The main indication for liver transplantation is the final stage of hepatic cirrhosis developed due to hepatitis C virus (HCV) infection. The recurrence of HCV infection after transplantation is a common situation. Recurrent hepatitis C is a progressive disease; in 20% of patients it produces liver cirrhosis without treatment beside immunosuppression within 5 years. Treatment of recurrent HCV infection is the most important factor of survival in patients with transplantation. Based on literary data and their observations, the authors review the factors influencing the progression of recurrent HCV infection. They discuss in details the effect of immunosuppressive therapy, the importance of selecting appropriate immunosuppressive drugs. They review the key points in the diagnosis of recurrent hepatitis C; underline the decisive role of liver biopsy carried out according to protocol in the diagnosis, as well as the hard consultation between specialists of pathology, hepatology and surgery. They demonstrate their observations with the treatment of patients on the waiting list, the results of early pre-emptive treatment of recurrent chronic hepatitis, furthermore treatment modalities and results in patients with histologically proven chronic hepatitis C. The drug of choice for chronic hepatitis C after transplantation is combined therapy with pegylated interferon and ribavirin. This therapy is able to assure sustained virological negativity in 20–50% of patients. In virus-free patients the inflammatory activity in the liver significantly decreases, and the histologic activity index improves. There are data showing a fibrosis-inhibiting effect of the treatment, however, multicentric studies are required for their confirmation. No advantage of early antiviral treatment without histologic alteration has been confirmed by most of the trials. In this group of patients common side effects of the treatment include anaemia and neutropenia, and therefore administration of erythropoietin and granulocyte stimulating factor is recommended. Further research and clinical studies are required in order to establish optimal treatment of patients with recurrent hepatitis C, to determine the dosage of pegylated interferon and ribavirin, to decrease duration of therapy, to reduce side effects and finally to achieve the healing phase in a greater percentage of patients.
[1]. S. H. Belle K. C. Beringer K.M. Detre 1996 Recent findings concerning liver transplantation in the United States Clin. Transpl. 10 15–29.
[2]. B. Nemes E. Sárváry Zs. Gerlei 2007 The recurrence of hepatitis C virus after liver transplantation Orv Hetil. 148 1971–1979.
[3]. L.M. Forman J. D. Lewis J. A. Berlin 2002 The association between hepatitis C infection and survival after orthotopic liver transplantation Gastroenterology 122 889–896.
[4]. M. Garcia-Retortillo X. Forns A. Feliu 2002 Hepatitis C virus kinetics during and immediately after liver transplantation Hepatology 35 680–687.
[5]. M. Berenguer F. X. Lopez-Labrador T. L. Wright 2001 Hepatitis C and liver transplantation J. Hepatol. 35 666–678.
[6]. T. Fukumoto T. Berg Y. Ku 1996 Viral dynamics of hepatitis C early after orthotopic liver transplantation: evidence for rapid turnover of serum virions Hepatology 24 1351–1354.
[7]. E. J. Gane N. V. Naoumov K. P. Qian 1996 A longitudinal analysis of hepatitis C virus replication following liver transplantation Gastroenterology 110 167–177.
[8]. A. Sanchez-Fueyo J. C. Restrepo L. Quinto 2002 Impact of the recurrence of hepatitis C virus infection after liver transplantation on the long-term viability of the graft Transplantation 15 73 56–63.
[9]. M. Berenguer J.M. Rayon M. Priet 2001 Are posttransplantation protocol liver biopsies useful in the long term? Liver Transpl. 7 790–796.
[10]. M. Bahra U. P. Neumann D. Jacob 2005 Repeated steroid pulse therapies in HCV-positive liver recipients: significant risk factor for HCV-related graft loss Transplant. Proc. 37 1700–1702.
[11]. M. Berenguer 2002 Natural history of recurrent hepatitis C Liver Transplant. 8 14–18.
[12]. U. P. Neumann T. Berg M. Bahra 2004 Fibrosis progression after liver transplantation in patients with reccurent hepatitis C J. Hepatol. 41 830–836.
[13]. B. Nemes E. Sárváry L. Kóbori 2005 Serum hepatitis C virus — ribonucleotide acid monitoring after liver transplantation. The Hungarian experience Dig. Liver Dis. 37 68–69.
