Controversies Regarding the Hepatitis B Immune Globulin Prophylaxis (HBIG) for Liver Transplantation Recipients

Seyed Mohammad Jazayeri, Mario Rizzetto, Seyed Moayed Alavian

Seyed Mohammad Jazayeri, Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
Mario Rizzetto, Department of Gastroenterology, Molinette, University of Torino, Torino, Italy
Seyed Moayed Alavian, Middle East Liver Diseases Center (MELD Centers), Tehran, Iran

Correspondence to: Seyed Moayed Alavian, MD, Middle East Liver Diseases Center (MELD Centers), No 178, Sepahboud Gharanee St. Tehran, Iran.
Email: chariman@meldcenter.com
Received: April 27, 2014
Revised: June 30, 2014
Accepted: July 6, 2014
Published online: November 21, 2014


Despite the impressive progress that has been made in developing highly effective prophylaxis regimen against HBV recurrence after liver transplantation which reduces the risk of recurrence to 30% in patients with chronic hepatitis B and to less than 10% in patients with fulminant liver failure, however, the effectiveness of such prophylactic options in preventing recurrence of hepatitis B virus (HBV) depends upon the dosage, route of administration, duration of treatment, type of anti-virals and the viremic status at the time of transplantation. This review will discuss the current status of the topic and consider the developments that made for liver pre- and post-transplantation. The ultimate efficacy of hepatitis B immunoglobulin (HBIg) for the prophylaxis against HBV recurrence after LT in relation to variable factors has been discussed in this review. Moreover, different regimen options based on using either concomitant nucleos (t) ide analogues (NA) and HBIg or drug monotherapy etc discussed.

Key words: HBIg; Liver transplantation; Nucleos (t) ide analogues; HBV recurrence

© 2014 The Authors. Published by ACT Publishing Group Ltd.

Jazayeri SM, Rizzetto M, Alavian SM. Controversies Regarding the Hepatitis B Immune Globulin Prophylaxis (HBIG) for Liver Transplantation Recipients. Journal of Gastroenterology and Hepatology Research 2014; 3(11): 1313-3125 Available from: URL: http://www.ghrnet.org/index.php/joghr/article/view/917


Hepatitis B virus (HBV) infection is among the top ten causes of death worldwide due to chronic liver disease[1] and accounts for an estimated 370 million chronic infections[2]. Approximately 10-15% of infected patients progress to chronic liver disease[3], and 3% will develop hepatocellular carcinoma (HCC)[4]. The ultimate interventional option for the end stage liver disease for chronic carriers is liver transplantation, however, this has been challenged by a recurrence rate of 80-100% of HBV infection[5], leading to rapid progression to cirrhosis and death. With the utilization of hepatitis B immunoglobulin (HBIg), this frequency has been reduced dramatically depends on the dose, route and the presence of antiviral prophylaxis. In this paper we reviewed the current knowledge about the role of HBIg alone or in combination with antivirals and how they influence the outcome of liver transplantation.


We performed a literature of review by search of National Library of Medicines PubMed and (NCBI) bibliographies of papers and journals from 2000 to April 2014 on the describing the efficacy of HBIg for the prophylaxis against HBV recurrence after LT in association with several factors using the MeSH terms: HBIg dose, HBIg route, HBIg monotherapy, HBIg combination therapy and finally HBIg and new nucleos (t) ide analogous (NA). We classified the selected papers which contained enough data alphabetically.

We included all cross sectional and prospective or retrospective cohort studies comparing the use of HBIg, antivirals, or both for prevention of recurrent HBV infection in liver transplanted patients. Due to the huge amounts of the data, results from some aspects of above criteria were published elsewhere[6] mainly focused on the route of injection and dosage of HBIg liver in transplant settings. Herein, we focused mainly on the different types of HBIG therapy in the era of new NA drugs.

