Hepato Cellular CarcinomaPSYLIVER-PILOTNCT07393074
PSYLIVER-PILOTE: Involvement of the Autonomic Nervous System in Hepatocellular Carcinoma (HCC)
A study testing Measurements of autonomic nervous system (ANS) activity at rest and during sensory stimulation., Self-administered questionnaires to assess psycho-behavioral traits and Analysis of nocturnal cardiac activity (at home): electrocardiographic (ECG) recording of heart activity during one night. in people with Hepato Cellular Carcinoma and Cirrhosis, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
Chronic liver diseases affect 1.5 billion people worldwide and can lead to cirrhosis and hepatocellular carcinoma (HCC), which ranks as the third leading cause of cancer-related mortality globally. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepato Cellular Carcinoma, Cirrhosis, Autonomic Nervous System
- What is being tested?
- Measurements of autonomic nervous system (ANS) activity at rest and during sensory stimulation., Self-administered questionnaires to assess psycho-behavioral traits and Analysis of nocturnal cardiac activity (at home): electrocardiographic (ECG) recording of heart activity during one night.
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteFrance
- Study dates
- 17 Apr 2026to 17 Apr 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Group A:
- Over 18 years of age
- Affiliated with a social security system
- Sufficient command of the French language to hold a conversation and read
- Signature of an informed consent form
- Compensated cirrhosis classified as CHILD-Pugh A with clinical indication for liver biopsy (either for the etiological diagnosis or confirmation of cirrhosis, or for the etiological diagnosis of liver damage)
Show all 14Show fewer
- Liver biopsy scheduled as part of routine care for a diagnosis of cirrhosis without HCC
- Group B:
- Over 18 years of age
- Affiliated with a social security system
- Sufficient command of the French language to hold a conversation and read
- Signature of an informed consent form
- Compensated cirrhosis classified as CHILD-Pugh A with clinical indication for liver biopsy (either for the etiological diagnosis of cirrhosis or its confirmation; or for the etiological diagnosis of liver damage)
- Liver biopsy scheduled as part of routine care for the diagnosis of suspected HCC (based on standard imaging criteria)
Who cannot join
- Personal history of cancer in the broad sense (including HCC prior to inclusion in the study)
- Pregnant or breastfeeding women
- Adults subject to legal protection measures (guardianship, curatorship)
- Contraindications to trans-parietal liver biopsy: clinical or radiological ascites, coagulation disorders, curative anticoagulation that cannot be suspended, dilation of the bile ducts
- Persons deprived of their liberty by judicial or administrative decision
- Wearers of electronic implants (pacemakers, implantable cardioverter defibrillators, cochlear implants, brain implants, etc.)
Show all 12Show fewer
- Psychotic disorders
- Degenerative neurological disorders (Parkinson's disease and related disorders, dementia, Korsakoff's syndrome, etc.)
- Antiarrhythmic treatment:
- Class Ia: Disopyramide and Quinidine
- Class Ic: Flecainide and Propafenone
- Neuroleptic psychotropic treatment affecting the ANS (haloperidol, chlorpromazine, olanzapine, clozapine, quetiapine), tricyclic antidepressants (e.g., amitriptyline, amoxapine, clomipramine, etc.)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Hôpital de la Croix Rousse
Lyon, 69004
VILLERET François, MD, PhD, +33 4 26 73 27 33, francois.villeret@chu-lyon.fr
About this study
Official title: Involvement of the Autonomic Nervous System in Hepatocellular Carcinoma (HCC): a Pilot Psycho-behavioral and Neurophysiological Study
Chronic liver diseases affect 1.5 billion people worldwide and can lead to cirrhosis and hepatocellular carcinoma (HCC), which ranks as the third leading cause of cancer-related mortality globally. Despite advances in the treatment of hepatitis B and C, metabolic diseases, and addiction, HCC incidence continues to rise. In France, between 2010 and 2015, the five-year survival rate for liver cancer (90% of which is HCC) was 18% for men and 19% for women. Treatment of HCC is based on the BCLC classification (Barcelona Clinic Liver Cancer), which evaluates both cancer progression and liver function (Child-Pugh classification). Patients at early stages (0 or A) have a survival rate of over 5 years, while those at more advanced stages (C or D) have significantly lower survival rates, highlighting the importance of better early detection tools.
Current screening for HCC in cirrhotic patients involves biannual US-scan. However, ultrasound sensitivity for detecting tumors smaller than 2 cm is around 25%. Therefore, developing personalized strategies to predict and detect early-stage HCC is crucial to improving patient outcomes. Various clinical and biological scores have been developed to assess the risk of developing HCC in cirrhotic patients, but these scores remain imperfect. Molecular heterogeneity in HCC, as revealed by transcriptomic studies, could explain the variability in outcomes and treatment responses. This heterogeneity in occurrence, phenotype, and progression of HCC suggests individual singularities that are not yet well understood.
Read more
These individual singularities are likely linked to the autonomic nervous system (ANS), particularly in the central nervous system (CNS), which regulates various physiological processes. The ANS consists of the sympathetic nervous system (SNS), mainly adrenergic, and the parasympathetic nervous system (PNS), mainly cholinergic. These two systems function antagonistically but with different temporal dynamics. A better understanding of the interaction between tumor cells and their environment through the ANS could lead to the identification of new biomarkers to predict HCC development and therapeutic targets.
The role of the ANS in cancer development has been explored in various cancers, including prostate, stomach, pancreatic, breast, and ovarian cancers, where the ANS regulates inflammation and immune responses. In chronic liver diseases, the liver is innervated by both sympathetic and parasympathetic fibers, and this innervation plays a role in regulating metabolism, liver regeneration, and fibrosis progression. Chronic liver disease etiologies, such as alcohol consumption, metabolic syndrome, and viral hepatitis, disrupt the balance between the SNS and PNS, contributing to liver dysfunction. The severity of liver damage is linked to autonomic dysfunction, and heart rate variability, a marker of PNS activity, is correlated with survival in patients with terminal-stage HCC.
Our recent research has shown that patients with HCC exhibit a reconfiguration of the intrahepatic ANS, with a consistent cholinergic orientation at the neuro-hepatic synapse. Patients with parasympathetic orientation (as compared to sympathetic orientation) have more aggressive tumors, shorter survival, and, from a pharmacological perspective, anticholinergics increase sensitivity to targeted HCC therapies. Tumor cells and cytotoxic lymphocytes are most strongly associated with cholinergic receptor enrichment and depletion, respectively.
In this context, the PSYLIVER-PILOTE study builds on these findings by investigating the involvement of the ANS in HCC through non-invasive extra-hepatic measures. The SNS and PNS are connected to brain regions involved in cognitive, emotional, and social information processing, such as the anterior cingulate cortex, insula, ventromedial prefrontal cortex, amygdala, and hypothalamus. These brain areas are involved in cognitive control and emotional processing. Additionally, experimental data from polyvagal theory and neurovisceral integration theory highlight the role of the ANS in regulating cognitive, emotional, and social processes, as well as psycho-behavioral traits. For instance, confronting a person with cognitive tasks and emotional or social information alters the balance of sympathetic and parasympathetic activity. Similar changes are observed in psycho-behavioral disorders like depression, emotional dysregulation, stress, and aggression.
Thus, the PSYLIVER-PILOTE study aims to identify extra-hepatic markers of ANS activity associated with HCC, analyzing both electrophysiological indices (from the peripheral nervous system) and psycho-behavioral indices (from the central nervous system). This project could open new avenues for early HCC detection and the development of personalized treatments
- Being tested
- Measurements of autonomic nervous system (ANS) activity at rest and during sensory stimulation., Self-administered questionnaires to assess psycho-behavioral traits, Analysis of nocturnal cardiac activity (at home): electrocardiographic (ECG) recording of heart activity during one night., Calculation of the NRS score. A study of the liver biopsy will be carried out to analyze ANS activity at the intrahepatic level., Intervention name 5 * (Limit: 100 characters) Optionnal biocollection
- Keywords
- HCC, cirrhosis, ANS, NRS
- Medical subject headings
- Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Measurements of autonomic nervous system (ANS) activity at rest and during sensory stimulation.Other
Participants are informed that they will need to watch the screen, on which images will appear around a central symbol. They must click the mouse button as quickly as possible when they see an "x" sign and do nothing when they see a "+" sign appear in the center of the screen.
