- Email: [email protected]
Revisiting the use of hepatitis B core antibody-positive donor kidneys
Revisiting the Use of Hepatitis B Core Antibody-Positive Donor Kidneys N.R. Krieger, C.M. Vial, M.T. Millan, J. Imperial, D.C. Dafoe, and J.D. Scandling
T
HE persistent and worsening shortage of organs for transplantation has led to an expansion of former criteria defining a cadaver donor. Organs from hepatitis B core antibody-positive (HBcAb⫹) donors have found limited use, due to the risk of transmission of hepatitis B virus (HBV). Past experience has shown the risk of transmission of HBV from a HBcAb cadaver kidney donor into a naı¨ve recipient to be 5–15%.1,2 In 1995 in an effort to expand donor criteria, we began to transplant kidneys from HBcAb⫹ cadaver donors into a select group of patients: either hepatitis B surface antibody-positive (HBsAb⫹) or HBcAb⫹ recipients. Subsequent reports have supported this approach.2,3 In the present study, we examined HBV-related outcomes in renal allograft recipients of HBcAb⫹ donors. MATERIALS AND METHODS This study is a retrospective analysis of 28 HBsAb⫹ or HBcAb⫹ recipients of HBcAb⫹ cadaver donor kidneys between March 1995 and August 1999. Two recipients were hepatitis B surface antigenpositive (HBsAg⫹). Standard maintenance immunosuppression was triple therapy with cyclosporine, azathioprine or mycophenolate mofetil, and corticosteroid. Three patients received induction therapy with muromonoab-CD3 (Orthoclone OKT3). Recipient characteristics are shown in Table 1. The two HBsAg⫹ recipients were treated with lamivudine, 150 mg daily, once immunosuppression was begun. All recipients were followed for evidence of clinical HBV disease, per routine post-transplant follow-up. Mean follow-up was 16 months (range, 12 to 65 months). HBV serology was repeated only if there were clinical symptoms and signs of hepatitis (n ⫽ 0) or liver enzymes were elevated above the normal range (n ⫽ 5). Transmitted HBV infection was defined as one in which Table 1. Recipient Characteristics Recipient HBV Status
n Male/Female Age at transplant (mean) Ethnicity Asian/Pacific Islander Hispanic Other
HBsAb⫹
HBcAb⫹
HBsAg⫹
7 5/2 42
19 12/7 52
2 2/0 42
2 3 2
14 2 3
2 0 0
© 2001 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
Table 2. Conversion to HBsAgⴙ Recipient HBV Status
n Time to conversion (mo) Follow-up since transplant (mo)
HBsAb⫹
HBcAb⫹
0/7 — —
1/19 24 49
the recipient converted to HBsAg⫹ after transplantation with no other source.
RESULTS
In four recipients, transient increases in liver enzymes (1 month to 4 years after transplant) were attributed to drug toxicity. There were no conversions to HBsAg⫹ in these cases. One patient (pretransplant serology HBcAb⫹, HBsAb⫹, HBsAg⫺) converted to HbsAg⫹ at two years post-transplant (Table 2). This recipient, who remained asymptomatic, was placed on treatment with lamivudine, 150 mg daily. Liver enzymes were normal at last follow-up appointment. No grafts were lost to hepatitis infection and all patients are alive to date (Table 3 and Figure 1). DISCUSSION
It has been previously shown that de novo posttransplant hepatitis B infection occurs at a high rate in recipients of liver donors that are HBcAb⫹.1,2,4 Dickson et al reported that 81% (19/23) of HBsAg⫺ recipients of liver allografts of HBcAb⫹ donors developed HBV hepatitis during a mean follow-up of 3.2 years.4 However, it has been suggested that although the rate of transmission is high, the clinical course may be relatively mild.5 It also appears that the recipient at greatest risk of HBV transmission from a HBcAb⫹ donor is the liver allograft recipient.1,3 In a report by Wachs et al,1 only one of 42 kidney and none of 7 heart allograft recipients became HBsAg⫹ following transplantation of organs from 25 HBcAb⫹ donors, while three of six liver recipients did. All recipients were HBsAg⫺ before transFrom the Departments of Surgery and Medicine, Stanford University Hospital, Stanford, California. Address reprint requests to John D. Scandling, 750 Welch Road, Suite 200, Palo Alto, CA 94304. 0041-1345/01/$–see front matter PII S0041-1345(00)02788-3 1535