[14]. G. Testa J. S. Crippin G. J. Netto 2000 Liver transplantation for hepatitis C: recurrence and disease progression in 300 patients Liver Transpl. 6 553–561.
[15]. S. Zhou N. A. Terrault L. Ferrell 1996 Severity of liver disease in liver transplantation recipients with hepatitis C virus infection: relationship to genotype and level of viremia Hepatology 24 1041–1046.
[16]. P. Martin R. W. Busuttil R. M. Goldstein 2004 Impact of tacrolimus versus cyclosporine in hepatitis C virus-infected liver transplant recipients on recurrent hepatitis: a prospective, randomized trial Liver Transpl. 10 1258–1262.
[17]. R. J. Firpi H. Zhu G. Morelli 2006 Cyclosporine suppresses hepatitis C virus in vitro and increases the chance of a sustained virological response after liver transplantation Liver Transpl. 12 51–57.
[18]. N. Selzner N. Girgrah I. Al-Adawi 2006 Genotype and choice of calcineurin inhibitor influence response to antiviral therapy in liver transplant recipients treated for recurrent HCV Hepatology 44 785.
[19]. M. Berenguer A. Palau A. Fernandez 2006 Efficacy, predictors of response, and potential risks associated with antiviral therapy in liver transplant recipients with recurrent hepatitis C Liver Transpl. 12 1067–1076.
[20]. M. Berenguer 2005 What determines the natural history of recurrent hepatitis C after liver transplantatio? J. Hepatol. 42 448–456.
[21]. L. Llado X. Xiol J. Figueras 2006 Immunsuppression without steroids in liver transplantation is safe and reduces infection and metabolic complications: results from a prospective multicenter randomized study J. Hepatol. 44 710–716.
[22]. C. Margarit I. Bilbao L. Castells 2005 A prospective randomized trial comparing tacrolimus and steroid with tacrolimus monotherapy in liver transplantation: the impact on recurrence of hepatitis C Transplant. Int. 18 1336–1345.
[23]. P. Neuhaus P.-A. Clavien D. Kittur 2002 Improved treatment response with basiliximab immunoprophylaxis after liver transplantation: results from a double-blind randomized placebo-controlled trial Liver Transpl. 8 132–142.
[24]. A. Jain R. Kashyap A. J. Demetris 2002 A prospective randomized trial of mycophenolate mofetil in liver transplant recipients with hepatitis C Liver Transpl. 8 40–46.
[25]. R. H. Wiesner J. S. Shorr B. J. Steffen 2005 Mycophenolate mofetil combination therapy improves long-term outcomes after liver transplantation in patients with and without hepatitis C Liver Transpl. 11 750–759.
[26]. M. W. Russo J. Galanko K. Beavers 2004 Patient and graft survival in hepatitis C recipients after adult living donor liver transplantation in the United States Liver Transpl. 10 340–346.
[27]. G.W. Neff N. Shire P. Ruiz 2005 The importance of clinical parameters when differentiating cholestatic hepatitis C virus from allograft rejection Transpl. Proc. 37 4397–4402.
[28]. A. Patonai B. Nemes D. Görög 2001 Pathologic evaluation of orthotopic liver transplantation in Hungary Orv. Hetil. 142 435–441.
[29]. L. Baiocchi G. Tisone G. Palmieri 1998 Hepatic steatosis: a specific sign of hepatitis C reinfection after liver transplantation Liver Transpl. 4 441–447.
[30]. A. Regev E. Molina R. Moura 2004 Reliability of histopathologic assessment for the differentiation of recurrent hepatitis C from acute rejection after liver transplantation Liver Transpl. 10 1233–1239.
[31]. R. H. Wiesner M. Sorrell F. Villamil 2003 Report of the first international Liver Transplantation Society expert panel consensus conference on liver transplantation and hepatitis C Liver Transpl. 9 1–9.
[32]. R. T. Stravitz M. L. Shiffman A. J. Sanyal 2004 Effects of interferon treatment on liver histology and allograft rejection in patients with recurrent hepatitis C following liver transplantation Liver Transpl. 10 850–858.
[33]. G. L. Davis D. R. Nelson N. Terrault 2005 A randomized, openlabel study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients Liver Transpl. 11 941–949.
