Hepatic Fibrosis Progression in HIV-Hepatitis C Virus Co-Infection – The Effect of Sex on Risk of Significant Fibrosis Measured by Aspartate-to-Platelet Ratio Index

PLOS ONE, Dec 2019

Background In Hepatitis C virus (HCV) mono-infection, male sex is associated with faster liver fibrosis progression but the effects of sex have not been well studied in HIV-HCV co-infected patients. We examined the influence of sex on progression to significant liver fibrosis in HIV-HCV co-infected adults receiving antiretroviral therapy (ART) using the aspartate aminotransferase-to-platelet ratio index (APRI) as a surrogate biomarker of liver fibrosis. Methods We evaluated 308 HIV infected, HCV RNA positive participants of a Canadian multicentre prospective cohort receiving antiretrovirals and without significant liver fibrosis or end-stage liver disease at baseline. We used multivariate discrete-time proportional hazards models to assess the effect of sex on time to significant fibrosis (APRI≥1.5) adjusting for baseline age, alcohol use, cigarette smoking, HCV duration, and APRI and time-updated CD4 count and HIV RNA. Results Overall, 55 (18%) participants developed an APRI ≥ 1.5 over 544 person-years of at-risk follow-up time; 18 (21%) women (incidence rate (IR)=14.0/100 PY; 7.5-20.4) and 37 (17%) men (IR=8.9/100 PY; 6.0-11.8). Women had more favourable profiles with respect to traditional risk factors for liver disease progression (younger, shorter duration of HCV infection and less alcohol use). Despite this, female sex was associated with a greater than two-fold increased risk of fibrosis progression (adjusted hazard rate (HR) =2.23; 1.22-4.08). Conclusions HIV-HCV co-infected women receiving antiretroviral therapy were at significantly greater risk of progressing to liver fibrosis as measured by APRI compared with men. Enhanced efforts to engage and treat co-infected women for HCV are needed.

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Hepatic Fibrosis Progression in HIV-Hepatitis C Virus Co-Infection – The Effect of Sex on Risk of Significant Fibrosis Measured by Aspartate-to-Platelet Ratio Index

June Hepatic Fibrosis Progression in HIV-Hepatitis C Virus Co-Infection - The Effect of Sex on Risk of Significant Fibrosis Measured by Aspartate-to-Platelet Ratio Index Kathleen C. Rollet-Kurhajec 0 1 Erica E. M. Moodie 0 1 Sharon Walmsley 0 1 Curtis Cooper 0 1 Neora Pick 0 1 Marina B. Klein 0 1 Canadian Co-infection Cohort Study (CTN 0 1 0 1 Department of Medicine, Division of Infectious Diseases/Chronic Viral Illness Service, McGill University Health Centre , Montreal , Canada , 2 Department of Epidemiology & Biostatistics, McGill University , Montreal , Canada , 3 University Health Network , Toronto , Canada , 4 CIHR Canadian HIV Trials Network, Vancouver , Canada , 5 The Ottawa Hospital Research Institute , Ottawa , Canada , 6 Oak Tree Clinic, BC Women's Hospital, Divisions of Infectious Diseases, Department of Medicine, University of British Columbia , Vancouver , Canada 1 Academic Editor: Jason Blackard, University of Cincinnati College of Medicine, UNITED STATES - Funding: This study was funded by the Fonds de recherche en santé du Québec, Réseau SIDA/ maladies infectieuses (FRQ-S), the Canadian In Hepatitis C virus (HCV) mono-infection, male sex is associated with faster liver fibrosis progression but the effects of sex have not been well studied in HIV-HCV co-infected patients. We examined the influence of sex on progression to significant liver fibrosis in HIV-HCV co-infected adults receiving antiretroviral therapy (ART) using the aspartate aminotransferase-to-platelet ratio index (APRI) as a surrogate biomarker of liver fibrosis. We evaluated 308 HIV infected, HCV RNA positive participants of a Canadian multicentre prospective cohort receiving antiretrovirals and without significant liver fibrosis or end-stage liver disease at baseline. We used multivariate discrete-time proportional hazards models to assess the effect of sex on time to significant fibrosis (APRI 1.5) adjusting for baseline age, alcohol use, cigarette smoking, HCV duration, and APRI and time-updated CD4 count Overall, 55 (18%) participants developed an APRI 1.5 over 544 person-years of at-risk tional risk factors for liver disease progression (younger, shorter duration of HCV infection Institutes of Health Research (CIHR MOP-79529) and the CIHR Canadian HIV Trials Network (CTN222). MBK is supported by a “Chercheurs nationaux” career award from the FRQ-S. EEMM is supported by a “chercheurs boursiers” career award from FRQ-S. SW has a career award from the Ontario HIV treatment Network. CC is supported by The Ontario HIV Treatment Network (Applied HIV Research Chair) and The Ottawa Hospital Department of Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: MBK reports receipt of grants to her institution from the Canadian Institute of Health Research (CIHR), Fonds de recherches en santé du Québec (FRQ-S) and CIHR Canadian HIV Trials Network (CTN); research support from Merck and Schering-Plough; board membership fees from the CTN; consulting fees from ViiV, Abbvie and Gilead; and honoraria for lectures from Janssen, ViiV and Merck. CC reports receipt of consulting fees from Merck and Vertex; honoraria for lectures from Merck and Roche; previous grants to his institution from Merck and Abbott; and funding support from The Ottawa Hospital Department of Medicine. SW reports receipt of grants to her institution from the CTN, Viiv and Merck; board membership fees, consulting fees and honoraria for lectures from Merck, Abbott, ViiV, Gilead, BMS, Tibotec and Janssen. NP reports receipt of grants to her institution from the CTN. EEMM and KCR-K report no conflicts of interest. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. and less alcohol use). Despite this, female sex was associated with a greater than two-fold increased risk of fibrosis progression (adjusted hazard rate (HR) =2.23; 1.22-4.08). HIV-HCV co-infected women receiving antiretroviral therapy were at significantly greater risk of progressing to liver fibrosis as measured by APRI compared with men. Enhanced efforts to engage and treat co-infected women for HCV are needed. Due to shared routes of transmission, hepatitis C virus (HCV) and HIV co-infection is common. Approximately one quarter of HIV-infected Canadians are seropositive for HCV [1–2]. With improved outcomes on combination antiretroviral therapy (cART) AIDS related mortality has declined significantly, yet liver-related morbidity and mortality has progressively increased among co-infected patients [3–4] owing in part to more rapid hepatic fibrosis progression [3, 5–6]. Residual HIV-related immune dysfunction [7–8], and immune activation, cumulative cART induced hepatotoxicity [9] and metabolic changes are among the potential causes of accelerated liver disease progression [10]. Worldwide women represent a rapidly growing segment of the HIV infected population a (...truncated)


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Kathleen C. Rollet-Kurhajec, Erica E. M. Moodie, Sharon Walmsley, Curtis Cooper, Neora Pick, Marina B. Klein, Canadian Co-infection Cohort Study (CTN 222). Hepatic Fibrosis Progression in HIV-Hepatitis C Virus Co-Infection – The Effect of Sex on Risk of Significant Fibrosis Measured by Aspartate-to-Platelet Ratio Index, PLOS ONE, 2015, Volume 10, Issue 6, DOI: 10.1371/journal.pone.0129868