Evaluation of Liver Fibrosis in HIV-infected Patients With Metabolic Syndrome

Study Overview
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Brief Summary
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This study aims to estimate the prevalence of bridging liver fibrosis and cirrhosis (METAVIR score ≥ F2) according to METAVIR score in HIV infected patients not chronically infected by viral hepatitis but exhibiting a metabolic syndrome according to the IDF definition (International Diabetes Foundation).

Detailed Description
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HIV-associated morbidity and mortality has been considerably modified ever since the availability of potent antiretroviral treatment in 1996. Recent studies have shown the impact of treatment, with the decreased frequency of AIDS-related diseases coinciding with the preponderance of non-AIDS related pathologies. Consequently, diseases of hepatic origin have become a key problem in the therapeutic course of HIV-infected patients, representing a major source of significant morbidity and mortality. Liver-related diseases comprise of various etiologies, including co-infection with chronic viral hepatitis and excessive alcohol consumption. When excluding these particular diseases, fibrotic patients exhibit an elevated prevalence of metabolic syndrome, regardless of lipodystrophy. Directly linked to metabolic syndrome, non-alcoholic hepatic steatosis has the capacity to induce necro-inflammatory lesions with an increased risk of evolving into cirrhosis and its complications thereto (i.e. hepatocellular carcinoma, liver decompensation, and end-stage liver disease). In the context of HIV, very little data is available concerning the link between metabolic syndrome and hepatic fibrosis, despite the increasing risk of developing such disease during extended life-span, the long-term disruption of glycolipid metabolism induced by antiretroviral treatment, and the presence of various social risk-factors (i.e. increasing trends in weight gain and decreased physical activity). The principal objective of the present study is to then characterize the prevalence and determinants associated with hepatic fibrosis among HIV-infected patients, without co-infection with other hepatitis viruses, and who present symptoms of metabolic syndrome according to the AHA 2009 definition. In order to more appropriately answer this research question, we will conduct a nested, matched case-control study including 300 HIV-infected patients per group. We will also aim to identify risk-factors of liver fibrosis other than metabolic syndrome, to study agreement in 4 non-invasive scores of liver fibrosis and 3 non-invasive score of steatosis, and to evaluate the performance of the Controlled Attenuation Parameter (CAP) method for use in diagnosing hepatic steatosis. All patients in this study will be recruited in a clinical center situated in the infectious disease unit at Saint-Antoine Hospital, where 3400 HIV-infected patients have regular consultations. Patients will be identified from an in-house informatics platform, serving as a surveillance tool for metabolic syndrome, among other diseases, with the intention of increasing better-adapted clinical and therapeutic care. Each patient presenting with metabolic syndrome will be matched with a control patient on the following characteristics: age (±5 years), duration of HIV-infection (±2 years), HIV-RNA viral load (in categories of <50-500, 501-1000, or >1000 copies/mL), and gender. Patients with abnormal transaminases will be excluded from this study. This study will bring about a clearer understanding of the frequency and importance of liver fibrosis risk in patients with metabolic syndrome, which will allow us to determine the more important elements of surveillance necessary in the prevention and development of hepatic lesions. Accordingly, this study will add more pertinent information regarding treatment guidelines specific to this patient population.

Conditions
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HIV, Liver Fibrosis, Abdominal Obesity Metabolic Syndrome

Intervention / Treatment
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* Procedure: Noninvasive evaluation of liver fibrosis and steatosis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A. For all patients: >18 years of age HIV-1 infection for a minimum of 5 years confirmed by Western Blot or ELISA Signed and full comprehension of informed consent Affiliation to Sécurité Sociale B. Specific to Cases : Presence of metabolic syndrome according to the International Diabetes Foundation (IDF) C. Matched Criteria specific to controls : Same age ± 7 years Same duration of HIV-1 infection ± 3 years Same criterion of HIV-1 viral load (according to 3 thresholds: 50 - 500, 501 - 1000 or > 1000 c/mL) Exclusion Criteria: Chronic hepatitis B (HBs-Ag positive or isolated positive antiHBc-Ab with positive HBV-DNA) Chronic hepatitis C (positive antiHCV-Ab) Active IV or oral drug use and/or ongoing substitution therapy Other known chronic hepatitis : auto-immune hepatitis, primary or secondary biliary cirrhosis, hemochromatosis, Wilson disease, alpha 1 anti-trypsin deficit, primary or secondary sclerosing cholangitis, biliary obstruction, liver vascular disease associated with HIV infection, biliary or liver cancer CD4 < 50/mm3 Any current opportunistic infection Serious condition influencing vital status Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cases<br>Presence of metabolic syndrome according to the International Diabetes Foundation (IDF) | Procedure: Noninvasive evaluation of liver fibrosis and steatosis<br>* Transient elastography (using the Fibroscan, CAP Fibroscan) and biomarker panels (FibroTest, Fibromètre, Hepascore, Steatotest, Nashtest)<br>|
| Controls<br>age ± 7 years from cases duration of HIV-1 infection ± 3 years from cases HIV-1 viral load matched to cases according to 3 thresholds: 50 - 500, 501 - 1000 or > 1000 copies/mL | Procedure: Noninvasive evaluation of liver fibrosis and steatosis<br>* Transient elastography (using the Fibroscan, CAP Fibroscan) and biomarker panels (FibroTest, Fibromètre, Hepascore, Steatotest, Nashtest)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver fibrosis | Liver fibrosis as measured by Fibroscanner | One time | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver steatosis | Sub group of patients who had IRM measurements | One time | 
| Hand osteoarthritis | Sub group of patients who had an X-Ray of their hands | One time |