Hepatitis B virus infection in renal transplant recipients
- Tak-Mao Chan, MD, FRCP
Tak-Mao Chan, MD, FRCP
- Chair Professor & Yu Chiu Kwong Endowed Professor in Medicine
- University of Hong Kong
- Anna SF Lok, MD
Anna SF Lok, MD
- Professor of Medicine
- University of Michigan Medical School
- Section Editors
- Daniel C Brennan, MD, FACP
Daniel C Brennan, MD, FACP
- Editor-in-Chief — Nephrology
- Section Editor — Renal Transplantation
- Professor of Medicine
- Medical Director and Co-Director of the Comprehensive Transplant Center, Department of Internal Medicine, Division of Nephrology
- Johns Hopkins Medical School
- Barbara Murphy, MB, BAO, BCh, FRCPI
Barbara Murphy, MB, BAO, BCh, FRCPI
- Section Editor — Renal Transplantation
- Professor of Medicine
- Mount Sinai School of Medicine
Hepatitis B virus (HBV) infection is a major risk factor for hepatic dysfunction after renal transplantation  because of the requirement for immunosuppressive therapies . Although the incidence of HBV infection has declined among dialysis patients, the prevalence is still high in endemic areas.
This topic reviews the prognosis and management of HBV in end-stage renal disease (ESRD) patients who are undergoing renal transplantation. The serologic diagnosis of HBV infection and a general overview of management are provided elsewhere. (See "Diagnosis of hepatitis B virus infection" and "Hepatitis B virus: Overview of management".)
EPIDEMIOLOGY AND RISK FACTORS
Incidence and prevalence — In endemic areas, a significant number of patients undergoing kidney transplantation are hepatitis B surface antigen (HBsAg) positive. The reported prevalence is approximately 15 percent of kidney transplant recipients in such locations . The prevalence is much lower in areas in which HBV is less common.
Overall, the prevalence appears to be declining in most countries as a result of HBV vaccination programs in the general and dialysis patient population, as well as the result of strict precautions to prevent transmission of HBV infection in dialysis units. A national surveillance in the United States in 2002, for example, revealed that only 1 percent of dialysis patients was seropositive for HBsAg . (See "Hepatitis B virus and dialysis patients".)
Risk factors for reactivation of HBV replication — Among HBsAg-positive patients, reactivation of HBV replication is variably defined by the appearance of HBV DNA in a patient who has had undetectable HBV DNA previously or by a >1 to 2 log increase in HBV DNA. Among HBsAg-negative, hepatitis B core antibody (anti-HBc)-positive patients, reactivation is defined by the reappearance of HBsAg or HBV DNA or an increase in HBV DNA in those with detectable HBV DNA prior to the start of immunosuppressive therapy.
- Parfrey PS, Forbes RD, Hutchinson TA, et al. The clinical and pathological course of hepatitis B liver disease in renal transplant recipients. Transplantation 1984; 37:461.
- Degos F, Lugassy C, Degott C, et al. Hepatitis B virus and hepatitis B-related viral infection in renal transplant recipients. A prospective study of 90 patients. Gastroenterology 1988; 94:151.
- Liaw YF, Chu CM. Hepatitis B virus infection. Lancet 2009; 373:582.
- Finelli L, Miller JT, Tokars JI, et al. National surveillance of dialysis-associated diseases in the United States, 2002. Semin Dial 2005; 18:52.
- Kotton CN, Fishman JA. Viral infection in the renal transplant recipient. J Am Soc Nephrol 2005; 16:1758.
- Duhart BT Jr, Honaker MR, Shokouh-Amiri MH, et al. Retrospective evaluation of the risk of hepatitis B virus reactivation after transplantation. Transpl Infect Dis 2003; 5:126.
- Fairley CK, Mijch A, Gust ID, et al. The increased risk of fatal liver disease in renal transplant patients who are hepatitis Be antigen and/or HBV DNA positive. Transplantation 1991; 52:497.
- Kanaan N, Kabamba B, Maréchal C, et al. Significant rate of hepatitis B reactivation following kidney transplantation in patients with resolved infection. J Clin Virol 2012; 55:233.
- Kudlacz E, Perry B, Sawyer P, et al. The novel JAK-3 inhibitor CP-690550 is a potent immunosuppressive agent in various murine models. Am J Transplant 2004; 4:51.
- 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.
- Magee CC. Evaluation of donors and recipients. In: Chronic Kidney Disease, Dialysis, and Transplantation, 2nd ed., Pereira BJ, Sayegh MH, Blake B (Eds), Elsevier Saunders, Philadelphia 2005.