Sensory stimulation is carried out using OpenSesame software. It is divided into four blocks of seven minutes each, with a break systematically offered to participants between each block. Each block comprises three phases: rest (sitting with hands on knees, palms facing upwards and eyes closed) for two minutes, responding to stimuli according to instructions for three minutes, and a second rest phase for two minutes. In fact, participants are only active for a total of 12 minutes. The blocks are presented in the same order for all participants: Go block, neutral Go/NoGo block, emotional Go/NoGo block, then social Go/NoGo block.
Self-administered questionnaires to assess psycho-behavioral traitsOther
Participants answer self-questionnaires on tablets by selecting the answer that seems most appropriate to them. They are told that there are no right or wrong answers and that they should answer as honestly as possible based on what they think and feel at that moment. The self-questionnaires are the QA-10 items, the short version of the UPPS-P, the BPAQ-SF, the CERQ, the DEX, the PSS-10, the HAD, and the ISI.
Analysis of nocturnal cardiac activity (at home): electrocardiographic (ECG) recording of heart activity during one night.Other
The investigator presents the NeuroCoach test kit to the participant and gives it to them. This kit consists of a recorder, two electrodes, a single-use pouch for nighttime use, a prepaid envelope for returning the equipment, and installation instructions. The investigator explains the installation instructions for the device, which the participant will set up independently at home.
The equipment used is CE 60601-1 certified (general requirements for basic safety and essential performance of medical electrical equipment). There is a risk of temporary local skin irritation where the electrodes come into contact with the skin.
A prepaid envelope will be given to the patient to return the device.
Calculation of the NRS score. A study of the liver biopsy will be carried out to analyze ANS activity at the intrahepatic level.Other
Liver biopsy is performed as part of routine care. After pathological analysis as part of routine care, the biopsy sample will be sent to the Unité PaThLiv laboratory (UMR UCBL1 INSERM U1350; PathLiv team) for NRS histological scoring.
Intervention name 5 * (Limit: 100 characters) Optionnal biocollectionOther
Venous blood samples (taken during two visits): for a total volume of 32mL(serum, plasma) for the biobank will be aliquoted and stored in cryotubes. Each sample taken will be labeled with the patient's anonymized code (the patient's first and last names will not appear on the tubes). The tubes will be transported to the laboratory (PaThLiv Unit - UMR UCBL1 INSERM U1350; PathLiv Team).
| Study group | Role | What they receive |
|---|---|---|
| Patients with histologically proven cirrhosis based on liver biopsy performed as part of routine car | Experimental | * Information gathering: patient history, medical history and current treatments, clinical examination and available paraclinical tests, assessment of alcohol consumption
* A dedicated consultation at the Croix Rousse hospital to perform:
* Measurements of autonomic nervous system (ANS) activity at rest and during sensory stimulation.
* Self-administered questionnaires to assess psycho-behavioral traits
* Analysis of nocturnal cardiac activity (at home): electrocardiographic (ECG) recording of heart activity during one night.
* A study of the liver biopsy (performed as part of routine care) will be carried out to analyze ANS activity at the intrahepatic level for calculating the NRS score Receives: Other: Measurements of autonomic nervous system (ANS) activity at rest and during sensory stimulation.; Other: Self-administered questionnaires to assess psycho-behavioral traits; Other: Analysis of nocturnal cardiac activity (at home): electrocardiographic (ECG) recording of heart activity during one night.; Other: Calculation of the NRS score. A study of the liver biopsy will be carried out to analyze ANS activity at the intrahepatic level.; Other: Intervention name 5 * (Limit: 100 characters) Optionnal biocollection |
| Patients with cirrhosis complicated by HCC, histologically confirmed by liver biopsy performed as pa | Experimental | * Information gathering: patient history, medical history and current treatments, clinical examination and available paraclinical tests, assessment of alcohol consumption
* A dedicated consultation at the Croix Rousse hospital to perform:
* Measurements of autonomic nervous system (ANS) activity at rest and during sensory stimulation.
* Self-administered questionnaires to assess psycho-behavioral traits
* Analysis of nocturnal cardiac activity (at home): electrocardiographic (ECG) recording of heart activity during one night.
