FIbrosis and Steatosis in Patients With Psychiatric Illness (FibroPsy)

• ClinicalTrials.gov Identifier: NCT05965232
• Recruitment Status: Completed
• First Posted: July 28, 2023
• Last Update Posted: July 28, 2023
• Sponsor: Centre Hospitalier Esquirol
• Information provided by (Responsible Party): Philippe Nubukpo, Centre Hospitalier Esquirol

Study Description

Brief Summary:

Background: Severe psychiatric diseases (schizophrenia, bipolarity, depression, anxious syndrome) are often associated with a metabolic syndrome, including Non-Alcoholic Steato Hepatitis, probably misdiagnosed in patients with psychiatric illness. Furthermore, long-term exposition to substances like alcohol or to one or more psychotropic treatments may involve liver detoxification role. Thanks to liver stiffness, based on FibroScan®, and CAP (controlled attenuation parameter), we wanted to study prevalence of severe fibrosis and steatosis in this population.

Material & Methods: Prospective study of 385 subjects hospitalised in a psychiatric hospital for schizophrenia, bipolar disorder, depression or anxiety-depression disorder and receiving psychotropic treatment for at least 2 years, for whom a FibroScan®, a blood test and a record of clinical data were carried out, after information and informed consent.

Benefits expected : This study should show an expected excess risk of fibrosis. FibroScan® in this population and determine the risk factors more associated risk factors. Generalized or targeted screening for identified risk factors in this population could help optimize in this population could help optimize the choice and dosage of psychotropic of psychotropic drugs, and above all, help to guide the strategy of hepatic and prevention strategy.

Condition or disease	Intervention/treatment
Severe Bipolar I Disorder (Diagnosis); Bipolar I Disorder, Most Recent Episode Mixed, in Remission; Depression Psychotic Feature; Mood-Incongruent Delusion	Diagnostic Test: Fibroscan

Detailed Description:

Patients with psychiatric illness are often exposed to an increase risk of mortality compared to the general population: a reduction of life expectancy between 7 and 24 years has been described . Somatic illnesses explain 60% of this excess of mortality, particularly cardiovascular diseases . Notably, patients with chronic psychiatric disorders, such as depression, bipolar disorders or schizophrenia are more frequently exposed to metabolic syndrome. A recent meta-analysis showed that patients with severe mental illness had a RR of 1.58 (1.35-1.86) of developing metabolic syndrome.

Steatosis, or fat excess in hepatocytes defines NAFLD (non-alcoholic fatty liver disease). NAFLD is a spectrum of liver illnesses associated with metabolic syndrome. Within NAFLD, NASH (non-alcoholic steatohepatitis) occurs in about 5 % of the cases, liver inflammation and/or fibrosis being associated to steatosis: Survival is then impaired, notably with a specific risk of cirrhosis in 20% of the patients with NASH and 3 % of patients with NAFLD . Hepatocarcinoma is a complication of cirrhosis but it may be observed in the absence of cirrhosis in nearly 30% of the cases. Its prevalence is progressively increasing, from 20 to 27%. It will probably be the leading cause of liver transplantation in the next years Otherwise, patients with NAFLD are also exposed to non-liver related complications: cardiovascular risk is higher in this population and is the main risk of mortality.

Although NAFLD is a frequent disease, it is yet generally misdiagnosed today, essentially because of the lack of symptoms and of systematic screening. Furthermore, it is key to diagnose the evolutionary stage: pure NAFLD, NASH and stage of fibrosis. The liver biopsy remains the gold standard, despite its limitations linked to the sample variability and the differences in interpretation even between expert pathologists.

However, specific risks associated with this procedure, such as bleeding and even a marginal risk of death have been described. Furthermore, liver biopsy is costly. All these arguments explain the difficulty to apply this invasive strategy in screening in the general population. That's why different methods, based on non-invasive tests, were developed to diagnose fibrosis - the main prognostic factor - and more recently in a more preliminary way to assess steatosis and inflammation. Two main methods are used to evaluate fibrosis stage: serum biomarkers and liver stiffness. Serum biomarkers are non-parametric (for example NAFLD fibrosis score, Fib4, Forns score and more recently, eLIFT.) or parametric (for example FibroTest, FibroMeter.). Liver stiffness is mainly assessed by FibroScan: it is easily available, and reproducible. It was largely validated in different liver diseases, including NAFLD. Steatosis is simultaneously evaluated, thanks to CAP (controlled attenuation parameter.). Strategies based on the associations of different markers have been evaluated to increase sensibility and specificity of each method taken alone to assess fibrosis. Specific combinations of elastometry and biomarkers have emerged, such as FibroMeterVCTE, and FAST.

