|Year : 2019 | Volume
| Issue : 4 | Page : 292-296
Successful kidney transplantation from a deceased donor with chronic hepatitis B infection and review of literature
Dhanin Puthiyottil1, AS Ramesh2, Rahul Dhodapkar3, Manikandan Ramanitharan4, Sandeep Kumar Mishra5, Nabadwip Pathak1, Satyaprakash Ray Choudhury6, Arjun Pradeep Vazhayil7, Dorairajan Narayanan Lalgudi4, Sreerag Sreenivasan Kodakkattil4, Puthenpurackal S Priyamvada1, Sreejith Parameswaran1
1 Department of Nephrology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
2 Department of Neurosurgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
3 Department of Microbiology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
4 Department of Urology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
5 Department of Anaesthesiology and Critical Care, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
6 Department of Surgical Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
7 Transplant Coordinator, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
|Date of Submission||19-May-2019|
|Date of Acceptance||03-Nov-2019|
|Date of Web Publication||31-Dec-2019|
Dr. Sreejith Parameswaran
Department of Nephrology, #5348, Super Speciality Block, Jawaharlal Institute of Postgraduate Medical Education and Research Campus, Dhanvantari Nagar P. O., Puducherry - 605 006
Source of Support: None, Conflict of Interest: None
There is huge gap between patients requiring organ transplantation and the available organ donor pool. Various strategies are being pursued to expand the organ donor pool. Infection with hepatitis B virus (HBV) in the donor is considered a contraindication for organ donation. However, HBV infection is endemic in some regions, and a significant number of donors may harbor chronic HBV infection. Safe transplantation from donors with chronic HBV infection may allow significant expansion of the donor pool in such areas. We report the first instance in India of successful organ harvesting and kidney transplantation from a deceased donor with chronic HBV infection with no evidence of transmission of infection for 1 year after transplantation, and we briefly review the relevant literature.
Keywords: Donor pool, end-stage renal disease, hepatitis B infection, organ donation, transplantation
|How to cite this article:|
Puthiyottil D, Ramesh A S, Dhodapkar R, Ramanitharan M, Mishra SK, Pathak N, Choudhury SR, Vazhayil AP, Lalgudi DN, Kodakkattil SS, Priyamvada PS, Parameswaran S. Successful kidney transplantation from a deceased donor with chronic hepatitis B infection and review of literature. Indian J Transplant 2019;13:292-6
|How to cite this URL:|
Puthiyottil D, Ramesh A S, Dhodapkar R, Ramanitharan M, Mishra SK, Pathak N, Choudhury SR, Vazhayil AP, Lalgudi DN, Kodakkattil SS, Priyamvada PS, Parameswaran S. Successful kidney transplantation from a deceased donor with chronic hepatitis B infection and review of literature. Indian J Transplant [serial online] 2019 [cited 2020 Apr 4];13:292-6. Available from: http://www.ijtonline.in/text.asp?2019/13/4/292/274598
| Introduction|| |
There is shortage of organ donors globally, and various options are being pursued to expand the donor pool. Hepatitis B virus (HBV) infection is endemic in certain regions, and accepting donors with HBV infection, when appropriate, may help in expanding the donor pool in such regions. Here, we report an instance of successful kidney transplantation from a deceased donor with chronic HBV infection without transmission of infection and briefly review the literature on the safety of this practice.
| Case Report|| |
A 54-year-old male was brought to the emergency medical service department of our hospital following head injury from a road traffic accident. He had large subdural hematoma with subarachnoid hemorrhage and underwent decompression craniectomy. Subsequently, he was found to have extensive and irreversible brain injury consistent with brain death, by the treating team, and the same was reported to the deceased donor transplantation team at our hospital. Formal brain death certification was done as per provisions of the Transplantation of Human Organs Act, and the family gave consent for organ donation. Multi-organ harvesting was planned, but routine screening tests sent for the deceased donor detected him to be positive for hepatitis B surface antigen (HBsAg) by the enzyme-linked immunosorbent assay. His liver enzymes were normal [Table 1], and the liver appeared normal on ultrasonography.
