The success of orthotopic liver transplantation for patients with hepatitis B virus
(HBV) disease has been compromised by reinfection. Prophylaxis has dramatically lowered
the rate of reinfection and increased patient survival. Long-term treatment with hepatitis
B immunoglobulin (HBIg), although expensive, is effective. New antiviral nucleoside
analogs have also been evaluated. In patients with cirrhosis and replicative HBV infection,
lamivudine before transplantation and in combination with HBIg post transplantation
reduces reinfection, but the rate of resistance mutation is rather high, reaching
25% at 2 years. Adefovir has been used as a rescue therapy and prior to transplantation
in lamivudine-resistant patients, significantly improving liver function and reducing
HBV DNA levels. Patients with active viral replication should receive preoperative
antiviral therapy with lamivudine. HBIg therapy may be discontinued in selected patients
after transplantation, albeit with caution, because low levels of HBV DNA have persisted.
Antiviral therapy has improved the prognosis after graft infection.
KEYWORDS
Orthotopic liver transplantation - reinfection - antiviral therapy - resistance mutation
REFERENCES
- 1 European Liver Transplant Registry-ELTR .Registry for the European Liver Transplant
Association. Data analysis, 05/1968-06/2002. Available at: www.eltr.org. Accessed
on November 20, 2003
- 2
O'Grady J G, Smith H M, Davies S E et al..
Hepatitis B virus re-infection after orthotopic liver transplantation. Serological
and clinical implications.
J Hepatol.
1992;
14
104-111
- 3
Steinmuller T, Seehofer D, Rayes N et al..
Increasing applicability of liver transplantation for patients with hepatitis B-related
liver disease.
Hepatology.
2002;
35
1528-1535
- 4
Shouval D, Samuel D.
Hepatitis B immune globulin to prevent HBV graft reinfection following liver transplantation:
a concise review.
Hepatology.
2000;
32
1189-1195
- 5
Samuel D, Muller R, Alexander G et al..
Liver transplantation in European patients with the hepatitis B surface antigen.
N Engl J Med.
1993;
329
1842-1847
- 6
Samuel D, Bismuth A, Mathieu D et al..
Passive immunoprophylaxis after liver transplantation in HBsAg-positive patients.
Lancet.
1991;
337
813-815
- 7
Lauchart W, Muller R, Pichlmayr R.
Long-term immunoprophylaxis of hepatitis B virus (HBV) re-infection in recipients
of human liver allografts.
Transpl Proc.
1987;
19
4051-4053
- 8
Roche B, Feray C, Gigou M et al..
HBV DNA persistence 10 years after liver transplantation despite successful anti-HBs
immunoprophylaxis.
Hepatology.
2003;
38
86-95
- 9
Terrault N A, Zhou S, Combs C et al..
Prophylaxis in liver transplant recipients using a fixed dosing schedule of hepatitis
B immunoglobulins.
Hepatology.
1996;
24
1327-1333
- 10
Muller R, Gubernatis G, Farle M et al..
Liver transplantation in HBs antigen (HBsAg) carriers. Prevention of hepatitis B virus
(HBV) recurrence by passive immunization.
J Hepatol.
1991;
13
90-96
- 11
Han S H, Martin P, Edelstein M et al..
Conversion from intravenous to intramuscular hepatitis B immune globulin in combination
with lamivudine is safe and cost-effective in patients receiving long-term prophylaxis
to prevent hepatitis B recurrence after liver transplantation.
Liver Transpl.
2003;
9
182-187
- 12
McGory R W, Ishitani M B, Oliveira W M et al..
Improved outcome of orthotopic liver transplantation for chronic hepatitis B cirrhosis
with aggressive passive immunization.
Transplantation.
1996;
61
1358-1364
- 13
Lowell J A, Burgess S, Shenoy S et al..
Mercury poisoning associated with high-dose hepatitis-B immune globulin administration
after liver transplantation for chronic hepatitis B.
Liver Transpl Surg.
