Skip to main content

Advertisement

Log in

Update on the management of hepatitis C in liver transplant recipients

  • Published:
Current Infectious Disease Reports Aims and scope Submit manuscript

Abstract

Hepatic failure due to hepatitis C is the leading indicator for orthotopic liver transplantation (OLT) in the United States. Unfortunately, recurrent hepatitis C virus infection is essentially universal following orthotopic liver transplantation. Although significant advances have been made in the past decade for the treatment of hepatitis C, a similar level of success has not yet been achieved for most hepatitis C virus-infected liver transplant recipients. In addition, deleterious side effects of the currently available antiviral agents continue to significantly hamper their use. Several recent reports, however, indicate that newer immunosuppressive regimens combined with novel modifications of existing treatment paradigms will likely lead to improved clinical outcomes for the hepatitis C virus-infected liver transplant recipient.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. RosenbergPM:Hepatitis C: a hepatologist’s approach to an infectious disease. Clin Infect Dis 2001, 33:1728–1732.

    Article  PubMed  CAS  Google Scholar 

  2. Lauer GM, Walker BD: Medical progress: hepatitis C virus infection. N Engl J Med 2001, 345:41–52. This article offers a complete overview of the natural history, pathogenesis, and clinical management of hepatitis C.

    Article  PubMed  CAS  Google Scholar 

  3. DiBisceglieAM: Natural history of hepatitis C: its impact on clinical management. Hepatology 2000, 31:1014–1018.

    Article  PubMed  Google Scholar 

  4. Powers JJ, Shumaker DA, Rosen HR: Liver transplantation for chronic hepatitis C: long-term results, role of antiviral therapy, and outcome of retransplantation. Curr Opin Organ Transplant 2001, 6:114–119. This report is a succinct and timely overview of the major issues related to the HCV-infected liver transplant recipient, including a cogent and well-balanced discussion on the outcome of retransplantation.

    Article  Google Scholar 

  5. RosenHR: Hepatitis B and C in the liver transplant recipient: current understanding and treatment. Liver Transplant 2001, 7(Suppl 1):S87-S98.

    Article  CAS  Google Scholar 

  6. Berenguer M, Lopez-Labrador FX, Wright TL: Hepatitis C and liver transplantation. J Hepatol 2001, 35:666–678. The authors present an excellent and comprehensive review of pre- and post-transplantation issues, including natural history, pathogenesis, treatment options, and clinical outcomes.

    Article  PubMed  CAS  Google Scholar 

  7. BurroughsAK: Posttransplantation prevention and treatment of recurrent hepatitis C. Liver Transplant 2000, 6(Suppl 2):S35-S40.

    Article  CAS  Google Scholar 

  8. Gane EJ, Portmann BC, Naoumouv NV, et al.: Long-term outcome of hepatitis C infection after liver transplantation. N Engl J Med 1996, 334:821–827.

    Article  Google Scholar 

  9. Berenguer M, Prieto M, Rayon JM, et al.: Natural history of clinically compensated hepatitis C virus-related graft cirrhosis after liver transplantation. Hepatology 2000, 32:852–858. This study reports that compared with nonimmunocompromised patients, HCV-infected liver transplant patients with compensated cirrhosis had an increased rate of clinical deterioration along with a decrease in graft and patient survival. Factors predicting clinical decompensation, need for retransplantation, and increased mortality included a low serum albumin level, rapid development of cirrhosis, and a high Child-Pugh score.

    Article  PubMed  CAS  Google Scholar 

  10. Ghobrial RM, Steadman R, Gornbein J: A 10-year experience of liver transplantation for hepatitis C: analysis of factors determining outcome in over 500 patients. Ann Surg 2001, 234:384–394. The authors present a detailed, retrospective analysis of graft and patient survival data from a single transplant center. Recipient age, clinical condition, serum creatinine, and donor gender carried prognostic significance for patient survival, whereas recipient condition, serum creatinine, serum transaminase levels, and warm ischemia time were found to be predictors of graft survival. Based on these results, the authors developed a prognostic model suitable for prospective evaluation in future studies.

