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Ann Thorac Surg 2006;81:1851-1852
© 2006 The Society of Thoracic Surgeons

Original article: General thoracic

Lamivudine Prophylaxis for Hepatitis B Virus Infection After Lung Transplantation

Ariella Bar-Gil Shitrit, MD a , Mordechai R. Kramer, MD b , * , Ilana Bakal b , Gilles Morali, MD a , Ziv Ben Ari, MD c , David Shitrit, MD b

a Gastroenterological Department, Shaare Zedek Medical Center, Jerusalem
b Pulmonary Institute, Rabin Medical Center, Beilinson Campus, Petah Tiqwa, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
c Liver Institute, Rabin Medical Center, Beilinson Campus, Petah Tiqwa, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

Accepted for publication December 7, 2005.

* Address correspondence to Dr Kramer, Pulmonary Institute, Rabin Medical Center, Beilinson Campus, Petah Tiqwa 49100, Israel (Email: davids3{at}clalit.org.il).


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 References
 
BACKGROUND: Several reports have shown the efficacy of prophylactic lamivudine treatment for hepatitis B virus (HBV) infection in liver and renal transplantations. No data are available, however, after lung transplantation. We report our experience with prophylactic lamivudine treatment in lung transplant recipients with HBV infection or when the donor was HBc antibody positive.

METHODS: All our 120 lung transplant recipients and their donors were routinely screened for HBV markers. All recipients who tested positive for hepatitis B surface antigen and negative for HBV-DNA, or had organs from donors who tested positive for hepatitis B core antibody, were treated prophylactically with lamivudine for 12 months after lung transplantation. Patients whose liver functions became abnormal during follow-up were tested for HBV serology and HBV-DNA.

RESULTS: Eleven of 120 lung transplant recipients (9.2%) were treated with prophylaxis lamivudine. Four recipients were hepatitis B surface antigen positive, and 7 recipients received organs from donors positive for HBc antibodies. Median follow-up after treatment was 24 months. All patients had normal alanine transaminase and undetectable levels of HBV-DNA before treatment. No side effects of lamivudine therapy were reported by any of the patients. Reactivation with alanine transaminase elevation and high HBV-DNA levels occurred in 2 patients. Both of them were recipients positive for hepatitis B surface antigen. In the first patient, lamivudine-resistant strain was detected and adefovir dipivoxil was started. In the other, reactivation developed 2 months after the end of lamivudine treatment. Lamivudine treatment was resumed, with rapid normalization of the HBV-DNA.

CONCLUSIONS: Use of lamivudine is considered safe for suppressing HBV infection after lung transplantation.


   Introduction
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 Abstract
 Introduction
Patients and Methods
 Results
 Comment
 References
 
The hepatitis B virus (HBV) infects more than 350 million people worldwide with significant morbidity and mortality [1, 2]. Reactivation of HBV infection is known to occur in chronic HbsAg carriers who receive immunosupression therapy. The transmission of hepatitis B virus infection through grafts positive for hepatitis B core antibody (anti-HBc) has also been established, especially in liver grafts [3].

No data are available about prophylaxis lamivudine after lung transplantation. We report our experience with prophylactic lamivudine treatment in lung transplant recipients with HBV infection or when the donor was positive for HBc antibody.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 References
 
We performed a retrospective chart review for all patients who underwent lung transplantation at Rabin Medical Center, Beilinson Campus, a major tertiary care facility in central Israel.

One hundred and twenty patients underwent lung transplantation at our institute between January 1997 and July 2005. Our entire 120 lung transplant recipients and their donors were routinely screened for HBV markers by an enzyme immunoassay.

All recipients who tested positive for Hbs antigen and negative for HBV-DNA, or had organs from donors who tested positive for hepatitis B core antibody were treated immediately after the lung transplantation prophylactically with lamivudine tablets 100 mg a day for 12 months after lung transplantation. The cost of 12 months of lamivudine treatment was US $2,244 per patient. Patients in whom abnormal liver functions developed were tested for HBV serology and HBV-DNA (polymerase chain reaction), complete viral profile.

The Institutional Human Subjects Review Board approved the study protocol, and all participants provided written informed consent.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 References
 
Eleven of 120 lung transplant recipients (9.2%) were treated with prophylaxis lamivudine. Four recipients were HBsAg positive, and 7 recipients received organs from HBcAb positive donors.

The median age of the treated patients was 48 years (range, 16 to 65). All the patients treated 12 months with lamivudine100 mg a day. Median follow-up after treatment was 24 months (range, 3 to 72).

All patients had normal alanine aminotransferase (ALT) and undetectable levels of HBV-DNA before lamivudine treatment. After treatment, reactivation with ALT elevation and high HBV-DNA levels occurred in 2 patients. Both of them were HBsAg-positive recipients. The first had the reactivation after 3 months of lamivudine treatment. Lamivudine treatment was stopped, and after lamivudine-resistant strain was detected, adefovir dipivoxil was started. The other patient had reactivation 2 months after the end of 12 months of lamivudine treatment. Lamivudine treatment was resumed, with rapid normalization of the HBV-DNA. Both patients completed 30 months of follow-up with no reactivation.

The compliance was 100%. No patient stopped the medication during the 12-month treatment protocol. No side effects of lamivudine therapy were reported by any of the patients, including the patient who was treated more than 12 months. No drug interactions were noted during the treatment.


   Comment
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 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
References
 
We here report our use of lamivudine prophylaxis for lung transplant recipients. We found that use of lamivudine is considered safe for suppression treatment of HBV infection after lung transplantation.

