Prospective Evaluation of HIV Patients Using Non-invasive Methods for Estimation of Liver Fibrosis and Steatosis

Liver Cirrhosis Clinical Trial

— Prospec-HIV  

Official title:

Prospective Evaluation of HIV Infected Patients Followed at Evandro Chagas National Institute of Infectious Disease (INI) - Oswaldo Cruz Foundation (FIOCRUZ) Using Non-invasive Methods for Estimation of Liver Fibrosis and Steatosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02542020
• Other study ID #: 32889514.4.0000.5262
• Status: Recruiting
• Start date: June 2015
• Est. completion date: May 2022

Study information

• Verified date: February 2018
• Source: Oswaldo Cruz Foundation
• Contact: Hugo Perazzo, PhD
• Phone: +55 21 3865-9587
• Email: hugo.perazzo[@]ini.fiocruz.br
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Human immunodeficiency virus (HIV) infection is a major global health issue with up to 40 million people infected worldwide. Due to highly active antiretroviral therapy, mortality related to acquired immunodeficiency syndrome (AIDS) has been reducing in the last decades. However, liver disease remains as an important cause of severe complications and death.

Hepatic fibrosis progression is the main responsible for liver-related outcomes in HIV-positive patients. Co-infection by hepatitis B (HBV) or hepatitis C virus (HCV) is highly prevalence in HIV patients. Chronic viral co-infection induces faster liver fibrosis progression compared to mono-infected HIV. However, published data have been reporting presence of significant liver fibrosis in HIV without HBV or HCV infection. This might be related to direct action of HIV in hepatocytes or association with others factors, such as non-alcoholic fatty liver disease (NAFLD). NAFLD is associated with metabolic factors, such as obesity and type-2 diabetes mellitus. However, antiretroviral drugs may induce abnormal body fat distribution (lipodistrophy) and insulin resistance playing an important role on this process. Liver biopsy has been historically considered as the gold standard to evaluate liver injury. However, this painful method presents several limitations. Therefore, several non-invasive methods for estimation of liver fibrosis, such as biomarkers (APRI, FIB-4, FibroTest and FibroMeter) and transient elastography by Fibroscan, have been developed as an alternative to liver biopsy. The diagnostic performance and prognostic value of biomarkers and transient elastography have been validated in patients with chronic liver diseases. However, few data are available in HIV patients, especially in those without chronic viral co-infection.

Therefore, patients, medical doctors and scientific community will be beneficiated by the future application of non-invasive methods for estimation of liver injury in clinical practice in HIV patients.

Description:

In HIV-positive patients with or without chronic viral hepatitis co-infection, the primary aims of this project are: (i) to estimate the prevalence and incidence of liver injury (including progression of fibrosis, necro-inflammatory activity and steatosis) and to report the normal values of non-invasive methods in HIV population; (ii) to validate the diagnostic performance of non-invasive methods using a method without a gold standard (Latent Class Analysis); (iii) to validate the prognostic value of non-invasive markers to predict overall mortality and liver-related outcomes and (iv) to correlate liver injury with nutritional status. The secondary aim will be the constitution of a cohort of HIV patients, with or without chronic viral hepatitis co-infection for long-term follow-up of severe outcomes.

This prospective cohort study has been approved by the Local Ethical Committee (CAAE:

32889514.4.0000.5262) and it has been enrolling patients from June 2015 at the Evandro Chagas National Institute of Infectious Diseases - Oswaldo Cruz Foundation (INI - FioCruz), Rio de Janeiro, Brazil. A total of 2,000 patients will be included in this study during the next 5 years. This project aims to report the prevalence and incidence of liver disease in a representative sample of HIV patients with and without chronic viral hepatitis co-infection. In addition, the risk factors associated to presence and progression of liver fibrosis and steatosis will be identified and an innovative non-invasive management for estimation of liver injury in HIV patients will be validated.

Patients have been submitted at the same day to the following procedures: (i) clinical examination (anthropometric and demographic characteristics), (ii) blood sample collection (for blood analysis, calculation of biomarkers and stockage of samples), (iii) transient elastography (with M and XL probes by a single experienced operator (>2,000 examinations) and (iv) nutritional status (bioelectrical impedance and 24h diet recall).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: May 2022
• Est. primary completion date: May 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• HIV infection

• Age >= 18 years

Exclusion Criteria:

• Auto-immune hepatitis

• Primary biliary cirrhosis

• Primary sclerosing cirrhosis

• Extra-hepatic cholestasis

• Acute viral hepatitis

• Hepatic ischemia

• Hepatic metastasis

Related Conditions & MeSH terms

• Acquired Immune Deficiency Syndrome Virus
• Acquired Immunodeficiency Syndrome
• Fibrosis
• HIV Infections
• Human Immunodeficiency Virus
• Immunologic Deficiency Syndromes
• Liver Cirrhosis
• Liver Diseases

Locations

Country	Name	City	State
Brazil	Evandro Chagas National Institute of Infectious Diseases	Rio de Janeiro	Rio De Janeiro/RJ

Sponsors (1)

Lead Sponsor	Collaborator
Oswaldo Cruz Foundation

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of stage of fibrosis and grade of steatosis in patients infected by HIV	Staging of liver fibrosis and quantification of steatosis using non-invasive methods and correlation with risk factors	change of fibrosis stage and steatosis grade from baseline at 5 years
Secondary	Prognostic value of non-invasive methods	Evaluation of the prognostic value of non-invasive methods for prediction of severe outcomes and mortality	up to 5 years
Secondary	Prevalence of liver fibrosis	Estimation of liver fibrosis by non-invasive methods	up to 3 years
Secondary	Prevalence of liver steatosis	Estimation of liver steatosis by non-invasive methods	up to 3 years
Secondary	Diagnostic performance of non-invasive methods	Evaluation of diagnostic accuracy (sensitivity and specificity) of non-invasive methods using the Latent Class Analysis	up to 3 years
Secondary	Nutritional status	Evaluation of the nutritional status by bioelectrical impedance and 24h diet recall	From date of inclusion until the date of first documented alteration on nutritional status, assessed up to 5 years
Secondary	Progression of liver fibrosis	Estimation of liver fibrosis by non-invasive methods	From date of inclusion until the date of first documented progression of liver fibrosis, assessed up to 5 years
Secondary	Progression of liver steatosis	Estimation of liver steatosis by non-invasive methods	From date of inclusion until the date of first documented progression of liver steatosis, assessed up to 5 years