    Article  PubMed  CAS  Google Scholar 

  11. Forman LM, Lucey MR:Orthotopic liver transplantation for hepatitis C: analysis of allograft survival using the UNOS database [abstract 82]. In Program and Abstracts of Transplant 2001, the Joint American Transplant Meeting. Chicago. May 11–16, 2001.

  12. Jones JW, Members of the SEOPF liver committee transplant center: Impact of hepatitis C on liver transplant survival over ten years - a report of the SEOPF liver committee [abstract83]. In Program and Abstracts of Transplant 2001, the Joint American Transplant Meeting. Chicago. May 11–16, 2001.

  13. Ghobrial RM, Farmer DG, Sedman R, et al.: Adverse effects of HCV recurrence in over five hundred liver transplantation patients [abstract 84]. In Program and Abstracts of Transplant 2001, the Joint American Transplant Meeting. Chicago. May 11–16, 2001.

  14. KeefeEB: Liver transplantation: current status and novel approaches to liver replacement. Gastroenterology 1997, 120:749–762.

    Article  Google Scholar 

  15. Allison MW, Wreghitt T, Palmer CR, et al.: Evidence for a link between hepatitis C virus infection and diabetes mellitus in a cirrhotic population. J Hepatol 1994, 21:1135–1139.

    Article  PubMed  CAS  Google Scholar 

  16. Mehta SH, Brancati FL, Sulkowski MS, et al.: Prevalence of type 2 diabetes mellitus among persons with hepatitis C virus infection in the United States. Ann Intern Med 2000, 133:592–599.

    PubMed  CAS  Google Scholar 

  17. Knobler H, Stagnaro-Green A, Wallenstein S, et al.: Higher incidence of diabetes in liver transplant recipients with hepatitis C. J Clin Gastroenterol 1998, 26:30–33.

    Article  PubMed  CAS  Google Scholar 

  18. Baid S, Cosimi AB, Farrell ML, et al.: Posttransplant diabetes mellitus in liver transplant recipients: risk factors, temporal relationship with hepatitis C virus allograft hepatitis, and impact on mortality. Transplantation 2001, 72:1066–1072. Compared with HCV-negative patients, the authors of this study found that the prevalance of PTDM was markedly increased in HCVinfected patients. The development of PTDM was associated with steroid use and significantly increased mortality. Interestingly, response to anti-HCV therapy resulted in improved glycemic control.

    Article  PubMed  CAS  Google Scholar 

  19. SheinerPA: Hepatitis C after liver transplantation. Semin Liver Dis 2000, 20:201–209.

    Article  PubMed  CAS  Google Scholar 

  20. Forns X, Garcia M, Feliu A, et al.: Hepatitis C virus (HCV) kinetics and quasispecies evolution during and immediately after liver transplantation [abstract 760]. Hepatology 2001, 34:362A. Preliminary data presented by this group indicates that HCV serum VL fluctuates during and immediately after transplantation, reaching a nadir at at median of 16 hours following the beginning of the transplant. The authors further observed that exceedingly few patients ever developed an undetectable VL and, intriguingly, also noted that corticosteroid-free immunosuppressive regimens appeared to be associated with a more prolonged, second phase decline in VL.

    Google Scholar 

  21. Laskus T, Wang LF, Rakela J, et al.: Dynamic behavior of hepatitis C virus in chronically infected patients receiving liver grafts from infected donors. Virology 1996, 220:171–176.

    Article  PubMed  CAS  Google Scholar 

  22. Vargas HE, Laskus T, Wang LF, et al.: Outcome of liver transplantation in hepatitis C virus-infected patients who received hepatitis C virus-infected grafts. Gastroenterology 1999, 117:149–153.

    Article  PubMed  CAS  Google Scholar 

  23. Radkowski M, Wang LF, Vargas H: Changes in hepatitis C virus population in serum and peripheral blood mononuclear cells in chronically infected patients receiving liver grafts from infected donors. Transplantation 2001, 72:833–838.

