Journal of Gastroenterology and Hepatology

Adefovir dipivoxil therapy in liver transplant recipients for recurrence of hepatitis B virus infection despite lamivudine plus hepatitis B immunoglobulin prophylaxis

Corresponding Author

Murat Akyildiz

Departments of Gastroenterology,

Murat Akyildiz, Ege University Medical School, Department of Gastroenterology, 35100, Bornova, Izmir, Turkey. Email: [email protected]Search for more papers by this author

Zeki Karasu,

Zeki Karasu

Departments of Gastroenterology,

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Murat Zeytunlu,

Murat Zeytunlu

General Surgery and

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Unal Aydin,

Unal Aydin

General Surgery and

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Tijen Ozacar,

Tijen Ozacar

Microbiology, Ege University Medical School, Bornova, Izmir, Turkey

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Murat Kilic,

Murat Kilic

General Surgery and

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Murat Akyildiz,

Corresponding Author

Murat Akyildiz

Departments of Gastroenterology,

Murat Akyildiz, Ege University Medical School, Department of Gastroenterology, 35100, Bornova, Izmir, Turkey. Email: [email protected]Search for more papers by this author

Zeki Karasu,

Zeki Karasu

Departments of Gastroenterology,

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Murat Zeytunlu,

Murat Zeytunlu

General Surgery and

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Unal Aydin,

Unal Aydin

General Surgery and

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Tijen Ozacar,

Tijen Ozacar

Microbiology, Ege University Medical School, Bornova, Izmir, Turkey

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Murat Kilic,

Murat Kilic

General Surgery and

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First published: 19 November 2007

https://doi.org/10.1111/j.1440-1746.2006.04609.x

Citations: 32

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Abstract

Background: Treatment of post-transplantation recurrence of hepatitis B virus (HBV) infection despite prophylaxis with hepatitis B immunoglobulin (HBIG) and lamivudine combination therapy is not easy. Because HBV reinfection has a severe course and could result in graft failure in liver transplant recipients, prompt medication is essential. Herein is reported the authors’ experience with adefovir dipivoxil (AD) therapy in 11 liver transplant recipients who had HBV reinfection despite the administration of lamivudine and HBIG.

Method: Two-hundred and nine patients underwent liver transplantation (100 deceased donor liver transplantations [DDLT], 109 living donor liver transplantation [LDLT]) due to chronic hepatitis B infection between April 1997 and May 2005 in Ege University Medical School, Liver Transplantation Unit. Patients had prophylaxis with lamivudine and low-dose HBIG combination after liver transplantation. Treatment of recurrence consisted of AD 10 mg once a day and lamivudine 300 mg/daily and HBIG was discontinued in those patients.

Results: In total there were 11 HBV recurrences: five occurred in DDLT recipients and six in LDLT recipients, at a median follow up of 18 months (range, 6–48 months). In one of 11 patients, pretransplant HBV-DNA and HBeAg were positive. Three patients had a severe course and one patient had fibrosing cholestatic hepatitis. After AD treatment, HBV-DNA level decreased in all patients and became negative in seven patients. Two patients died due to hepatocellular carcinoma recurrence after 12 and 14 months of follow up. Serum creatinine level increased mildly in one patient and no other side-effect was observed, and all patients continued therapy.

Conclusion: Adefovir dipivoxil is a safe, effective treatment option for post-transplant HBV recurrence even among patients with fibrosing cholestatic hepatitis caused by lamivudine-resistant HBV.

