation, cardiovascular autonomic neuropathy, autonomic neuropathy, mortality

Ann Gastroenterol 2024; 37 (5): 588-601

Introduction

Autonomic neuropathy (AN), a disorder of the autonomic nervous system [1], was first studied through the assessment of cardiac AN (CAN) [2]. The latter, a condition of impaired autonomic control of the cardiovascular system, can be evaluated by measuring changes in blood pressure, heart rate and the heart’s electrophysiological activity [3,4]. Cardiovascular autonomic reflex tests (CARTs), assessment of the rate-corrected QT interval (QTc), heart rate variability (HRV), and baroreflex sensitivity (BRS) tests, all represent useful tools in the evaluation of CAN [2,5-8]. CAN is a well-established complication in patients with type 2 diabetes mellitus (T2DM) [9,10], while it has been associated with an increased risk of cardiovascular events and mortality [10,11]. According to a recent meta-analysis of patients with T2DM, in those with CAN, compared to those without CAN, the pooled relative risks for future cardiovascular events and for all-cause mortality were 3.16 (95% confidence interval [CI] 2.42-4.13; P<0.001), and 3.17 (95%CI 2.11-4.78; P<0.001), respectively [12].

AN has also been reported in patients with cirrhosis, and is considered to be the consequence of metabolic, inflammatory, toxic, and immunological changes occurring alongside the establishment of hyperdynamic circulation and portal hypertension [3,13]. Regenerative fibrotic nodules release substances that induce endothelial dysfunction and vasoconstriction [14], while increased portal vein pressure stimulates the synthesis of vasodilators. The subsequent activation of the sympathetic nervous system (SNS) and the renin–angiotensin–aldosterone system (RAAS) contributes to hemodynamic and neurohumoral alterations, potentially leading to autonomic dysfunction [3]. The presence of ascites and decompensated liver disease accentuates the progression of these mechanisms, ultimately contributing to the development of AN in cirrhosis [13].

The prevalence of AN in cirrhosis ranges from 30-67% [15,16]. It is estimated that at least 1 of the CARTs is abnormal in 36-77% of cirrhotics, while a prolonged QTc is observed in 37-84% of cirrhotics [13]. In cirrhosis, AN has also been linked to increased death rates and negative outcomes following liver transplantation (LT) [15-20]. A recent meta-analysis [17] showed a significantly higher survival hazard ratio (HR) in cirrhotic patients with QTc <440 msec, compared to those with QTc >440 msec (HR 2.228, 95%CI: 1.640-2.815; P<0.001). Additionally, a systematic review [19] concluded that low values of HRV indices can predict mortality independently of the severity of cirrhosis. However, the prognostic utility of CART- and BRS-based AN in cirrhosis, as well as the impact of AN before LT on post-LT outcomes, have only been evaluated in a few individual studies, with inconsistent results.

The aim of this systematic review and meta-analysis was to compile and summarize all the relevant studies that provide insight into the predictive role of AN in cirrhosis, as well as the impact of pre-LT AN on the prognosis after LT.

Materials and methods

CAN evaluation

CARTs

CARTs are 5 noninvasive diagnostic tests, including the deep breathing test, the supine-to-stand test, the Valsalva maneuver, the orthostatic hypotension test and the sustained handgrip test [2]. They indirectly assess ANS function by measuring the variability of heart rate and blood pressure. Based on CARTs, CAN is defined on the basis of 1 (possible/early CAN) or ≥2 (definite CAN) positive tests [1].

QTc

The QT interval represents the time from the onset of ventricular depolarization to the end of repolarization [21]. It is measured from the beginning of the QRS complex to the end of the T wave on a standard 12-lead electrocardiogram (ECG) [22]. To account for heart rate variability, the QT interval should be adjusted based on the heart rate.

HRV

HRV analysis provides measures of heart rate variations in an ECG over a short monitoring period, reflecting the balance between the SNS and the parasympathetic nervous system (PNS) [23].