- Baccaro ME, Pépin MN, Guevara M, et al. Combined liver-kidney transplantation in patients with cirrhosis and chronic kidney disease. Nephrol Dial Transplant 2010; 25:2356.
- Nho KW, Kim YH, Han DJ, et al. Kidney transplantation alone in end-stage renal disease patients with hepatitis B liver cirrhosis: a single-center experience. Transplantation 2015; 99:133.
- Liaw YF, Sung JJ, Chow WC, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med 2004; 351:1521.
- Kim WR, Terrault NA, Pedersen RA, et al. Trends in waiting list registration for liver transplantation for viral hepatitis in the United States. Gastroenterology 2009; 137:1680.
- Loomba R, Rowley A, Wesley R, et al. Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy. Ann Intern Med 2008; 148:519.
- Chan TM, Fang GX, Tang CS, et al. Preemptive lamivudine therapy based on HBV DNA level in HBsAg-positive kidney allograft recipients. Hepatology 2002; 36:1246.
- Han DJ, Kim TH, Park SK, et al. Results on preemptive or prophylactic treatment of lamivudine in HBsAg (+) renal allograft recipients: comparison with salvage treatment after hepatic dysfunction with HBV recurrence. Transplantation 2001; 71:387.
- Filik L, Karakayali H, Moray G, et al. Lamivudine therapy in kidney allograft recipients who are seropositive for hepatitis B surface antigen. Transplant Proc 2006; 38:496.
- Perrillo RP. Acute flares in chronic hepatitis B: the natural and unnatural history of an immunologically mediated liver disease. Gastroenterology 2001; 120:1009.
- Lewandowska D, Durlik M, Kukuła K, et al. Treatment of chronic hepatitis B with lamivudine in renal allograft recipients. Transplant Proc 2000; 32:1369.
- Lee WC, Wu MJ, Cheng CH, et al. Lamivudine is effective for the treatment of reactivation of hepatitis B virus and fulminant hepatic failure in renal transplant recipients. Am J Kidney Dis 2001; 38:1074.
- Lau GK, Yiu HH, Fong DY, et al. Early is superior to deferred preemptive lamivudine therapy for hepatitis B patients undergoing chemotherapy. Gastroenterology 2003; 125:1742.
- Hsu C, Hsiung CA, Su IJ, et al. A revisit of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in non-Hodgkin's lymphoma: a randomized trial. Hepatology 2008; 47:844.
- Huang YH, Hsiao LT, Hong YC, et al. Randomized controlled trial of entecavir prophylaxis for rituximab-associated hepatitis B virus reactivation in patients with lymphoma and resolved hepatitis B. J Clin Oncol 2013; 31:2765.
- Yap DY, Yung S, Tang CS, et al. Entecavir treatment in kidney transplant recipients infected with hepatitis B. Clin Transplant 2014; 28:1010.
- Huang H, Li X, Zhu J, et al. Entecavir vs lamivudine for prevention of hepatitis B virus reactivation among patients with untreated diffuse large B-cell lymphoma receiving R-CHOP chemotherapy: a randomized clinical trial. JAMA 2014; 312:2521.
- Cho JH, Lim JH, Park GY, et al. Successful withdrawal of antiviral treatment in kidney transplant recipients with chronic hepatitis B viral infection. Transpl Infect Dis 2014; 16:295.
- Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant 2009; 9 Suppl 3:S1.
- Chan TM, Wu PC, Li FK, et al. Treatment of fibrosing cholestatic hepatitis with lamivudine. Gastroenterology 1998; 115:177.
- Yang YW, Lee CY, Hu RH, et al. Long-term effects of prophylactic and therapeutic lamivudine treatments in hepatitis B surface antigen-positive renal allograft recipients. Clin Exp Nephrol 2014; 18:144.
- Fabrizi F, Martin P. Management of hepatitis B and C virus infection before and after renal transplantation. Curr Opin Organ Transplant 2006; 11:583.
- Chan TM, Tse KC, Tang CS, et al. Prospective study on lamivudine-resistant hepatitis B in renal allograft recipients. Am J Transplant 2004; 4:1103.
- Gwak GY, Huh W, Lee DH, et al. The incidence and clinical outcome of YMDD mutants in hepatitis B surface antigen-positive renal allograft recipients after prolonged lamivudine therapy. Transplant Proc 2007; 39:3121.
- Tse KC, Yap DY, Tang CS, et al. Response to adefovir or entecavir in renal allograft recipients with hepatitic flare due to lamivudine-resistant hepatitis B. Clin Transplant 2010; 24:207.