* A study of the liver biopsy (performed as part of routine care) will be carried out to analyze ANS activity at the intrahepatic level for calculating the NRS score Receives: Other: Measurements of autonomic nervous system (ANS) activity at rest and during sensory stimulation.; Other: Self-administered questionnaires to assess psycho-behavioral traits; Other: Analysis of nocturnal cardiac activity (at home): electrocardiographic (ECG) recording of heart activity during one night.; Other: Calculation of the NRS score. A study of the liver biopsy will be carried out to analyze ANS activity at the intrahepatic level.; Other: Intervention name 5 * (Limit: 100 characters) Optionnal biocollection |
What is being measured
The primary outcome is the main question the study is designed to answer.
RNA expression values encoding all adrenergic receptors, and all cholinergic receptors or subunits.
The NRS is based on the RNA expression values of 6 human genes encoding all adrenergic receptors, and 21 genes encoding all cholinergic receptors or subunits.
The NRS is defined by the difference between the sum of the expression values of adrenergic receptors on the one hand, and the sum of the expression values of cholinergic receptors on the other hand. Hence, the lower the NRS, the more cholinergic the sample is.
Measured: At liver biopsy, within 6 months after inclusion
Secondary outcomes (26)
Identify autistic traits
A short screening questionnaire (AQ-10 (Autism Spectrum Quotient - 10 items)) designed to identify autistic traits in adults, focusing on social skills, attention switching, communication, and imagination.
Measured: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
Measure assessing five dimensions of impulsivity
A self-report measure assessing five dimensions of impulsivity: negative urgency, positive urgency, lack of premeditation, lack of perseverance, and sensation seeking.
Measured: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
Measure assessing different aspects of aggression
A questionnaire (BPAQ (Buss-Perry Aggression Questionnaire)) measuring different aspects of aggression, including physical aggression, verbal aggression, anger, and hostility.
Measured: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
Evaluation of the cognitive strategies individuals
A self-report instrument (CERQ (Cognitive Emotion Regulation Questionnaire)) that evaluates the cognitive strategies individuals use to regulate their emotions after experiencing stressful or negative events.
Measured: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
Measure assessing everyday problems related to executive dysfunction
A measure (DEX (Dysexecutive Questionnaire)) assessing everyday problems related to executive dysfunction, such as difficulties with planning, emotional regulation, inhibition, and self-awareness.
Measured: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
Screening to detect symptoms of anxiety and depression
A screening tool (HADS (Hospital Anxiety and Depression Scale)) designed to detect symptoms of anxiety and depression, particularly in medical or clinical settings, while minimizing the influence of physical symptoms.
Measured: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
Measure of heart rate variability
A global measure of heart rate variability (SDNN (Standard Deviation of NN intervals)) reflecting overall autonomic nervous system activity.
Measured: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion
An index of parasympathetic (vagal) activity
An index (pNN50 (Percentage of NN intervals differing by more than 50 ms) of parasympathetic (vagal) activity based on short-term heart rate variability.
Measured: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion
Measure of HRV reflecting parasympathetic nervous system activity.
A time-domain (rMSSD (Root Mean Square of Successive Differences)) measure of HRV mainly reflecting parasympathetic nervous system activity.
Measured: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
Measure of total variance of heart rate variability
The total (Ptot (Total Power)) variance of heart rate variability across all frequency bands, reflecting overall autonomic regulation.
Measured: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
An index (HF (High-Frequency)) of the parasympathetic activity
An index of the parasympathetic activity .
Measured: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
An index often used to estimate the balance between sympathetic and parasympathetic activity
An index (LF/HF-HRV Ratio) often used to estimate the balance between sympathetic and parasympathetic activity (with interpretative limitations).
Measured: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
A measure of cardiac vagal modulation.
A measure (DC (Deceleration Capacity)) of the heart's ability to slow down, reflecting cardiac vagal modulation.
Measured: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
Mesure spectrale du pouls cardiaque
A spectral measure (PIP (Pulse Interval Power)) of pulse interval variability indicating autonomic modulation of heart rate.
Measured: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
A measure associated with slow regulatory mechanisms of the autonomic nervous system
A measure (VLFI (Very Low Frequency Index)) associated with slow regulatory mechanisms of the autonomic nervous system, including thermoregulation and hormonal influences.
Measured: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
A measure of rapid changes in skin conductance
A measure (EDR (Electrodermal Response)) of rapid changes in skin conductance reflecting phasic sympathetic nervous system activity.
