Liver-related deaths in persons infected with the human immunodeficiency virus: The D:A:D Study

S. Collins, T. Mertenskoetter, E. Loeliger, R. Tressler, I. Weller, N. Friis-Møller, S.W. Worm, C.A. Sabin, A. Sjøl, J.D. Lundgren, A. Sawitz, M. Rickenbach, P. Pezzotti, E. Krum, L. Gras, E. Balestre, A. Sundström, B. Poll, E. Fontas, F. TorresK. Petoumenos, J. Kjær, R. Weber, P. Reisswafaamel-Sadr, O. Kirk, F. Dabis, M.G. Law, C. Pradier, S. De Wit, B. Akerlund, G. Calvo, A.D. Monforte, B. Ledergerber, A.N. Phillips, F. De Wolf, S. Zaheri, W. Bronsveld, M.E. Hillebrand-Haverkort, J.M. Prins, J.C. Bos, J.K.M.E. Schattenkerk, S.E. Geerlings, M.H. Godfried, J.M.A. Lange, F.C. Van Leth, S.H. Lowe, J.T.M. Van Der Meer, F.J.B. Nellen, K. Pogány, T. Van Der Poll, P. Reiss, Th.A. Ruys, S.U. Sankatsing, R. Steingrover, G. Van Twillert, M. Van Der Valk, M.G.A. Van Vonderen, S.M.E. Vrouenraets, M.V. Van Vugt, F.W.M.N. Wit, A. Van Eeden, J.H. Ten Veen, P.S. Van Dam, J.C. Roos, K. Brinkman, P.H.J. Frissen, H.M. Weigel, J.W. Mulder, E.C.M. Van Gorp, P.L. Meenhorst, A.T.A. Mairuhu, J. Veenstra, S.A. Danner, M.A. Van Agtmael, F.A.P. Claessen, R.M. Perenboom, A. Rijkeboer, C. Richter, J. Van Der Berg, R. Van Leusen, R. Vriesendorp, F.J.F. Jeurissen, R.H. Kauffmann, E.L.W. Koger, B. Bravenboer, C.H.H. Ten Napel, G.J. Kootstra, H.G. Sprenger, W.M.A.J. Miesen, R. Doedens, E.H. Scholvinck, R.W. Ten Kate, D.P.F. Van Houte, M. Polee, F.P. Kroon, P.J. Van Den Broek, J.T. Van Dissel, E.F. Schippers, G. Schreij, S. Van De Geest, A. Verbon, P.P. Koopmans, M. Keuter, F. Post, A.J.A.M. Van Der Ven, M.E. Van Der Ende, I.C. Gyssens, M. Van Der Feltz, J.G. Den Hollander, S. De Marie, J.L. Nouwen, B.J.A. Rijnders, T.E.M.S. De Vries, J.R. Juttmann, C. Van De Heul, M.E.E. Van Kasteren, M.M.E. Schneider, M.J.M. Bonten, J.C.C. Borleffs, P.M. Ellerbroek, I.M. Hoepelman, C.A.J.J. Jaspers, I. Schouten, C.A.M. Schurink, W.L. Blok, A.A. Tanis, P.H.P. Groeneveld, R. Salamon, J. Beylot, M. Dupon, M. Le Bras, J.L. Pellegrin, J.M. Ragnaud, G. Chêne, H. Jacqmin-Gadda, R. Thiébaut, S. Lawson-Ayayi, V. Lavignolle, M.J. Blaizeau, M. Decoin, A.M. Formaggio, S. Delveaux, S. Labarerre, B. Uwamaliya, E. Vimard, L. Merchadou, G. Palmer, D. Touchard, D. Dutoit, F. Pereira, B. Boulant, P. Morlat, N. Bernard, M. Bonarek, F. Bonnet, B. Coadou, P. Gelie, D. Jaubert, C. Nouts, D. Lacoste, H. Dutronc, G. Cipriano, S. Lafarie, I. Chossat, J.Y. Lacut, B. Leng, P. Mercié, J.F. Viallard, I. Faure, P. Rispal, C. Cipriano, S. Tchamgoué, F. Djossou, D. Malvy, J.P. Pivetaud, D. Chambon, C. De La Taille, T. Galperine, D. Neau, A. Ochoa, C. Beylot, M.S. Doutre, J.H. Bezian, J.F. Moreau, J.L. Taupin, C. Conri, J. Constans, P. Couzigou, L. Castera, H. Fleury, M.E. Lafon, B. Masquelier, I. Pellegrin, P. Trimoulet, F. Moreau, C. Mestre, C. Series, A. Taytard, M. Law, J. Anderson, K. Lowe, A. Mijch, K. Watson, N. Roth, H. Wood, M. Bloch, A. Gowers, D. Baker, R. McFarlane, A. Carr, D. Cooper, J. Chuah, W. Fankhauser, S. Mallal, J. Skett, S. Mateu, P. Domingo, M.A. Sambeat, J. Gatell, E. Del Cacho, J. Cadafalch, M. Fuster, C. Codina, G. Sirera, A. Vaqué, N. Clumeck, G. Eran, M. Gerard, K. Kabeya, D. Konopnicki, A. Libois, M.C. Payen, Y. Van Laethem, J. Neaton, G. Bartsch, W.M. El-Sadr, G. Thompson, D. Wentworth, R. Luskin-Hawk, E. Telzak, D.I. Abrams, D. Cohn, N. Markowitz, R. Arduino, D. Mushatt, G. Friedland, G. Perez, E. Tedaldi, E. Fisher, F. Gordin, L.R. Crane, J. Sampson, J. Baxter, C.H. Olsen, A. Mocroft, N. Vetter, I. Karpov, A. Vassilenko, P. Pollard, R. Colebunders, L. Machala, H. Rozsypal, D. Sedlacek, J. Nielsen, T. Benfield, J. Gerstoft, T. Katzenstein, A.B. Ehansen, P. Skinhøj, C. Pedersen, K. Zilmer, C. Katlama, J.