The increasing disparity between lung allograft supply and demand has led to a renewed interest in donors who are hepatitis B surface antigen negative, antihepatitis B core antibody positive. Reactivation of latent HBV infection reportedly occurs in 33% to 100% of North American recipients receiving antiHBc-positive solid organ transplant [4, 5]. Lamivudine has been proven efficacious in preventing de novo HBV infection in compliant recipients [6, 7].

Previous studies of liver and renal transplantations found that lamivudine is safe and effective for prevention of HBV infection after organ transplantations [8–12].

Fabrizi and colleagues [9] evaluated the efficacy and safety of lamivudine for the treatment of hepatitis B virus–related liver disease after renal transplantation. The mean overall estimate for HBV-DNA, HBeAg clearance, ALT normalization, and lamivudine resistance was 91%, 27%, 81%, and 18%, respectively. Tolerance to lamivudine was excellent. They concluded that the majority of renal transplant recipients with hepatitis B had high virologic and biochemical response with lamivudine.

What is the efficacy of lamivudine in heart and lung transplantation? Several reports evaluated the role of lamivudune treatment (not prophylaxis) for HBV infection after heart and lung transplantations [13–16]. In these studies, lamivudine was effective in the treatment of posttransplant hepatitis B reactivation. Only one small report is available about lamivudine prophylaxis after heart transplantation [17]. Based on our results, it is therefore recommended as a prophylactic treatment for recipients who are HBsAg positive or when the donor is HBcAb positive. In cases of reactivation despite lamivudine treatment, adefovir dipivoxil could be a reasonable alternative.

In conclusion, our study suggests that lamivudine can safely induce a complete biochemical, virologic, and serologic response in lung transplant recipients with HBV infection.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 References
 

  1. Lee WM. Hepatitis B virus infection N Engl J Med 1997;337:1733-1745.[Free Full Text]
  2. Degos F, Lugassy C, Degott C, et al. Hepatitis B virus and hepatitis B-related viral infection in renal transplant recipientsa prospective study of 90 patients. Gastroenterology 1988;94:151-156.[Medline]
  3. De Villa VH, Chen YS, Chen CL. Hepatitis B core antibody-positive graftsrecipients's risk. Transplantation 2003;75(Suppl):S49-S53.[Medline]
  4. Wachs ME, Amend WJ, Ascher NL, et al. The risk of transmission of hepatitis B from HBsAg (-), HBcAb (+), HBIgM (-) organ donors Transplantation 1995;59:230-234.[Medline]
  5. Dickson RC, Everhart JE, Lake JR, et al. Transmission of hepatitis B by transplantation of livers from donors positive for antibody to hepatitis B core antigen. The national institute of diabetes and digestive and kidney diseases liver transplantation database Gastroenterology 1997;113:1668-1674.[Medline]
  6. Yu AS, Vierling JM, Colqubhoun SD, et al. Transmission of hepatitis B infection from hepatitis B core antibody-positive liver allografts is prevented by lamivudine therapy Liver Transpl 2001;7:513-517.[Medline]
  7. Dodson SF. Prevention of de novo hepatitis B infection after liver transplantation with allografts from hepatitis B core antibody positive donors Clin Transplant 2000;14(Suppl 2):20-24.
  8. Nery JR, Nery-Avila C, Reddy KR, et al. Use of liver grafts from donors positive for antihepatitis B-core antibody in the era of prophylaxis with hepatitis B immunoglobulin and lamivudine Transplantation 2003;75:1179-1186.[Medline]
  9. Fabrizi F, Dulai G, Dixit V, et al. Lamivudine for the treatment of hepatitis B virus-related liver disease after renal transplantationmeta-analysis of clinical trials. Transplantation 2004;77:859-864.[Medline]
  10. Loss GE, Mason AL, Nair S, et al. Does lamivudine prophylaxis eradicate persistent HBV-DNA allografts derived from anti-HBc-positive donors? Liver Transpl 2003;9:1258-1264.[Medline]
  11. De Villa VH, Chen YS, Chen CL. Hepatitis B core antibody-positive grafts:recipient's risk Transplantation 2003;75(Suppl):S49-S53.[Medline]
  12. Alavian SM, Hajarizadeh B, Einollahi B. Efficacy and safety of lamivudine for treatment of chronic hepatitis B in renal allograft recipients Transplant Proc 2003;35:2687-2688.[Medline]
  13. Grossi P, Gasperina D, Furino M, et al. Lamivudine treatment for HBV infection following thoracic organ transplantation Transplant Proc 2001;33:1576-1578.[Medline]
  14. Wang SS, Chou NK, Ko WJ, et al. Heart transplantation using donors positive for hepatitis Transplant Proc 2004;36:2371-2373.[Medline]
  15. Liu CJ, Lai MY, Lee PH, et al. Lamivudine treatment for hepatitis B reactivation in BsAG carriers after organ transplantationa 4-years experience. J Gastroenterol Hepatol 2001;16:1001-1008.[Medline]
  16. Ko WJ, Chou NK, Hsu RB, et al. Hepatitis B virus infection in heart transplant recipients in a hepatitis B endemic area J Heart Lung Transplant 2001;20:865-875.[Medline]
  17. Pinney SP, Cheema FH, Hammond K, Chen JM, Edwards NM, Mancini D. Acceptable recipient outcomes with the use of hearts from donors with Hepatitis B core antibodies J Heart Lung Transplant 2005;24:34-37.[Medline]




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