1996;
2
475-478
- 14
Ghany M G, Ayola B, Villamil F G et al..
Hepatitis B virus S mutants in liver transplant recipients who were reinfected despite
hepatitis B immune globulin prophylaxis.
Hepatology.
1998;
27
213-222
- 15
Terrault N A, Zhou S, McGory R W et al..
Incidence and clinical consequences of surface and polymerase gene mutations in liver
transplant recipients on hepatitis B immunoglobulin.
Hepatology.
1998;
28
555-561
- 16
Brind A, Jiang J J, Samuel D et al..
Evidence for selection of hepatitis B mutants after liver transplantation through
peripheral blood mononuclear cell infection.
J Hepatol.
1997;
26
228-235
- 17
Villeneuve J P, Condreay L D, Willems B et al..
Lamivudine treatment for decompensated cirrhosis resulting from chronic hepatitis
B.
Hepatology.
2000;
31
207-210
- 18
Kapoor D, Guptan R C, Wakil S M et al..
Beneficial effects of lamivudine in hepatitis B virus-related decompensated cirrhosis.
J Hepatol.
2000;
33
308-312
- 19
Perrillo R P, Wright T, Rakela J et al..
A multicenter United States-Canadian trial to assess lamivudine monotherapy before
and after transplantation for chronic hepatitis B.
Hepatology.
2001;
33
424-432
- 20
Fontana R, Keeffe E, Carey W et al..
Effect of lamivudine treatment on survival of 309 North American patients awaiting
liver transplantation for chronic hepatitis B.
Liver Transpl.
2002;
8
433-439
- 21
Perrillo R, Schiff E, Yoshida E et al..
Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants.
Hepatology.
2000;
32
129-134
- 22
Stärkel P, Horsmans Y, Geubel A et al..
Favorable outcome of orthotopic liver transplantation in a patient with subacute liver
failure due to emergence of a hepatitis B YMDD escape mutant virus.
J Hepatol.
2001;
35
679-681
- 23
Saab S, Kim M, Wright T et al..
Successful orthotopic liver transplantation for lamivudine associated YMDD mutant
hepatitis B virus.
Gastroenterology.
2000;
119
1382-1384
- 24
Rosenau J, Bahr M, Tillmann H L et al..
Lamivudine and low-dose hepatitis B immune globulin for prophylaxis of hepatitis B
reinfection after liver transplantation. Possible role of mutations in the YMDD motif
prior to transplantation as a risk factor for reinfection.
J Hepatol.
2001;
34
895-902
- 25
Grellier L, Mutimer D, Ahmed M et al..
Lamivudine prophylaxis against reinfection in liver transplantation for hepatitis
B cirrhosis.
Lancet.
1996;
348
1212-1215
- 26
Mutimer D, Dusheiko G, Barrett C et al..
Lamivudine without HBIg for prevention of graft reinfection by hepatitis B: long-term
follow-up.
Transplantation.
2000;
70
809-815
- 27
Schiff E, Lai C L, Hadziannis S et al..
Adefovir dipivoxil therapy for lamivudine resistant hepatitis B in pre- and post-liver
transplantation patients.
Hepatology.
2003;
38
1419-1427
- 28
Markowitz J S, Martin P, Conrad A J et al..
Prophylaxis against hepatitis B recurrence following liver transplantation using combination
Lamivudine and hepatitis B immune globulin.
Hepatology.
1998;
28
585-589
- 29
Marzano A, Salizzoni M, Debernardi-Venon W et al..
Prevention of hepatitis B virus recurrence after liver transplantation in cirrhotic
patients treated with Lamivudine and passive immunoprophylaxis.
J Hepatol.
2001;
34
903-910
- 30
Angus P W, McCaughan G W, Gane E J et al..
Combination low-dose hepatitis B immune globulin and lamivudine therapy provides effective
prophylaxis against posttransplantation hepatitis B.
Liver Transpl.
2000;
6
429-433
- 31
Sanchez-Fueyo A, Rimola A, Grande L et al..