-P. Viard, P.-M. Girard, T. Saint-Marc, P. Vanhems, M. Dietrich, C. Manegold, J. Van Lunzen, H.-J. Stellbrink, S. Staszewski, M. Bieckel, F.D. Goebel, G. Fätkenheuer, J. Rockstroh, R.E. Schmidt, J. Kosmidis, P. Gargalianos, H. Sambatakou, J. Perdios, G. Panos, A. Filandras, D. Banhegyi, F. Mulcahy, I. Yust, M. Burke, D. Turner, S. Pollack, J. Hassoun, Z. Sthoeger, S. Maayan, S. Vella, A. Chiesi, C. Arici, R. Pristerá, F. Mazzotta, A. Gabbuti, R. Esposito, A. Bedini, A. Chirianni, E. Montesarchio, V. Vullo, P. Santopadre, P. Narciso, A. Antinori, P. Franci, M. Zaccarelli, A. Lazzarin, A. Castagna, L. Viksna, S. Chaplinskas, R. Hemmer, T. Staub, J. Bruun, A. Maeland, V. Ormaasen, B. Knysz, J. Gasiorowski, A. Horban, D. Prokopowicz, A. Wiercinska-Drapalo, A. Boron-Kaczmarska, M. Pynka, M. Beniowski, E. Mularska, H. Trocha, F. Antunes, K. Mansinho, F. Maltez, D. Duiculescu, V. Babes, A. Streinu-Cercel, E. Vinogradova, A. Rakhmanova, D. Jevtovic, M. Mokráš, D. Staneková, J. González-Lahoz, M. Sanchez-Conde, T. García-Benayas, L. Martin-Carbonero, V. Soriano, B. Clotet, A. Jou, J. Conejero, L. Ruiz, C. Tural, J.M. Gatell, J.M. Miró, L. Zamora, M. Gutierrez, G. Mateo, A. Blaxhult, A. Karlsson, P. Pehrson, P. Francioli, A. Telenti, B. Hirschel, V. Soravia-Dunand, H. Furrer, E. Kravchenko, N. Chentsova, M. Fisher, R. Brettle, S. Barton, A.M. Johnson, D. Mercey, M. Murphy, M.A. Johnson, J. Weber, G. Scullard, L. Morfeldt, G. Thulin, K. Koppel, L. Flamholc, C. Hakangard, M. Moroni, A. Cargnel, S. Merli, G.M. Vigevani, C. Pastecchia, G. Morsica, L. Caggese, C. Moioli, M.S. Mura, M. Mannazzu, F. Suter, P.E. Manconi, P. Piano, S. Lo Caputo, A. Poggio, G. Bottari, G. Pagano, A. Alessandrini, A. Scasso, A. Vincenti, V. Abbadessa, S. Mancuso, F. Alberici, A. Ruggieri, M. Arlotti, P. Ortolani, F. De Lalla, G. Tositti, G. Cassola, R. Piscopo, E. Raise, F. Ebo, F. Soscia, L. Tacconi, U. Tirelli, R. Cinelli, D. Santoro, L. Pusterla, G. Carosi, C. Torti, G. Cadeo, D. Bertelli, G. Carnevale, P. Citterio, G. Filice, R. Bruno, G. Di Perri, I. Arnaudo, P. Caramello, G.C. Orofino, M.L. Soranzo, M. Bonasso, G. Rizzardini, S. Melzi, F. Chiodo, V. Colangeli, G. Magnani, M. Ursitti, F. Menichetti, C. Martinelli, C. Mussini, F. Ghinelli, L. Sighinolfi, O. Coronado, G. Ballardini, E. Rizzo, M. Montroni, M.C. Braschi, E. Petrelli, A. Cioppi, R. Cauda, A. De Luca, N. Petrosillo, P. Noto, G. Bontempo, R. Acinapura, G. Antonucci, P. De Longis, M. Lichtner, G. Pastore, N. Ladisa, R. Viglietti, M. Piazza, S. Nappa, N. Abrescia, M. De Marco, A. Colomba, T. Prestileo, C. De Stefano, A. La Gala, L. Cosco, A. Scerbo, P. Grima, P. Tundo, J. Vecchiet, M. D'Alessandro, B. Grisorio, S. Ferrara, C. Caissotti, P. Dellamonica, L. Bentz, E. Bernard, F. De Salvador-Guillouet, J. Durant, V. Mondain-Miton, I. Perbost, B. Prouvost-Keller, P. Pugliese, V. Rahelinirina, P.M. Roger, F. Vandenbos, M. Rickenbacher, M. Battegay, H. Bucher, L. Elzi, P. Erb, T. Klimkait, C. Rudin, S. Cattacin, M. Egger, H.J. Furrer, M. Gorgievski, L. Kaiser, L. Perrin, S. Yerly, Ph. Bürgisser, M. Cavassini, F. Paccaud, G. Pantaleo, E. Bernasconi, J.-C. Piffaretti, C. Kind, P. Schmid, P. Vernazza, J. Böni, R. Dubs, M. Fischer, M. Flepp, A. Fontana, H. Günthard, U. Lauper, M. Opravil, J. Schüpbach, R. Speck, A. Trkola, The Data Collection on Adverse Events of Anti-HIV Drugs Study Group

