Download PDF
Hamostaseologie 2015; 35(02): 175-180
DOI: 10.5482/HAMO-14-07-0027
Original article
Schattauer GmbH

Long-term outcome of liver transplantation in HCV/HIV coinfected haemophilia patients

A single centre study of 10 patientsLangzeit-Ergebnisse nach Lebertransplantation bei HCV/HIV-koinfizierten Hämophilie-PatientenEine Studie mit 10 Patienten
G. Goldmann   *
1   Institute of Experimental Haematology and Transfusion Medicine, University of Bonn
,
H. Zeitler   *
2   Centre of Extracorporeal Therapy and Autoimmunity (CETA), Internal Medical Clinic I of the University of Bonn, Germany
,
N. Marquardt
1   Institute of Experimental Haematology and Transfusion Medicine, University of Bonn
,
S. Horneff
1   Institute of Experimental Haematology and Transfusion Medicine, University of Bonn
,
Z. Balta
2   Centre of Extracorporeal Therapy and Autoimmunity (CETA), Internal Medical Clinic I of the University of Bonn, Germany
,
C. P. Strassburg
2   Centre of Extracorporeal Therapy and Autoimmunity (CETA), Internal Medical Clinic I of the University of Bonn, Germany
,
J. Oldenburg
1   Institute of Experimental Haematology and Transfusion Medicine, University of Bonn
› Author Affiliations
Further Information

Publication History

received: 08 July 2014

accepted in revised form: 21 October 2014

Publication Date:
28 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

The outcome and clinical features during long term follow-up of 10 haemophilia patients (haemophilia A n = 9, haemophilia B n = 1), who underwent successful orthotopic liver transplantation (OLT) due to hepatitis associated liver disease, are summarised.

Patients

Eight patients were HIV/HCV co-infected. Despite severe postoperative complications, which were not bleeding-associated, all patients survived OLT.

Results

Long-term survival was 70% after in mean 8 years follow- up. Twelve years after OLT one patient developed a cyclosporine-induced nephropathy requiring haemodialysis. HIV-HAART was initiated in all patients after OLT, and allowed a successful HCV treatment in 6 patients. Factor VIII production was sufficient in mean 72 h after OLT and remained stable at subnormal to normal FVIII levels of in median 30% (range 14–96%) also during long-term follow-up. Post-OLT spontaneous bleeding events were rare compared to pre-OLT, therefore, the performance status improved in all patients.

Discussion

OLT substitutes the hepatic FVIII but has no effect on the extrahepatic endothelial FVIII production, suggesting that in case of severe tissue injury enhanced bleeding might occur. Additionally, after OLT there is no acute phase reaction of the FVIII protein. Therefore, our OLT patients received in case of a reduced FVIII activity a peri-interventional prophylactic short-term FVIII substitution in surgical and diagnostic interventions with high bleeding risk.

Conclusion

Bleeding and wound healing disturbances were not seen.

Zusammenfassung

Wir berichten über 10 Hämophilie-Patienten (Hämophilie A n = 9, Hämophilie B n = 1), die sich aufgrund einer viral bedingten schwersten Lebererkrankung erfolgreich einer Lebertransplantation (OLT) unterzogen hatten.

Patienten

Bei 8 Patienten bestand eine HCV/ HIV-Koinfektion.

Ergebnisse

Trotz z. T. schwer wiegender postoperativer Komplikationen, die nicht blutungsassoziiert waren, überlebten alle Patienten den primären Eingriff der Transplantation. Im Langzeit-Follow-up über im Median 8 Jahre betrug das Überleben in unserem Kollektiv 70%. Ein Patient entwickelte ein Cyclosporin-induziertes Nierenversagen und wurde 12 Jahre nach OLT dialysepflichtig. Die HCV-Therapie war nach Initiierung der HIV- HAART post-OLT in 6 Fällen erfolgreich. In allen Fällen erreichte die Transplantation postoperativ nach im Median 72 h einen subnormalen bis normalen FVIII-Wert von im Median 30% (Spannbreite: 14–96%), der im weiteren Verlauf stabil blieb. Die Anzahl spontaner Blutungsereignisse ging deutlich zurück, entsprechend verbesserte sich der Mobilitätsstatus aller Patienten.

Diskussion

Die OLT ersetzt lediglich den hepatisch produzierten FVIII, sodass Blutungskomplikationen auch nach erfolgreicher OLT bei größeren Gefäß- und Gewebetraumata möglich sind. Insbesondere fehlt nach OLT die Akutphase-Eigenschaft des FVIII. In unserem Kollektiv wurde, sofern der FVIII-Wert unterhalb des Referenzbereichs lag, bei allen blutungsgefährdeten Eingriffen prophylaktisch perinterventionell eine kurzfristige FVIII-Substitutionstherapie durchgeführt.

Schlussfolgerung

Blutungskomplikationen oder Wundheilungsstörungen traten nicht auf.

Keywords

Haemophilia - liver transplantation - hepatitis - factor VIII - inhibitor

Schlüsselwörter

Hämophilie - Lebertransplantation - Hepatitis - Faktor VIII - Hemmkörper

* Both authors contributed equally to this work.