Time domain HRV analysis assesses both the short- and long-term variability of the heart [23-25]. The standard deviation of normal-to-normal (NN) intervals (SDNN) measures the total variability of the time intervals between successive NN heartbeats on an ECG. The root mean square of differences of successive RR intervals (RMSSD) and pNN50 (a time domain HRV parameter that quantifies the percentage of NN intervals that differ from each other by more than 50 msec) provide information about short time intervals and reflect the influence of the PNS on HRV [26-28].

Frequency domain HRV analysis decomposes HRV into specific frequency bands. The high frequency (HF) band is associated with PNS function, while the low frequency (LF) band is associated with both SNS and PNS function. Their ratio LF: HF assesses the balance between SNS and PNS. Poincaré plot analysis uses standard deviation (SD)1 and SD2 values to graphically represent the relationship between 2 consecutive data points in a time series. SD1 and SD2 reflect both the short- and long-term influence of the autonomic nervous system on the heart rate [27,28].

Detrended fluctuation analysis is a complex technique that evaluates long-range correlations or fractal-like patterns within a time series. The slope of the plot, known as the α scaling exponent, gives insight into those long-range correlations in the time series. The Α2 scaling exponent is associated with long-term correlations [29].

BRS test

The BRS test reflects the functionality of arterial baroreceptors, expressing the degree of heart rate variation per unit change in arterial pressure [30]. In recent years, BRS evaluation has been based on noninvasive, computer-assisted analysis of spontaneous fluctuations of cardiovascular variables [31,32].

Data sources and searches

PubMed/Medline was searched from 1992 to September 2023, in accordance with the Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guidelines [33], in order to carry out a systematic review and meta-analysis of observational studies. We aimed to identify all relevant medical literature included under the following search text terms: “Liver cirrhosis”, “Cardiovascular autonomic neuropathy”, “Heart rate variability”, “QT prolongation” and “Baroreflex sensitivity”. In addition, we performed a full manual search of all relevant review articles and original studies. All studies identified from the search were uploaded to Rayyan software, duplicates were removed and 2 independent reviewers (AN, VL) performed title and abstract screening.

Study selection

All studies published in English as full papers were included if they fulfilled all of the following criteria: 1) they were observational studies; 2) they included adults with cirrhosis; 3) they evaluated CAN through CARTs, the HRV test, the BRS test and/or the assessment of QTc; and 4) they compared indices—CARTs, HRV indices, BRS, prolonged QTc (defined as QTc >440/450 msec for men, >470 msec for women—between survivors and non-survivors, or between patients with and without major adverse events post-LT. Exclusion criteria were: 1) review articles, case reports, and letters; 2) duplicated or overlapping studies; and 3) studies published only as abstracts. The process was performed independently by 2 authors (AN, VL).

Data extraction and quality assessment

Data extraction from selected papers was carried out based on a predefined form, in accordance with the PRISMA guidelines (Supplementary Table 1) [33]. The Newcastle–-Ottawa scale [34], which allocates a maximum score of 5 for selection, 2 for comparability, and 2 for outcome, was used to assess the quality of the included studies. Data extracted from selected studies included: country and center(s) of origin, date of publication, first author, type of study, sex, etiology of cirrhosis, Child–-Pugh (CP) and model for end-stage liver disease (MELD) scores, aim of the study, follow-up data, sample and group sizes (sample, survivors/non-survivors, with/without cirrhosis-related complications), CAN/HRV/BRS indices calculated, QTc prolongation definition, hazard/odds ratios, cutoff values for area under receiver operating characteristic curve, LT status, mean CAN/QTc/HRV/BRS values of survivors and non-survivors, or patients with and without major adverse events of cirrhosis, cirrhosis-related complications and peri- or post-LT adverse events.