Measured: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
A tonic measure of skin conductance
A tonic measure of skin conductance (SCL (Skin Conductance Level)) indicating baseline sympathetic arousal.
Measured: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
A cardiac measure inversely related to sympathetic activity
A cardiac measure inversely (PEP (Pre-Ejection Period)) related to sympathetic activity; shorter PEP reflects increased sympathetic drive.
Measured: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
A frequency-domain measure associated with parasympathetic (vagal) activity and respiratory influences.
A frequency-domain measure (HF-HRV (High-Frequency Heart Rate Variability)) associated with parasympathetic (vagal) activity and respiratory influences.
Measured: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
An index representing overall sympathetic nervous system activation
A composite index (SAI (Sympathetic Activity Index)) representing overall sympathetic nervous system activation.
Measured: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
An index representing overall parasympathetic (vagal) nervous system activity
A composite index (PAI (Parasympathetic Activity Index)) representing overall parasympathetic (vagal) nervous system activity.
Measured: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
An index describing the relative balance between sympathetic and parasympathetic cardiac control
An index (CAB (Cardiac Autonomic Balance)) describing the relative balance between sympathetic and parasympathetic cardiac control
Measured: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion
Measure the contribution of sympathetic activity to cardiac autonomic regulation
A measure (CSAB (Cardiac Sympathetic Autonomic Balance)) emphasizing the contribution of sympathetic activity to cardiac autonomic regulation.
Measured: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion
An indicator of overall effectiveness and flexibility of autonomic control over cardiac function
An indicator (CAR (Cardiac Autonomic Regulation)) of overall effectiveness and flexibility of autonomic control over cardiac function.
Measured: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion
Measure reflecting the efficiency of sympathetic regulation of cardiac activity
A measure (CSAR (Cardiac Sympathetic Autonomic Regulation)) reflecting the efficiency of sympathetic regulation of cardiac activity
Measured: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion
A ratio expressing dominance of sympathetic versus parasympathetic autonomic activity
A ratio (SAI/PAI Ratio) expressing the relative dominance of sympathetic versus parasympathetic autonomic activity.
Measured: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2026
- Study start17 Apr 2026
- Primary completion17 Apr 2028 (estimated)
- Study completion17 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepato Cellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Prospective, single-center, case-control pilot study
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07393074
- Sponsor's protocol ID
- 69HCL25_0750
- Other IDs
- 2025-A01879-40
- Acronym
- PSYLIVER-PILOT
- Status last verified
- Apr 2026
- First submitted
- 13 Jan 2026
- Last updated
- 29 Apr 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Involvement of the Autonomic Nervous System in Hepatocellular Carcinoma (HCC): a Pilot Psycho-behavioral and Neurophysiological Study
- ClinicalTrials.gov ID
- NCT07393074
- Acronym / sponsor ID
- PSYLIVER-PILOT / 69HCL25_0750
- Keywords
- HCC, cirrhosis, ANS, NRS
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 17 Apr 2026 (actual)
- Primary completion
- 17 Apr 2028 (estimated)
- Study completion
- 17 Apr 2028 (estimated)
- First posted
- 6 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Chronic liver diseases affect 1.5 billion people worldwide and can lead to cirrhosis and hepatocellular carcinoma (HCC), which ranks as the third leading cause of cancer-related mortality globally. Despite advances in the treatment of hepatitis B and C, metabolic diseases, and addiction, HCC incidence continues to rise. In France, between 2010 and 2015, the five-year survival rate for liver cancer (90% of which is HCC) was 18% for men and 19% for women. Treatment of HCC is based on the BCLC classification (Barcelona Clinic Liver Cancer), which evaluates both cancer progression and liver function (Child-Pugh classification). Patients at early stages (0 or A) have a survival rate of over 5 years, while those at more advanced stages (C or D) have significantly lower survival rates, highlighting the importance of better early detection tools.
Current screening for HCC in cirrhotic patients involves biannual US-scan. However, ultrasound sensitivity for detecting tumors smaller than 2 cm is around 25%. Therefore, developing personalized strategies to predict and detect early-stage HCC is crucial to improving patient outcomes. Various clinical and biological scores have been developed to assess the risk of developing HCC in cirrhotic patients, but these scores remain imperfect. Molecular heterogeneity in HCC, as revealed by transcriptomic studies, could explain the variability in outcomes and treatment responses. This heterogeneity in occurrence, phenotype, and progression of HCC suggests individual singularities that are not yet well understood.