Hepatitis B immunoglobulin discontinuation followed by hepatitis B virus vaccination:
a new strategy in the prophylaxis of hepatitis B virus recurrence after liver transplantation.
Hepatology.
2000;
31
496-501
- 32
Sanchez-Fueyo A, Martinez-Bauer E, Rimola A.
Hepatitis B vaccination after liver transplantation.
Hepatology.
2002;
36
257-258
- 33
Bienzle U, Gunther M, Neuhaus R et al..
Immunization with an adjuvant hepatitis B vaccine after liver transplantation for
hepatitis B virus-related disease.
Hepatology.
2003;
38
811-819
- 34
Angelico M, Di Paolo D, Trinito M et al..
Failure of a reinforced triple course of hepatitis B vaccination in patients transplanted
for HBV-related cirrhosis.
Hepatology.
2002;
35
176-181
- 35
Dodson S F, De Vera M E, Bonham C A et al..
Lamivudine after hepatitis B immune globulin is effective in preventing hepatitis
B recurrence after liver transplantation.
Liver Transpl.
2000;
6
434-439
- 36
Naoumov N V, Lopes A R, Burra P et al..
Randomized trial of lamivudine versus hepatitis B immunoglobulin for long-term prophylaxis
of hepatitis B recurrence after liver transplantation.
J Hepatol.
2001;
34
888-894
- 37
Buti M, Mas A, Prieto M et al..
A randomized study comparing lamivudine monotherapy after a short course of hepatitis
B immune globulin (HBIg) and lamivudine with long-term lamivudine plus HBIg in the
prevention of hepatitis B virus recurrence after liver transplantation.
J Hepatol.
2003;
38
811-817
- 38
Terrault N A, Holland C C, Ferrell L et al..
Interferon alfa for recurrent hepatitis B infection after liver transplantation.
Liver Transpl Surg.
1996;
2
132-138
- 39
Roche B, Samuel D, Gigou M et al..
Long-term ganciclovir therapy for hepatitis B virus infection after liver transplantation.
J Hepatol.
1999;
31
584-592
- 40
Perrillo R, Rakela J, Dienstag J et al..
Multicenter study of lamivudine therapy for hepatitis B after liver transplantation.
Hepatology.
1999;
29
1581-1586
- 41
Fontana R J, Hann H W, Wright T et al..
A multicenter study of lamivudine treatment in 33 patients with hepatitis B after
liver transplantation.
Liver Transpl.
2001;
7
504-510
- 42
Bock C T, Tillmann H L, Torresi J et al..
Selection of hepatitis B virus polymerase mutants with enhanced replication by lamivudine
treatment after liver transplantation.
Gastroenterology.
2002;
122
264-273
- 43
Walsh K M, Woodall T, Lamy P et al..
Successful treatment with adefovir dipivoxil in a patient with fibrosing cholestatic
hepatitis and lamivudine resistant hepatitis B virus.
Gut.
2001;
49
436-440
- 44
Yang H, Westland C E, Delaney W E et al..
Resistance surveillance in chronic hepatitis B patients treated with adefovir dipivoxil
for up to 60 weeks.
Hepatology.
2002;
36
464-473
- 45
Crippin J, Foster B, Carlen S et al..
Retransplantation in hepatitis B-a multicenter experience.
Transplantation.
1994;
57
823-826
- 46
Roche B, Samuel D, Feray C et al..
Retransplantation of the liver for recurrent hepatitis B virus infection: the Paul
Brousse experience.
Liver Transpl Surg.
1999;
5
166-174
Dr.
Didier Samuel
Centre Hépatobiliaire, EA 3541 et association Claude Bernard “virus et transplantation,”
Université Paris-Sud, Hôpital Paul Brousse, Assistance Publique-Hopitaux de Paris
14 avenue Paul Vaillant Couturier
94800, Villejuif, France
Email: didier.samuel@pbr.ap-hop-paris.fr