Diminished survival due to hepatitis B has been observed after renal transplantation (RT). Lamivudine, a second-generation nucleoside analogue, has been approved for the treatment of chronic hepatitis B virus (HBV) infection in patients with normal renal function. Numerous clinical experiences with lamivudine after RT have been recently published. Despite numerous shortcomings, all of these reports have shown encouraging results. The rate of clearance of HBV viremia ranged between 67% and 100%, and the frequency of ALT normalization was between 50% and 100% with lamivudine use. Even patients with fibrosing cholestatic hepatitis, a serious form of HBV-related liver disease with ominous course, have been successfully treated with lamivudine. Lamivudine therapy significantly improved the survival of HBsAg positive renal allograft recipients. However, numerous issues concerning the treatment of hepatitis B after RT remain unclear: the optimal time to initiate lamivudine, the appropriate duration of antiviral therapy after RT, and the role for pre-transplantation liver biopsy. Also, the management of lamivudine resistance remains a concern for physicians. Clinical trials are under way.
MaynardJ.E.Hepatitis B: Global importance and need for control. Vaccine1990; 8: 518–20.
2.
BangB.K., YangC.W., YoonS.A., KimY.S., ChangY.S., YoonY.S., KohY.B.Prevalence and clinical course of hepatitis B and hepatitis C liver disease in cyclosporin-treated renal allograft recipients. Nephron1995; 70: 397–401.
Pouteil-NobleC., TardyJ.C., ChossegrosP., MionF., ChevallierM., GerardF., ChevallierP., MegasF., LefrancoisN., TouraineJ.L.Co-infection by hepatitis B virus and hepatitis C virus in renal transplantation: Morbidity and mortality in 1098 patients. Nephrol Dial Transplant1995; 10: 122–4.
5.
FabriziF., MartinP., PonticelliC.Hepatitis B virus and renal transplantation. Nephron2002; 90: 241–51.
6.
FabriziF., LunghiG., PoordadF.P., MartinP.Management of hepatitis B after renal transplantation: An update. J Nephrol2002; 15: 113–22.
7.
PerrilloR.P.Hepatitis B and renal transplantation: Securing the sword of Damocles. Hepatology2002; 36: 1041–5.
8.
HuangC.C., LaiM.K., FongM.T.Hepatitis B liver disease in cyclosporin-treated renal allograft recipients. Transplantation1990; 49: 540–4.
9.
RivoltaE., De VecchiA., TarantinoA., CastelnovoC., BerardinelliL., PonticelliC.Prognostic significance of hepatitis B surface antigenemia in cadaveric renal transplant patients. Transplant Proc1987; 19: 2153–4.
10.
FlaggG.L., SilbermanH., TakamotoS.K., BerneT.V.The influence of hepatitis B infection on the outcome of renal allotransplantation. Transplant Proc1987; 19: 2155–8.
BerneT.V., FitzgibbonsT.J., SilbermanH.The effect of hepatitis B antigenemia on long-term success and hepatic disease in renal transplant recipients. Transplantation1977; 24: 412–5.
13.
ChatterjeeS.N., PayneJ.E.D., BischelM.D., RedekerA.G., BerneT.V.Successful transplantation in patients positive for hepatitis B antigen. N Engl J Med1974; 29: 62–6.
14.
PirsonY., AlexandreG.P.J., van Ypersele de StrihouC.Long-term effect of HBs antigenemia on patient survival after renal transplantation. N Engl J Med1997; 296: 194–6.
15.
HiesseC., BuffetC., NeyratN., RieuP., CharpentierB., EtienneJ.P., FriesD.Impact of HBs antigenemia on long-term patient survival and causes of death after renal transplantation. Clin Transplant1992; 46: 461–7.
16.
MathurinP., MouquetC., PoynardT., SyllaC., BenaliaH., FretzC., ThibaultV., CadranelJ.F., BernardP., OpolonP., CoriatP., BitkerM.O.Impact of hepatitis B and C virus on kidney transplantation outcome. Hepatology1999; 29: 257–3.
17.
PaparellaM., TarantinoA., PonticelliC.How to manage the dialysis patient with chronic viral hepatitis who is considered for renal transplantation. Nephrol Dial Transplant1996; 11: 2122–4.