Transplantation Proceedings, 33, 1535–1536 (2001)
1536
KRIEGER, VIAL, MILLAN ET AL Table 3. Patient and Graft Survival Recipient HBV Status
Patient survival (%) 1 year 3 year Graft survival (%) 1 year 3 year
HBsAb⫹
HBcAb⫹
HBsAg⫹
100 100
100 100
100 100
100 100
95 80
100 100
plantation. In a second study, by Paletta,6 52 HBsAg⫺ recipients of allografts from 21 HBcAb⫹ donors were analyzed. Four of 16 liver allograft recipients converted to HBsAg⫹, while none of the kidney or heart recipients did so. In our series, one of 19 HBcAb⫹ recipients of a HBcAb⫹ cadaver donor kidney converted to HBsAg⫹, during the second posttransplant year. This patient has not developed clinical sequellae, also confirming minimal risk. This conversion may have represented reactivation disease rather than transmission of HBV from donor to recipient. In addition, none of seven HBsAb⫹ recipients of a HBcAb⫹ cadaver donor kidney converted to HBsAg⫹. No grafts have been lost to complications of HBV infection, and all patients are alive. These short-term results suggest that the cadaver donor pool can be safely expanded with the transplantation of HBcAb⫹ kidneys into immunized HBsAb⫹ or HBcAb⫹ recipients.
Fig 1. Graft survival in the HBsAg⫹ (䊐), HBcAb⫹ (‚), and HBsAb⫹ (E) recipients. No grafts were lost to complications of HBV infection.
2. Satterthwaite R, Ozgu I, Shidban H, et al: Transplantation 64:432, 1997 3. Madayag RM, Johnson LB, Bartlett ST, et al: Transplantation 64:1781, 1997 4. Dickson R, Everhart J: Gastroenterology 110:A1182, 1996
REFERENCES
5. Douglas D, Rakela J, Wright T, et al: Liver Transplant Surg 3:105, 1997
1. Wachs ME, Amend WJ, Ascher NL, et al: Transplantation 59:230, 1995
6. Paletta L: In Lewis DD, McCoy J (eds): Donor management notes, Vol 2; 1996, p 1
T
HE persistent and worsening shortage of organs for transplantation has led to an expansion of former criteria defining a cadaver donor. Organs from hepatitis B core antibody-positive (HBcAb⫹) donors have found limited use, due to the risk of transmission of hepatitis B virus (HBV). Past experience has shown the risk of transmission of HBV from a HBcAb cadaver kidney donor into a naı¨ve recipient to be 5–15%.1,2 In 1995 in an effort to expand donor criteria, we began to transplant kidneys from HBcAb⫹ cadaver donors into a select group of patients: either hepatitis B surface antibody-positive (HBsAb⫹) or HBcAb⫹ recipients. Subsequent reports have supported this approach.2,3 In the present study, we examined HBV-related outcomes in renal allograft recipients of HBcAb⫹ donors. MATERIALS AND METHODS This study is a retrospective analysis of 28 HBsAb⫹ or HBcAb⫹ recipients of HBcAb⫹ cadaver donor kidneys between March 1995 and August 1999. Two recipients were hepatitis B surface antigenpositive (HBsAg⫹). Standard maintenance immunosuppression was triple therapy with cyclosporine, azathioprine or mycophenolate mofetil, and corticosteroid. Three patients received induction therapy with muromonoab-CD3 (Orthoclone OKT3). Recipient characteristics are shown in Table 1. The two HBsAg⫹ recipients were treated with lamivudine, 150 mg daily, once immunosuppression was begun. All recipients were followed for evidence of clinical HBV disease, per routine post-transplant follow-up. Mean follow-up was 16 months (range, 12 to 65 months). HBV serology was repeated only if there were clinical symptoms and signs of hepatitis (n ⫽ 0) or liver enzymes were elevated above the normal range (n ⫽ 5). Transmitted HBV infection was defined as one in which Table 1. Recipient Characteristics Recipient HBV Status
n Male/Female Age at transplant (mean) Ethnicity Asian/Pacific Islander Hispanic Other
HBsAb⫹
HBcAb⫹
HBsAg⫹
7 5/2 42
19 12/7 52
2 2/0 42
2 3 2
14 2 3
2 0 0
© 2001 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
Table 2. Conversion to HBsAgⴙ Recipient HBV Status
n Time to conversion (mo) Follow-up since transplant (mo)
HBsAb⫹
HBcAb⫹
0/7 — —
1/19 24 49
the recipient converted to HBsAg⫹ after transplantation with no other source.
