HCC Innervation Assessment

NCT06886763 | Active Not Recruiting

• 1 other identifier: 69HCL24_1190
• Study Type: observational
• Target: 300
• Locations: 2 countries
• Sites: 2

Brief Summary

Primary liver cancer casualties are ranked 3rd worldwide and are still on the rise despite the recent advent of adequate hepatitis B and C therapies. Genetic diseases of the liver and hepatic comorbidities, such as alcoholic liver disease and metabolic syndrome with metabolic-associated steatohepatitis, are long-term cooperators or independent factors fostering the onset of hepatocellular carcinoma (HCC) and enhancing disease heterogeneity. Though HCC is known to develop in 90% of cases of cirrhosis, its onset and clinical outcomes, in terms of phenotypes and speed of progression, are highly variable from one patient to another. Despite the identification of several potential therapeutic targets, most drugs have failed to exceed the efficacy of currently available compounds. Treatments with tyrosine kinase inhibitors for instance lead to short-term, unavoidable relapse, whereas treatment with immune checkpoints inhibitors or growth factors inhibitors currently provide some hope for only a minority of patients with unresectable HCC. In this respect, cellular/tissular structures linking the general pathophysiology of the patient with HCC may be of interest, as they are patient-specific and may uncover novel ways of defining stratification criteria. In line with such notions, several recent original papers and related commentaries highlighted the relevance of studying cancer neurosciences of peripheral organs. In that context, pathological innervation and autonomous nervous system involvement or dysregulation have been identified in ovarian, prostate, gastric and pancreatic cancers, nurturing tumor stroma and conferring stronger carcinogenic properties. Moreover, the autonomic nervous system post-synaptic receptors have been shown to be favorably actionable in some experimental conditions in cancer. The autonomic nervous system comprises the sympathetic (adrenergic signaling) and parasympathetic (cholinergic signaling) arms that relay signals both ways along the brain-liver neural axis in order to regulate involuntary functions of the body by adjusting its internal functions, after an external stimulus. The liver is an innervated organ that hosts autonomic afferent and efferent autonomic nervous system nerves, in constant communication with the central nervous system through the brainstem. Afferent and efferent nerves are made of adrenergic (relies on epinephrine or norepinephrine as its neurotransmitter, stress signal) and cholinergic (relies on acetylcholine as its neurotransmitter, resting signal) fibers that each convey mediators to regulate liver functions in real-time. As a consequence, as also notably pointed out by Tracey's theory and evidence for cholinergic blockade of inflammation, these signals also regulate several processes that may directly or indirectly impact HCC onset and growth. However, data on the association between HCC and neural factors are scarce and sometimes conflicting. It was reported that portal hypertension, a recognized risk factor for HCC development and recurrence, is correlated with autonomic nervous system dysfunction. In addition, proliferation of hepatocytic progenitors, instrumental in HCC, is impaired by adrenergic signaling. Conversely, cholinergic signaling was shown to attenuate apoptosis in the mouse liver, and liver angiogenesis is under positive sympathetic regulation. Interestingly, human liver autonomic nervous system innervation is more developed than in rodents. Indeed, it extends deeper into the lobule, increasing its capacities of regulation. This latter notion suggests that autonomic nervous system-related mechanisms observed in animals may play more important roles in humans. The primary goal of this study is to assess the innervation of tumor and peritumor tissues in HCC patients who undergo liver resection or liver transplant.

Conditions

Hepatocarcinoma

Outcome Measures

Primary Outcomes (1)

• Assessment of morphological parameters (mature, immature, sympathetic and parasympathetic nerves) of innervation of peritumoral and tumor tissue using tissue transparisation (clearing) techniques.

  Outcome measure will be assessed immediately after the surgery on fresh tissues. No follow-up is required.

Study Arms (1)

Patients with HCC candidates for hepatectomy or liver transplantation, with and without treatment

Other: Liver innervation markers

Interventions

Liver innervation markers OTHER

Liver innervation markers will be quantified immediately after resection by transparisation technique.

Patients with HCC candidates for hepatectomy or liver transplantation, with and without treatment

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

300 patients with hepatocarcinoma who undergo surgical resection or liver transplant will be recruited at Hospitals of Lyon (GHN, GHS)

You may qualify if:

• Patients with hepatocarcinoma who undergo surgical resection or liver transplant
• Patients with and without treatment

You may not qualify if:

• \- Pregnant or lactating women
• Minor patient
• Patient under legal protection measure or deprived of their liberty

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (2)

Groupement hospitalier Sud, Hospices Civils de Lyon

France, 69230, Egypt

Location

Groupement Hospitalier Nord, Hospices Civils de Lyon

France, 69004, France

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2025
• First Posted: March 20, 2025
• Study Start: June 30, 2024
• Primary Completion (Estimated): April 30, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: March 20, 2025

Record last verified: 2025-03

Locations

FR (1); EG (1)