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Viral hepatitis in renal transplantation
Viral Hepatitis in Renal Transplantation A. Vathsala
L
IVER DISEASE is an important cause of late transplant morbidity in patients who have undergone renal transplantation (RT) and is reported to occur in as many as 38% of long-term survivors.1 The majority of liver disease after RT is due to hepatitis B (HepB) or hepatitis C (HepC) infections. Two new viruses, hepatitis G and the Transfusion Transmitted (TT) virus, also have been found to have an increased prevalence in patients who have undergone dialysis and RT, however, there is currently no evidence of adverse impact of these viruses on liver disease or graft and patient outcomes.2,3 Immunosuppression postRT has been suggested to lead to increased viral replication and a range of hepatic complications, such as chronic persistent hepatitis (CPH), chronic active hepatitis (CAH), fibrosing cholestatic hepatitis, fulminant liver failure (FLF), or hepatocellular carcinoma (HCC). Renal complications also may occur and include membranous nephropathy due to HepB or HepC and membranoproliferative glomerulonephritis and cryoglobulinaemia in HepC. HepB is a hepadna virus that is found with a higher prevalence among dialysis patients. Although early studies suggested the relative safety of RT in HepB carriers with asymptomatic disease prior to RT, more recent studies attest to the increased morbidity due to liver disease and patient mortality in these patients. Bang et al documented chronic hepatitis in 25.7%, FLF in 10.1%, and HCC in 1.3% of HepB⫹ patients who have undergone RT.4 Pfaff et al, from a large multicentre database, also documented reduced patient survival in patients with HepB who have undergone RT, with excessive risks attributed to HepC or Delta coinfection, evidence of increased viral replication, or with evidence of CAH on liver biopsy.5 Mathurin et al have documented significantly lower 10-year graft (36%) and patient (55%) survival rates in HepB than in control patients (63% and 80%, respectively; P ⬍ .001), with liver disease being the most common cause of death.6 Given the increased mortality in patients with HepB who have undergone RT, HepB⫹ patients undergoing dialysis should be evaluated prior to consideration for RT. Those with Delta or HCV co-infection, those with evidence of viral replication, such as positive HepB e antigen or elevated hepatitis B virus (HBV) DNA, and those with liver dysfunction should be considered for liver biopsy and appropriate therapy with interferon alpha (IFN␣) and/or Lamivudine therapy. Patients in whom high levels of immunosuppres0041-1345/02/$–see front matter PII S0041-1345(02)03164-0 2426
sion may be required postRT may be advised to opt for dialysis instead of RT. Minimising immunosuppression, avoiding of azathioprine (Aza) and antilymphocyte (AL) preparations, and using anticytomegolovirus (CMV) prophylaxis to further reduce the immmunomodulating effects of superimposed CMV infection are some strategies used to reduce viral replication postRT. Subsequently, continued monitoring of HBV DNA will detect HepB reactivation so that at-risk patients may be considered for treatment with IFN␣ or Lamivudine. IFN␣ therapy may lead to rejection episodes in patients who have undergone RT and is not routinely advised for these patients.7 However, although HBV DNA clearance and normalisation of transaminases following therapy with Lamivudine has been documented, emergence of Lamuvidine resistance, some due to mutations in the YMDD motif of the HepB polymerase gene, may be a limiting factor in therapy.8,9 HepC is an RNA flavovirus that is responsible for most non-A, non-B posttransfusion hepatitis. Pereira et al have shown an increased relative risk for death and an increased risk for death due to sepsis in patients with HepC who have undergone RT.10 Mathurin et al have demonstrated significantly worse 10-year graft (49%) and patient (65%) survival rates in comparison to uninfected controls.6 An increased risk for liver disease is also reported, with increased risk attributed to HepB confection, positive hepatitis C virus (HCV) polymerase chain reaction (PCR); therapy with