 

  • References

  • 1 Yokoyama S, Bartlett A, Dar FS. et al. Outcome of liver transplantation for Haemophilia. HPB 2011; 13: 40-45.
    CrossrefPubMedGoogle Scholar
  • 2 Wilde J, Teixeira P, Bramhall SR. et al. Liver transplantation in haemophilia. Brit J Haematol 2002; 117: 952-956.
    CrossrefPubMedGoogle Scholar
  • 3 Lerut JP, Laterre PF, Pardponge EL. et al. Liver transplantation in haemophilia. J Hepatol 1995; 22: 583-585.
    CrossrefPubMedGoogle Scholar
  • 4 Ragni MV, Devera ME, Roland ME. et al. Liver transplant outcomes in HIV (+) haemophilia. Haemophilia 2013; 19: 134-140.
    CrossrefPubMedGoogle Scholar
  • 5 Starzl TE, Demetris AJ. Liver transplantation: A 31 Year Perspective. Chicago: Year Book Med Publ; 1990
    Google Scholar
  • 6 Vogel M, Voigt E. Schäfer et al. Orthopic liver transplantation in human immunodeficiency virus (HIV)-positive patients. Liver Transplantation 2005; 11: 1515-1521.
    CrossrefPubMedGoogle Scholar
  • 7 Aznar JA, Marco A, Parra R. et al. Liver transplantation in Spanish haemophiliacs. Haemophilia 2012; 18: e1-e41.
    CrossrefPubMedGoogle Scholar
  • 8 Unos: MELD/PELD calculator documentation. 2004 www.unos.org/waitlist/includes local/pdfs/ meld_peld_calculator.pdf
    PubMed
  • 9 Verger E, Salamero M, Conill C. Can Karnofsky performance status be transformed to the Eastern Cooperative Oncology Group Scoring Scale and vice-versa. Eur J Cancer 1992; 28: 1328-1330.
    CrossrefPubMedGoogle Scholar
  • 10 Lozier J. Factor VIII biosynthesis. Blood 2006; 108: 414-415.
    PubMedGoogle Scholar
  • 11 Fahs SA, Hille MT, Shi Q. et al. A conditional knockout mouse model reveals endothelial cells as the predominant and possibly exclusive source of plasma factor VIII. Blood 2014; 123: 3706-3713.
    CrossrefPubMedGoogle Scholar
  • 12 Fomin ME, Zhou Y, Beyyer Al. Production of factor VIII by human liver sinusoidal endothelial cells transplanted in immunodeficient uPA mice. PLoS One 2013; 10: e77255.
    PubMedGoogle Scholar
  • 13 Lamont PA, Ragni MV. Lack of desmopressin response in men with haemophilia A following liver transplantation. J Thromb Haemost 2004; 03: 2259-2263.
    PubMedGoogle Scholar
  • 14 Shahani T, Covens K, Lavend'home R. et al. Human liver sinusoidal cells but not hepatocytes contain factor VIII. Thromb Haemost 2014; 12: 36-42.
    CrossrefPubMedGoogle Scholar
  • 15 Liberal R, Longhi MS, Grant CR. et al. Autoimmune hepatitis after liver transplantation. Clin Gastroenterol Hepatol 2012; 10: 346-353.
    CrossrefPubMedGoogle Scholar
  • 16 Carbone M. Neuberger JM autoimmune liver disease, autoimmunity and liver transplantation. J Hepatol 2014; 60: 210-223.
    CrossrefPubMedGoogle Scholar
  • 17 Oldenburg J. Immune tolerance therapy for inhibitors in haemophilia A. Hämostaseologie 2008; 28: 23-25.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Oldenburg J, Barthels M. Congenital coagulopathies and coagulation factor inhibitors. Hämostaseologie 2008; 28: 335-337.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Gregg R, Lester W, Bramhall S. et al. Orthotopic liver transplantation in a patient with severe haemophlia A and a high-titer factor VIII inhibitor from an antithrombin-deficient cadaveric donor. Haemophilia 2013; 19: e84-e102.
    CrossrefPubMedGoogle Scholar
  • 20 Stabler S, Riske B, Geragthy S. et al. Recurrence of inhibitor after orthotopic liver transplantation in severe haemophlia A. Haemophlilia 2009; 15: 634-636.
    PubMedGoogle Scholar
  • 21 Horton S, Martlew V, Wilde J. et al. Re-emergence of a low-titre factor VIII inhibitor after liver transplant. Haemophilia 2012; 18: e60-e87.
    CrossrefPubMedGoogle Scholar
  • 22 Sulkowski M, Pol S, Mallolas J. et al. Boceprevir versus placebo with PEGylated interferon alfa-2b and ribavirin for treatment of hepatitis C virus genotype 1 in patients with HIV. Lancet Infect Dis 2013; 13: 597-605.
    CrossrefPubMedGoogle Scholar
  • 23 Evatt BL, Austin H, Leon G. et al. Haemophilia therapy assessing the cumulative risk of HIV exposure by cryoprecipitate. Haemophilia 2011; 05: 295-300.
    PubMedGoogle Scholar
  • 24 Zimmermann MA, Oldenburg CRJ Müller. et al. Expression studies of mutant factor VIII alleles with premature termination codon with regard to inhibitor formation. Haemophilia 2014; 20: e215-e221.
    CrossrefPubMedGoogle Scholar