Data synthesis and statistical analysis

The generalized linear mixed model was used to conduct the meta-analysis [35]. CIs for individual study proportions were determined using the Clopper and Pearson method [36]. Estimation of the between-study variance component (τ2) was achieved through maximum likelihood estimation, utilizing marginal distribution [37]. Heterogeneity was assessed using the I2 statistic, with values of 25%, 50% and 75% indicating low, moderate and high degrees of heterogeneity, respectively [38]. Pooled proportions, along with 95%CI and prediction intervals (PI), were computed [39]. The analysis was carried out using R version 4.3.1, utilizing meta-packages and metaprop functions [40]. In addition, standardized mean differences (SMD) were calculated for each study, using the formula SMD = X1 – X2/SDP, where X1 and X2 represent the means of the experimental and control groups, respectively, and SDp is the pooled standard deviation [41]. We fitted a random-effects meta-analysis model to the calculated effect sizes using the “metafor” package in R. This model allowed for heterogeneity between studies and provided estimates of the overall effect size, along with its confidence interval [38].

Results

A total of 35 articles were initially identified from the literature review that discussed the predictive role of AN in cirrhosis or after LT. However, 10 articles [42-51] were excluded after the full text review; thus, a total of 25 were finally included (Supplementary Fig. 1). Among these, 5 [15,16,52-54], 12 [18,52,55-64], 9 [4,20,65-71], and 1 [20] articles assessed the predictive role of CARTs, prolonged QTc, HRV indices and BRS, respectively. The main characteristics of the included studies are provided in Tables 1, 2 and 3, respectively.

Table 1 Characteristics of studies with available data on CARTs-based AN

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Table 2 Characteristics of studies with available data on prolonged QTc

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Table 3 Characteristics of studies with available data on HRV-based AN

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CARTs

A total of 5 articles discussed the predictive role of CARTs [15,16,52-54]. One retrospective and 4 prospective cohort studies were included, with follow-up durations ranging from 10-50 months.

A total of 336 patients—138 (41%) women, 147 (44%) CP class A, 121 (36%) CP class B, and 68 (20%) CP class C—were evaluated (Table 1).

CARTs and pre-LT mortality

Three studies examined the association between CARTs-based AN and pre-LT mortality in 223 patients [15,16,52]. The pooled mortality rate was significantly higher in patients with CARTs-based AN compared to those without AN: 20% (95%CI 27-14%; heterogeneity I2=0%; P=0.37) vs. 6% (95%CI 2-14%; heterogeneity I2= 0%; P=0.98), P=0.01 (Fig. 1A). Two of the aforementioned studies further examined the association between severity of CARTs-based AN (namely definite vs. possible/early vs. absent CAN) and pre-LT mortality in 163 patients. The pooled mortality was 21% (95%CI 13-32%; heterogeneity I2=0%) vs. 14% (95%CI 7-26%; heterogeneity I2=0%; P=0.55) vs. 5% (95%CI 1-19%; heterogeneity I2=0%; P>0.99), respectively, but the difference was only significant between definite-AN compared to absent-AN (P=0.05) (Fig. 1B).

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Figure 1 (A) Pooled mortality rate in cirrhotic patients with and without CARTs-based AN. (B) Pooled mortality rate in cirrhotic patients according to the severity of AN

CARTs, cardiovascular autonomic reflex tests; AN, autonomic neuropathy

CARTs and complications of cirrhosis

Only 1 study including 72 patients (55 with AN at baseline) assessed the association between CARTs-based AN and the development of major cirrhosis-related complications [53]. During the follow-up period, 30 individuals developed hepatic encephalopathy (HE): patients with AN had a higher incidence of HE, compared to those without (49% vs. 18%), but this difference was not significant (no P-value was provided).

CARTs and peri-transplant risk

One study investigated the association between AN and the perioperative risk of complications in 41 patients [54]. The results showed that patients with AN before LT exhibited higher hemodynamic instability, arterial hypotension, and a greater need for vasopressor therapy during operation for LT, compared to those without AN (Table 1).