In the psychiatric field, NAFLD screening may be important to help to identify patients at liver risk and also at a potential metabolic risk especially since a specific management is available.

Even if the association between NAFLD and psychiatric disorders has been described, its exact prevalence and impact are not well identified.

This is why we aimed to explore the prevalence of liver fibrosis and steatosis in patients with chronic psychiatric illnesses. We led a prospective descriptive single-center study in the Esquirol psychiatric hospital in Limoges.

Study Design

• Study Type: Observational
• Actual Enrollment: 385 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Screening for Severe Hepatic Fibrosis by FibroScan in a Population Presenting a Severe Psychiatric Disorder Under Treatment for at Least Two Years.
• Actual Study Start Date: October 26, 2017
• Actual Primary Completion Date: February 8, 2018
• Actual Study Completion Date: July 12, 2021

Groups and Cohorts

Intervention Details:

• Diagnostic Test: Fibroscan

  Performing FibroScan :

  The patient is positioned supine, with the right arm in maximum abduction to clear the intercostal spaces.The measurement itself is performed on the right lobe of the liver via the intercostal (intersection of the mid-axillary line and the xiphoid process) using a dedicated probe (3.5 MHz) after application of a conduction gel to the skin. FibroScan® examinations are carried out by personnel trained in the use of the device.This training is specific and validated by the device's manufacturer manufacturer, EchosensTM (Paris). Ten valid measurements at the same measurement point in the right liver must be be performed, with an interquartile range/median ratio ≤ 30 (required only if the elastometry value is > 7.1 KPa.

  Other Name: Blood sample

Outcome Measures

Primary Outcome Measures :

1. Severe fibrosis assessed by FibroScan® in the population of subjects with a severe psychiatric disorder who have been on psychotropic medication for more than than two years [ Time Frame: one day ]
   The cut-off selected for FibroScan® ≥ 8.7 kPa is that published for the diagnosis of severe fibrosis. It is considered clinically relevant associated with a poorer prognosis.

Biospecimen Retention:   Samples With DNA

1 dry tube to obtain serum (7 mL) and one heparinized tube for whole blood (7 mL) will be collected

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

Subjects hospitalised in a psychiatric hospital for schizophrenia, bipolar disorder, depression or anxiety-depression disorder and receiving psychotropic treatment for at least 2 years,

Criteria

Inclusion Criteria:

• Patients with a severe psychiatric disorder (psychotic disorder, mood disorder, anxiety or anxiety disorder), and under psychotropic treatment (neuroleptic and/or antidepressant) for at least two years.

and/or antidepressant) for at least two years, and hospitalized in units treating these disorders in the investigating centers.

- Subjects or their legal representatives who have given informed consent, with social insurance, aged over 18 years of age.

Exclusion Criteria:

• Short-term life-threatening conditions
• Liver disease already diagnosed at inclusion: cancer, cirrhosis, chronic or acute or acute liver disease
• No antipsychotic or antidepressant treatment
• Anti-viral treatment demonstrating infection with hepatitis viruses or the HIV virus (or known positive HIV serology)

Contacts and Locations

Locations

France

Centre Hospitalier Esquirol

Limoges, France, 87025

Sponsors and Collaborators

Centre Hospitalier Esquirol

Investigators

• Principal Investigator: Philippe B NUBUKPO, PhD; Centre Hospitalier Esquirol

More Information

• Responsible Party: Philippe Nubukpo, Professor, Centre Hospitalier Esquirol
• ClinicalTrials.gov Identifier: NCT05965232
• Other Study ID Numbers: 2017-A01998-45
• First Posted: July 28, 2023
• Last Update Posted: July 28, 2023
• Last Verified: July 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Delusions; Behavioral Symptoms