Clinical trial NCT04190498: Sleep Apnoea Syndrome and Hepatocellular Carcinoma
Official title: Evaluation of the Prevalence of Sleep Apnea Syndrome in Patients With Hepatocellular Carcinoma
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Sleep Apnea, Obstructive
Hepatocellular Carcinoma
Non Alcoholic Steato Hepatitis
Keywords: Sleep Apnea, Obstructive
Hepatocellular carcinoma
Non Alcoholic Steato Hepatitis
hepatitis C virus
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
First posted: 2019-12-09
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients will prospectively included in the French Liver Biobanks network - INCa, BB-0033-00085 (CRB-Foie). Patients suffering from a NASH-related or HCV-related hepatocellular carcinoma who were only treated by surgery will be selected.

Each NASH-related HCC patient will be adjusted with two HCV-related HCC patients based on a propensity score according to their age range, sex, BMI, tumor stage.

For each patient, the duration of the study will be 1 month maximum, with only one visit for inclusion. Survival data at 12 and 24 months will be from the medical record and will not require a visit. The total duration of study will be 48 months.

Brief summary: Obstructive sleep apnea (OSA), one of the most frequent respiratory diseases, could represent a major worsening factor in a non alcoholic steatohepatitis and neoplastic context. Our hypothesis is that OSA promotes the prevalence of HCC related to NASH. This national, multicenter study aims to compare the prevalence of OSA in a group of patient curatively resected for NASH-related HCC with a group of HCV-related HCC.

Detailed description: Obstructive Sleep Apnea (OSA) is a common respiratory disease characterized by the occurrence of recurrent episodes of partial or total obstruction of the upper airway called hypopneas and apneas respectively. These episodes are associated with the repetitive occurrence of the desaturation-reoxygenation sequences, the so-called chronic intermittent hypoxia (IH) which is the major stimulus underlying main cardiovascular, metabolic consequences and pro-inflammatory state found in patients with OSA. Recent data from cohort studies have established that OSA is an even greater risk factor for cancer-related mortality. Hepatocellular carcinoma (HCC) is the second cancer related death worldwide and has an increasing impact in developed countries. The epidemic of metabolic syndrome (MS) plays a growing role in the occurrence of metabolic steatohepatitis (NASH) related HCC. Concerning transition from NASH to NASH-related HCC, neither the frequency nor the underlying mechanism are known. Very recently, a link between OSA (IH) and NASH has been highlighted. OSA and intermittent hypoxia should be a major worsening factor in a neoplastic context. Our hypothesis is that OSA promotes the prevalence of HCC in a context of NASH.

The objective is to compare the prevalence of OSA between patients with NASH-related and hepatitis C virus (HCV)-related HCC. In this type 3, cross-sectional, multicenter, national, non-randomized study patients suffering from a NASH-related or HCV-related hepatocellular carcinoma will be recruited. Investigators expect to show a higher prevalence of OSA in patients with HCC NASH-related but also a shorter overall survival. Complementary ex vivo studies on tumor samples will be conducted in order to explore the mechanisms by which OSA and IH would promote carcinogenesis

Eligibility criteria: Inclusion Criteria:

* Man and woman
* \>18 years
* Diagnosis of NASH-induced HCC or HCV-induced HCC
* Patients treated by surgical excision
* Patients not opposed to the study

Exclusion Criteria:

* Patient refusal
* Alcohol consumption\> 20g / day for women and\> 30g / day for men
* Patient with HCV genotype 3
* Tumor vascular invasion identified preoperatively
* Other etiologies of hepatopathies (alcoholic, viral B, autoimmune, hemochromatosis)
* Other chronic respiratory diseases: chronic obstructive pulmonary disease, respiratory insufficiency
* Patient weight variation \>5% since surgical treatment of his HCC
* Subject deprived of liberty or under guardianship

Primary outcomes:
measure: The study will compare OSA prevalence in a group of patient curatively resected for NASH-related HCC with a group of HCV-related HCC.
timeFrame: 2 years
Secondary outcomes:
measure: The study will compare the 3% oxygen desaturation index between groups.
timeFrame: 2 years
measure: The study will compare the 2% oxygen desaturation index between groups.
timeFrame: 2 years
measure: The study will compare the 4% oxygen desaturation index between groups.
timeFrame: 2 years
measure: This study will compare the number of micro-arousals between groups.
timeFrame: 2 years
measure: This study will compare the time spent with a saturation less than 90 % between groups.
timeFrame: 2 years
measure: This study will compare the Pittsburgh Sleep Quality Index (PSQI) between groups.
timeFrame: 2 years
measure: This study will compare the Epworth Sleepiness Score between groups.
timeFrame: 2 years
measure: The study will compare the prevalence of OSA in patients with NASH-induced CHC with cirrhotic context compared to NASH-induced CHC patients without cirrhosis.
timeFrame: 2 years
measure: The study will compare the NAFLD Activity Score (NAS score) between OSA and non-OSA subgroups of NASH patients.
timeFrame: 2 years
measure: The study will compare the Brunt score between OSA and non-OSA subgroups of NASH patients.
timeFrame: 2 Years
measure: The study will compare the METAVIR score data between HCV OSA and HCV non-OSA patients.
timeFrame: 2 Years
measure: The study will compare BCLC classification of HCC tumor between groups.
timeFrame: 2 years
measure: The study will compare HCC tumor size between each groups.
timeFrame: 2 years
measure: The study will compare HCC tumor differentiation degree between groups.
timeFrame: 2 years
measure: The study will compare vascular invasion of HCC tumor between groups.
timeFrame: 2 years
measure: The study will compare the number of satellite nodules of HCC between between groups.
timeFrame: 2 years
measure: The study will compare plasma alpha fetoprotein level between groups.
timeFrame: 2 years
measure: The study will compare overall survival rate between groups.
timeFrame: 2 years
measure: The study will compare tumor-free survival rate between groups.
timeFrame: 2 years
measure: The study will compare non-recurrence-free survival rate between groups.
timeFrame: 2 years
Other outcomes:
Locations:
city: La Tronche
country: France
facility: Minovés-Kotzki
state: Rhones-Alpes
Study officials:
affiliation: University Hospital, Grenoble
name: Jean-Louis Pépin, MD,PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Grenoble
name: Thomas Decaens, MD,PHD
role: PRINCIPAL_INVESTIGATOR
References: