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

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

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