Aza or AL and longer duration of follow-up.11 Patients with HepC who have renal failure and HepB co-infection may be better treated with dialysis while those with transaminitis should undergo liver biopsy and further consideration of treatment with IFN␣. Nevertheless, asymptomatic liver disease is common in HepC and transaminase levels are a poor index of underlying liver disease caused by HepC. One strategy to reduce HepC reactivation postRT is the avoidance of excessive immunosuppression. Although IFN␣ and ribavirin therapy are treatment options, allograft rejection and hemolysis, respectively, may complicate therFrom the Department of Renal Medicine, Singapore General Hospital, Singapore, Singapore. Address reprint requests to A. Vathsala, Department of Renal Medicine, Singapore General Hospital, Outram Road, Singapore 169608. © 2002 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation Proceedings, 34, 2426 –2427 (2002)
VIRAL HEPATITIS IN RENAL TRANSPLANTATION
apy. Combination therapy of IFN␣ and ribavirin may improve response rates and may be particularly useful in some patients who have undergone RT. In summary, liver disease caused by viral HepB or HepC is associated with significant morbidity and mortality in patients who have undergone RT; however, current treatment remains unsatisfactory. Thus, careful selection of patients for RT and minimising immunosuppression postRT is likely to improve outcomes in these patients. REFERENCES 1. Ware AJ, Luby JP, Hollinger B, et al: Ann Intern Med 91:364, 1979
2427 2. Murthy BV, Muerhoff AS, Desa AM, et al: J Am Soc Nephrol 8:1164, 1997 3. Bonis PAL: J Am Soc Nephrol 10:1828, 1999 4. Bang BK, Yang CW, Yoon SA, et al: Nephron 70:397, 1995 5. Pfaff WW, Blanton JW: Clin Transplant 11:476, 1997 6. Mathurin P, Mouquet C, Poynard T, et al: Hepatology 29:257, 1999 7. Durlik M, Gaciong Z, Rowinska D, et al: Transplant Int 11:S135, 1998 8. Rostaing L, Henry S, Cisterne JM, et al: Transplantation 64:1624, 1997 9. Fontaine H, Thiers V, Chretien Y, et al: Transplantation 69:2090, 2000 10. Pereira BJG, Wright TL, Schmid CH, et al: Transplantation 60:799, 1995 11. Morales JM: Nephrol Dial Transplant 10:S125, 1995
L
IVER DISEASE is an important cause of late transplant morbidity in patients who have undergone renal transplantation (RT) and is reported to occur in as many as 38% of long-term survivors.1 The majority of liver disease after RT is due to hepatitis B (HepB) or hepatitis C (HepC) infections. Two new viruses, hepatitis G and the Transfusion Transmitted (TT) virus, also have been found to have an increased prevalence in patients who have undergone dialysis and RT, however, there is currently no evidence of adverse impact of these viruses on liver disease or graft and patient outcomes.2,3 Immunosuppression postRT has been suggested to lead to increased viral replication and a range of hepatic complications, such as chronic persistent hepatitis (CPH), chronic active hepatitis (CAH), fibrosing cholestatic hepatitis, fulminant liver failure (FLF), or hepatocellular carcinoma (HCC). Renal complications also may occur and include membranous nephropathy due to HepB or HepC and membranoproliferative glomerulonephritis and cryoglobulinaemia in HepC. HepB is a hepadna virus that is found with a higher prevalence among dialysis patients. Although early studies suggested the relative safety of RT in HepB carriers with asymptomatic disease prior to RT, more recent studies attest to the increased morbidity due to liver disease and patient mortality in these patients. Bang et al documented chronic hepatitis in 25.7%, FLF in 10.1%, and HCC in 1.3% of HepB⫹ patients who have undergone RT.4 Pfaff et al, from a large multicentre database, also documented reduced patient survival in patients with HepB who have undergone RT, with excessive risks attributed to HepC or Delta coinfection, evidence of increased viral replication, or with evidence of CAH on liver biopsy.5 Mathurin et al have documented significantly lower 10-year graft (36%) and patient (55%) survival rates in HepB than in control patients (63% and 80%, respectively; P ⬍ .001), with liver disease being the most common cause of death.6 Given the increased mortality in patients with HepB who have undergone RT, HepB⫹ patients undergoing dialysis should be evaluated prior to consideration for RT. Those with Delta or HCV co-infection, those with evidence of viral replication, such as positive HepB e antigen or elevated hepatitis B virus (HBV) DNA, and those with liver dysfunction should be considered for liver biopsy and appropriate therapy with interferon alpha (IFN␣) and/or Lamivudine therapy. Patients in whom high levels of immunosuppres0041-1345/02/$–see front matter PII S0041-1345(02)03164-0 2426