References

1 O’Grady JG, Smith HM, Davies SE et al. Hepatitis B virus re-infection after orthotopic liver transplantation. Serological and clinical implications. J. Hepatol. 1992; 14: 104–11.
10.1016/0168-8278(92)90138-F
CAS PubMed Web of Science® Google Scholar
2 Shouval D, Samuel D. Hepatitis B immune globulin to prevent HBV graft reinfection following liver transplantation: a concise review. Hepatology 2000; 32: 1189–95.
10.1053/jhep.2000.19789
CAS PubMed Web of Science® Google Scholar
3 Rosenau J, Bahr MJ, Tilmann HL et al. Lamivudine and low-dose hepatitis B immune globulin for prophylaxis of hepatitis B infection after liver transplantation: possible role of mutations in the YMDD motif before transplantation as a risk factor for reinfection. J. Hepatol. 2001; 34: 895–902.
10.1016/S0168-8278(01)00089-7
CAS PubMed Web of Science® Google Scholar
4 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: 1842–7.
10.1056/NEJM199312163292503
CAS PubMed Web of Science® Google Scholar
5 Lok ASF. Prevention of recurrent hepatitis B post-liver transplantation. Liver Transpl. 2002; 8: S67–S73.
10.1053/jlts.2002.35780
PubMed Web of Science® Google Scholar
6 Markowitz JS, Martin P, Conrad AJ et al. Prophylaxis against hepatitis B recurrence following liver transplantation using combination Lamivudine and hepatitis B immune globulin. Hepatology 1998; 28: 585–9.
10.1002/hep.510280241
CAS PubMed Web of Science® Google Scholar
7 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: 903–10.
10.1016/S0168-8278(01)00080-0
CAS PubMed Web of Science® Google Scholar
8 Angus PW, McCaughan GW, Gane EJ et al. Combination low-dose hepatitis B immune globulin and lamivudine therapy provides effective prophylaxis against posttransplantation hepatitis B. Liver Transpl. 2000; 6: 429–33.
10.1053/jlts.2000.8310
CAS PubMed Web of Science® Google Scholar
9 Han SH, Ofman J, Holt C et al. An efficacy and cost-effectiveness analysis of combination hepatitis B immune globulin and lamivudine to prevent recurrent hepatitis B after orthotopic liver transplantation compared with hepatitis B immune globulin monotherapy. Liver Transpl. 2000; 6: 741–8.
10.1053/jlts.2000.18702
CAS PubMed Web of Science® Google Scholar
10 Roche B, Feray C, Gigou M et al. HBV DNA persistence 10 years after liver transplantation despite successful anti-HBS passive immunoprophylaxis. Hepatology 2003; 38: 86–95.
10.1053/jhep.2003.50294
PubMed Web of Science® Google Scholar
11 Yao FY, Osorio RW, Roberts JP et al. Intramuscular hepatitis B immune globulin combined with lamivudine for prophylaxis against hepatitis B recurrence after liver transplantation. Liver Transpl. Surg. 1999; 5: 491–6.
10.1002/lt.500050605
CAS PubMed Web of Science® Google Scholar
12 Yoshida EM, Erb SR, Partovi N et al. Liver transplantation for chronic hepatitis B infection with the use of combination lamivudine and low-dose hepatitis B immune globulin. Liver Transpl. Surg. 1999; 5: 520–5.
10.1002/lt.500050602
CAS PubMed Web of Science® Google Scholar
13 McCaughan GW, Spencer J, Koorey D et al. Lamivudine therapy in patients undergoing liver transplantation for hepatitis B virus precore mutant-associated infection: high resistance rates in treatment of recurrence but universal prevention if used as prophylaxis with very low dose hepatitis B immune globulin. Liver Transpl. Surg. 1999; 5: 512–19.
10.1002/lt.500050601
CAS PubMed Web of Science® Google Scholar
14 Karasu Z, Ozacar T, Akyildiz M et al. Low-dose hepatitis B immune globulin and higher-dose lamivudine combination to prevent hepatitis B virus recurrence after liver transplantation. Antiviral Ther. 2004; 9: 921–7.
CAS PubMed Web of Science® Google Scholar
15 Marcellin P, Chang T-T, Lim GS, et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen positive chronic hepatitis B. N. Engl. J. Med. 2003; 348: 808–16.
10.1056/NEJMoa020681
CAS PubMed Google Scholar
16 Hadziyannis SJ, Tassopoulos NC, Heathcote EJ et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepatitis B. N. Engl. J. Med. 2003; 348: 800–7.
10.1056/NEJMoa021812
CAS PubMed Web of Science® Google Scholar
17 Xiong X, Flores C, Yang H, Toole JJ, Gibs CS. Mutations in hepatitis B DNA polymerase associated with resistance to lamivudine do not confer resistance to adefovir in vitro. Hepatology 1998; 28: 1669–73.
10.1002/hep.510280629
CAS PubMed Web of Science® Google Scholar
18 Perrillo R, Schiff E, Yoshida E et al. Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants. Hepatology 2000; 32: 129–34.
10.1053/jhep.2000.8626
CAS PubMed Web of Science® Google Scholar
19 Benhamou Y, Bochet M, Thibault V et al. Safety and efficacy of adefovir dipivoxil in patients co-infected with HIV-1 and lamivudine-resistant hepatitis B virus: an open label pilot study. Lancet 2001; 358: 718–23.
10.1016/S0140-6736(01)05840-8
CAS PubMed Web of Science® Google Scholar
