Clinical trial NCT02093754: Assessing the Severity of Metabolic-related Liver Injuries in Aging HIV-monoinfected Patients
Official title: Assessing the Severity of Metabolic-related Liver Injuries in Aging HIV-monoinfected Patients: a European Multicentre Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infection
Liver Injuries
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
First posted: 2014-03-21
Enrollment: 460
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: This study will allow to assess liver related injuries in HIV patients.

Detailed description: 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

Eligibility criteria: Inclusion Criteria:

1. Age ≥40 years
2. Infection with HIV-1
3. Cumulative exposure to cART for at least 5 years and currently under cART
4. Viral load \< 400 copies/mL
5. CD4 count \> 100 CD4/mm3
6. 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
7. Informed consent signed prior to any study procedure
8. To be covered by a medical insurance (only for French centres)
9. 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:

1. Coinfection with hepatitis B (positive HBs antigen or isolated positive HBc antibody with positive PCR)
2. Positive HCV serology
3. Coinfection HIV-1 and HIV-2
4. Use of intravenous drugs within the last six months
5. Excessive alcohol intake (male \> 50 g/d, female \> 40 g/d)
6. 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
7. 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
8. Active opportunistic infection except for candida oesophagitis
9. Current Cancer
10. Pregnancy
11. Decompensated heart failure
12. Subject under legal guardianship
13. Inability to give informed consent or incapacitation
14. Contra-indication to MRI: pace-maker, neurovascular surgery, intraocular materials, cochlear implant, severe claustrophobia
15. Participation in another study with an ongoing exclusion period at screening

Primary outcomes:
measure: Percentage of steatosis detected by MRI
timeFrame: Within 6 months after all patients have completed MRI
Secondary outcomes:
measure: Percentage of fibrosis or cirrhosis using non invasive markers and concordance of non invasive markers
timeFrame: Within 6 months after all patients have completed the study
measure: Risk factors (age, duration of infection, treatment, clinical and biological metabolic and adipose tissue parameters) of liver injuries
timeFrame: Within 6 months after all patients have completed the study
measure: Independent risk factors of NAFLD, NASH and fibrosis (including markers of insulin resistance, inflammatory cytokines, markers of immune activation, adipokines)
timeFrame: Within 6 months after all patients have completed the study
measure: Establish a diagnosis score based on biomarkers of liver injuries (Adiponectin, leptin, IL6, CRP, CD14)
timeFrame: Within 6 months after all patients have completed the study
measure: Description of pathogenetic factors and correlates with autophagy in liver biopsies of patients with evidence for liver fibrosis
timeFrame: Within 6 months after all patients have completed the study
measure: 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)
timeFrame: Within 6 months after all patients have completed the study
measure: Impact of IL28B and PNPLA3 genetic polymorphisms on the severity of liver steatosis, inflammation and fibrosis
timeFrame: Within 6 months after all patients have completed the study
measure: Percentage of patients with NASH, fibrosis and cirrhosis on liver biopsy
timeFrame: Within 6 months after all patients have completed the study
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: CHU Brussels
city: Paris
country: France
facility: Hôpital la Salpêtrière
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Berlin
country: Germany
facility: Medical Center for Infectious Diseases
city: Düsseldorf
country: Germany
facility: Center for HIV and Hepato-Gastroenterology
city: Hamburg
country: Germany
facility: University Medical Center
city: Hannover
country: Germany
facility: Hannover Medical School
Study officials:
affiliation: Medical Research Council
name: Maud LEMOINE, MD
role: PRINCIPAL_INVESTIGATOR
References: