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Bacterial infection in compensated viral cirrhosis impairs 5-year survival (ANRS CO12 CirVir prospective cohort)
  1. Pierre Nahon1,
  2. Mathilde Lescat2,
  3. Richard Layese3,
  4. Valérie Bourcier1,
  5. Nabila Talmat1,
  6. Setty Allam4,
  7. Patrick Marcellin5,
  8. Dominique Guyader6,
  9. Stanislas Pol7,
  10. Dominique Larrey8,
  11. Victor De Lédinghen9,
  12. Denis Ouzan10,
  13. Fabien Zoulim11,
  14. Dominique Roulot12,
  15. Albert Tran13,
  16. Jean-Pierre Bronowicki14,
  17. Jean-Pierre Zarski15,
  18. Odile Goria16,
  19. Paul Calès17,
  20. Jean-Marie Péron18,
  21. Laurent Alric19,
  22. Marc Bourlière20,
  23. Philippe Mathurin21,
  24. Jean-Frédéric Blanc22,
  25. Armand Abergel23,
  26. Lawrence Serfaty24,
  27. Ariane Mallat25,
  28. Jean-Didier Grangé26,
  29. Pierre Attali27,
  30. Yannick Bacq28,
  31. Claire Wartelle29,
  32. Thông Dao30,
  33. Yves Benhamou31,
  34. Christophe Pilette32,
  35. Christine Silvain33,
  36. Christos Christidis34,
  37. Dominique Capron35,
  38. Brigitte Bernard-Chabert36,
  39. Sophie Hillaire37,
  40. Vincent Di Martino38,
  41. Jean-Claude Trinchet1,
  42. Richard Moreau5,
  43. Françoise Roudot-Thoraval3
  44. for the ANRS CO12 CirVir and Microcir Groups
    1. 1AP-HP, Hôpital Jean Verdier, Service d'Hépatologie, Bondy, Université Paris 13, Bobigny et INSERM U1162, Université Paris 5, Paris, France
    2. 2AP-HP, Hôpital Jean Verdier, Service de Microbiologie, Bondy, Université Paris 13, Bobigny, et INSERM UMR 1139, Paris, France
    3. 3AP-HP, Hôpital Henri Mondor, Département de Santé Publique, Créteil, France
    4. 4Unit for Basic and Clinical research on Viral Hepatitis, ANRS (France REcherche Nord & sud Sida-HIV Hépatites-FRENSH), Paris, France
    5. 5AP-HP, Hôpital Beaujon, Service d'Hépatologie, Clichy, France
    6. 6CHU Pontchaillou, Service d'Hépatologie, Rennes, France
    7. 7AP-HP, Hôpital Cochin, Département d'Hépatologie et INSERM UMS20, Institut Pasteur, Université Paris Descartes, Paris, France
    8. 8Hôpital Saint Eloi, Service d'Hépatologie, Montpellier, France
    9. 9Hôpital Haut-Lévêque, Service d'Hépatologie, Bordeaux, France
    10. 10Institut Arnaud Tzanck, Service d'Hépatologie, St Laurent du Var, France
    11. 11Hôpital Hôtel Dieu, Service d'Hépatologie, Lyon, France
    12. 12AP-HP, Hôpital Avicenne, Service d'Hépatologie, Bobigny, France
    13. 13CHU de Nice, Service d'Hépatologie, et INSERM U1065, Université de Nice-Sophia-Antipolis, Nice, France
    14. 14Hôpital Brabois, Service d'Hépatologie, Vandoeuvre-les-Nancy, France
    15. 15Hôpital Michallon, Service d'Hépatologie, Grenoble, France
    16. 16Hôpital Charles-Nicolle, Service d'Hépatologie, Rouen, France
    17. 17CHU d'Angers, Service d'Hépatologie, Angers, France
    18. 18Hôpital Purpan, Service d'Hépatologie, Toulouse, France
    19. 19CHU Toulouse, Service de Médecine Interne-Pôle Digestif UMR 152, Toulouse, France
    20. 20Hôpital Saint Joseph, Service d'Hépatologie, Marseille, France
    21. 21Hôpital Claude Huriez, Service d'Hépatologie, Lille, France
    22. 22Hôpital St André, Service d'Hépatologie, Bordeaux, France
    23. 23Hôpital Hôtel Dieu, Service d'Hépatologie, Clermont-Ferrand, France
    24. 24AP-HP, Hôpital Saint-Antoine, Service d'Hépatologie, Paris, France
    25. 25AP-HP, Hôpital Henri Mondor, Service d'Hépatologie, Créteil, France
    26. 26AP-HP, Hôpital Tenon, Service d'Hépatologie, Paris, France
    27. 27AP-HP, Hôpital Paul Brousse, Service d'Hépatologie, Villejuif, France
    28. 28Hôpital Trousseau, Unité d'Hépatologie, CHRU de Tours, Tours, France
    29. 29Hôpital d'Aix-En-Provence, Service d'Hépatologie, Aix-En-Provence, France
    30. 30Hôpital de la Côte de Nacre, Service d'Hépatologie, Caen, France
    31. 31AP-HP, Groupe Hospitalier de La Pitié-Salpêtrière, Service d'Hépatologie, Paris, France
    32. 32CHU Le Mans, Service d'Hépatologie, Le Mans, France
    33. 33CHU de Poitiers, Service d'Hépatologie, Poitiers, France
    34. 34Institut Mutualiste Montsouris, Service d'Hépatologie, Paris, France
    35. 35Hôpital Amiens Nord, Service d'Hépatologie, Amiens, France
    36. 36Hôpital Robert Debré, Service d'Hépatologie, Reims, France
    37. 37Hôpital Foch, Service d'Hépatologie, Suresnes, France
    38. 38Hôpital Jean Minjoz, Service d'Hépatologie, Besançon, France
    1. Correspondence to Dr Pierre Nahon, Service d'Hépato-gastroentérologie, Hôpital Jean Verdier, Bondy 93140, France; pierre.nahon{at}


