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Role of fatty liver in the epidemic of advanced chronic liver disease among people with HIV: protocol for the Canadian LIVEHIV multicentre prospective cohort
  1. Felice Cinque1,2,
  2. Sahar Saeed3,
  3. Dana Kablawi1,2,
  4. Luz Ramos Ballesteros1,2,
  5. Wesal Elgretli4,
  6. Erica E M Moodie5,
  7. Colleen Price6,
  8. Ken Monteith7,
  9. Curtis Cooper8,
  10. Sharon L Walmsley9,
  11. Neora Pick10,
  12. Melanie C M Murray10,
  13. Joseph Cox1,5,
  14. Nadine Kronfli1,
  15. Cecilia T Costiniuk11,
  16. Alexandra de Pokomandy1,
  17. Jean-Pierre Routy1,
  18. Bertrand Lebouché1,12,
  19. Marina B Klein1,5,
  20. Giada Sebastiani1,2,4,5
  1. 1 Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada
  2. 2 Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
  3. 3 Public Health Sciences, Queen's University, Kingston, Ontario, Canada
  4. 4 Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada
  5. 5 Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
  6. 6 Canadian HIV/AIDS and Chronic Pain Society, Ottawa, Ontario, Canada
  7. 7 COCQ SIDA, Montreal, Quebec, Canada
  8. 8 Department of Medicine, Division of Infectious Diseases, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
  9. 9 Department of Medicine, Division of Infectious Diseases, University of Toronto, Toronto, Ontario, Canada
  10. 10 Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada
  11. 11 Chronic Viral Illness Service, McGill University, Montreal, Quebec, Canada
  12. 12 Department of Family Medicine, McGill University Faculty of Medicine and Health Sciences, Montreal, Quebec, Canada
  1. Correspondence to Dr Giada Sebastiani; giada.sebastiani{at}


Introduction Advanced chronic liver disease (ACLD) is a major cause of death for people with HIV (PWH). While viral hepatitis coinfections are largely responsible for this trend, metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging concern for PWH. We aimed to assess the contribution of MASLD to incident ACLD in PWH.

Methods and analysis This multicentre prospective observational cohort study will enrol 968 consecutive HIV monoinfected patients from four Canadian sites, excluding subjects with alcohol abuse, liver disease other than MASLD, or ACLD at baseline. Participants will be followed annually for 4 years by clinical evaluation, questionnaires, laboratory testing and Fibroscan to measure liver stiffness measurement (LSM) and controlled attenuation parameter (CAP). The primary outcome will be incidence of ACLD, defined as LSM>10 kPa, by MASLD status, defined as CAP≥285 dB/m with at least one metabolic abnormality, and to develop a score to classify PWH according to their risk of ACLD. Secondary outcomes will include health-related quality of life (HRQoL) and healthcare resource usage. Kaplan-Meier survival method and Cox proportional hazards regression will calculate the incidence and predictors of ACLD, respectively. Propensity score methods and marginal structural models will account for time-varying exposures. We will split the cohort into a training set (to develop the risk score) and a validation set (for validation of the score). HRQoL scores and healthcare resource usage will be compared by MASLD status using generalised linear mixed effects model.

Ethics and dissemination This protocol has been approved by the ethics committees of all participating institutions. Written informed consent will be obtained from all study participants. The results of this study will be shared through scientific publications and public presentations to advocate for the inclusion of PWH in clinical trials of MASLD-targeted therapies and case-finding of ACLD in PWH.

  • HIV & AIDS
  • Hepatology
  • Quality of Life
  • Patient-Centered Care

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  • FC and SS are joint first authors.

  • Twitter @WesalElgretli, @DrMelanieMurray

  • FC and SS contributed equally.

  • Contributors The principal investigator of the study is GS. Site investigators of the study are MBK, CTC, SLW, NP, MCMM. Other CTN coapplicants are SS (Methodologist), EM (Methodologist), KM (Community Representatives), CP (Community Representatives). GS conceived the study, led the proposal and protocol development. SS and EM provided methodological expertise and performed sample size calculations. FC, DK, LRB, WE, BL, JC, NK, CTC, J-PR and AdP are involved in patient enrolment. FC, SS and GS wrote the first draft of the manuscript. MNK, CTC, SLW, EEMM, NP, MCMM, DK, LRB, WE, JC, BL, NK, CTC, J-PR and AdP reviewed and edited the manuscript. All authors have read and agreed to the published version of the manuscript.

  • Funding The study was funded by an operating grant from the Canadian Institute of Health Research (CIHR) and by the CIHR Canadian HIV Trials Network. WE has received PhD fellowship from the Canadian Network on Hepatitis C (CanHepC). CanHepC is funded by a joint initiative of the Canadian Institutes of Health Research (NPC-178912) and the Public Health Agency of Canada. SLW is the Speck Family Chair in emerging infectious diseases. NK and CTC are supported by a Fonds de Recherche du Québec–Santé (FRQS) Junior two career award. AdP is supported by a Senior Salary Award from FRQS. BL is supported by two career awards: a Senior Salary Award from Fonds de recherche du Québec–Santé (FRQS) (#311200) and the LE 250 (from the Québec Ministry of Health for researchers in Family Medicine), from the Quebec’s Ministry of Health for researchers in Family Medicine and holds a Canadian Institutes for Health Research, Strategy for Patient-Oriented Research Mentorship Chair in Innovative Clinical Trials for HIV Care. J-PR is the holder of the Louis Lowenstein Chair in Haematology and Oncology, McGill University. GS is supported by a Senior Salary Award from FRQS (#296306).

  • Competing interests BL has acted as a speaker and advisory board member for ViiV, Gilead and Merck, and received research funding from ViiV, Merck and Gilead. CTC has received research funding from Merck, Gilead and Tilray, speaker honorarium from Gilead and consultant fees from ViiV Healthcare and Moderna. She has received funding to attend conferences from Gilead and ViiV Healthcare, and cannabinoids from Tilray for use in a clinical trial. SLW has served on advisory board, and spoken at CME event for Merck, Gilead, Viiv, and has received research funds from ViiV, Gilead and Merck. JC has received funding for investigator-initiated research from ViiV Healthcare and remuneration for advisory work from Gilead Canada and ViiV Healthcare. MCMM has served on advisory boards and spoken at CME events for Merck, Gilead and Viiv, and has received research funds from Viiv. GS has acted as speaker for Merck, Gilead, Abbvie, NovoNordisk, Pfizer, served as an advisory board member for Pfizer, Merck, NovoNordisk, Gilead and Intercept and has received unrestricted research funding from Theratecnologies. FC, SS, DK, LRB, WE, EEMM, CP, KM, NP, NK, AdP, J-PR, MBK have no conflict of interests.

  • Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

  • Provenance and peer review Not commissioned; externally peer reviewed.