The plan for liver harvesting was abandoned, and the kidney transplantation waiting list was checked for potential recipients who had completed vaccination for hepatitis B and in whom protective levels of anti-HBsAb titres were documented within the past 1 year. Seven potential recipients who met these criteria were contacted and offered transplantation from the deceased donor. All of them, except one patient, refused the organ, once they were told about the HBsAg-positive status of the donor.
The patient who agreed to accept the organ was a 26-year-old male from Orissa, who had no potential voluntary kidney donor in his family and who was on regular hemodialysis for 15 months. He had experienced two life-threatening complications after being initiated on dialysis. He had difficult to control blood pressure despite adequate dialysis, multiple antihypertensives, and optimization of dry weight based on bioimpedance analysis using body composition monitor (Fresenius Medical care, Germany). He had developed intracerebral hemorrhage (ICH) requiring hospitalization 2 months earlier. Subsequently, after discharge from the hospital after treatment for the ICH, he developed pulmonary edema with respiratory failure requiring endotracheal intubation and intensive care unit admission. He was registered under the deceased donor kidney transplantation waiting list 9 months back. He held a graduate degree in business administration, and in the treatment team's assessment, he could take an informed decision on his treatment. In the interest of abundant caution, informed consent was obtained under video recording with all aspects about the transplantation with the kidney from a donor who was HBsAg positive, including the possibility of fulminant hepatic failure, explained to the patient and his father, in his mother tongue (Odia) by two members of the kidney transplantation team, whose mother tongue was also Odia. The patient was steadfast in his willingness to undergo transplantation with the kidney from the HBsAg-positive donor, and it was decided to proceed with organ harvesting and transplantation.
He had received four doses of hepatitis B vaccine; the last dose was 5 weeks earlier. His antibody titer (anti-HBs) checked 1 week earlier was protective (more than 10 IU/L - [Table 2]). He was administered 600 IU of hepatitis B immunoglobulin before the transplantation operation and he was started on lamivudine prophylaxis. His serum samples were sent for HBsAg, anti-hepatitis B core antibody (HBcAb), and HBV DNA by Nucleic Acid Testing (NAT) just before the transplantation operation [Table 2]. He was given induction with rabbit anti-thymoglobulin (3 mg/kg in two divided doses on D0 and D1) and was started on immunosuppression with tacrolimus, mycophenolate mofetil, and prednisolone. He had prompt diuresis on declamping.
Since there were no other potential recipients, the second kidney was discarded. After 1 year of follow-up, his liver function has remained normal. He was monitored for hepatitis B viremia every 3 months and he did not develop viremia for transplantation till now, 1 year after the transplantation.
| Discussion|| |
The demand for organs far exceed availability in almost all countries. Efforts to expand the donor pool have explored different options, and accepting organs from donors with infections is one such strategy. Transplantation from donors with active hepatitis C and HIV is increasingly being reported. According to the epidemiological classification of hepatitis B, India comes under the intermediate prevalence zone (2%–7%). In endemic regions, the prevalence of anti-HBcAb-positive deceased donors may reach up to 24%. Accepting such donors may allow expanding the donor pool, especially in areas endemic for HBV. The reported prevalence of HBsAg positivity in healthy blood donors in Tamil Nadu is 0.58%. Of 98 potentially brain-dead patients reported to the deceased donor team at our center, 55 were tested for HBV infection, of whom 4 (7.2%) were found to be HBsAg positive (unpublished observation). The prevalence of occult HBV infection was found to be 4.71% among healthy blood donors at our center. It is evident that considering potential donors with chronic HBV infection for organ harvesting, in situ ations where it can be undertaken safely, will allow a significant expansion of the donor pool.
It is pertinent to emphasize that accepting organs, including kidney, from a donor who is HBsAg positive is not usual practice and one need to exercise extreme caution if contemplating it. It is also important to understand that the risk of transmission of infection depends on the infection status of the donor as well as the immune status of the recipient, and both their status should be evaluated thoroughly before considering transplantation. The interpretation of the infection status of an individual based on a panel of serologic tests for HBV is depicted in [Table 3] and [Table 4].
|Table 3: Interpretation of screening tests for hepatitis B virus infection|
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TheOrgan Procurement and Transplantation Network (OPTN), USA, recommends testing for HBsAg and anti-HBcAb in the potential deceased donor. A living donor should undergo further testing including HBV DNA by the NAT. Transplantation of kidneys from anti-HBcAb-positive donors was associated with negligible de novo hepatitis B infection in the recipients compared to liver transplantation., However, there are reports of seroconversion after receiving the kidney from anti-HBcAb-positive donors, particularly when the recipient is anti-HBcAb or HBsAg negative. Among the anti-HBcAb-positive kidney recipients, 27% developed new anti-HBcAb and/or HBV surface antibody after transplant in one study. A review by Mahboobi et al. reported an overall seroconversion rate of 3.24% when transplanting organs from HBsAg-negative but anti-HBcAb-positive donors. None of these patients had clinical signs of hepatitis, higher mortality, or decreased graft survival.
