Vincent Lo Re1,2,3, Craig W Newcomb1, Dena M Carbonari1,2, Jason A Roy1,2, Keri N Althoff4, Mari M Kitahata3, K Rajender Reddy3, Joseph K Lim5, Michael J Silverberg6, Angel M Mayor7, Michael A Horberg8, Edward R Cachay9, Gregory D Kirk4, Mark Hull10, John Gill11, Timothy R Sterling12, Jay R Kostman13, Marion G Peters14, Richard D Moore15, Marina B Klein16,17, H Nina Kim18. 1. Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. 2. Department of Biostatistics, Epidemiology, and Informatics, Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. 3. Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. 4. Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD. 5. Department of Medicine, Yale University School of Medicine, New Haven, CT. 6. Division of Research, Kaiser Permanente Northern California, Oakland, CA. 7. Department of Medicine, Retrovirus Research Center, Universidad Central del Caribe School of Medicine, Bayamon, Puerto Rico. 8. Mid-Atlantic Permanente Research Institute, Kaiser Permanente Mid-Atlantic States, Rockville, MD. 9. Department of Medicine, University of California, San Diego, CA. 10. Department of Medicine, British Columbia Centre for Excellence in HIV/AIDS, University of British Columbia, Vancouver, Canada. 11. Department of Medicine, University of Calgary, Calgary, Alberta, Canada. 12. Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN. 13. John Bell Health Center, Philadelphia Field Initiating Group for HIV Trials, Philadelphia, PA. 14. Department of Medicine, University of California San Francisco, San Francisco, CA. 15. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD. 16. Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada. 17. Division of Infectious Diseases and Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada. 18. Department of Medicine, University of Washington, Seattle, WA.
Abstract
BACKGROUND: Hepatitis B virus (HBV) infection is a leading cause of end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) in HIV. Factors contributing to the high rates of liver complications among HIV/HBV-coinfected individuals remain unknown. SETTING: North American AIDS Cohort Collaboration on Research and Design. METHODS: We performed a retrospective cohort study among HIV/HBV-coinfected patients in 10 US and Canadian cohorts of the North American AIDS Cohort Collaboration on Research and Design that validated ESLD (ascites, spontaneous bacterial peritonitis, variceal hemorrhage, and/or hepatic encephalopathy) and HCC diagnoses from 1996 to 2010. Multivariable Cox regression was used to examine adjusted hazard ratios [aHRs with 95% confidence interval (CIs)] of liver complications (first occurrence of ESLD or HCC) associated with hypothesized determinants and with increasing durations of HIV suppression (≤500 copies/mL). RESULTS: Among 3573 HIV/HBV patients with 13,790 person-years of follow-up, 111 liver complications occurred (incidence rate = 8.0 [95% CI: 6.6 to 9.7] events/1000 person-years). Rates of liver complication were increased with non-black/non-Hispanic race [aHR = 1.76 (1.13-2.74)], diabetes mellitus [aHR = 2.07 (1.20-3.57)], lower time-updated CD4 cell count [<200 cells/mm: aHR = 2.59 (1.36-4.91); 201-499 cells/mm: aHR = 1.75 (1.01-3.06) versus ≥500 cells/mm], heavy alcohol use [aHR = 1.58 (1.04-2.39)], and higher FIB-4 at start of follow-up [>3.25: aHR = 9.79 (5.73-16.74); 1.45-3.25: aHR = 3.20 (1.87-5.47) versus FIB-4 <1.45]. HIV suppression for ≥6 months was associated with lower liver complication rates compared with those with unsuppressed HIV [aHR = 0.56 (0.35-0.91)]. CONCLUSIONS: Non-black/non-Hispanic race, diabetes, lower CD4 cell count, heavy alcohol use, and advanced liver fibrosis were determinants of liver complications among HIV/HBV patients. Sustained HIV suppression should be a focus for HIV/HBV-coinfected patients to reduce the risks of ESLD/HCC.
