Antiviral maintenance treatment with interferon and ribavirin for recurrent hepatitis C after liver transplantation: Pilot study
Corresponding Author
Arno Kornberg
Department of General and Visceral Surgery, Friedrich Schiller University, Jena, and
Dr Arno Kornberg, Department of General and Visceral Surgery, Friedrich Schiller University, Erlangerallee 101, D-07740 Jena, Germany.Email: [email protected]Search for more papers by this authorBernadett Küpper
Department of General and Visceral Surgery, Friedrich Schiller University, Jena, and
Search for more papers by this authorAndrea Tannapfel
Department of Pathology, University of Leipzig, Germany
Search for more papers by this authorErik Bärthel
Department of General and Visceral Surgery, Friedrich Schiller University, Jena, and
Search for more papers by this authorKatharina Thrum
Department of General and Visceral Surgery, Friedrich Schiller University, Jena, and
Search for more papers by this authorUtz Settmacher
Department of General and Visceral Surgery, Friedrich Schiller University, Jena, and
Search for more papers by this authorCorresponding Author
Arno Kornberg
Department of General and Visceral Surgery, Friedrich Schiller University, Jena, and
Dr Arno Kornberg, Department of General and Visceral Surgery, Friedrich Schiller University, Erlangerallee 101, D-07740 Jena, Germany.Email: [email protected]Search for more papers by this authorBernadett Küpper
Department of General and Visceral Surgery, Friedrich Schiller University, Jena, and
Search for more papers by this authorAndrea Tannapfel
Department of Pathology, University of Leipzig, Germany
Search for more papers by this authorErik Bärthel
Department of General and Visceral Surgery, Friedrich Schiller University, Jena, and
Search for more papers by this authorKatharina Thrum
Department of General and Visceral Surgery, Friedrich Schiller University, Jena, and
Search for more papers by this authorUtz Settmacher
Department of General and Visceral Surgery, Friedrich Schiller University, Jena, and
Search for more papers by this authorAbstract
Background: The aim of this pilot study was to evaluate efficacy of a long-term antiviral maintenance therapy (AMT) with interferon-α2b and ribavirin in liver transplant recipients with recurrent hepatitis C.
Methods: Twenty-one patients with recurrent hepatitis C after liver transplantation received AMT with interferon and ribavirin, following 12 months of a basic antiviral combination treatment. Allograft function, viremia loads and allograft morphology were evaluated continuously.
Results: After 12 months of basic antiviral therapy, 14 patients (66.6%) had achieved initial clearance of viremia levels, and 17 recipients (81%) demonstrated normalization of allograft function, respectively. Inflammation score declined significantly (6.0 vs 3.9; P = 0.002), while stage of fibrosis remained unchanged. In virological responders maintenance therapy led to further regression of inflammation score (4.0 at baseline vs 3.1 at 24 months AMT) and fibrosis score (1.6 at baseline vs 1.1 at 24 months AMT). Despite persistence of viremia levels, continued antiviral therapy prevented progression to severe allograft inflammation in virological non-responders. Hematologic adverse effects resulted in treatment discontinuation in seven patients (33.3%).
Conclusion: Long-term AMT, if tolerable, might be an effective approach for preventing progression to severe allograft fibrosis and thereby improving long-term survival in liver transplant recipients with recurrent hepatitis C.
References
- 1 Forman LM, Lewis JD, Berlin JA, Feldman HI, Lucey MR. The association between hepatitis C infection and survival after orthotopic liver transplantation. Gastroenterology 2002; 122: 889–96.
- 2 Berenguer M, Prieto M, Rayon JM et al. Natural history of clinically compensated hepatitis C virus-related graft cirrhosis after liver transplantation. Hepatology 2000; 32: 852–8.
- 3 Gane E. The natural history and outcome of liver transplantation in hepatitis C-virus infected recipients. Liver Transpl. 2003; 9: 28–34.
- 4 Berenguer M. Natural history of recurrent hepatitis C. Liver Transpl. 2002; 8: 14–18.
- 5 McHutchison JG, Poynard T. Combination therapy with interferon plus ribavirin for the initial treatment of chronic hepatitis C. Semin. Liver Dis. 1999; 19 (Suppl. 1): 57–65.
- 6 Poynard T, McHutchison J, Manns M et al. Impact of pegylated interferon-alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C. Gastroenterology 2002; 122: 1303–30.
- 7 Poynard T, Marcellin P, Lee SS et al. Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Interventional Therapy Group (IHIT). Lancet 1998; 31: 1426–32.
- 8 Samuel D, Bizollon T, Feray C et al. Interferon-α 2b plus ribavirin in patients with chronic hepatitis C after liver transplantation: a randomized study. Gastroenterology 2003; 124: 642–50.
- 9 Lavezzo B, Franchello A, Smedile A et al. Treatment of recurrent hepatitis C in liver transplants: efficacy of a six versus a twelve month course of interferon alfa 2b with ribavirin. J. Hepatol. 2002; 37: 247–52.