QTc

A total of 12 studies (9 retrospective and 3 prospective) investigated the predictive impact of prolonged QTc on cirrhosis, or on peri- and post-LT prognosis [18,52,55-64]. A total of 5020 patients were evaluated (1597 women, 32%). Based on the available data, 1767 (35%) and 801 (16%) patients had ascites and HE, respectively (Table 2).

Prolonged QTc and pre-LT mortality

Four studies assessed the association between prolonged QTc (defined as >440 msec) and mortality in 735 patients with cirrhosis [50,60-62]. One study investigated the 1-year mortality rate in cirrhotics with markedly prolonged QTc (defined as >500 msec) and was therefore excluded from this subgroup analysis [64]. The pooled mortality rate was higher in patients with QTc >440 ms, compared to those with QTc <440 ms—41% (95%CI 19-68%; heterogeneity I2=95%; P=0.04) vs. 18% (95%CI 10-30%; heterogeneity I2=87%; P=0.01)—but this difference was not significant (P=0.08) (Fig. 2A).

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Figure 2 (A) Pooled mortality rate in cirrhotic patients with and without preoperative prolonged QTc in the pre-LT setting. (B) Pooled peri-LT risk of major complications in LT recipients with and without prolonged QTc. (C) Pooled mortality rate in cirrhotic patients with and without preoperative prolonged QTc in the post-LT setting

LT, liver transplantation; CI, confidence interval

Pre-operative prolonged QTc and peri-transplant risk

Four studies examined the peri-transplant risk of major complications in 3748 patients, with vs. without prolonged QTc (defined as longer than 440 msec in 2 studies [18,63] and longer than 450/470 msec for men and women, respectively in 2 studies [59,64]). The recorded perioperative complications were major cardiovascular adverse events [59,63,64], and complications including infections, bleeding and thrombosis [18]. The pooled risk for perioperative complications was higher in patients with prolonged QTc compared to those without prolonged QTc—29% (95%CI 17-45%; heterogeneity I2=97%; P=0.01) vs. 17% (95%CI 13-22%; heterogeneity I2=84%; P<0.001)—but this difference was not significant (P=0.08) (Fig. 2B).

Preoperative prolonged QTc and post-LT prognosis

Six studies assessed the association between preoperative prolonged QTc and post-LT mortality risk in 1472 patients [18,55-59]. The pooled mortality rate was similar between the patients with and without prolonged QTc, defined as longer than 440 msec in 5 studies [18,55-58] and longer than 450/470 msec for men and women, respectively, in 1 study [59]: 15% (95%CI 11-19%; heterogeneity I2 = 66%; P=0.01) vs. 12% (95%CI 8-16%; heterogeneity I2=57%; P=0.04), respectively (P=0.36) (Fig. 2C).

HRV

A total of 9 studies evaluated the predictive role of HRV indices in cirrhosis [4,20,65-71], while no study assessed the impact of pre-LT HRV tests on peri- and post-LT prognosis. All 9 were prospective cohort studies, with a follow-up duration from 3-24 months. A total of 513 patients were included, 174 (34%) women, 172 (34.2%) CP class A, 160 (32%) CP class B, and 170 (33.8%) CP class C (Table 3).

SDNN and pre-LT mortality

A total of 5 studies evaluated the predictive role of SDNN in 356 patients (127 women, 36%), of whom 75 died during the follow- up [4,65-67,69]. A large effect size was observed, with significantly lower SDNN in non-survivors compared to survivors: SMD (95%CI) -2.59 (-4.75 to -0.43); heterogeneity I2=94%; P=0.04 (Fig. 3).