Role of HBIG in the Prophylaxis

Over the past two decades, prophylactic treatment for the prevention of HBV re-infection following liver transplantation involves passive immunity offered by low- to high-dose HBIG alone or in combination with an antiviral NA has been suggested as a gold standard regimen[7], which reduces the risk of recurrence to 30% in patients with chronic hepatitis B and to less than 10% in patients with fulminant liver failure[7-10]. This strategy has led to the concomitant improvement in graft and overall survival rates. Despite being effective as an immunomodulator for HBV infection prophylaxis, however, the effectiveness of HBIg in preventing recurrence of HBV depends upon multiple factors: dosage, route, type of therapy, duration of HBIg, HBV DNA levels pre-LT etc. Also, there is currently no consensus over those factors for prevention and/or suppression recurrence of HBV post-LT and yet have not been standardized and tend to vary widely from one transplant center to another[11-15]. Some of those important controversial factors include:

1. Route of HBIG administration.

As a standard procedure, high dosage of HBIg requires intravenous (IV) administration. As an accepted alternative for intravenous route, intramuscular injection (IM) of HBIg has been studied in many reports worldwide. Regarding the limited volumes that can be given per IM injection, only patients with low HBIG requirements are suited for intramuscular HBIG administration[16,17]. Currently, switching from intravenous HBIg during anehepatic and a few days post-LT (which usually involved the application of high-dosage) to IM route for either short term or indefinitely has been using widely in different centers (Table 1). Subcutaneous (SC) HBIg either alone or in combination with NA to prevent recurrent HBV infection before LT has been reported only in few studies (Tables 1 and 2). Low recurrence rate, lower dosage of HBIg (500 to 1,000 IU), self-administration by the patients, low drug adverse effects, stability of anti-HBs levels were the advantages[18-23].

In a cost-effectiveness analysis by Dan et al the overall cost for intravenous HBIg for the first and subsequent years were 108,300 and 51,300 US Dollar, respectively. However, the same calculation for intramuscular HBIg for the first and subsequent years were 80,000 and 90,00-10,000 US Dollars, respectively[24].

2. HBIG doses (low dose versus high dose).

During 1990s, numerous reports from US and European centers have shown the benefit of continuous use of high-dose HBIg post liver transplantation that dramatically reduced the incidence of recurrent HBV infection[25-27], prior to the availability of effective antiviral therapy[10]. However, selection of surface protein mutants, high costs and patients incompliance have limited the efficacy of this application[7,16,28-31]. Therefore, HBIG at lower doses (300-800 IU) and conversion of intravenous to intramuscular route have been used instead[32-50] (Table 1). Combination of low-dose HBIg with NA resulted in lower costs as well as similar recurrence and survival rates with high dosage regimen[34,51].

3. Duration of therapy

Many centers worldwide have employed lifelong prophylaxis by the administration of either low or high HBIg dose in combination with NAs[7,52-54] despite no significant differences for HBV recurrence 5 years after LT for different HBIG regimens[52]. However, the cost of such treatment is very high and, in recent years, several centers have used short-term HBIg in combination with indefinite nucleos(t)ide analogue therapy[30,38,50]. Discontinuation of HBIG after some defined interval and continuing treatment with new antivirals alone have been applied by some centers with a promising results indicating no rate of recurrence[55-57] (Table 1).

4. Type of HBIG Therapy (mono vs combination with NA).

Although some studies showed that high-dose HBIG monotherapy to be equivalent to the combination regimen for prevention of HBV post-LT[21,58], combination therapy have become a common strategy to reduce HBV recurrence rate post-LT and the efficacy has been investigated extensively[30,32,37,40,45,48,49,51] (Table 1). Development of new antiviral agents and the use of HBIG plus antiviral NA have decreased the risk of recurrent hepatitis and death in transplant recipients by decreasing the amount of circulating virus at the time of transplant and by prolonging the half-life of HBIG[10,59]. Generally, HBIg plus antiviral NA combination prophylaxis consists of antiviral agents administered pre-transplantation (especially in HBV-DNA-positive patients) to reduce the viral load, followed by high (IV) or low (IM) dose (2,000 to 10,000 IU) during the anhepatic phase and a combination of long term antiviral NA and high (IV) or low (IM) dose (400 to 10,000 IU HBIg) with different intervals following transplantation (Table 1)[21,60].

