Nonalcoholic Steatohepatitis in HIV Mono-infection: Exploring Non-invasive Methods for Diagnosis and the Therapeutic Role of Vitamin E

Effective combination antiretroviral therapy (cART) has resulted in a dramatic reduction in AIDS mortality. Over the last decade, the proportion of deaths caused by liver-related etiologies, including co-infection with hepatitis C (HCV) and hepatitis B (HBV) viruses, alcohol abuse, and fatty liver, has increased between 8 to 10 fold in the post-cART era while AIDS-related mortality has fallen more than 90-fold. HIV infection without viral hepatitis is also at risk for liver disease. Indeed, HIV mono-infected persons experience common conditions, such as obesity, diabetes and dyslipidemia, which are risk factors for non-alcoholic fatty liver disease (NAFLD). NAFLD is the most common liver disease in Canada. It is a fatty infiltration of the liver that is not evolutive per se, but it is the first histopathological step for non-alcoholic steatohepatitis (NASH), a progressive disease characterized by much inflammation leading to liver fibrosis and cirrhosis. NASH may be frequent in the setting of HIV mono-infection due to excess of metabolic risk factors, long-term cART, HIV itself and lipodystrophy. An early diagnosis of NASH is essential to establish a prognosis and initiate interventions to reduce progression of liver disease towards cirrhosis. Early diagnosis of NASH is critical for targeting metabolic and hepatologic interventions, which can impact on progression to cirrhosis and end-stage complications. Non-invasive tools for liver fibrosis and NASH, including Fibroscan/CAP and CK-18, are accurate and ideal for screening and serial monitoring. No study has specifically targeted the non-invasive diagnosis of NASH in HIV mono-infected patients. There has been no study about the use of CK-18 as a biomarker for NASH in the setting of HIV mono-infection. Furthermore, CAP has never been applied to this specific population. Finally, there is no data about the potential beneficial therapeutic effect of vitamin E on NASH associated to HIV infection. The investigators hypothesize that CK-18 and Fibroscan/CAP can be used as non-invasive tests to diagnose NASH in HIV mono-infected persons. Likewise, the investigators hypothesize that there will be a significant prevalence of NASH diagnosed by non-invasive tools among patients with HIV mono-infection. The investigators further hypothesize that a 6 months treatment trial with vitamin E supplementation will improve non-invasive diagnostic tests, and/or the metabolic and hepatic profile in HIV mono-infected patients with a non-invasive diagnosis of NASH.

Study Overview

• Status: Completed
• Conditions: HIV Mono Infection
• Intervention / Treatment: Dietary supplement: Vitamin E

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada
      • Chronic Viral Illness Center at Royal Victoria Hospital in McGill university Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Confirmed positive serology for HIV mono-infection and 18 years or older; valid Fibroscan/CAP;
• Able to provide informed consent, signing forms available in French or English.
• Fatty liver (CAP>237.8 dB/m) AND CK-18 levels > 246 U/L OR
• Fatty liver (CAP>237.8 dB/m) AND CK-18 149 U/L + chronically elevated liver function tests (transaminases) + at least 1 metabolic risk factor (among diabetes, insulin resistance, dyslipidemia or overweight).

Exclusion Criteria:

• Co-infection with HCV or HBV (presence of serum HCV-Ab or HbsAg); HCC, liver transplantation
• Significant alcohol consumption, as per AASLD guidelines on NAFLD: "ongoing or recent alcohol consumption > 21 drinks on average per week in men and > 14 drinks on average per week in women"
• Patients taking anticoagulants (warfarin, heparin)
• Patients undergoing chemotherapy or radiotherapy for cancer
• History of diagnosis of prostate cancer
• Planning to become, suspected to be, pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Vitamin E intervention; All study participants receive Vitamin E 800 IU once daily for 6 months	Dietary supplement: Vitamin E; Vitamin E 800 IU once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement of NASH diagnosed by non-invasive methods	Assessed by i) difference in AST and/or ALT	6 months
Improvement of NASH diagnosed by non-invasive methods	Assessed by ii) difference in Fibroscan/CAP measurements	6 months
Improvement of NASH diagnosed by non-invasive methods	Assessed by iii) difference in CK-18 levels	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in metabolic markers	HOMA	6 months
Change in metabolic markers	Cholesterol or triglyceride levels	6 months
Change in metabolic markers	Weight and height will be combined to report BMI in kg/m^2	6 months

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Collaborators: CIHR Canadian HIV Trials Network
• Investigators: Principal Investigator: Giada Sebastiani, Chronic Viral Illness Service, MUHC

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 11, 2014
• Primary Completion (ACTUAL): March 11, 2019
• Study Completion (ACTUAL): March 11, 2019

Study Registration Dates

• First Submitted: June 12, 2019
• First Submitted That Met QC Criteria: June 14, 2019
• First Posted (ACTUAL): June 17, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 17, 2019
• Last Update Submitted That Met QC Criteria: June 14, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease Attributes; Liver Diseases; Infections; Communicable Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Vitamin E
• Other Study ID Numbers: CTNPT 024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No