BACKGROUND:Hepatitis B virus (HBV) infection is a leading cause of end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) in HIV. Factors contributing to the high rates of liver complications among HIV/HBV-coinfected individuals remain unknown. SETTING: North American AIDS Cohort Collaboration on Research and Design. METHODS: We performed a retrospective cohort study among HIV/HBV-coinfectedpatients in 10 US and Canadian cohorts of the North American AIDS Cohort Collaboration on Research and Design that validated ESLD (ascites, spontaneous bacterial peritonitis, variceal hemorrhage, and/or hepatic encephalopathy) and HCC diagnoses from 1996 to 2010. Multivariable Cox regression was used to examine adjusted hazard ratios [aHRs with 95% confidence interval (CIs)] of liver complications (first occurrence of ESLD or HCC) associated with hypothesized determinants and with increasing durations of HIV suppression (≤500 copies/mL). RESULTS: Among 3573 HIV/HBVpatients with 13,790 person-years of follow-up, 111 liver complications occurred (incidence rate = 8.0 [95% CI: 6.6 to 9.7] events/1000 person-years). Rates of liver complication were increased with non-black/non-Hispanic race [aHR = 1.76 (1.13-2.74)], diabetes mellitus [aHR = 2.07 (1.20-3.57)], lower time-updated CD4 cell count [<200 cells/mm: aHR = 2.59 (1.36-4.91); 201-499 cells/mm: aHR = 1.75 (1.01-3.06) versus ≥500 cells/mm], heavy alcohol use [aHR = 1.58 (1.04-2.39)], and higher FIB-4 at start of follow-up [>3.25: aHR = 9.79 (5.73-16.74); 1.45-3.25: aHR = 3.20 (1.87-5.47) versus FIB-4 <1.45]. HIV suppression for ≥6 months was associated with lower liver complication rates compared with those with unsuppressed HIV [aHR = 0.56 (0.35-0.91)]. CONCLUSIONS: Non-black/non-Hispanic race, diabetes, lower CD4 cell count, heavy alcohol use, and advanced liver fibrosis were determinants of liver complications among HIV/HBVpatients. Sustained HIV suppression should be a focus for HIV/HBV-coinfectedpatients to reduce the risks of ESLD/HCC.
Authors: M Puoti; A Spinetti; A Ghezzi; F Donato; S Zaltron; V Putzolu; E Quiros-Roldan; B Zanini; S Casari; G Carosi Journal: J Acquir Immune Defic Syndr Date: 2000-07-01 Impact factor: 3.731
Authors: Richard K Sterling; Eduardo Lissen; Nathan Clumeck; Ricard Sola; Mendes Cassia Correa; Julio Montaner; Mark S Sulkowski; Francesca J Torriani; Doug T Dieterich; David L Thomas; Diethelm Messinger; Mark Nelson Journal: Hepatology Date: 2006-06 Impact factor: 17.425
Authors: J F Colin; D Cazals-Hatem; M A Loriot; M Martinot-Peignoux; B N Pham; A Auperin; C Degott; J P Benhamou; S Erlinger; D Valla; P Marcellin Journal: Hepatology Date: 1999-04 Impact factor: 17.425
Authors: Deborah Konopnicki; Amanda Mocroft; S de Wit; Francisco Antunes; Bruno Ledergerber; Christine Katlama; K Zilmer; Stefano Vella; Ole Kirk; Jens D Lundgren Journal: AIDS Date: 2005-03-24 Impact factor: 4.177
Authors: V Paradis; G Perlemuter; F Bonvoust; D Dargere; B Parfait; M Vidaud; M Conti; S Huet; N Ba; C Buffet; P Bedossa Journal: Hepatology Date: 2001-10 Impact factor: 17.425
Authors: Chun-Tao Wai; Joel K Greenson; Robert J Fontana; John D Kalbfleisch; Jorge A Marrero; Hari S Conjeevaram; Anna S-F Lok Journal: Hepatology Date: 2003-08 Impact factor: 17.425
Authors: Patrick G Yeni; Scott M Hammer; Charles C J Carpenter; David A Cooper; Margaret A Fischl; Jose M Gatell; Brian G Gazzard; Martin S Hirsch; Donna M Jacobsen; David A Katzenstein; Julio S G Montaner; Douglas D Richman; Michael S Saag; Mauro Schechter; Robert T Schooley; Melanie A Thompson; Stefano Vella; Paul A Volberding Journal: JAMA Date: 2002-07-10 Impact factor: 56.272
Authors: Chloe L Thio; Eric C Seaberg; Richard Skolasky; John Phair; Barbara Visscher; Alvaro Muñoz; David L Thomas Journal: Lancet Date: 2002-12-14 Impact factor: 79.321
Authors: Jim Young; Vincent Lo Re; H Nina Kim; Timothy R Sterling; Keri N Althoff; Kelly A Gebo; M John Gill; Michael A Horberg; Angel M Mayor; Richard D Moore; Michael J Silverberg; Marina B Klein Journal: Pharmacoepidemiol Drug Saf Date: 2021-11-23 Impact factor: 2.732
Authors: Jing Sun; Keri N Althoff; Yuezhou Jing; Michael A Horberg; Kate Buchacz; M John Gill; Amy C Justice; Charles S Rabkin; James J Goedert; Keith Sigel; Edward Cachay; Lesley Park; Joseph K Lim; H Nina Kim; Vincent Lo Re; Richard Moore; Timothy Sterling; Marion G Peters; Chad J Achenbach; Michael Silverberg; Jennifer E Thorne; Angel M Mayor; Heidi M Crane; Mari M Kitahata; Marina Klein; Gregory D Kirk Journal: JAMA Netw Open Date: 2021-02-01