5. Pre-LT HBV DNA levels.

a: Early recurrence: Typically, early recurrence graft infection (80% to 100%) in the absence of prophylaxis occurs between 6 and 12 months after LT[5]. Several reports have noted that serum HBV DNA level at the time of transplant would be an important predictor of the half-life of HBIG[10,17,61] and different high levels of pre-operative viral load (>104 copy/mL) have been suggested to be a risk factor for graft HBV re-infection[32,52,62-64]. Lenci et al showed that patients without detectable HBV DNA in the liver before transplantation have a low risk of HBV recurrence[7,65] and long-term follow-up studies confirmed that recurrence rates differed with HBV DNA titers prior to antiviral therapy[34,45]. Neff et al[13] found that none of the 51 patients with undetectable HBV DNA pre-LT experienced evidence of HBV viral recurrence post-LT regardless of the different prophylactic strategy[30,50]. However, following studies showed that suppression of HBV-DNA in serum does not indicate clearance of the virus from hepatocytes[46,66] and the long half-life of cccDNA in reinfected hepatocytes is responsible for viral recurrence following OLT[67-71]. Therefore, the authors suggested the complete withdrawal of prophylaxis with caution.

b: Late recurrence: Late recurrences are usually caused by the emergence of mutations caused by the selection pressure of HBIg on the surface protein[28,29,72,73]. Moreover, the emergence of YMDD variants following NA resulted in HBV reinfection following LT as a result of selection pressure of the drugs on the polymerase protein. However, in contrast to HBIg, this emergence being variable according to the type of drug regimen, in a range being highest (16%) to lowest (0%) following lamivudine and entecavir combination therapy. On the other hand, higher occurrence of resistance have been reported following monotherapy with either HBIg (0% to 71%) or NA (lamivudine) (0% to 39.7%)[74,75] (Table 1). Further, multiple drug/HBIg variants have been reported in patients receiving both interventions (especially in combination with lamivudine)[72,73,76, 77]. Obviously with current new NA agents like adefovir, entecavir, tenofovir, etc, the recurrence rate decreased to 0% to 12.9% (Tables 1-3). However, there are only limited data available for these new antiviral NAs and further studies needed to test their effectiveness as part of combination therapy with HBIG and/or montherapy strategies[78-80].

6. Anti-HBs target levels

Despite there is no consensus regarding sustained levels of anti-HBs following HBIg administration before and after LT, it is widely accepted that anti-HBs plasma titers should not fall below 100 IU/L during HBIg therapy. Protection against HBV recurrence seems to obtain better with higher anti-HBs levels (300-500 IU/ L)[81,82]. The proposed levels ranges from >70 to >500 IU/mL among centers. Furthermore, serum HBsAb levels monitoring after HBIg injections is also controversy among centers and the need for an intensive care of the level of anti-HBs (and subsequent frequent reinjection) to prevent HBV recurrence are still unclear[13,30,50]. The ideal method for establishment of anti-HBs variability in response to HBIg administration would be through individualized dosing proportional to anti-HBs levels obtained in a timely fashion interpatiently[59].

Prophylaxis with NA

1. NA monotherapy

Among the NAs, lamivudine was the first that introduced as a monotherapy before and after LT for prophylaxis against HBV recurrence post-LT especially in certain patients such as those who were HBV-DNA-negative and at low risk of re-infection[36,75,83]. Subsequently, there was a dramatic decrease of the HBV recurrence rate in patients receiving lamivudine (LAM) monotherapy (3 years post-LT recurrence rate of 40%)[75,84].

Unfortunately a recurrence rate of 3.8 to 40% at 2 years post-LT have been reported by multiple centers as a consequence of drug-resistance phenomenon caused by the emergence of mutants in the highly conserved motif YMDD within the polymerase[30,72,73,77,85]. Lu et al investigated two groups of LT recipients receiving lamivudine (in combination with HBIG) at long and short term periods. The longer period-group (mean 698.5 days) showed 9% HBV recurrence compared to 0% for shorter period group (mean 36.9 days)[39]. Moreover, others showed that in patients on lamivudine monotherapy, high viral load pretransplantation could be a predictor for the development of posttransplantation lamivudine resistance[51,74]. Therefore, long term LT prophylaxis using lamivudine monotherpy has been not recommended, particularly in replicative patients[30,35,84,86].

The data on using new NA monotherapy for prophylaxis in the absence of HBIg are few. Adefovir (ADV) monotherpay has been used by few studies with encouraging results (Tables 1-3)[87]. The rate of recurrence after LT was 0%. Similarly, entecavir, Telbivudine monotherapy[78,88-91] pre-and post LT resulted in 0% to 8% HBV recurrence rate (Table 2). Only one study found a relatively high rate of recurrent HBV infection (22.5%) using ENT[91] (Table 3). Based on experience in non-transplant patients, telbivudine can be substituted for lamivudine. Similar to lamivudine, telbivudine should not be used as monotherapy, and if used it should be combined with adefovir or tenofovir to minimize the risk of drug resistance[10].

2. Rescue therapy

During the new NA era for the prophylaxis against HBV recurrence following LT, many centers have been using these drugs only in the case of drug resistance following lamivudine administration as either add-on or switching approaches in combination with HBIg as rescue therapy[13,37,45,49,92-97] (Table 4). ADV has been at the top of this list for only cases who acquired HBV reinfection due to LAM-resistance. Schiff et al[94] reported a survival of one-year 84% for pre-LT and 93% for post-LT patients with no cases of ADV-resistance in patients who experienced HBV recurrence after LT. HBV DNA was undetectable at week 144 in 78% of cases. Longer follow up study showed a 3 year sustained survival of 87% in these patients group[87]. Also, entecavir showed promising results for these patients with no cases of recurrence[38,88,93,98]. However, despite entecavir is an ideal antiviral agent in nucleoside-naïve patients for its potent antiviral effects, low rate of drug resistance, and lack of nephrotoxicity, as entecavir-resistant mutations are more likely to be selected in the presence of lamivudine-resistant mutations, some authors have not recommended this drug in patients with lamivudine-resistant HBV[10]. Other new NA agents like Emtricitabine (FTC), Tenofovir (TDF); Famciclovir (FAM)[13,28,38,93] (Table 4) showed to be effective for lamivudine-resistant variants following liver transplantation. However, the sample sizes in these studies on the effectiveness of new NA agents were too small to make a definite conclusion.

3. NA combination therapy

New NAs including adefovir, entecavir, tenofovir, and telbivudine are antiviral agents of choice for the treatment of HBV. However, due to lack of data and despite some few studies that showed their effectiveness when they included in the prophylactic regimen[38,93,96] (Table 3), combination of NAs without the concomitant use of HBIg is generally not recommended. Further, comparison of trails that used a combination of antivirals compared with a combination of HBIg plus either NA alone showed that both regimens provides equivalent protection against recurrent HBV infection after LTx with fewer side effects and lower cost[32,88]. Furthermore, treatment with adefovir plus lamivudine before LTx and the addition of HBIg after LTx has shown to prevent graft reinfection[7,87,94,99].

Due to the potential nephrotoxicity, tenofovir is not an ideal drug in the transplant setting in nucleoside naïve patients but tenofovir alone or in combination with a nucleoside, lamivudine, emtricitabine, telbivudine or entecavir, is recommended for patients with lamivudine resistance[10].

4. HBIg+NA prophylaxis

As it shown in the table 1, the incidence of de novo HBV was ranged from zero to 2.7% in patients receiving LAM-only prophylaxis versus zero to 20% in those receiving HBIG plus LAM combination therapy. Thus, both prophylactic treatment strategies were associated with HBV breakthrough post-LT.

Following lamivudine, adefovir has been introduced as more potent NA antiviral for post-LT prophylaxis. Although the sample size of the patients-studied was low in compare with Lam-receiving patients, the reported recurrence after prophylaxis with ADV was 0%[44,87,99]. Among new NAs, entecavir, telbivudine, tenofovir and emtricitabine have been used with 0% recurrence rate (Table 2) [22,46,56,93,95,100-105].