    Article  PubMed  CAS  Google Scholar 

  24. Laskus T, Radkowski M, Wang LF, et al.: Uneven distribution of hepatitis C virus quasispecies in tissues from subjects with end-stage liver disease: confounding effects of viral adsorption and mounting evidence for the presence of low-level extraheptatic replication. J Virol 2000, 74:1014–153.

    Article  PubMed  CAS  Google Scholar 

  25. Vargas H, Wilkinson J, Radkowski M, et al.: The origin of hepatitis C virus reinfecting liver grafts: serum versus peripheral blood mononuclear cells-derived virus [abstract 710]. In Program and Abstracts of Transplant 2001, the Joint American Transplant Meeting. Chicago. May 11–16, 2001.

  26. Charlton M, Seaberg E, Wiesner R, et al.: Predictors of patient and graft survival following liver transplantation for hepatitis C. Hepatology 1998, 28:823–830.

    Article  PubMed  CAS  Google Scholar 

  27. Pelletier SJ, Raymond DP, Crabree TD, et al.: Hepatitis Cinduced hepatic allograft injury is associated with a pre-transplantation elevated viral replication rate. Hepatology 2000, 32:418–426. Hepatitis C virus-infected patients with higher pre- or early posttransplant rates of viral replication were found to have an increased risk of developing a more severe recurrence of hepatitis C (as measured by hepatitis acitivity index and extent of fibrosis seen on liver biopsies).

    Article  PubMed  CAS  Google Scholar 

  28. Berengeur M, Lopez-Labrador FX, Greenberg HB, et al.: Hepatitis C virus and the host: a balance induced by immunosuppression? Hepatology 2000, 32:433–435.

    Article  Google Scholar 

  29. Sreekumar R, Gonzalez-Koch A, Maor-Kendler Y, et al.: Early identification of recipients with progressive histologic recurrence of hepatitis C after liver transplantation. Hepatology 2000, 32:1125–1130. In this study, patients with higher HCV viral loads at 4 months post-transplantation had worse hepatitis activity indices and higher rates of fibrosis observed in liver biopsies performed at 1 and 3 years post-transplant.

    Article  PubMed  CAS  Google Scholar 

  30. Suarez R, Otero A, Gomez-Gutierrez M, et al.: HCV viral load at one month after liver transplantation is a prognostic factor for the development of recurrent hepatitis C and liver failure after transplantation [abstract 85]. In Program and Abstracts of Transplant 2001, the Joint American Transplant Meeting. Chicago. May 11–16, 2001. The authors of this preliminary report found that a high HCV viral load at 1 month post-transplant was associated with a worse histologic outcome on biopsy, an increased incidence of hepatic failure, and a higher mortality rate.

  31. McCaughan GW, Zekry A: Effects of immunosuppression and organ transplantation on the natural history and immunopathogenesis of hepatitis C virus infection. Transplant Infect Dis 2000, 2:166–185.

    Article  CAS  Google Scholar 

  32. Rosen HR, Martin P, Shackleton CR, et al.: Use of OKT3 is associated with early and severe hepatitis C recurrence following liver transplantation. Am J Gastroenterol 1997, 92:1453–1456.

    PubMed  CAS  Google Scholar 

  33. Papatheodoridis GV, Davies S, Dhillon AP, et al.: The role of different immunosuppression in the long-term histological outcome of HCV reinfection after liver transplantation for HCV cirrhosis. Transplantation 2001, 72:412–418.

    Article  PubMed  CAS  Google Scholar 

  34. Rosen HR, Chou S, Corless CL, et al.: Cytomegalovirus viremia: risk factor for allograft cirrhosis after liver transplantation for hepatitis C. Transplantation 1997, 64:721–726.

    Article  PubMed  CAS  Google Scholar 

  35. Teixeira R, Pastacaldi S, Davies S, et al.: The influence of cytomegalovirus viraemia on the outcome of recurrent hepatitis C after liver transplantation. Transplantation 2000, 70:1454–1458.