18.
PfaffW.W., BlantonJ.W.Hepatitis antigenemia and survival after renal transplantation. Clin Transplant1997; 11: 476–9.
19.
BreitenfeldtM.K., RasenackJ., BertholdH., OlschewskiM., SchroffJ., StreyC., GrotzW.H.Impact of hepatitis B and C on graft loss and mortality of patients after kidney transplantation. Clin Transplant2002; 16: 130–6.
20.
LeeW.C., ShuK.H., ChengC.H., WuuM.J., ChenC.H., LianJ.D.Long-term impact of hepatitis B, C virus infection on renal transplantation. Am J Nephrol2001; 21: 300–6.
21.
LaQuagliaM.P., Tolkoff-RubinN.E., DienstagJ.L., CosimiA.B., HerrinJ.T., KellyM., RubinR.H.Impact of hepatitis on renal transplantation. Transplantation1981; 32: 504–7.
22.
FornaironS., PolS., LegendreC., CarnotF., Mamzer-BreenelM.F., BrechotC., KreisH.The long-term virologic and pathologic impact of renal transplantation on chronic hepatitis B virus infection. Transplantation1996; 62: 298–9.
23.
ChenJ.B., HsiehH., HsuK.T., ChenC.H.Impact of donor hepatitis B antigenemia on renal allograft in hepatitis B recipients. Transplant Proc1996; 28: 1490–2.
ChanT.M., FangG.X., TangC.O.S., ChengI.K.P., LaiK.N., HoS.K.N.Preemptive lamivudine therapy based on HBV DNA level in HBsAg-positive kidney allograft recipients. Hepatology2002; 36: 1246–52.
26.
FarzaH., SalmonA.M., HadchouelM., MoreauJ.L., BabinetC., TiollaisP., PourcelC.Hepatitis B surface antigen gene expression is regulated by sex steroids and glucocorticoids in transgenic mouse. Proc Natl Acad Sci USA1987; 84: 1187–91.
27.
Tur KaspaR., BurkR.D., ShaulY., MooreD.D., ShafrotzD.A.Hepatitis B virus DNA contains a glucocorticoid response element. Proc Natl Acad Sci USA1986; 83: 1627–31.
28.
Tur KaspaR., LaubO.Corticosteroids stimulate hepatitis B virus DNA, mRNA, and protein production in a stable expression system. J Hepatol1990; 11: 34–6.
29.
McMillanJ.S., ShawT., AngusP.W., LocarniniS.A.Effect of immunosuppressive and antiviral agents on hepatitis B virus replication in vitro. Hepatology1995; 22: 36–43.
30.
CoteP.J., TennatB.C., BaldwinB., KorbaB.E., GerinJ.L.Modulation of WHV infection and disease with cyclosporine A and dexamethasone. International Symposium on Viral Hepatitis and Liver Disease, Houston, 1990.
31.
MartinP., FriedmanL.S.Chronic viral hepatitis and the management of chronic renal failure. Kidney Int1995; 47: 1231–41.
32.
LamK., LaiC., TrepoC., WuP.Deleterious effect of prednisone in HBsAg positive chronic active hepatitis. N Engl J Med1981; 304: 380–6.
33.
LoertscherR., BrunnerF.P., HarderF., ThielG.Withdrawal of azathioprine in renal transplant patients with chronic active hepatitis: Is it wise or not?Nephron1983; 33: 150–5.
34.
FargeD., ParfreyP.S., ForbesR.D.C., DandavinoR.R., GuttmannR.D.Reduction of azathioprine in renal transplant patients with chronic hepatitis. Transplantation1986; 41: 55–9.
35.
MonteonF.J., ContrerasA.M., EspinosaL., VazquezG., AguilarS., CuevaL.Interferon alfa-2b in renal transplant recipients with viral chronic hepatitis: A pilot study. Transplant Proc1996; 28: 3306–8.
36.
GrotzW., GondolfK., RasenackJ., BertholdH., RumpL.C., SchollmeyerP.Imminent liver failure in a hepatitis B positive renal allograft recipient: Successful therapy with interferon alpha. Nephrol Dial Transplant1995; 10: 1932–4.
37.