5. NAs cross-regimen

There are some recommendation regarding switching from HBIg monotherapy or combination therapy to NAs monotherapy (Tables 1-2). Patients without virus replication at the time of LTx, with at least 2 years of HBIg treatment and those who are negative for HBV DNA by polymerase chain reaction before stopping HBIg seem to be the best candidates to switch to a monotherapy with NAs[7,13,28,49,74]. In a study by Xie et al, of 17 patients who experienced HBV recurrence after LT, 12 switched from LAM+HBIg to adefovir plus lamivudine. HBV DNA fell below 103 copy/mL in 10 cases after 6 months (one case died due to HCC) and subsequently in one patient who switched to entecavir[95].

Concluding remarks

Despite the absence a consensus on prophylaxis against HBV reinfection following liver transplantation, in an attempt to determine an optimal regimen for HBIG administration that can be more cost-effective, convenient, and widely-accepted alternative approaches have been studied including: lower HBIG doses, the use of intramuscular or subcutaneous HBIG rather than the intravenous route, non-HBIG forms of anti-HBs, and low-dose or short-term HBIG in combination with antivirals and tailoring HBIG administration guided by plasma concentrations rather according to a fixed time schedule. The choice of options depend on the availability of antivirals and cost of HBIG regimen. Regarding new NA monotherapy, due to the lack of adequate data, for a definite conclusion more prospective, cohort studies needed though the available results are optimistic.


There are no conflicts of interest with regard to the present study.


1 Alter MJ, Epidemiology and prevention of hepatitis B. Semin Liver Dis 2003; 23(1): 39-46

2 Ott JJ, Stevens GA, Groeger J, Wiersma ST. Global epidemiology of hepatitis B virus infection: New estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine 2012; 30(12): 2212-2219

3 Viral hepatitis guidelines in hemodialysis and transplantation. Am J Transplant 2004. 4 Suppl 10: 72-82

4 Colombo M, Sangiovanni A, Etiology, natural history and treatment of hepatocellular carcinoma. Antiviral Res 2003; 60(2): 145-150

5 Zheng SS, Wu J, Liang TB, Wang WL, Huang DS, Xu X. Prophylaxis and treatment of hepatitis B virus reinfection following liver transplantation. Hepatobiliary Pancreat Dis Int 2002; 1(3): 327-329

6 Dindoost P, Jazayeri SM, Alavian SM. Hepatitis B immune globulin in liver transplantation prophylaxis: an update. Hepat Mon 2012; 12(3): 168-176

7 Mehrabi A, Majid Esmaeilzadeh, Hamidreza Fonouni, Mohammadreza Hafezi, Nuh N. Rahbari, Mohammad Golriz, Ali Majlesara, Morva Tahmasbi Rad, Mahmoud Sadeghi, Jan Schmidt, Tom M Ganten. The role of HBIg as hepatitis B reinfection prophylaxis following liver transplantation. Langenbecks Arch Surg 2012; 397(5): 697-710

8 Samuel D, Feray C, Bismuth H. Hepatitis viruses and liver transplantation. J Gastroenterol Hepatol 1997; 12(9-10): S335-41

9 Samuel D. The option of liver transplantation for hepatitis B: where are we? Dig Liver Dis 2009; 41 Suppl 2: S185-9

10 Lok A. Liver transplantation for chronic hepatitis B virus infection. Up to date, 2011. www.uptodate.com

11 Ben-Ari Z, Mor E, Tur-Kaspa R. Experience with lamivudine therapy for hepatitis B virus infection before and after liver transplantation, and review of the literature. J Intern Med 2003; 253(5): 544-552

12 Lo CM, Fan ST, Liu CL, Lai CL, Wong J. Prophylaxis and treatment of recurrent hepatitis B after liver transplantation. Transplantation 2003; 75(3 Suppl): S41-4

13 Neff GW, O’brien CB, Nery J. Outcomes in liver transplant recipients with hepatitis B virus: resistance and recurrence patterns from a large transplant center over the last decade. Liver Transpl 2004; 10(11): 1372-1378

14 Nery JR, Nery-Avila C, Reddy KR, Cirocco R, Weppler D, Levi DM. Use of liver grafts from donors positive for antihepatitis B-core antibody (anti-HBc) in the era of prophylaxis with hepatitis-B immunoglobulin and lamivudine. Transplantation 2003; 75(8): 1179-1186