- Kamar N, Milioto O, Alric L, et al. Entecavir therapy for adefovir-resistant hepatitis B virus infection in kidney and liver allograft recipients. Transplantation 2008; 86:611.
- Yap DY, Tang CS, Yung S, et al. Long-term outcome of renal transplant recipients with chronic hepatitis B infection-impact of antiviral treatments. Transplantation 2010; 90:325.
- Rostaing L, Henry S, Cisterne JM, et al. Efficacy and safety of lamivudine on replication of recurrent hepatitis B after cadaveric renal transplantation. Transplantation 1997; 64:1624.
- Kletzmayr J, Watschinger B, Müller C, et al. Twelve months of lamivudine treatment for chronic hepatitis B virus infection in renal transplant recipients. Transplantation 2000; 70:1404.
- Lau SC, Tse KC, Lai WM, Chiu MC. Use of prophylactic lamivudine and mycophenolate mofetil in renal transplant recipients with chronic hepatitis B infection. Pediatr Transplant 2003; 7:376.
- Fabrizi F, Dulai G, Dixit V, et al. Lamivudine for the treatment of hepatitis B virus-related liver disease after renal transplantation: meta-analysis of clinical trials. Transplantation 2004; 77:859.
- Kamar N, Sandres-Saune K, Ribes D, et al. Effects of long-term lamivudine therapy in renal-transplant patients. J Clin Virol 2004; 31:298.
- Thabut D, Thibault V, Bernard-Chabert B, et al. Long-term therapy with lamivudine in renal transplant recipients with chronic hepatitis B. Eur J Gastroenterol Hepatol 2004; 16:1367.
- Viganò M, Colombo M, Aroldi A, et al. Long-term lamivudine monotherapy in renal-transplant recipients with hepatitis-B-related cirrhosis. Antivir Ther 2005; 10:709.
- de Silva HJ, Herath CA, Sheriff MH. Lamivudine therapy for hepatitis B infection in post-renal transplant patients: results after 36 months follow-up. Liver Int 2005; 25:1074.
- Fontaine H, Vallet-Pichard A, Chaix ML, et al. Efficacy and safety of adefovir dipivoxil in kidney recipients, hemodialysis patients, and patients with renal insufficiency. Transplantation 2005; 80:1086.
- Kamar N, Huart A, Tack I, et al. Renal side effects of adefovir in hepatitis B virus-(HBV) positive kidney allograft recipients. Clin Nephrol 2009; 71:36.
- Ha NB, Ha NB, Garcia RT, et al. Renal dysfunction in chronic hepatitis B patients treated with adefovir dipivoxil. Hepatology 2009; 50:727.
- Rostaing L, Modesto A, Baron E, et al. Acute renal failure in kidney transplant patients treated with interferon alpha 2b for chronic hepatitis C. Nephron 1996; 74:512.
- Durlik M, Gaciong Z, Rowińska D, et al. Long-term results of treatment of chronic hepatitis B, C and D with interferon-alpha in renal allograft recipients. Transpl Int 1998; 11 Suppl 1:S135.
- Fehr T, Ambühl PM. Chronic hepatitis virus infections in patients on renal replacement therapy. Nephrol Dial Transplant 2004; 19:1049.
- Fabrizi F, Martin P, Dixit V, et al. HBsAg seropositive status and survival after renal transplantation: meta-analysis of observational studies. Am J Transplant 2005; 5:2913.
- Reddy PN, Sampaio MS, Kuo HT, et al. Impact of pre-existing hepatitis B infection on the outcomes of kidney transplant recipients in the United States. Clin J Am Soc Nephrol 2011; 6:1481.
- EPIDEMIOLOGY AND RISK FACTORS
- Incidence and prevalence
- Risk factors for reactivation of HBV replication
- Risk factors for liver failure among infected patients
- Risk factors for de novo HBV infection following transplantation
- EVALUATION PRIOR TO TRANSPLANTATION
- PREVENTION OF REACTIVATION OF HBV REPLICATION AFTER TRANSPLANTATION
- HBsAg-positive patients
- - Antiviral therapy
- - Reduction of immunosuppression
- HBsAg-negative, anti-HBc-positive patients
- MONITORING AFTER TRANSPLANTATION
- APPROACH TO PATIENTS WHO HAVE REACTIVATION OF HBV REPLICATION AFTER TRANSPLANTATION
- Antiviral agents
- - Entecavir, telbivudine, and tenofovir
- - Lamivudine
- - Adefovir
- - Interferon
- SUMMARY AND RECOMMENDATIONS