[34]. R. Eren D. Landstein D. Terkieltaub 2006 Preclinical evaluation of two neutralizing human monoclonal antibodies against hepatitis C virus (HCV): a potential treatment to prevent HCV reinfection in liver transplant patients J. Virol. 80 2654–2664.
[35]. G. T. Everson J. Trotter L. Forman 2005 Treatment of advanced hepatitis C with a low accelerating dosage regimen of antiviral therapy Hepatology 42 255–262.
[36]. X. Forns M. Garcia-Retortillo T. Serrano 2003 Antiviral therapy of patients with decompensated cirrhosis to prevent recurrence of hepatitis C after liver transplantation J. Hepatol. 39 389–396.
[37]. E. Martinez-Bauer J. A. Carrion S. Ramirez 2006 Antiviral therapy of patients with decompensated cirrhosis to prevent hepatitis C recurrence after liver transplantation J. Hepatol. 44 Suppl.2 64.
[38]. L. Zileri Dal Verme J. A. Ilyas G. Merra 2006 HCV treatment in patients with end stage liver disease awaiting liver transplantation J. Hepatol. 44 Suppl.2 232.
[39]. P. A. Sheiner P. Boros F. M. Klion 1998 The efficacy of prophylactic interferon alfa-2b in preventing recurrent hepatitis C after liver transplantation Hepatology 28 831–838.
[40]. V. Mazzaferro A. Tagger M. Schiavo 2001 Prevention of recurrent hepatitis C after liver transplantation with early interferon and ribavirin treatment Transpl., Proc. 33 1355–1357.
[41]. A. K. Shergill M. Khalili S. Straley 2005 Applicability, tolerability and efficacy of preemptive antiviral therapy in hepatitis C infected patients undergoing liver transplantation Am. J. Transpl. 5 118–124.
[42]. N. Chalasani C. Manzarbeitia P. Ferenci 2005 Peginterferon alfa-2a for hepatitis C after liver transplantation: two randomized, controlled trials Hepatology 41 289–298.
[43]. A. Kuo B. Lan S. Feng 2006 Long-term histological effects of preemptive antiviral therapy in liver transplant recipients with hepatitis C virus (HCV) infection Hepatology 44 4Suppl.1 3.
[44]. M. F. Abdelmalek R. J. Firpi C. Soldevila-Pico 2004 Sustained viral response to interferon and ribavirin in liver transplant recipients with recurrent hepatitis C Liver Transpl. 10 199–207.
[45]. D. Samuel T. Bizollon C. Feray 2003 Interferon-alpha 2b plus ribavirin in patients with chronic hepatitis C after liver transplantation: a randomized study Gastroenterology 124 642–650.
[46]. G. Lengyel L. Kóbori I. Fehérvári 2003 Combined interferon-alfa-2b and ribavirin therapy in patients with recurrent chronic hepatitis C after liver transplantation Orv. Hetil. 48 2367–2370.
[47]. J. Dumortier J. Y. Scoazec P. Chevallier 2004 Treatment of reccurent hepatitis C after liver transplantation: a pilot study of peginterferon alfa-2b and ribavirin combination J. Hepatol. 40 669–674.
[48]. J.M. Moreno Planas E. Rubio Gonzalez E. Boullosa Grana 2005 Peginterferon and ribavirin in patients with HCV cirrhosis after liver transplantation Transpl. Proc. 37 2207–2208.
[49]. M. Aesatie N. Chalasani P. Y. Kwo 2007 Management of hepatitis C infection after liver transplantation Drugs 67 871–885.
[50]. A. Kuo N. A. Terrault 2007 Antiviral therapy in liver transplant recipients: Is SVR the only endpoint that matters? J. Hepatol. 46 359–361.
[51]. J. Dumortier E. Ducos J. Y. Scoazec 2006 Plasma ribavirin concentrations during treatment of recurrent hepatitis C with peginterferon alpha-2b and ribavirin combination after liver transplantation J. Viral Hepatol. 13 538–543.
[52]. D. L. Paterson T. Gayowski C. F. Wannstedt 2000 Quality of life in long-term survivors after liver transplantation: impact of recurrent viral hepatitis C virus hepatitis Clin. Transpl. 14 48–54.