15 Van Nunen AB, de Man RA, Heijtink RA, Vossen ACTM. Passive immunization of chronic hepatitis B patients on lamivudine therapy: a feasible issue? J Viral Hepat 2002; 9(3): 221-228

16 Shouval D, Samuel D. Hepatitis B immune globulin to prevent hepatitis B virus graft reinfection following liver transplantation: a concise review. Hepatology 2000; 32(6): 1189-1195

17 Terrault N, Roche B, Samuel D. Management of the hepatitis B virus in the liver transplantation setting: a European and an American perspective. Liver Transpl 2005; 11(7): 716-732

18 Hooman N, Rifai K, Hadem J, Vaske B, Philipp G, Priess A, Klempnauer J, Tillmann HL, Manns MP, Rosenauet J. Antibody to hepatitis B surface antigen trough levels and half-lives do not differ after intravenous and intramuscular hepatitis B immunoglobulin administration after liver transplantation. Liver Transpl 2008; 14(4): 435-442

19 Powell JJ, Apiratpracha W, Partovi N, Erb SR, Scudamore CH, Steinbrecher UP, Buczkowski AK, Chung SW, Yoshida EM. Subcutaneous administration of hepatitis B immune globulin in combination with lamivudine following orthotopic liver transplantation: effective prophylaxis against recurrence. Clin Transplant 2006; 20(4): 524-525

20 Singham J, Greanya ED, Lau K, Erb SR, Partovi N, Yoshida EM. Efficacy of maintenance subcutaneous hepatitis B immune globulin (HBIG) post-transplant for prophylaxis against hepatitis B recurrence. Ann Hepatol 2010; 9(2): 166-171

21 Shafique U, Watson C. Current and Evolving Prophylactic Strategies Against Hepatitis B Virus Re-infection Following Liver Transplantation. European Gastroenterology & Hepatology Review 2010; 6(1): 4

22 Di Costanzo GG, Lanza AG, Picciotto PF, Imparato M, Migliaccio C, De Luca M, Scuderi V, Tortora R, Cordone G, Utech W, Calise F. Safety and efficacy of subcutaneous hepatitis B immunoglobulin after liver transplantation: an open single-arm prospective study. Am J Transplant 2013; 13(2): 348-352

23 Klein CG, Cicinnati VR, Schmidt H, Ganten T, Scherer MN, Braun F. Compliance and tolerability of subcutaneous hepatitis B immunoglobulin self-administration in liver transplant patients: a prospective, observational, multicenter study. Ann Transplant 2013; 18: 677-684

24 Dan YY, Wai CT, Yeoh KG, Lim SG. Prophylactic strategies for hepatitis B patients undergoing liver transplant: a cost-effectiveness analysis. Liver Transpl 2006; 12(5): 736-746

25 Didier Samuel, Rainer Muller, Graeme Alexander, Luigi Fassati, Beatrice Ducot, Jean-Pierre Benhamou, Henri Bismuth. Liver transplantation in European patients with the hepatitis B surface antigen. N Engl J Med 1993; 329(25): 1842-1847

26 McGory RW, Muller R, Alexander G, Fassati L, Ducot B, Benhamou JP, Bismuth H, and the Investigators of the European Concerted Action on Viral Hepatitis Study. Improved outcome of orthotopic liver transplantation for chronic hepatitis B cirrhosis with aggressive passive immunization. Transplantation 1996; 61(9): 1358-1364

27 Terrault NA, Zhou S, Combs C, Hahn JA, Lake JR, Roberts JP, Ascher NL, Wright TL. Prophylaxis in liver transplant recipients using a fixed dosing schedule of hepatitis B immunoglobulin. Hepatology 1996; 24(6): 1327-1333

28 Roche B, Roque-Afonso AM, Sebagh M, Delvart V, Duclos-Vallee JC, Castaing D, Samuel D. Escape hepatitis B virus mutations in recipients of antibody to hepatitis B core antigen-positive liver grafts receiving hepatitis B immunoglobulins. Liver Transpl 2010; 16(7): 885-894