20 Perillo R, Hann HW, Mutimer D et al. Adefovir dipivoxil added to ongoing lamivudine in chronic hepatitis B with YMDD mutant hepatitis B virus. Gastroenterology 2004; 126: 81–90.
10.1053/j.gastro.2003.10.050
CAS PubMed Web of Science® Google Scholar
21 Peters MG, Hann HW, Martin P et al. Adefovir dipivoxil alone or in combination with lamivudine in patients with lamivudine-resistant chronic hepatitis B. Gastroenterology 2004; 126: 91–101.
10.1053/j.gastro.2003.10.051
CAS PubMed Web of Science® Google Scholar
22 Schiff EU, Lai CL, Hadziyannis S et al. Adefovir dipivoxil therapy for lamivudine resistant hepatitis B in pre- and post-liver transplantation patients. Hepatology 2003; 38: 1419–27.
10.1016/j.hep.2003.09.040
CAS PubMed Web of Science® Google Scholar
23 Walsh KM, 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: 436–40.
10.1136/gut.49.3.436
CAS PubMed Web of Science® Google Scholar
24 Tillmann HL, Bock CT, Bleck SJ et al. Successful treatment of fibrosing cholestatic hepatitis using adefovir dipivoxil in a patient with cirrhosis and renal insufficiency. Liver Transpl. 2003; 9: 191–6.
10.1053/jlts.2003.50010
PubMed Web of Science® Google Scholar
25 Akay S, Karasu Z, Akyildiz M, Tokat Y. Adefovir treatment in posttransplant hepatitis B virus infection resistant to lamivudine plus hepatitis B virus immunoglobulin. Transplant. Proc. 2004; 36: 2768–70.
10.1016/j.transproceed.2004.09.062
CAS PubMed Web of Science® Google Scholar
26 Terault NA. Treatment of recurrent hepatitis B infection in liver transplant recipients. Liver Transpl. 2002; 8 (Suppl. 1): S74–81.
10.1053/jlts.2002.35784
PubMed Web of Science® Google Scholar
27 Marzano A, Lampertico P, Mazzaferro V et al. Prophylaxis of hepatitis B virus recurrence after liver transplantation in carriers of lamivudine-resistant mutants. Liver Transpl. 2005; 11: 532–8.
10.1002/lt.20393
CAS PubMed Web of Science® Google Scholar
28 Beckebaum S, Malago M, Dirsch O et al. Efficacy of combined lamivudine and adefovir dipivoxil treatment for severe HBV graft reinfection after living donor liver transplantation. Clin. Transplant. 2003; 17: 554–9.
10.1046/j.0902-0063.2003.00097.x
PubMed Web of Science® Google Scholar
29 Lo CM, Cheung ST, Oi-Lin I, Liu CL, Lai CL, Fan ST. Fibrosing cholestatic hepatitis secondary to precore/core promoter hepatitis B variant with lamivudine resistance: Successful retransplantation with combination adefovir dipivoxil and hepatitis B immunoglobulin. Liver Transpl. 2004; 10: 557–63.
10.1002/lt.20133
CAS PubMed Web of Science® Google Scholar
30 Papatheodoridis GV, Sevastianos V, Burroughs AK. Prevention of and treatment of hepatitis B virus infection after liver transplantation in the nucleoside analogues era. Am. J. Transplant. 2003; 3: 250–8.
10.1034/j.1600-6143.2003.00063.x
CAS PubMed Web of Science® Google Scholar
31 Vierling JM. Management of HBV infection in liver transplantation patients. Int. J. Med. Sci. 2005; 2: 41–9.
10.7150/ijms.2.41
CAS PubMed Google Scholar
32 Lo CM, Liu CL, Lau GK, Chan SC, Ng IO, Fan ST. Liver transplantation for chronic hepatitis B with lamivudine resistant YMDD mutant using add-on adefovir dipivoxil plus lamivudine. Liver Transpl. 2005; 11: 807–13.
10.1002/lt.20416
CAS PubMed Web of Science® Google Scholar
33 Steinmuller T, Seehofer D, Rayes N et al. Increasing applicability of liver transplantation for patients with hepatitis B-related liver disease. Hepatology 2002; 35: 1528–35.
10.1053/jhep.2002.33681
CAS PubMed Web of Science® Google Scholar
34 Lau JY, Bain VG, Davies SE et al. High-level expression of hepatitis B viral antigens in fibrosing cholestatic hepatitis. Gastroenterology 1992; 102: 956–62.
10.1016/0016-5085(92)90182-X
PubMed Web of Science® Google Scholar
35 Chan TM, Wu PC, Li FK et al. Treatment of fibrosing cholestatic hepatitis with lamivudine. Gastroenterology 1998; 115: 177–81.
10.1016/S0016-5085(98)70380-4
CAS PubMed Web of Science® Google Scholar
36 Thabut D, Ratziu V, Bernard-Chabert B et al. Unsuccessful rescue therapy with adefovir dipivoxil for lamivudine resistant HBV in a patient with liver failure. Gut 2003; 52: 614.
10.1136/gut.52.4.614-a
CAS PubMed Web of Science® Google Scholar
37 Samuel D. Management of hepatitis B in liver transplantation patients. Semin. Liver Dis. 2004; 24: 55–62.
10.1055/s-2004-828679
CAS PubMed Web of Science® Google Scholar

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Volume22, Issue12

December 2007

Pages 2130-2134

Adefovir dipivoxil therapy in liver transplant recipients for recurrence of hepatitis B virus infection despite lamivudine plus hepatitis B immunoglobulin prophylaxis

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Adefovir dipivoxil therapy in liver transplant recipients for recurrence of hepatitis B virus infection despite lamivudine plus hepatitis B immunoglobulin prophylaxis

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