DienstagJ.L., PerrilloR.P., SchiffE.R., BartholomewM., VicaryC., RubinM.A preliminary trial of lamivudine for chronic hepatitis B infection. N Engl J Med1995; 333: 1657–61.
38.
LaiC.L., ChienR.N., LeungN.W.Y., ChangT.T., GuanR., TaiD.I., NgK.Y., WuP.C., DentJ.C., BarberJ., StephensonS.I., GrayD.F., for the Asia Hepatitis Lamivudine Study Group. A one-year trial of lamivudine for chronic hepatitis B. N Engl J Med1998; 339: 61–8.
39.
DienstagJ.L., SchiffE.R., WrightT.L., PerrilloR.P., HannH.W.L., GoodmanZ., CrowtherL., CondreayL.D., WoessnerM., RubinM., BrownN.A., for theU.S. Lamivudine Investigator Group. Lamivudine as initial treatment for chronic hepatitis B in the United States. N Engl J Med1999; 341: 1256–63.
40.
LungN.W.Y., LaiC.L., ChangT.T., GuanR., LeeC.M., NgK.Y., LimS.G., WuP.C., DentJ.C., EdmunsonS., CondreayL.D., ChienR.N., on behalf of the Asia Hepatitis Lamivudine Study Group. Extended lamivudine treatment in patients with chronic hepatitis B enhances hepatitis B e antigen seroconversion rates: Results after 3 years of therapy. Hepatology2001; 33: 1527–32.
41.
Ben-AriZ., BroidaE., KittaiY., ChagnacA., Tur-KaspaR.An open-label study of lamivudine for chronic hepatitis B in six patients with chronic renal failure before and after kidney transplantation. Am J Gastroenterol2000; 95: 3579–83.
42.
LewandowskaD., DurlikM., KukulaK., CieciuraT., CiecierskiR., Walewska-ZieleckaB., SzmidtJ., RowinskiW., LaoM.Treatment of chronic hepatitis B with lamivudine in renal allograft recipients. Transplant Proc2000; 32: 1369–70.
43.
RostaingL., HenryS., CisterneJ.M., DuffautM., DurandD.Efficacy and safety of lamivudine on replication of recurrent hepatitis B after cadaveric renal transplantation. Transplantation1997; 64: 1624–7.
44.
MouquetC., BernardB., PoynardT., ThibaultV., OpolonP., CoriatP., BitkerM.O.Chronic hepatitis B treatment with lamivudine in kidney transplant patients. Transplant Proc2000; 32: 2762.
45.
JungY.O., LeeY., YangW.S., HanD.J., ParkJ.S., ParkS.K.Treatment of chronic hepatitis B with lamivudine in renal transplant recipients. Transplantation1998; 66: 733–7.
46.
TsaiM.K., LaiM.Y., HuR.H., LeeC.J., LeeP.H.Managing hepatitis B reactivation in renal transplant recipients: A 12-year review with emphasis on early detection and early use of lamivudine. Transplant Proc2000; 32: 1935–6.
47.
KletzmayrJ., WatschingerB., MullerC., DemetriouD., Puchhammer-StocklE., FerenciP., KovaricJ.Twelve months of lamivudine treatment for chronic hepatitis B virus infection in renal transplant recipients. Transplantation2000; 70: 1404–7.
48.
GoffinE., HorsmansY., SquiffletJ.P., PirsonY.Lamivudine inhibits hepatitis B virus replication in kidney graft recipients. Transplantation1997; 12: 322–7.
49.
AntoineC., LandauA., MenoyoV., DuongJ.P., DuboustA., GlotzD.Efficacy and safety of lamivudine in renal transplant patients with chronic hepatitis B. Transplant Proc2000; 32: 384–5.
50.
HanD.J., KimT.H., ParkS.K., LeeS.K., KimS.B., YangW.S., ParkJ.S., JungJ.G., YuE.S., KimS.C.Results on preemptive or prophylactic treatment of lamivudine in HBsAg(±) renal allograft recipients: Comparison with salvage treatment after hepatic dysfunction with HBV recurrence. Transplantation2001; 71: 387–94.
51.
