POPPY hepatic steatosis sub-study
Research type
Research Study
Full title
Hepatic steatosis in people living with HIV older than 50 years of age: \nThe POPPY Hepatic Steatosis Sub-Study
IRAS ID
216098
Contact name
Alejandro Arenas-Pinto
Contact email
Sponsor organisation
University College London
Clinicaltrials.gov Identifier
Z6364106/2018/07/11 , UCL Data Protection Registration
Duration of Study in the UK
2 years, 0 months, 0 days
Research summary
Summary of Research
Chronic liver disease is the fifth most common cause of death in the UK and non-alcoholic fatty infiltration of the liver (steatosis) is the most common cause of chronic liver disease in the general population. Ageing has been associated with most rapid progression from the benign form of the disease to severe liver inflammation. Data on the prevalence of fatty liver disease in HIV positive population, particularly those not co-infected with viral hepatitis, is scanty. However, available data seems to suggest that in HIV-positive individuals ageing may accelerate the deleterious effect of HIV infection itself, anti-retroviral therapy (ART), co-morbidities and their treatment. \nThe POPPY cohort aims to examine the effects of ageing on the clinical outcomes of people living with HIV. The study planned to recruit 1000 HIV-infected patients older than 50, 500 HIV-infected participants younger than 50 and a control group of 500 HIV-negative participants that were older than 50 years of age. \nThe main aim of this cross-sectional sub-study is to compare prevalence of fatty liver disease between HIV-positive and negative individuals over 50 years of age and younger HIV-positive patients who have participated in the POPPY cohort study. To do so we will invite 330 POPPY participants (110 per study group) to attend an additional study visit in which the presence of fatty liver infiltration will be measured by controlled attenuation parameter measurement based on vibration-controlled liver transient elastography (Fibroscan with the CAP probe), which is a non-invasive method. In addition blood samples will be collected from all participants to batch measure a number of bio-markers of fibrosis and inflammation of the liver. \nThe sub-study will be conducted at POPPY study sites and only patients who have taken part in the main POPPY study would be eligible for this sub-study.Summary of Results
Hepatic steatosis in people living with HIV older than 50 years of age: The POPPY Hepatic Steatosis Sub-StudyThis sub-study was done to try to understand fatty liver disease (hepatic steatosis) better. Liver disease is the fifth most common cause of death in the UK. Non-alcoholic fatty liver disease (NAFLD) is the most common cause of long-term liver disease in the general population in Western countries. It gets more common with age. Little is known about the effect ageing may have in the development of fatty liver disease in people living with HIV.
The study aimed to find out whether NAFLD was more frequent in people living with HIV older than 50 years of age compared to HIV negative individuals of a similar age. It was also trying to find out whether NAFLD was more frequent or severe in people living with HIV older than 50 compared to younger participants also living with HIV.
Study visits took place between February 2019 to March 2020 at 6 participating sites in London and Brighton. It was sponsored by University College London and funded by ViiV Healthcare UK (investigator-initiated study grant).
The study proposal was discussed with patient representatives from the co-ordinating site. They had the opportunity of discussing the study protocol, participant information sheet and consent form. They made important suggestions which were incorporated. In addition, a community representative was included in the sub-study management team.
Participants of the main POPPY (Pharmacokinetic and clinical Observations in PeoPle over fifty) study who met certain criteria were invited to take part in this sub-study. They did not have an active hepatitis B or C infection and were not pregnant. They also had not been told by a doctor that they had alcoholic liver disease, or any other long-term liver disease.
The study aimed to recruit 330 participants split evenly across the 3 study groups. In total 319 participants were enrolled:
- 109 people living with HIV older than 50 years of age
- 103 people living with HIV younger than 50 years of age
- 107 HIV negative controls older than 50 years of age72 participants were not included in the main analysis. Most of these were excluded because they scored highly on an alcohol consumption questionnaire. The others were excluded because their liver scan scores were not valid. However, an additional analysis including all participants with valid liver scan results was done to look at the effect of higher than recommended alcohol consumption on the chance of having fatty liver disease.
This was a single visit study, but in some cases the visit was split and the scan done at a separate appointment. Participants had a liver scan, Fibroscan®, and a blood sample collected as part of the study. They also completed a questionnaire about alcohol consumption and recreational drug use.
No serious adverse events related to the sub-study were reported during the study period.
The prevalence of fatty liver disease (hepatic steatosis) was found to be similar in the older people with HIV and the HIV negative controls over 50 years of age. The prevalence was higher in the older people with HIV than in the younger people with HIV.
The prevalence of liver scarring (fibrosis) was found to be higher in the older people with HIV and HIV negative controls over 50 years of age than in the younger people with HIV.
When all study participants were included in the additional analysis (regardless of their score on the alcohol consumption questionnaire), the findings from the main analysis remained. Higher than recommended alcohol consumption did not change the effect of age on the probability of having fatty liver disease.
Age, being male and having a large accumulation of fat around the belly (abdominal obesity) were found to be associated with fatty liver disease. We found no association of any HIV-related factor with fatty liver disease.
The results of this study indicate that lifestyle changes and other interventions for controlling body weight (in particular fat around the belly) should be included into routine HIV care. In addition, the results show the importance of further investigation on the link between other obesity-related disorders that can affect metabolism, with fatty liver disease. This would be important to identify interventions likely to reduce the risk of problems such as heart and blood vessel damage.
Participants wishing to learn more about the study results should speak to their local POPPY research team. The study team would like to thank all study participants for their contribution to this research.
A new proposal is being put together to repeat the liver assessment on the study participants in the near future. This would allow the study team to look at how fatty liver disease has progressed in the three study groups. It would also provide additional evidence of the impact of ageing on fatty liver disease.
REC name
London - South East Research Ethics Committee
REC reference
18/LO/1669
Date of REC Opinion
24 Oct 2018
REC opinion
Favourable Opinion