Compared to HBsAg-negative/anti-HBc positive donors, HBsAg-positive donors are generally considered as associated with more risk of de novo infection. Most of the centers used to consider transplant from HBsAg-positive donors to only matched HBsAg-positive recipients previously. The use of effective antiviral agents both as prophylaxis and as treatment along with hepatitis B immunoglobulin created more opportunities to receive the kidney from HBsAg-positive donors. Initial studies mentioned the use of hepatitis B immunoglobulin for the recipient at the time of transplant and lamivudine prophylaxis following transplant, particularly if the recipient was HBsAg positive.,
The dose and duration of immunoglobulin and lamivudine varied in different studies. [Table 5] describes different protocols used when recipients with nonprotective level of anti-HbS antibody received the kidney from donors with positive anti-HBc, and all of them had good outcomes.
|Table 5: Reported protocols for hepatitis B virus prophylaxis in transplant recipients|
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Even though the need for prophylaxis is well recognized, especially in recipients with nonprotective antibody titers, there are no uniformly accepted protocols. The role of immunoglobulin and antiviral prophylaxis in recipients with protective titers of antibody is controversial. A recent study by Asuman Yavuz et al. from Turkey compared HBsAg-positive and negative donors in live renal transplantation. In their study, 111 donors were HBsAg positive and 2057 were HBsAg negative; kidney transplantations were undertaken only if the recipient had hepatitis B antibody titer >10 mIU/mL and donor HBV DNA was negative. None of the patient received immunoglobulin or lamivudine. The study revealed no new HBV infections throughout the study period. Acute rejection rates, graft loss, and patient loss were similar between the two groups.
Jiang et al. reported seven recipients, who received grafts from donors with hepatitis B viremia, whose mean HBV DNA level was 6.2 × 107 copies/mL. These patients were all positive for both anti HBs and anti-HBc and received lamivudine and HBV immunoglobulin treatment. They were negative for HBsAg or HBV DNA at all follow-up visits and exhibited normal liver function to the end of follow-up. A significantly higher incidence of hepatitis (3 of 26 patients) was observed in recipients of kidneys from HBV DNA-positive donors on lamivudine prophylaxis, but none developed fulminant hepatitis, rejection, or graft loss.
It appears that renal transplantation from HBsAg-positive or anti-HBc-positive donors to recipients with a protective antibody is safe. A recent study suggests that the outcomes were similar whether the recipient received no prophylaxis, lamivudine alone, or lamivudine in combination with immunoglobulin.
Our case is unique, in that this is the first reported instance of kidney transplantation from an HBsAg-positive deceased donor from India. There were two earlier reports of kidney transplantation from HBsAg-positive donors, but both were living donors., Unlike deceased donor transplantation, living donor transplantation is an elective procedure and allows proper evaluation of the donor as well as recipients; treatment of the donor if necessary and preparation of the recipient in case, he was not vaccinated earlier or anti-HBsAb titers were not checked. Successful transplantation from a deceased donor is possible only if the center has a policy of vaccinating all patients in the deceased donor waiting list with hepatitis B vaccine as well as checking the anti-HBsAb titers.
| Conclusion|| |
Transplantation of a kidney from a deceased donor with chronic HBV infection to a patient with protective levels of anti-HBs antibody titers did not result in the transmission of infection. Accepting donors with chronic HBV infection may be a safe option to expand the organ donor pool under appropriate circumstances.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
We thank Dr Apurba Shankar Shastri, Associate Professor, Department of Microbiology and faculty in charge of Hospital Infection Control Committee, for arranging for the supply of anti-HBV immune globulin prior to the transplantation operation.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]