    Objective To assess incidence and prognostic significance of bacterial infections (BIs) occurring in compensated viral cirrhosis.

    Design This prospective study involved 35 French centres. Inclusion criteria were biopsy-proven HCV or HBV cirrhosis, Child–Pugh A and no previous hepatic complications. Cumulative incidence (CumI) of events was estimated in a competing risks framework.

    Results 1672 patients were enrolled (HCV 1323, HBV 318, HCV-HBV 31). During a median follow-up of 43 months, 234 BIs occurred in 171 patients (5 year CumI: 12.9%), among whom 14.6% had septic shock. Main localisations included the urinary tract (27.4%), lung (25.2%) and peritoneum (10.7%) (other, 86 (36.7%)). Most BIs occurred as a first event prior to liver decompensation (n=140, 81.8%) and were community-acquired (CA, 84.2%). The risk of BI was higher in patients with HCV than in patients with HBV (5 year CumI: 15.2% vs 5.5%, p=0.0008). Digestive localisation, concomitant interferon-based treatment, isolation of resistant bacteria and non-CA BIs were associated with lowest probability of resolution. The occurrence of a first BI impaired survival in patients infected with HCV (5 year survival: 60.2% vs 90.4%, p<0.001) and patients infected with HBV (5 year survival: 69.2% vs 97.6%, p<0.001). BIs represented the third cause of death (14.1%) after liver failure and liver cancer. BI risk factors comprised older age, lower albumin, proton pump inhibitor intake and absence of virological eradication/control.

    Conclusion BI mostly occurs as a first complication and represents a turning point in the course of compensated viral cirrhosis. Its occurrence impacts long-term prognosis and may define a subgroup of patients in whom adaptation of management is warranted.


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    • Collaborators Microcir group: Marie Kempf (CHU Angers, laboratoire de Bactériologie, Angers), Fréderic Bert (APHP Hôpital Beaujon, Service de Microbiologie, Clichy), Alexandra Doloy (APHP, Hôpital Cochin, Laboratoire de Bactériologie, Paris), Isabelle Poilane (AP-HP, Hôpital Jean Verdier, Service de Microbiologie, Bondy), Olivia Peuchant (CHU Haut Lévêque, Laboratoire de Bactériologie, Bordeaux), Etienne Carbonnelle (AP-HP Hôpital Avicenne, Laboratoire de Bactériologie-Virologie Hygiène, Bobigny), Bertrand Picard (AP-HP Hôpital Avicenne, Laboratoire de Bactériologie-Virologie Hygiène, Bobigny), Christophe Burucoa (CHU Poitiers, Laboratoire de Bactériologie, Poitiers), Vincent Cattoir (CHU Caen, Service de Microbiologie, Caen), Dominique Decré (AP-HP Hôpital Saint Antoine, Paris), Nicolas Degand (CHU Nice, Laboratoire de Bactériologie, Nice), Laurent Dortet (AP-HP Hôpital Bicêtre, Laboratoire de Bactériologie Le Kremlin Bicêtre), Samer Kayal (CHU Pontchaillou, Service de Bactériologie et Hygiène Hospitalière, Rennes), Véronique Vernet-Garnier (CHU Robert Debré, Laboratoire de Bactériologie, Reims), Alain Lozniewski (CHU Nancy, Laboratoire de Bactériologie, Nancy), Edouard Tuaillon (CHU-Hôpital Saint Eloi, Laboratoire de Bactériologie, Montpellier), Sophie Vimont (APHP, Hôpital Tenon, Laboratoire de Bactériologie, Paris), Emilie Bessède (CHU Pellegrin, Laboratoire de Bactériologie, Bordeaux), Isabelle Patry (CHU Jean Minjoz, Laboratoire de Bactériologie, Besançon), Nadine Lemaitre (CHRU Lille, Laboratoire de Bactériologie, Lille) and Christine Pachetii (CH Aix, Laboratoire de Diagnostic des Maladies Infectieuses, Aix en Provence).

    • Contributors PN, J-CT, ML, VB and FR-T had full access to all data in the study and take responsibility for the integrity of data and the accuracy of data analysis. Study concept and design: PN, J-CT, VB and FR-T. Acquisition of data: PN, VB, ML, RL, NT, PM, DG, SP, D, VDL, DO, FZ, DR, AT, J-PB, J-PZ, OG, PC, J-MP, LA, MB, PM, J-FB, AA, LS, AM, J-DG, Buffet, YB, CW, TD, YB, CP, CS, CC, DC, BB-C, SH, VDM, J-CT and FR-T. Analysis and interpretation of data: PN, VB, RL, ML, J-CT, RM and FR-T. Drafting of the manuscript: PN, VB, RL, ML and FR-T. Critical revision of the manuscript for important intellectual content: PN, VB, RL, ML, PM, DG, SP, DL, VDL, DO, FZ, DR, AT, J-PB, J-PZ, OG, PC, J-MP, LA, MB, PM, J-FB, AA, LS, AM, J-DG, Buffet, YB, CW, TD, YB, CP, CS, CC, DC, BB-C, SH, VDM, RM and FR-T. Statistical analysis: RL and FR-T. Funding obtained: J-CT. Administrative, technical and material support: PN, VB, RL, NT, J-CT and FR-T. Study supervision: PN, VB, RL, ML, J-CT and FR-T.

    • Funding The promoter of the study was the ANRS (France REcherche Nord and sud Sida-HIV Hépatites-FRENSH), with the cohort funded by the same institution.

    • Competing interests None declared.

    • Patient consent Obtained.

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

    • Ethics approval The study protocol was in conformity with ethical guidelines of the 1975 Declaration of Helsinki and was approved by the Institutional review board (Comité de Protection des Personnes, Aulnay-sous-Bois, France).