These individual singularities are likely linked to the autonomic nervous system (ANS), particularly in the central nervous system (CNS), which regulates various physiological processes. The ANS consists of the sympathetic nervous system (SNS), mainly adrenergic, and the parasympathetic nervous system (PNS), mainly cholinergic. These two systems function antagonistically but with different temporal dynamics. A better understanding of the interaction between tumor cells and their environment through the ANS could lead to the identification of new biomarkers to predict HCC development and therapeutic targets.
The role of the ANS in cancer development has been explored in various cancers, including prostate, stomach, pancreatic, breast, and ovarian cancers, where the ANS regulates inflammation and immune responses. In chronic liver diseases, the liver is innervated by both sympathetic and parasympathetic fibers, and this innervation plays a role in regulating metabolism, liver regeneration, and fibrosis progression. Chronic liver disease etiologies, such as alcohol consumption, metabolic syndrome, and viral hepatitis, disrupt the balance between the SNS and PNS, contributing to liver dysfunction. The severity of liver damage is linked to autonomic dysfunction, and heart rate variability, a marker of PNS activity, is correlated with survival in patients with terminal-stage HCC.
Our recent research has shown that patients with HCC exhibit a reconfiguration of the intrahepatic ANS, with a consistent cholinergic orientation at the neuro-hepatic synapse. Patients with parasympathetic orientation (as compared to sympathetic orientation) have more aggressive tumors, shorter survival, and, from a pharmacological perspective, anticholinergics increase sensitivity to targeted HCC therapies. Tumor cells and cytotoxic lymphocytes are most strongly associated with cholinergic receptor enrichment and depletion, respectively.
In this context, the PSYLIVER-PILOTE study builds on these findings by investigating the involvement of the ANS in HCC through non-invasive extra-hepatic measures. The SNS and PNS are connected to brain regions involved in cognitive, emotional, and social information processing, such as the anterior cingulate cortex, insula, ventromedial prefrontal cortex, amygdala, and hypothalamus. These brain areas are involved in cognitive control and emotional processing. Additionally, experimental data from polyvagal theory and neurovisceral integration theory highlight the role of the ANS in regulating cognitive, emotional, and social processes, as well as psycho-behavioral traits. For instance, confronting a person with cognitive tasks and emotional or social information alters the balance of sympathetic and parasympathetic activity. Similar changes are observed in psycho-behavioral disorders like depression, emotional dysregulation, stress, and aggression.
Thus, the PSYLIVER-PILOTE study aims to identify extra-hepatic markers of ANS activity associated with HCC, analyzing both electrophysiological indices (from the peripheral nervous system) and psycho-behavioral indices (from the central nervous system). This project could open new avenues for early HCC detection and the development of personalized treatments
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Prospective, single-center, case-control pilot study
| Arm | Type | Receives |
|---|---|---|
| Patients with histologically proven cirrhosis based on liver biopsy performed as part of routine car | Experimental | Other: Measurements of autonomic nervous system (ANS) activity at rest and during sensory stimulation., Other: Self-administered questionnaires to assess psycho-behavioral traits, Other: Analysis of nocturnal cardiac activity (at home): electrocardiographic (ECG) recording of heart activity during one night., Other: Calculation of the NRS score. A study of the liver biopsy will be carried out to analyze ANS activity at the intrahepatic level., Other: Intervention name 5 * (Limit: 100 characters) Optionnal biocollection* Information gathering: patient history, medical history and current treatments, clinical examination and available paraclinical tests, assessment of alcohol consumption * A dedicated consultation at the Croix Rousse hospital to perform: * Measurements of autonomic nervous system (ANS) activity at rest and during sensory stimulation. * Self-administered questionnaires to assess psycho-behavioral traits * Analysis of nocturnal cardiac activity (at home): electrocardiographic (ECG) recording of heart activity during one night. * A study of the liver biopsy (performed as part of routine care) will be carried out to analyze ANS activity at the intrahepatic level for calculating the NRS score |
| Patients with cirrhosis complicated by HCC, histologically confirmed by liver biopsy performed as pa | Experimental | Other: Measurements of autonomic nervous system (ANS) activity at rest and during sensory stimulation., Other: Self-administered questionnaires to assess psycho-behavioral traits, Other: Analysis of nocturnal cardiac activity (at home): electrocardiographic (ECG) recording of heart activity during one night., Other: Calculation of the NRS score. A study of the liver biopsy will be carried out to analyze ANS activity at the intrahepatic level., Other: Intervention name 5 * (Limit: 100 characters) Optionnal biocollection* Information gathering: patient history, medical history and current treatments, clinical examination and available paraclinical tests, assessment of alcohol consumption * A dedicated consultation at the Croix Rousse hospital to perform: * Measurements of autonomic nervous system (ANS) activity at rest and during sensory stimulation. * Self-administered questionnaires to assess psycho-behavioral traits * Analysis of nocturnal cardiac activity (at home): electrocardiographic (ECG) recording of heart activity during one night. * A study of the liver biopsy (performed as part of routine care) will be carried out to analyze ANS activity at the intrahepatic level for calculating the NRS score |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Over 18 years of age
