European Journal of Cardiovascular Medicine

Liver cirrhosis is a progressive chronic liver disease associated not only with hepatic dysfunction and portal hypertension but also with systemic complications such as autonomic nervous system (ANS) dysfunction. Autonomic neuropathy in cirrhotic patients often goes unrecognized but plays a significant role in disease progression and prognosis. Studies have shown that autonomic dysfunction, particularly reduced heart rate variability (HRV), is common and correlates with increasing Child-Pugh and MELD scores, indicating worsening liver function.   Heart rate indices such as SDNN and RMSSD have been validated as markers for both severity and portal hypertension.  Furthermore, recent evidence shows that HRV complexity improves significantly after liver transplantation, suggesting that cirrhotic autonomic impairment is at least partially reversible.  Given its prevalence and prognostic relevance, routine assessment of ANS function in patients with cirrhosis may offer valuable insights into clinical management and risk stratification.

We undertook this study to systematically assess autonomic function in cirrhotic patients of any etiology, identify the pattern of autonomic impairment, and evaluate its correlation with liver disease severity. By including both parasympathetic and sympathetic function tests and classifying patients based on Child-Pugh score, this study aims to clarify the clinical relevance of autonomic neuropathy in cirrhosis. Understanding this relationship may help integrate autonomic testing into routine assessment and potentially guide risk stratification and therapeutic decisions.

Aim: To evaluate the presence and extent of autonomic nervous system dysfunction in patients diagnosed with hepatic cirrhosis.

This study was conducted after obtaining ethical clearance and informed consent. Thirty patients with clinically and radiologically confirmed liver cirrhosis (of any etiology) and thirty age- and sex-matched healthy controls were included. Cirrhotic patients were classified according to the Child-Pugh scoring system into Class A, B, or C. Inclusion criteria included age above 20 years and confirmed cirrhosis, while patients with diabetes mellitus, ischemic heart disease, arrhythmias, cardiac failure, emphysema, or those on medications known to affect autonomic function were excluded. Each participant underwent a detailed clinical and biochemical evaluation. Autonomic function tests were performed to assess both sympathetic and parasympathetic activity. Sympathetic tests included postural fall in blood pressure, cold pressor test, and sustained handgrip, while parasympathetic tests included heart rate variation with deep breathing (E/I ratio), Valsalva maneuver, and heart rate response to standing (30:15 ratio). ECG (Lead II) and standard sphygmomanometry were used for recordings. Each test was performed three times, and the average was recorded. Statistical analysis was carried out using Student’s t-test, Chi-square test, and ANOVA, with significance set at p < 0.05.

A total of 60 subjects were included in the study 30 cirrhotic patients (Group II) and 30 age- and sex-matched healthy controls (Group I). The age range in both groups was 31–80 years. The mean age in Group I was 51.33 ± 4.54 years, and in Group II was 53.57 ± 9.03 years, with no significant difference (p = 0.231). Males constituted 66.67% of Group I and 70% of Group II (p = 0.781). (Table 1)

Table 1: Demographic parameters

Among cirrhotic patients, the most common etiology was alcohol-related liver disease (56.67%), followed by HCV (23.33%), cryptogenic (16.67%), and HBV (3.33%). Based on the Child-Pugh classification, 5 patients were in Class A, 10 in Class B, and 15 in Class C. Baseline cardiovascular parameters showed a significantly higher mean heart rate (85.63 ± 13.21 bpm) and systolic blood pressure (147.63 ± 21.72 mmHg) in Group II compared to controls (p < 0.001 and p = 0.024, respectively). Diastolic pressure differences were also significant (p = 0.014).

Table 2: Comparison of Autonomic Function Parameters between Cirrhotic Patients and Healthy Controls

Autonomic function tests revealed that parasympathetic dysfunction was most prominent in Group II. The mean expiration/inspiration (E/I) ratio was significantly reduced in cirrhotics (1.17 ± 0.18) versus controls (1.48 ± 0.18; p < 0.001), with 60% showing abnormal values. Valsalva ratio and lying-to-standing ratio were similarly decreased in cirrhotics (p < 0.001), with 56.7% and 33.3% abnormal results respectively. (Table 2)

Sympathetic function also showed significant impairment. Postural fall in SBP (21.53 ± 9.91 mmHg vs. 5.40 ± 1.86 mmHg) and diminished responses to cold pressor and hand grip tests were observed in cirrhotics (p < 0.001). Specifically, 46.7% had an abnormal handgrip response and 43.3% had abnormal postural SBP fall.

Table 3: Comparison of Autonomic Function Parameters across Child-Pugh Categories in Cirrhotic Patients

When analyzed across Child-Pugh classes, autonomic dysfunction increased significantly with disease severity. E/I ratio, Valsalva ratio, L/S ratio, and all sympathetic responses progressively worsened from Class A to C (p < 0.001 for all). Class A patients showed no autonomic dysfunction. In Class B, 70% had parasympathetic impairment (5 early, 2 definite), while in Class C, 73.3% showed combined parasympathetic and sympathetic dysfunction. Notably, sympathetic dysfunction never occurred in isolation. (Table 3)

Our study revealed that 73.3% of patients with hepatic cirrhosis exhibited autonomic dysfunction, with a strong correlation between dysfunction severity and Child-Pugh class. Parasympathetic abnormalities were more frequent and appeared earlier than sympathetic dysfunction. This aligns with recent findings by Miceli et al.,   who reported that heart rate variability (HRV) indices such as SDNN and RMSSD declined significantly with worsening liver function and were independently associated with portal hypertension and disease progression.

In our cohort, the E/I ratio was the most frequently altered test, similar to the findings of Choudhary et al., who demonstrated that HRV-derived parasympathetic dysfunction reliably distinguished cirrhotic patients from healthy controls with over 80% diagnostic accuracy. The reduction in Valsalva and Lying/Standing ratios reinforces this pattern of early parasympathetic involvement, which has also been documented in studies by Gentile et al.  and Annese et al.,  where parasympathetic dysfunction predominated, especially in patients with fatigue or primary biliary cirrhosis.

Sympathetic dysfunction, observed mostly in Child-Pugh Class C patients, likely represents a later-stage decompensatory failure. This finding is in accordance with Paternostro et al., who emphasized that impaired autonomic cardiac regulation in advanced cirrhosis significantly predicted mortality. Tandon et al.  Similarly found that autonomic cardiovascular control worsens in proportion to hepatic dysfunction, and may help forecast clinical deterioration. Importantly, autonomic dysfunction may be at least partially reversible. A 2024 study by Shih et al.  showed that HRV complexity normalized within one week of liver transplantation, even before full clinical recovery, highlighting the functional nature of the dysautonomia. This was also supported by Newton et al., who observed significant autonomic recovery post-transplant in patients with primary biliary cirrhosis.

A recent systematic review by Farias et al.   also confirmed that autonomic dysfunction in cirrhosis triples the risk of perioperative complications and short-term mortality, reinforcing its prognostic value. Furthermore, Wong et al.  highlighted that autonomic failure is central to the pathophysiology of cirrhotic cardiomyopathy, further supporting its clinical importance.

Overall, our findings support the routine use of bedside autonomic tests for risk stratification, especially in patients progressing toward decompensation. Future studies should include larger cohorts and continuous HRV monitoring to better define therapeutic windows.

Autonomic dysfunction is a common and clinically significant complication of hepatic cirrhosis, observed in over 70% of patients in our study, with severity increasing in parallel with Child-Pugh class. Parasympathetic abnormalities typically appear early, while combined sympathetic and parasympathetic dysfunction becomes more evident in advanced stages. Tests such as the expiration/inspiration ratio, Valsalva ratio, and postural blood pressure changes proved to be effective in identifying these impairments. Importantly, the reversibility of autonomic dysfunction post-liver transplantation emphasizes its functional nature and the importance of timely detection. Incorporating simple, non-invasive autonomic testing into routine evaluation may enhance risk stratification, guide clinical decision-making, and improve overall management in patients with cirrhosis.

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