Assessing the Severity of Metabolic-related Liver Injuries in Aging HIV-monoinfected Patients

Study Overview
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Brief Summary
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This study will allow to assess liver related injuries in HIV patients.

Detailed Description
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This study is a cross-sectional, multicentre study including 7 centres from 3 European countries (Belgium, France, Germany). The maximum duration of the study for each patient will be 4 months, consisting of: a screening visit, an inclusion visit to perform the biologic tests and exams necessary for the study, within 1 month after the screening visit, a result delivery visit within 1 month after inclusion visit, to disclose results of previous investigations. Patients with one or two non invasive markers suggesting significant fibrosis (≥F2) will be invited for liver biopsy within the next 2 months. a liver biopsy visit, within 2 months after visit 2, liver biopsy in selected and consented patients

Official Title
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Assessing the Severity of Metabolic-related Liver Injuries in Aging HIV-monoinfected Patients: a European Multicentre Study

Conditions
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HIV Infection, Liver Injuries

Intervention / Treatment
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* Procedure: MRI and biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥40 years Infection with HIV-1 Cumulative exposure to cART for at least 5 years and currently under cART Viral load < 400 copies/mL CD4 count > 100 CD4/mm3 Female may be eligible to enter and participate in the study if she: is of non-child-bearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or is of child-bearing potential with a negative blood pregnancy test at screening visit Informed consent signed prior to any study procedure To be covered by a medical insurance (only for French centres) Presence of: the metabolic syndrome as defined by the most recent international consensus definition (Alberti et al. Circulation 2009) including three components among the following criteria: visceral obesity (waist circumference: Europeans and Africans ≥ 94 cm for men and ≥ 80 cm for women, Americans ≥ 102 cm for men and ≥ 88 cm for women, Asians ≥ 90 cm for men and ≥ 80 cm for women) blood glucose ≥ 1 g/L (5,6 mmol/L) or anti-diabetic treatment, serum triglycerides ≥ 1,5 g/L (1,7 mmol/L) or hypertriglycerides treatment, serum HDL cholesterol < 0,4 g/L (1 mmol/L) for men and < 0,5 g/L (1,3 mmol/L) for women or hypercholesterolemia treatment, blood pressure (Diastolic ≥130 mmHg and/or Systolic ≥ 85 mmHg) or antihypertensive treatment and/or clinical lipoatrophy and/or lipohypertrophy using clinical questionnaires used and validated in previous published studies (ANRS 121 Hippocampe trial), and/or chronic elevated transaminases ≥ 1.5 ULN and / or GGT ≥ 2 ULN confirmed by two blood samples within at least three-month interval over twelve months prior screening visit. Exclusion Criteria: Coinfection with hepatitis B (positive HBs antigen or isolated positive HBc antibody with positive PCR) Positive HCV serology Coinfection HIV-1 and HIV-2 Use of intravenous drugs within the last six months Excessive alcohol intake (male > 50 g/d, female > 40 g/d) Other causes of liver diseases i.e: viral hepatitis, hemochromatosis, Wilson disease, autoimmune hepatitis, primary or secondary biliary cirrhosis, primary or secondary cholangitis, α1 antitrypsine deficiency Other causes of liver steatosis: current steroid therapy, current therapy with amiodarone, tamoxifen, methotrexate, nifedipine, or hycanthone; history of cancer chemotherapy; short bowel syndrome, polycystic ovarian syndrome, Weber-Christian disease Active opportunistic infection except for candida oesophagitis Current Cancer Pregnancy Decompensated heart failure Subject under legal guardianship Inability to give informed consent or incapacitation Contra-indication to MRI: pace-maker, neurovascular surgery, intraocular materials, cochlear implant, severe claustrophobia Participation in another study with an ongoing exclusion period at screening

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: MRI and biopsy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of steatosis detected by MRI |  | Within 6 months after all patients have completed MRI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of fibrosis or cirrhosis using non invasive markers and concordance of non invasive markers |  | Within 6 months after all patients have completed the study | 
| Risk factors (age, duration of infection, treatment, clinical and biological metabolic and adipose tissue parameters) of liver injuries |  | Within 6 months after all patients have completed the study | 
| Independent risk factors of NAFLD, NASH and fibrosis (including markers of insulin resistance, inflammatory cytokines, markers of immune activation, adipokines) |  | Within 6 months after all patients have completed the study | 
| Establish a diagnosis score based on biomarkers of liver injuries (Adiponectin, leptin, IL6, CRP, CD14) | Quantifiable levels of serum adiponectin, serum leptin, serum HS-IL-6, HS-CRP, serum s-CD14 will be measured. | Within 6 months after all patients have completed the study | 
| Description of pathogenetic factors and correlates with autophagy in liver biopsies of patients with evidence for liver fibrosis | Autophagosome formation in the liver biopsies (only for patients presenting liver fibrosis equal or > 2 will be quantified. | Within 6 months after all patients have completed the study | 
| Identification of features of the adaptive immune system associated to NAFLD, NASH and fibrosis (T cell activation, surface expression of Treg, NK cells, NKT cells) | Quantifiable levels of T cell activation (in PBMC), Frequency and phenotype of Tregs (in PBMC), Quantifiable levels of NK cells (in PBMC), Quantifiable levels of Th17 and γδ T cell (in PBMC), Quantifiable levels of Plasma LPS and LPB (sCD163, CD26, Cytokeratin 18) will be measured. | Within 6 months after all patients have completed the study | 
| Impact of IL28B and PNPLA3 genetic polymorphisms on the severity of liver steatosis, inflammation and fibrosis |  | Within 6 months after all patients have completed the study | 
| Percentage of patients with NASH, fibrosis and cirrhosis on liver biopsy |  | Within 6 months after all patients have completed the study |