- Affiliated with a social security system
- Sufficient command of the French language to hold a conversation and read
- Signature of an informed consent form
- Compensated cirrhosis classified as CHILD-Pugh A with clinical indication for liver biopsy (either for the etiological diagnosis or confirmation of cirrhosis, or for the etiological diagnosis of liver damage)
Key exclusion criteria (12 listed)
- Personal history of cancer in the broad sense (including HCC prior to inclusion in the study)
- Pregnant or breastfeeding women
- Adults subject to legal protection measures (guardianship, curatorship)
- Contraindications to trans-parietal liver biopsy: clinical or radiological ascites, coagulation disorders, curative anticoagulation that cannot be suspended, dilation of the bile ducts
- Persons deprived of their liberty by judicial or administrative decision
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Measurements of autonomic nervous system (ANS) activity at rest and during sensory stimulation.Participants are informed that they will need to watch the screen, on which images will appear around a central symbol. They must click the mouse button as quickly as possible when they see an "x" sign and do nothing when they see a "+" sign appear in the center of the screen. Sensory stimulation is carried out using OpenSesame software. It is divided into four blocks of seven minutes each, with a break systematically offered to participants between each block. Each block comprises three phases: rest (sitting with hands on knees, palms facing upwards and eyes closed) for two minutes, responding to stimuli according to instructions for three minutes, and a second rest phase for two minutes. In fact, participants are only active for a total of 12 minutes. The blocks are presented in the same order for all participants: Go block, neutral Go/NoGo block, emotional Go/NoGo block, then social Go/NoGo block. | Other | Patients with cirrhosis complicated by HCC, histologically confirmed by liver biopsy performed as pa, Patients with histologically proven cirrhosis based on liver biopsy performed as part of routine car |
| Self-administered questionnaires to assess psycho-behavioral traitsParticipants answer self-questionnaires on tablets by selecting the answer that seems most appropriate to them. They are told that there are no right or wrong answers and that they should answer as honestly as possible based on what they think and feel at that moment. The self-questionnaires are the QA-10 items, the short version of the UPPS-P, the BPAQ-SF, the CERQ, the DEX, the PSS-10, the HAD, and the ISI. | Other | Patients with cirrhosis complicated by HCC, histologically confirmed by liver biopsy performed as pa, Patients with histologically proven cirrhosis based on liver biopsy performed as part of routine car |
| Analysis of nocturnal cardiac activity (at home): electrocardiographic (ECG) recording of heart activity during one night.The investigator presents the NeuroCoach test kit to the participant and gives it to them. This kit consists of a recorder, two electrodes, a single-use pouch for nighttime use, a prepaid envelope for returning the equipment, and installation instructions. The investigator explains the installation instructions for the device, which the participant will set up independently at home. The equipment used is CE 60601-1 certified (general requirements for basic safety and essential performance of medical electrical equipment). There is a risk of temporary local skin irritation where the electrodes come into contact with the skin. A prepaid envelope will be given to the patient to return the device. | Other | Patients with cirrhosis complicated by HCC, histologically confirmed by liver biopsy performed as pa, Patients with histologically proven cirrhosis based on liver biopsy performed as part of routine car |
| Calculation of the NRS score. A study of the liver biopsy will be carried out to analyze ANS activity at the intrahepatic level.Liver biopsy is performed as part of routine care. After pathological analysis as part of routine care, the biopsy sample will be sent to the Unité PaThLiv laboratory (UMR UCBL1 INSERM U1350; PathLiv team) for NRS histological scoring. | Other | Patients with cirrhosis complicated by HCC, histologically confirmed by liver biopsy performed as pa, Patients with histologically proven cirrhosis based on liver biopsy performed as part of routine car |
| Intervention name 5 * (Limit: 100 characters) Optionnal biocollectionVenous blood samples (taken during two visits): for a total volume of 32mL(serum, plasma) for the biobank will be aliquoted and stored in cryotubes. Each sample taken will be labeled with the patient's anonymized code (the patient's first and last names will not appear on the tubes). The tubes will be transported to the laboratory (PaThLiv Unit - UMR UCBL1 INSERM U1350; PathLiv Team). | Other | Patients with cirrhosis complicated by HCC, histologically confirmed by liver biopsy performed as pa, Patients with histologically proven cirrhosis based on liver biopsy performed as part of routine car |
Primary outcome
RNA expression values encoding all adrenergic receptors, and all cholinergic receptors or subunits.