LeeW.C., WuM.J., ChengC.H., ChenC.H., ShuK.H., LianJ.D.Lamivudine is effective for the treatment of reactivation of hepatitis B virus and fulminant hepatic failure in renal transplant recipients. Am J Kidney Dis2001; 38: 1074–81.
52.
MosconiG., ScolariM.P., MannaC., CanovaC., CristinoS., CampieriC., Liviano D'ArcangeloG., MorelliC., FaenzaA., StefoniS.Lamivudine in recurrent hepatitis B after renal transplantation. Transplant Proc2001; 33: 1873–4.
53.
FontaineH., ThiersV., ChretienY., ZylberbergH., PouponR.E., BrechotC., LegendreC., KreisH., PolS.HBV genotypic resistance to lamivudine in kidney recipients and hemodialyzed patients. Transplantation2000; 69: 2090–4.
54.
ParkS.K., YangW.S., LeeY.S., JungH.H., ChangJ.W., ChoiH.J., HanD.J., ParkJ.S.Outcome of renal transplantation in hepatitis B surface antigen-positive after introduction of lamivudine. Nephrol Dial Transplant2002; 16: 2222–8.
55.
TsangW.K., TongK.L., ChangH.W.H.Lamivudine therapy in renal allograft recipients with hepatitis B virus infection. Transplant Proc2003; 35: 278–9.
56.
FabriziF., DulaiG., DixitV., BunnapradistS., MartinP.Lamivudine for the treatment of HBV-related liver disease after renal transplantation: Meta-analysis of clinical trials. Transplantation2004; 77: 859–64.
57.
PetersM.G., SingerG., HowardT., JacobsmeyerS., XiongX., GibbsC.S., LamyP., MurrayA.Fulminant hepatic failure resulting from lamivudine-resistant hepatitis B virus in a renal transplant recipient: Durable response after orthotopic liver transplantation on adefovir dipivoxil and hepatitis B immune globulin. Transplantation1999; 68: 1912–4.
58.
MutimerD., PillayD., ShieldsP., CaneP., RatcliffeD., MartinB., BuchanS.Outcome of lamivudine resistant hepatitis B virus infection in the liver transplant recipient. Gut2000; 46: 107–13.
59.
ChanT.M., TseK.C., TangC.S.O., LaiK.N., HoS.K.N.Prospective study on lamivudine-resistant hepatitis B in renal allograft recipients. Am J Transplant2004; 4: 1103–9.
60.
BartholomeuszA., GroenenL.C., LocarniniS.A.Clinical experience with famciclovir against hepatitis B virus. Intervirology1997; 40: 337–40.
61.
MutimerD., PillayD., CookP.Selection of multiresistant hepatitis B virus during sequential nucleoside-analogue therapy. J Infect Dis2000; 181: 713–6.
62.
TangS., HoS.K.N., MoniriK., LaiK.N., ChanT.M.Efficacy of famciclovir in the treatment of lamivudine resistance related to an atypical hepatitis B virus mutant. Transplantation2002; 73: 148–51.
63.
PerrilloR., SchiffE., HannH.W., ButiM., StrasserS., WatkinsK.M., MooratA.E.The addition of adefovir dipivoxil to lamivudine in decompensated chronic hepatitis B patients with YMDD variant HBV and reduced response to lamivudine – preliminary 24 week result. Hepatology2001; 34: 349A.
64.
McIvorC., MortonJ., BryantA.Fatal reactivation of precore mutant hepatitis B virus associated with fibrosing cholestatic hepatitis after bone marrow transplantation. Ann Intern Med1994; 121: 274–7.
FangJ.W.S., WrightT.L., LauJ.Y.N.Fibrosing cholestatic hepatitis in patients with HIV and hepatitis B. (Letter). Lancet1993; 342: 1175.
67.
Al FaraidyK., YoshidaE.M., DavisJ.E., VartanianR.K., AndersonF.H., SteinbrecherU.P.Alteration of the dismal natural history of fibrosing cholestatic hepatitis secondary to hepatitis B virus with the use of lamivudine. Transplantation1997; 64: 926–8.
68.
BrindA.M., BennettM.K., BassendineM.F.Nucleoside analogue therapy in fibrosing cholestatic hepatitis – a case report in an HBsAg positive renal transplant recipient. Liver1998; 18: 134–9.
