Hepatitis B surface antigen-positive allografts may be a source of transmission in patients who undergo renal transplantation. Treatment of hepatitis B virus infection with nucleoside/nucleotide analogs in kidney recipients who have hepatitis B virus infection or who have received transplants from hepatitis B surface antigen-positive donors improves long-term patient survival. Antiviral agents are administered as a preemptive or prophylactic therapy at the time of kidney transplantation, rather than as salvage treatment. In this report, we present 2 renal transplant recipients who had hepatitis B virus reinfection or who had developed seroconversion with immunosuppressive treatment. These case reports also demonstrate the unexpectedly different courses of hepatitis B reinfection after kidney transplantation.
Key words : Anti-viral treatment; Hepatitis B; Reinfection; Renal transplantation
Renal transplant is the best treatment option for patients with end-stage renal disease. The prognosis is generally excellent; however, a variety of complications such as activation and worsening of hepatic viral infections may occur. There is a growing consensus that hepatitis B virus (HBV) infection increases morbidity and mortality in renal transplant recipients. Hepatitis B surface antigen (HBsAg)-positive allografts may be another source of transmission in these patients. Treatment of HBV infection with nucleoside/nucleotide analogs in kidney recipients who have HBV infection or who have received a transplant from an HBsAg-positive donor improves long-term patient survival. The antiviral agent is administered as a preemptive or prophylactic therapy at the time of renal transplantation, rather than as salvage treatment.1,2 We present 2 renal transplant recipients who had HBV reinfection or who developed seroconversion with immunosuppressive treatment.
A 25-year-old female with end-stage renal disease of unknown cause received a living-donor kidney transplant 6 years previously. The living donor had been HBsAg positive and HBV DNA negative. The patient had been vaccinated for HBV before transplant, and her serology results were as follows: HBsAg antibody (anti-HBs) was higher than 100 IU/L, HBsAg negative, and hepatitis B core antigen (HBcAg) antibody (anti-HBc) immunoglobulin G (IgG) positive. Because of immunosuppressive treatment, the patient had been given 100 mg lamivudine daily preoperatively. Her immunosuppressive regimen was mycophenolate mofetil 500 mg twice daily, tacrolimus 1 mg twice daily, and prednisolone 5 mg once daily.
After the transplant procedure, the blood tests showed that aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and bilirubin levels were within normal ranges. Also HBsAg had been negative and anti-HBs was higher than 100 IU/L.
During an examination 4 years after transplant, the patient had no complaints; however, blood biochemical tests revealed AST of 320 IU/L (5-42 IU/L), ALT of 754 IU/L (5-45 IU/L), ALP of 115 IU/L (35-105 IU/L), and GGT of 147 IU/L (5-85 IU/L). On examination, the patient showed body temperature of 36.6°C, blood pressure of 120/80 mmHg, pulse of 62 beats/min, and respiratory rate of 16 breaths/min. There was no hepatosplenomegaly, palmar erythema, spider angioma, or ascites.
Serologic investigations showed a positive result of anti-HBc immunoglobulin M (IgM) and IgG antibodies, positive HBsAg, and a titration of anti-HBs higher than 100 IU/L. Hepatitis B virus DNA viral load was measured as 24,751.358 IU/mL without HBV DNA mutations. Other hepatotropic virus investigations, including hepatitis D virus RNA and hepatitis C virus RNA, had been unremarkable. The patient was diagnosed as having acute hepatitis virus infection, and tenofovir was initiated instead of lamivudine. During the next 6 months, hepatic enzyme levels gradually decreased, with investigations after 6 months of tenofovir treatment showing anti-HBs of 332 IU/L and negative HBV DNA and HBsAg tests. The patient is still under tenofovir treatment.
A 57-year-old male with end-stage renal disease of unknown cause received a living-donor kidney transplant 15 years previously. Preoperative serologic testing of the patient was as follows: positive HBsAg, positive hepatitis B e antigen antibody (anti-HBe), negative anti-HBs, negative anti-HBc IgM, positive anti-HBc IgG, negative HBeAg, negative HBV DNA, and negative delta virus antigen. Preoperative donor serologic investigations showed positive HBsAg and positive anti-HBc IgG. Because of positivity of HBsAg, lamivudine treatment had been initiated. His immunosuppression regimen consisted of mycophenolate mofetil 500 mg twice daily, tacrolimus 1.5 mg twice daily, and prednisolone 5 mg once daily.
On clinical follow-up, a physical examination revealed no sign of hepatic failure. After transplant, serum levels of ALT, AST, ALP, GGT, and bilirubin were within normal ranges, HBsAg was positive, and anti-HBs was negative. Lamivudine treatment had been continued.
At an examination 15 years after transplant, the patient’s serologic test revealed a positive anti-HBs antibody (64 IU/L), with HBsAg also still positive. Coexistence of HBsAg and anti-HBs was detected. Hepatitis B virus DNA viral load measured as 105 IU/mL. Tenofovir was initiated instead of lamivudine.
Use of organs from donors testing positive for HBV may safely expand the donor pool. However, risk of transmission of HBV infection continues to be a major concern. Transmission risks are highest with liver donors and significantly lower with nonliver (kidney and thoracic) donors.3
Immunization against HBV in kidney transplant recipients is recommended. Despite a high prevalence of protective anti-HBs titer at kidney transplantation, the loss of protective immunity during the following year has been considerable, particularly when the initial anti-HBs titer is < 100 IU/L.4 Antiviral prophylaxis significantly reduces the rate of transmission to kidney recipients from isolated HBsAg and anti-HBc IgG-positive donors. Antiviral prophylaxis may be considered for up to 1 year in susceptible nonliver recipients but is not recommended in immune nonliver recipients.3
The Kidney Disease Improving Global Outcomes (KDIGO) guideline suggests prophylaxis with tenofovir, entecavir, or lamivudine to all HBsAg-positive renal transplant recipients, and treatment with adefovir or tenofovir is recommended for transplant recipients with lamivudine resistance (45 log10 copies/mL rebound of HBV DNA).5 However, reinfection or reactivation of HBV may also occur without resistance of lamivudine. There is no consensus on which antiviral drugs are more safe or effective in renal transplant recipients.
Despite all of these preventive approaches, acute exacerbation of HBV infection can be seen, as in our case 1. Although HBsAg clearance and seroconversion to anti-HBs positive after renal transplantation can also occur very rarely, as in our case 2, prophylactic/preemptive therapy with antiviral drugs and routine monitoring of Anti-HBs and HBV DNA titers would be beneficial to renal transplant recipients from HBV carrier donors.
DOI : 10.6002/ect.2016.0063
From the Division of Nephrology, Department of Internal Medicine, Istanbul
Faculty of Medicine, Istanbul University, Istanbul, Turkey
Acknowledgements: The authors declare that they have no sources of funding for this study, and they have no conflicts of interest to declare.
Corresponding author: Ozan Yegit, Division of Nephrology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
Phone: +90 212 414 20 00/33040