- 10 De Vera ME, Smallwood GA, Rosado K et al. Interferon-alpha and ribavirin for the treatment of recurrent hepatitis C after liver transplantation. Transplantation 2001; 5: 678–86.
- 11 Tannapfel A, Kohlhaw K, Ebelt J et al. Apoptosis and the expression of Fas and Fas ligand (FasL) antigen in rejection and reinfection in liver allograft specimens. Transplantation 1999; 67: 1079–83.
- 12 Ishak K, Baptista A, Bianchi L et al. Histological grading and staging of chronic hepatitis. J. Hepatol. 1995; 22: 696–9.
- 13 Knodell RG, Ishak KG, Black WC et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1981; 1: 431–5.
- 14 Berenguer M, Prieto M, San Juan F et al. Contribution of donor age to the recent decrease in patient survival among HCV-infected liver transplant recipients. Hepatology 2002; 36: 202–10.
- 15 Gane E, Portmann B, Naoumov N et al. Long-term outcome of hepatitis C infection after liver transplantation. N. Engl. J. Med. 1996; 334: 821–7.
- 16 Sanchez-Fueyo A, Restrepo JC, Quinto L et al. Impact of recurrence of hepatitis C virus infection after liver transplantation on the long-term viability of the graft. Transplantation 2002; 73: 56–63.
- 17 Berenguer M, Ferrell L, Watson J et al. HCV-related fibrosis progression following liver transplantation: increase in recent years. J. Hepatol. 2000; 32: 673–84.
- 18 Wali M, Harrison RF, Gow PJ, Mutimer D. Advancing donor liver age and rapid fibrosis progression following transplantation for hepatitis C. Gut 2002; 51: 248–52.
- 19 Poynard T, Bedossa P, Opolon N. Natural history of liver fibrosis progression in patients with chronic hepatitis C. Lancet 1997; 349: 825–32.
- 20 Niederau C, Lange S, Heinges T et al. Prognosis of chronic hepatitis C. Hepatology 1998; 28: 1687–95.
- 21 Prieto M, Berenguer M, Rayon J et al. High incidence of allograft cirrhosis in HCV genotype 1b following transplantation. Hepatology 1999; 29: 250–6.
- 22 Samuel D. I favor therapy for hepatitis C virus recurrence after transplantation. Liver Transpl. 2002; 8: 55–8.
- 23 Abdelmalek MF, Firpi R, Soldevila-Pico C et al. Sustained viral response to interferon and ribavirin in liver transplant recipients with recurrent hepatitis C. Liver Transpl. 2004; 2: 199–207.
- 24 Bizollon T, Pradat P, Mabrut J-Y et al. Benefit of sustained virological response to combination therapy on graft survival of liver transplanted patients with recurrent chronic hepatitis C. Am. J. Transplant. 2005; 5: 1909–13.
- 25 Alberti AB, Belli LS, Airoldi A et al. Combined therapy with interferon and low-dose ribavirin in post-transplantation recurrent hepatitis C: a pragmatic study. Liver Transpl. 2001; 7: 870–6.
- 26 Stravitz RT, Shiffmann ML, Sanyal AJ et al. Effects of interferon treatment on liver histology and allograft rejection in patients with recurrent hepatitis C following liver transplantation. Liver Transpl. 2004; 10: 850–8.
- 27 Narayanan Menon K, Poterucha J, El-Amin O et al. Treatment of post-transplantation recurrence of hepatitis C with interferon and ribavirin: lessons on tolerability and efficacy. Liver Transpl. 2002; 8: 623–9.
- 28 Pelletier SJ, Lezzoni JC, Crabtree TD, Hahn YS, Sawyer RG, Pruett TL. Prediction of liver allograft fibrosis after transplantation for hepatitis C virus: persistent elevation of serum transaminase levels versus necroinflammatory activity. Liver Transpl. 2000; 6: 44–53.
- 29 Rodriguez-Luna H, Khatib A, Sharma P et al. Treatment of recurrent hepatitis C infection after liver transplantation with combination of pegylated interferon α2b and ribavirin: an open-label series. Transplantation 2004; 2: 190–4.
- 30 Wiesner R, Sorrell M, Villamil F and the International Liver Transplantation Society Panel. Report of the first International Liver Transplantation Society expert panel consensus conference on liver transplantation and hepatitis C. Liver Transpl. 2003; 9 (Suppl. 3): 1–29.
- 31 Feray C, Samuel D, Gigou M et al. An open trial of interferon alfa recombinant for hepatitis C after liver transplantation: antiviral effects and risk of rejection. Hepatology 1995; 27: 1222–3.
- 32 Dousser B, Conti F, Houssin D, Calmus Y. Acute vanishing bile duct syndrome after interferon therapy for recurrent HCV infection in liver transplant recipients. N. Engl. J. Med. 1994; 330: 1160–1.
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