Chronic hepatitis B virus (HBV) infection is an important cause of morbidity and mortality in renal-transplant recipients. The aim of the study was to assess the efficacy and safety of long-term lamivudine monotherapy in renal-transplant recipients with HBV-related cirrhosis.
Methods
Seventeen such patients [median age: 45 years; 7 with hepatitis B e antigen (HBeAg)] received daily oral doses of 75–150 mg lamivudine for a median of 48 (range 11–81) months. All patients had baseline serum levels of HBV DNA of over 6 log copies per ml and of 10 alanine transaminase (ALT) of over 1.5 times the upper normal limit (UNL). Clinical lamivudine resistance was defined as a rebound of serum HBV DNA above 5.3 log 10 copies per ml and of serum ALT of over 1.5 times the UNL in patients who initially responded with HBV DNA levels of less than 5.3 log copies per ml and normal ALT 10 values. Controls were 14 renal-transplant patients (median age 44 years; 3 with HBeAg) with HBV-related cirrhosis, naive to any anti-HBV therapy, followed for 58 months (4–135).
Results
Thirteen (77%) treated patients had a persistent response throughout the study period, including three (18%) who developed genotypic resistance, compared with none of the untreated controls (77% versus 0%, P<0.0001). Four (23%) developed clinical resistance. Two of three patients with initially decompensated cirrhosis had a durable response and clinical improvement compared with the transient responder, whose liver function worsened following lamivudine resistance. Two responders developed chronic rejection requiring chronic haemodialysis. Overall, one treated patient developed liver-related complications, compared with eight untreated controls (6% versus 57%, P<0.01).
Conclusions
Most renal-transplant patients treated with lamivudine achieved a rapid and durable suppression of HBV, which substantially lowered the risk of liver decompensation and death.
References
1.
GaneE., & PilmoreH.Management of chronic viral hepatitis before and after renal transplantation.Transplantation2002; 74: 427–437.
2.
MathurinP., MouquetC., PoynardT., SyllaC., BenaliaH., FretzC., ThibaultV., CadranelJ.F., BernardB., OpolonP., CoriatP., & BitkerM.O.Impact of hepatitis B and C on kidney transplantation outcome.Hepatology1999; 29: 257–263.
3.
DegosF., LugassyC., DegottC., DebureA., CarnotF., TheirsV., TiollaisP., KreisH., & BrechotC.Hepatitis B virus and hepatitis B-related viral infection in renal transplant recipients.Gastroenterology1997; 97: 151–156.
4.
FornaironS., PolS., LegendreC., CarnotF., Mamzer-BruneelM.F., BrechotC., & KreisH.The long-term virologic and pathologic impact of renal transplantation on chronic hepatitis B virus infection.Transplantation1996; 62: 297–299.
5.
RostaingL., ModestoA., BaronE., CisterneJ.M., ChabannierM.H., & DurandD.Acute renal failure in kidney transplant patients treated with interferon alpha 2b for chronic hepatitis C.Nephron1996; 74: 512–516.
6.
ConjeevaramH.S., LokA.S.Management of chronic hepatitis B.Journal of Hepatology2003; 38: S90–103.
7.
RostaingL., HenryS., CisterneJ.M., DuffautM., IcartJ., & DurandD.Efficacy and safety of lamivudine on replication of recurrent hepatitis B after cadaveric renal transplantation.Transplantation1997; 64: 1624–1627.
8.
GoffinE., HorsmansY., CornuC., SquiffletJ.P., & PirsonY.Lamivudine inhibits hepatitis B virus replication in kidney graft recipients.Transplantation1998; 66: 407–409.
9.
JungY.O., LeeY.S., YangW.S., HanD.J., ParkJ.S., ParkS.K.Treatment of chronic hepatitis B with lamivudine in renal transplant recipients.Transplantation1998; 66: 733–737.
10.
MouquetC., BernardB., PoynardT., ThibaultV., OpolonP., CoriatP., & BitkerM.O.Chronic hepatitis B treatment with lamivudine in kidney transplant patients.Transplantation Proceedings2000; 32: 2762.
11.
FontaineH., ThiersV., ChretienY., ZylberbergH., PouponR.E., BrechotC., LegendreC., KreisH., & PolS.HBV genotypic resistance to lamivudine in kidney recipients and hemodialyzed patients.Transplantation2000; 69: 2090–2094.
12.