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Figure 3 Standardized mean difference of SDNN values between survivors and non-survivors

SDNN, standard deviation of normal-to-normal (NN) intervals on the surface electrocardiogram; SD, standard deviation; CI, confidence interval

HRV indices in cirrhosis

The limited number of studies available did not allow a meta-analysis of HRV indices other than SDNN. In our systematic research, we found 9 studies that assessed the predictive role of HRV indices in cirrhosis. All studies found that, compared to survivors, non-survivors had lower HRV indices, including corrected SDNN (cSDNN), SDANN, SD1, SD2, VLF, a2 and HF (Table 3), while in 3 studies, this difference was significant regarding SDANN [4,20,73], with a cutoff value of 100 msec (P=0.001, b=19.25, 95%CI -19.86 to -18.3) [69]. The measures a2, SD2 and cSDNN were good predictors of mortality in 4 studies [65,66,68,69], independently of MELD and CP scores, with a cutoff value of 1.07 for a2 (log-rank test, chi square=13.08; P<0.001) [58]. Finally, in 2 studies, lower values of HRV indices (SDNN, HF, LF, total power, HF/LF, SD1, SD2) were significantly associated with an increased risk for HE [70,71].

BRS

Only 1 study assessed the relationship between BRS and mortality in 45 patients with cirrhosis (median age 55 years, 24±11 months follow- up) [20]. The results showed that non-survivors had significantly lower mean values of BRS compared to survivors (6.3±2.5 vs. 9.7±3.6 ms/mmHg; P=0.03). No study assessed the impact of pre-LT BRS on post-LT outcomes.

Discussion

In this systematic review and meta-analysis, we synthesized data from 25 studies that used all the main tools for AN assessment, including CARTs, HRV, QTc, and/or BRS, in order to assess the predictive role of AN in cirrhosis and/or post-LT prognosis. In fact, this is the first meta-analysis to evaluate the predictive role of CARTs and HRV indices in the pre-LT setting, as well as the impact of prolonged pre-LT QTc on the post-LT outcome. Our results reveal an association between CARTs- and HRV-based AN and mortality in patients with cirrhosis, particularly in those with more advanced stages of AN. However, prolonged QTc before LT did not appear to be a predictor of pre- or post-LT risk for adverse events and mortality.

In our meta-analysis, CARTs-based AN was significantly associated with mortality, since cirrhotics with AN had a significantly higher pooled mortality rate compared to those without (20% vs. 6%; P=0.01). Interestingly, when patients with cirrhosis were stratified based on the severity of CAN (namely definite vs. possible vs. absent CAN), the only significantly higher risk of mortality was seen in those with definite CAN, compared to those without CAN (21% vs. 5%; P=0.05). This finding aligns with previous studies in patients with T2DM [12,72] and underscores the importance of specific criteria in AN diagnosis.

In addition, regarding HRV-based AN, we found in this meta-analysis that SDNN in cirrhotic patients differed significantly between survivors and non-survivors (SMD 2.59, 95% CI -4.75 to -0.43; P=0.04). In fact, this is the first meta-analysis to investigate the predictive role of HRV indices, especially SDNN, in cirrhosis. In the literature, there is only 1 previous relevant systematic review [19] that showed an association between HRV indices and mortality in the cirrhotic setting, but the authors did not conduct a meta-analysis because of the limited number of studies included.

Concerning the risk for major cirrhosis-related complications, we were not able to perform a meta-analysis. However, based on our systematic review, we found that lower values of specific time and frequency domain HRV indices were associated with a higher risk for HE [70,71]. Moreover, this association was confirmed in patients with CARTs-based AN [53,54]. Interestingly, HRV indices, particularly SDNN, have been correlated with inflammatory biomarkers [60], while a decrease in SDNN has been associated with the progression to acute decompensation and the development of the inflammatory syndrome in acute-on-chronic liver failure [67]. Thus, it could be suggested that the regular assessment of CAN through CARTs or HRV tests might be a valuable tool for stratifying cirrhotics at heightened risk of major complications or death.