    Article  PubMed  CAS  Google Scholar 

  36. DieterichDT: Hepatitis C virus and human immunodeficiency virus: clinical issues in coinfection. Am J Med 1999, 107:85S-89S.

    Article  Google Scholar 

  37. MoormanJP: Issues in HIV/hepatitis C co-infection. Curr Infect Dis Rep 2001, 3:131–136. This article is a current overview of important issues regarding the care of coinfected patients.

    PubMed  Google Scholar 

  38. Gow PJ, Pilay D, Mutimer D: Solid organ transplantation in patients with HIV infection. Transplantation 2001, 72:177–181.

    Article  PubMed  CAS  Google Scholar 

  39. Prachalias AA, Pozniak A, Taylor C: Liver transplantation in adults coinfected with HIV. Transplantation 2001, 72:1684–1688.

    Article  PubMed  CAS  Google Scholar 

  40. Neff GT, Jayaweera D, Hung O, et al.: Initial successful liver transplantation in patients with HIV-HBV or HCV co-infection: a report of 6 cases [abstract I-203]. In Program and Abstracts of the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago. December 16–19, 2001.

  41. Teixeira R, Papatheodoridis GK, Burroughs AK: Management of recurrent hepatitis C after liver transplantation. J Viral Hepat 2001, 8:159–168. The authors summarize and critique recent studies involving pre-emptive, monotherapy, and combination treatment protocols for the HCV-infected liver transplant recipient. They also discuss pertinent issues relating to the topic of retransplantation.

    Article  PubMed  CAS  Google Scholar 

  42. Cotler SJ, Ganger DR, Kaur S, et al.: Daily interferon therapy for hepatitis C virus infection in liver transplant recipients. Transplantation 2001, 71:261–268.

    Article  PubMed  CAS  Google Scholar 

  43. Gopal DV, Rabkin JM, Berk BS, et al.: Treatment of progressive hepatitis C recurrence following liver transplantation with combination interferon plus ribavirin. Liver Transplant 2001, 7:181–190.

    Article  CAS  Google Scholar 

  44. de VeraME, Smallwood GA, Rosado K, et al.: Interferon-a and ribavirin for the treatment of recurrent hepatitis C after liver transplantation. Transplantation 2001, 71:678–686.

    Article  PubMed  Google Scholar 

  45. Alberti AB, Belli LS, Airoldi A, et al.: Combined therapy with interferon and low-dose ribavirin in posttransplantation recurrent hepatitis C: a pragmatic study. Liver Transplant 2001, 7:870–876.

    Article  CAS  Google Scholar 

  46. Belli LS, Alberti AB, Rondinara GF, et al.: Early ribavirin treatment and avoidance of corticosteroids in hepatitis C virus (HCV)-positive liver transplant recipients: interim report of a prospective randomized trial. Transplant Proc 2001, 33:1353–1354. The preliminary indication from this brief interim report is that early ribavirn "prophylaxis" combined with steroid-sparing immunosuppression may significantly decrease and delay the occurrence of HCV-related hepatitis post-transplantation. Of note, however, was the significant incidence of moderate to severe ribavirin-associated anemia noted to occur, even in patients receiving lower dose therapy.

    Article  PubMed  CAS  Google Scholar 

  47. Ahmad J, Dodson F, Demetris AJ, et al.: Recurrent hepatitis C after liver transplantation: a nonrandomized trial of interferon alfa alone versus interferon alfa and ribavirin. Liver Transplant 2001, 7:863–869. Although the patients were nonrandomized, this report is one of the few recent studies to directly and prospectively compare different treatment regimens for HCV-infected transplant patients. Although significant numbers of patients withdrew from both arms of the study due to treatment toxicities, the overall results appeared to indicate that combination therapy with interferon and ribavirin, compared with interferon monotherapy, improved viral clearance but not biochemical or histologic responses.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bobak, D.A., Yadavalli, G. Update on the management of hepatitis C in liver transplant recipients. Curr Infect Dis Rep 4, 105–111 (2002). https://doi.org/10.1007/s11908-002-0049-4

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11908-002-0049-4

Keywords

Navigation