Liver, cardiovascular and metabolic factors as predictors of all-cause mortality in a rural Ugandan Cohort

Abstract Markers of liver and metabolic disease have not been well described for many populations in Africa, but could be important to inform individual and public health interventions that reduce morbidity and mortality. We studied longitudinal data from a population in rural Uganda to determine how liver, metabolic and cardiovascular parameters are associated with all-cause mortality. Demographic and laboratory data were collected through the General Population Cohort (GPC) in South-Western Uganda. We summarised cohort characteristics at baseline using descriptive statistics, and used univariable and multivariable Cox proportional hazards models to investigate factors associated with hazards of death. Our dataset includes 7896 individuals, of whom 56% were female and 73% were aged under 45 years. Prevalence of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) was 3% and 7%, respectively, and ALT was above the upper limit of normal in 26%. During the period observed, death was associated with older age (p<0.0001), male sex (aHR 1.56, 95% CI 1.3 to 1.86) and HIV infection (aHR 1.67, 95% CI 1.25 to 2.22). Excess mortality was associated with increase in AST:ALT ratio (aHR 1.17, 95% CI 1.08 to 1.26), a marker of alcoholic hepatitis. A 10mmHg increase in systolic blood pressure was associated with 7% increased hazards of death (aHR 1.07, 95% CI 1.03 to 1.11), and one unit increases in serum HbA1c were associated with 25% increased hazards of death (aHR 1.25, 95% CI 1.13 to 1.38). Under sensitivity analysis restricted to participants with longitudinal follow-up data, HBV infection was associated with death (aHR 5.38, 95% CI 2.01-14.42). Simple interventions to prevent, diagnose and treat hypertension, diabetes, alcohol excess, and HIV and HBV infection could have an important impact on mortality in this setting. Competing Interest Statement Under the supervision of PCM, CC received doctoral funding from GSK. PCM has also received GSK funding support for her work on the UK NIHR Health Informatics Collaborative for viral hepatitis, outside the scope of this study. Funding Statement CC received doctoral funding from the University of Oxford and GSK. PCM received Wellcome funding (ref 110110/Z/15/Z), and core funding from the Francis Crick Institute (ref CC2223) and University College London Biomedical Research Centre (NIHR BRC). This work received funding support from the University of Oxford John Fell Fund to the Uganda Liver Disease study ('ULIDS'). Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics approval for the General Population Cohort was provided by the Science and Ethics Committee of the Uganda Virus Research Institute (GC/127/12/11/06), and the Ugandan National Council for Science and Technology (HS870). All adults provided informed consent for participation including collection of data and samples. Parental/guardian consent for those less than 18 years of age were obtained following Uganda National Council of Science and Technology (UNCST) guidelines. Additional data generation and analysis were approved by the Oxford Tropical Research Ethics Committee (OxTREC; Ref 50-18) for the Uganda Liver Disease Study (ULiDS). The research has been supported by an active community engagement programme led from the MRC site at Kyambulibwa, which provides health advice and information about research projects, and addresses questions and feedback. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes ↵* Joint first authors ↵† joint senior authors The manuscript has been updated to account for the following: 1. Revised the authorship list to add two additional authors who have contributed. 2. Amended ethics and funding statements for completeness. 3. Corrections to methods regarding biomarkers used to assess liver health. 4. Updated figures. Data Availability A description of the study dataset, as well as access information/instruction for external individuals, is available on the London School of Hygiene and Tropical Medicine Data Compass: https://doi.org/10.17037/DATA.00004497.