RESULTS
In four recipients, transient increases in liver enzymes (1 month to 4 years after transplant) were attributed to drug toxicity. There were no conversions to HBsAg⫹ in these cases. One patient (pretransplant serology HBcAb⫹, HBsAb⫹, HBsAg⫺) converted to HbsAg⫹ at two years post-transplant (Table 2). This recipient, who remained asymptomatic, was placed on treatment with lamivudine, 150 mg daily. Liver enzymes were normal at last follow-up appointment. No grafts were lost to hepatitis infection and all patients are alive to date (Table 3 and Figure 1). DISCUSSION
It has been previously shown that de novo posttransplant hepatitis B infection occurs at a high rate in recipients of liver donors that are HBcAb⫹.1,2,4 Dickson et al reported that 81% (19/23) of HBsAg⫺ recipients of liver allografts of HBcAb⫹ donors developed HBV hepatitis during a mean follow-up of 3.2 years.4 However, it has been suggested that although the rate of transmission is high, the clinical course may be relatively mild.5 It also appears that the recipient at greatest risk of HBV transmission from a HBcAb⫹ donor is the liver allograft recipient.1,3 In a report by Wachs et al,1 only one of 42 kidney and none of 7 heart allograft recipients became HBsAg⫹ following transplantation of organs from 25 HBcAb⫹ donors, while three of six liver recipients did. All recipients were HBsAg⫺ before transFrom the Departments of Surgery and Medicine, Stanford University Hospital, Stanford, California. Address reprint requests to John D. Scandling, 750 Welch Road, Suite 200, Palo Alto, CA 94304. 0041-1345/01/$–see front matter PII S0041-1345(00)02788-3 1535
Transplantation Proceedings, 33, 1535–1536 (2001)
1536
KRIEGER, VIAL, MILLAN ET AL Table 3. Patient and Graft Survival Recipient HBV Status
Patient survival (%) 1 year 3 year Graft survival (%) 1 year 3 year
HBsAb⫹
HBcAb⫹
HBsAg⫹
100 100
100 100
100 100
100 100
95 80
100 100
plantation. In a second study, by Paletta,6 52 HBsAg⫺ recipients of allografts from 21 HBcAb⫹ donors were analyzed. Four of 16 liver allograft recipients converted to HBsAg⫹, while none of the kidney or heart recipients did so. In our series, one of 19 HBcAb⫹ recipients of a HBcAb⫹ cadaver donor kidney converted to HBsAg⫹, during the second posttransplant year. This patient has not developed clinical sequellae, also confirming minimal risk. This conversion may have represented reactivation disease rather than transmission of HBV from donor to recipient. In addition, none of seven HBsAb⫹ recipients of a HBcAb⫹ cadaver donor kidney converted to HBsAg⫹. No grafts have been lost to complications of HBV infection, and all patients are alive. These short-term results suggest that the cadaver donor pool can be safely expanded with the transplantation of HBcAb⫹ kidneys into immunized HBsAb⫹ or HBcAb⫹ recipients.
Fig 1. Graft survival in the HBsAg⫹ (䊐), HBcAb⫹ (‚), and HBsAb⫹ (E) recipients. No grafts were lost to complications of HBV infection.
2. Satterthwaite R, Ozgu I, Shidban H, et al: Transplantation 64:432, 1997 3. Madayag RM, Johnson LB, Bartlett ST, et al: Transplantation 64:1781, 1997 4. Dickson R, Everhart J: Gastroenterology 110:A1182, 1996
REFERENCES
5. Douglas D, Rakela J, Wright T, et al: Liver Transplant Surg 3:105, 1997
1. Wachs ME, Amend WJ, Ascher NL, et al: Transplantation 59:230, 1995
6. Paletta L: In Lewis DD, McCoy J (eds): Donor management notes, Vol 2; 1996, p 1