QTc prolongation in cirrhosis reflects a delay in ventricular repolarization, mainly observed in the presence of “cirrhotic cardiomyopathy”, a term used to describe the long-term impact of cirrhosis on the heart. Although there is a well-established association between QTc prolongation and the presence of CAN in T2DM [6], it is controversial in the setting of cirrhosis [52,57,73,74]. Moreover, it is debatable whether QTc is a good predictor of mortality during the clinical course of cirrhosis [60,61], or of peri- and/or postoperative mortality in the case of LT [18,59,63]. A recent meta-analysis with 3 studies indicated significantly better survival in patients with QTc <440 msec (HR 2.228; 95%CI 1.640-2.815; P<0.001) [17]. In our meta-analysis, based on 4 studies with 735 patients, we found that the pooled mortality rate was lower in patients with QTc <440 msec, compared to those with QTc >440 msec (18% vs. 41%, respectively), but this difference was not significant (P=0.08). This discrepancy may be due to the fact that, in our analysis, we used a different statistical methodology based on the absolute number of deaths and the total population at risk in order to mitigate potential bias. Nevertheless, given the limited number of studies included, the high heterogeneity among them, and the different follow-up periods, more studies are needed to better clarify the impact of QTc prolongation on pre-LT mortality. Interestingly, our study represents the first meta-analysis to investigate the predictive impact of prolonged QTc on peri- and post-LT prognosis. Our findings reveal that the cirrhotics with prolonged QTc, compared with those without, had a higher pooled peri-transplant risk of major complications, although the difference was non-significant (29% vs. 17%; P=0.08). This slightly higher perioperative LT risk may be due to additional perioperative stress and the hemodynamic instability, in the setting of reduced ventricular repolarization and diastolic dysfunction, which characterizes cirrhotic cardiomyopathy. In addition, no difference was found in the post-LT pooled mortality rates between the patients with versus those without pre-LT prolonged QTc (15% vs. 12%; P=0.36). This finding is not surprising, given that QTc tends to improve [17] or may even be fully restored after LT in up to 70% of patients [75]. Nevertheless, more research is necessary before final conclusions can be drawn regarding these issues.

Finally, to our knowledge, only 1 study [20] has focused on the predictive role of impaired BRS in cirrhosis. In that study, Genovesi et al [20], concluded that a more severe impairment of BRS was associated with more severe liver dysfunction, worse survival and lower HRV indices.

This meta-analysis represents the first attempt to evaluate the predictive role of all main diagnostic tools for CAN assessment in patients with cirrhosis. Additionally, it is the first study that sought to assess the prognostic ability of preoperative CAN in the peri- and post-LT settings. However, certain limitations should be acknowledged. These include the limited number of studies included in certain subgroup analyses, the variability in the follow-up data, and the absence of several variables, such as data on the etiology of death or the influence of comorbidities. Furthermore, when investigating the impact of QTc prolongation on the peri-transplant risk of major complications, not all studies provided specific details regarding the nature of these complications.

In conclusion, based on our systematic review/meta-analysis, both CARTs- and HRV-based AN were linked to a higher risk of mortality in cirrhotics, as well as the development of adverse events in the pre-LT setting. Preoperative prolonged QTc, on the other hand, did not seem to be associated with pre-, peri- or post-LT adverse events or mortality. Regular assessment of AN, based on CARTs or HRV indices, might be suggested as a useful prognostic tool in cirrhosis. Future research on determining cutoff values for HRV indices in AN diagnosis could aid clinical implementation.

Summary Box

What is already known:

  • Autonomic neuropathy (AN) is a well-established complication in patients with cirrhosis, with a considerably high prevalence

  • AN can be evaluated indirectly through cardiovascular autonomic reflex tests (CARTs), rate-corrected QT (QTc) measurement, heart rate variability (HRV), and baroreflex sensitivity tests

  • In cirrhosis, AN is considered the result of metabolic, inflammatory, toxic and immunological changes that occur alongside the development of hyperdynamic circulation and portal hypertension

What the new findings are:

  • CARTs- and HRV- based AN was associated with mortality in cirrhosis

  • CARTs- and HRV-based AN appears to be associated with an increased risk of cirrhosis-related complications

  • QTc prolongation does not appear to be a predictor of pre- or post-liver transplantation risk for complications or mortality

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Notes

Conflict of Interest: None