KletzmayrJ., WatschingerB., MullerC., DemetriouD., Puchhammer-StocklE., FerenciP., & KovarikJ.Twelve months of lamivudine treatment for chronic hepatitis B virus infection in renal transplant recipients.Transplantation2000; 70: 1404–1407.
13.
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: 387–394.
14.
ParkS.K., YangW.S., LeeY.S., JungH.H., ChangJ.J., ChoiH.J., HanD.J., & ParkJ.S.Outcome of renal transplantation in hepatitis B surface antigen-positive patients after introduction of lamivudine.Nephrology Dialysis Transplantation2001; 16: 2222–2228.
15.
SchvoererE., KabissaI., CottoE., JouvencelA.C., BalabaundC., De LedinghenV., CouzigouP., QuintonA., SchvoererC., LafonM.E., FleuryH., & BernardP.H.Lamivudine therapy of chronic hepatitis B in the three groups of patients: non transplant patients, liver recipients and kidney recipients.Gastroenterologie Clinique et Biologique2002; 26: 62–66.
16.
TsangW.K., TongK.L., & ChanH.W.H.Lamivudine therapy in renal allograft recipients with hepatitis B virus infection.Transplantation Proceedings2003; 35: 278–279.
17.
ChanT.M., TseK.C., TangC.S.O., LaiK.N., & HoS.K.N.Prospective study on lamivudine-resistant hepatitis B in renal allograft recipients.American Journal of Transplantation2004; 4: 1103–1109.
18.
EASL Jury.EASL International Consensus Conference on Hepatitis B.Journal of Hepatology2003; 39: S3–S25.
19.
BruixJ., ShermanM., LlovetJ.M., BeaugrandM., LencioniR., BurroughsA.K., ChristensenE., PagliaroL., ColomboM., & RodesJ.; EASL Panel of experts on HCC. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference.Journal of Hepatology2001; 35: 421–430.
20.
StuyverL., Van GeytC., De GendtS., Van ReybroeckG., ZoulimF., Leroux-RoelsG., & RossauR.Line probe assay for monitoring drug resistance in hepatitis B virus-infected patients during antiviral therapy.Journal of Clinical Microbiology2000; 38: 702–707.
21.
FontanaR.J., & LokA.S.Lamivudine treatment in patients with decompensated hepatitis B cirrhosis.Journal of Hepatology2000; 33: 329–332.
22.
FabriziF., DulaiG., DixitV., BunnapradistS., & MartinP.Lamivudine for the treatment of hepatitis B virus related liver disease after renal transplantation: meta-analysis of clinical trials.Transplantation2004; 77: 859–864.
23.
ThabutD., ThibaultV., Bernard-ChabertB., MouquetC., Di MartinoV., Le CalvezS., OpolonP., BenhamouY., BitkerM.O., & PoynardT.Long-term therapy with lamivudine in renal transplant recipients with chronic hepatitis B.European Journal of Gastroenterology and Hepatology2004; 16: 1367–1373.
24.
KamarN., Sandres-sauneK., RibesD., DuffautM., SelvesJ., DurandD., IzopetJ., & RostaingL.Effects of long-term lamivudine therapy in renal-transplant patients.Journal of Clinical Virology2004; 31: 298–303.
25.
Di MarcoV., MarzanoA., LamperticoP., AndreoneP., SantantonioT., AlmasioP.L., RizzettoM., & CraxìA. for the Italian Association for the Study of the Liver (AISF) Lamivudine Study Group. Clinical outcome of HBeAg-negative chronic hepatitis B in relation to virological response to lamivudine.Hepatology2004; 40: 883–891.
26.
LokA.S., LaiC.L., LeungN., YaoG.B., CuiZ.Y., SchiffE.R., DienstagJ.L., HeathcoteE.J., LittleN.R., GriffithsD.A., GardnerS.D., & CastigliaM.Long-term safety of lamivudine treatment in patients with chronic hepatitis B.Gastroenterology2003; 125: 1714–1722.
27.
HadziyannisS.J., PapatheodoridisG.V., DimouE., LarasA., & PapaioannouC.Efficacy of long-term lamivudine monotherapy in patients with hepatitis B e antigen–negative chronic hepatitis B.Hepatology2000; 32: 847–851.
28.
BoniC., BertolettiA., PennaA., CavalliA., PilliM., UrbaniS., ScognamiglioP., BoehmeR., PanebiancoR., FiaccadoriF., & FerrariC.Lamivudine treatment can restore T cell responsiveness in chronic hepatitis B.Journal of Clinical Investigation1998; 102: 867–868.