Time frame: At liver biopsy, within 6 months after inclusion
The NRS is based on the RNA expression values of 6 human genes encoding all adrenergic receptors, and 21 genes encoding all cholinergic receptors or subunits. The NRS is defined by the difference between the sum of the expression values of adrenergic receptors on the one hand, and the sum of the expression values of cholinergic receptors on the other hand. Hence, the lower the NRS, the more cholinergic the sample is.
26 secondary outcomes
Identify autistic traits
Time frame: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
Measure assessing five dimensions of impulsivity
Time frame: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
Measure assessing different aspects of aggression
Time frame: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
Evaluation of the cognitive strategies individuals
Time frame: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
Measure assessing everyday problems related to executive dysfunction
Time frame: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
Screening to detect symptoms of anxiety and depression
Time frame: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
Measure of heart rate variability
Time frame: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion
An index of parasympathetic (vagal) activity
Time frame: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion
Measure of HRV reflecting parasympathetic nervous system activity.
Time frame: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
Measure of total variance of heart rate variability
Time frame: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
An index (HF (High-Frequency)) of the parasympathetic activity
Time frame: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
An index often used to estimate the balance between sympathetic and parasympathetic activity
Time frame: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
A measure of cardiac vagal modulation.
Time frame: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
Mesure spectrale du pouls cardiaque
Time frame: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
A measure associated with slow regulatory mechanisms of the autonomic nervous system
Time frame: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
A measure of rapid changes in skin conductance
Time frame: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
A tonic measure of skin conductance
Time frame: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
A cardiac measure inversely related to sympathetic activity
Time frame: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
A frequency-domain measure associated with parasympathetic (vagal) activity and respiratory influences.
Time frame: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
An index representing overall sympathetic nervous system activation
Time frame: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
An index representing overall parasympathetic (vagal) nervous system activity
Time frame: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
An index describing the relative balance between sympathetic and parasympathetic cardiac control
Time frame: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion
Measure the contribution of sympathetic activity to cardiac autonomic regulation
Time frame: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion
An indicator of overall effectiveness and flexibility of autonomic control over cardiac function
Time frame: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion
Measure reflecting the efficiency of sympathetic regulation of cardiac activity
Time frame: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion
A ratio expressing dominance of sympathetic versus parasympathetic autonomic activity
Time frame: During the visit, before the liver biopsy, within a maximum of 6 months after inclusion.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Measurements of autonomic nervous system (ANS) activity at rest and during sensory stimulation., Self-administered questionnaires to assess psycho-behavioral traits and Analysis of nocturnal cardiac activity (at home): electrocardiographic (ECG) recording of heart activity during one night. in people with Hepato Cellular Carcinoma and Cirrhosis, run by Hospices Civils de Lyon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dr VILLERET François (+33 4 26 73 27 33, francois.villeret@chu-lyon.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
RNA expression values encoding all adrenergic receptors, and all cholinergic receptors or subunits. (time frame: At liver biopsy, within 6 months after inclusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2026.