sion may be required postRT may be advised to opt for dialysis instead of RT. Minimising immunosuppression, avoiding of azathioprine (Aza) and antilymphocyte (AL) preparations, and using anticytomegolovirus (CMV) prophylaxis to further reduce the immmunomodulating effects of superimposed CMV infection are some strategies used to reduce viral replication postRT. Subsequently, continued monitoring of HBV DNA will detect HepB reactivation so that at-risk patients may be considered for treatment with IFN␣ or Lamivudine. IFN␣ therapy may lead to rejection episodes in patients who have undergone RT and is not routinely advised for these patients.7 However, although HBV DNA clearance and normalisation of transaminases following therapy with Lamivudine has been documented, emergence of Lamuvidine resistance, some due to mutations in the YMDD motif of the HepB polymerase gene, may be a limiting factor in therapy.8,9 HepC is an RNA flavovirus that is responsible for most non-A, non-B posttransfusion hepatitis. Pereira et al have shown an increased relative risk for death and an increased risk for death due to sepsis in patients with HepC who have undergone RT.10 Mathurin et al have demonstrated significantly worse 10-year graft (49%) and patient (65%) survival rates in comparison to uninfected controls.6 An increased risk for liver disease is also reported, with increased risk attributed to HepB confection, positive hepatitis C virus (HCV) polymerase chain reaction (PCR); therapy with Aza or AL and longer duration of follow-up.11 Patients with HepC who have renal failure and HepB co-infection may be better treated with dialysis while those with transaminitis should undergo liver biopsy and further consideration of treatment with IFN␣. Nevertheless, asymptomatic liver disease is common in HepC and transaminase levels are a poor index of underlying liver disease caused by HepC. One strategy to reduce HepC reactivation postRT is the avoidance of excessive immunosuppression. Although IFN␣ and ribavirin therapy are treatment options, allograft rejection and hemolysis, respectively, may complicate therFrom the Department of Renal Medicine, Singapore General Hospital, Singapore, Singapore. Address reprint requests to A. Vathsala, Department of Renal Medicine, Singapore General Hospital, Outram Road, Singapore 169608. © 2002 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation Proceedings, 34, 2426 –2427 (2002)
VIRAL HEPATITIS IN RENAL TRANSPLANTATION
apy. Combination therapy of IFN␣ and ribavirin may improve response rates and may be particularly useful in some patients who have undergone RT. In summary, liver disease caused by viral HepB or HepC is associated with significant morbidity and mortality in patients who have undergone RT; however, current treatment remains unsatisfactory. Thus, careful selection of patients for RT and minimising immunosuppression postRT is likely to improve outcomes in these patients. REFERENCES 1. Ware AJ, Luby JP, Hollinger B, et al: Ann Intern Med 91:364, 1979
2427 2. Murthy BV, Muerhoff AS, Desa AM, et al: J Am Soc Nephrol 8:1164, 1997 3. Bonis PAL: J Am Soc Nephrol 10:1828, 1999 4. Bang BK, Yang CW, Yoon SA, et al: Nephron 70:397, 1995 5. Pfaff WW, Blanton JW: Clin Transplant 11:476, 1997 6. Mathurin P, Mouquet C, Poynard T, et al: Hepatology 29:257, 1999 7. Durlik M, Gaciong Z, Rowinska D, et al: Transplant Int 11:S135, 1998 8. Rostaing L, Henry S, Cisterne JM, et al: Transplantation 64:1624, 1997 9. Fontaine H, Thiers V, Chretien Y, et al: Transplantation 69:2090, 2000 10. Pereira BJG, Wright TL, Schmid CH, et al: Transplantation 60:799, 1995 11. Morales JM: Nephrol Dial Transplant 10:S125, 1995