Research output: Contribution to journalArticleResearchpeer-review

934 Citations (Scopus)

Abstract

Background: An increasing proportion of deaths among human immunodeficiency virus (HIV)-infected persons with access to combination antiretroviral therapy (cART) are due to complications of liver diseases. Methods: We investigated the frequency of and risk factors associated with liver-related deaths in the Data Collection on Adverse Events of Anti-HIV Drugs study, which prospectively evaluated 76 893 person-years of follow- up in 23 441 HIV-infected persons. Multivariable Poisson regression analyses identified factors associated with liver-related, AIDS-related, and other causes of death. Results: There were 1246 deaths (5.3%; 1.6 per 100 person- years); 14.5% were from liver-related causes. Of these, 16.9% had active hepatitis B virus (HBV), 66.1% had hepatitis C virus (HCV), and 7.1% had dual viral hepatitis coinfections. Predictors of liver-related deaths were latest CD4 cell count (adjusted relative rate [RR], 16.1; 95% confidence interval [CI], 8.1-31.7 for 500/ μL), age (RR, 1.3; 95% CI, 1.2-1.4 per 5 years older), intravenous drug use (RR, 2.0; 95% CI, 1.2-3.4), HCV infection (RR, 6.7; 95% CI, 4.0-11.2), and active HBV infection (RR, 3.7; 95% CI, 2.4-5.9). Univariable analyses showed no relationship between cumulative years patients were receiving cART and liver-related death (RR, 1.00; 95% CI, 0.93-1.07). Adjustment for the most recent CD4 cell count and patient characteristics resulted in an increased risk of liver-related mortality per year of mono or dual antiretroviral therapy before cART (RR, 1.09; 95% CI, 1.02-1.16; P=.008) and per year of cART (RR, 1.11; 95% CI, 1.02-1.21; P=.02). Conclusions: Liver-related death was the most frequent cause of non-AIDS-related death.Wefound a strong association between immunodeficiency and risk of liverrelated death. Longer follow-up is required to investigate whether clinically significant treatment-associated liver-related mortality will develop. © 2006 American Medical Association. All rights reserved.
Original languageEnglish
Pages (from-to)1632-1641
Number of pages10
JournalArchives of Internal Medicine
Volume166
Issue number15
DOIs
Publication statusPublished - 2006

Keywords

  • antiretrovirus agent
  • acquired immune deficiency syndrome
  • adult
  • aged
  • article
  • CD4 lymphocyte count
  • clinical feature
  • confidence interval
  • controlled study
  • female
  • hepatitis B
  • Hepatitis B virus
  • hepatitis C
  • Hepatitis C virus
  • human
  • Human immunodeficiency virus infected patient
  • Human immunodeficiency virus infection
  • liver disease
  • male
  • mortality
  • priority journal
  • prospective study
  • risk factor
  • virus hepatitis

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