29 Protzer-Knolle U, Naumann U, Bartenschlager R, Berg T, Hopf U, Karl-Hermann Meyer zum Büschenfelde, Neuhaus P, Gerkenet G. Hepatitis B virus with antigenically altered hepatitis B surface antigen is selected by high-dose hepatitis B immune globulin after liver transplantation. Hepatology 1998; 27(1): 254-263

30 Zheng S, Chen YM, Liang TB, Lu AW, Wang WL, Shen Y, Zhang M. Prevention of hepatitis B recurrence after liver transplantation using lamivudine or lamivudine combined with hepatitis B Immunoglobulin prophylaxis. Liver Transpl 2006; 12(2): 253-258

31 Gow PJ, Mutimer F. Mechanisms of hepatitis B virus escape after immunoglobulin therapy. Curr Opin Infect Dis 2000; 13(6): 643-646

32 Angus PW, Patterson SJ, Strasser SI, McCaughan GW, Gane E. A randomized study of adefovir dipivoxil in place of HBIG in combination with lamivudine as post-liver transplantation hepatitis B prophylaxis. Hepatology 2008; 48(5): 1460-1466

33 Anselmo DM, Ghobrial RM, Jung LC, Weaver M, Cao C, Saab S, Kunder G, Chen PW, Farmer DG, Yersiz H, Baquerizo A, Geevarghese S, Han SH, Goldstein L, Holt CD, Gornbein JA, Busuttil RW. New era of liver transplantation for hepatitis B: a 17-year single-center experience. Ann Surg 2002; 235(5): 611-619; discussion 619-20.

34 Gane EJ, Angus PW, Strasser S, Crawford DHG, Ring J, Jeffrey GP, McCaughan GW. Lamivudine plus low-dose hepatitis B immunoglobulin to prevent recurrent hepatitis B following liver transplantation. Gastroenterology 2007; 132(3): 931-937

35 Han SH, Ofman J, Holt C, King K, Kunder G, Chen P, Dawson S, Goldstein L, Yersiz H, Farmer DG, Ghobrial RM, Busuttil RW, Martin P. An efficacy and cost-effectiveness analysis of combination hepatitis B immune globulin and lamivudine to prevent recurrent hepatitis B after orthotopic liver transplantation compared with hepatitis B immune globulin monotherapy. Liver Transpl 2000; 6(6): 741-748

36 Marzano A, Salizzoni M, Debernardi-Venon W, Smedile A, Franchello A, Ciancio A, Gentilcore E, Piantino P, Barbui AM, David E, Negro F, Rizzetto M. Prevention of hepatitis B virus recurrence after liver transplantation in cirrhotic patients treated with lamivudine and passive immunoprophylaxis. J Hepatol 2001; 34(6): 903-910

37 Alfredo Marzano, Mauro Salizzoni, Wilma Debernardi-Venon, Antonina Smedile, Alessandro Franchello, Alessia Ciancio, Elena Gentilcore, Paolo Piantino, Anna Maria Barbui, Ezio David, Francesco Negro, Mario Rizzetto. Adefovir dipivoxil therapy in liver transplant recipients for recurrence of hepatitis B virus infection despite lamivudine plus hepatitis B immunoglobulin prophylaxis. J Gastroenterol Hepatol 2007; 22(12): 2130-2134

38 Campos-Varela I, Castells L, Buti M, Vargas V, Bilbao I, Rodríguez-Frías F, Jardí R, Charco R, Guardia J, Esteban R. Does pre-liver transplant HBV DNA level affect HBV recurrence or survival in liver transplant recipients receiving HBIg and nucleos(t)ide analogues? Ann Hepatol 2011; 10(2): 180-187

39 Lu AW, Zheng SS, Wu MP, Shen Y, Yang RW. Reevaluation of the effect of lamivudine therapy preoperative to prevent HBV recurrence after liver transplantation. Hepatobiliary Pancreat Dis Int 2008; 7(4): 357-361

40 Suehiro, T., Shimada M, Kishikawa K, Shimura T, Soejima Y, Yoshizumi T. Prevention of hepatitis B virus infection from hepatitis B core antibody-positive donor graft using hepatitis B immune globulin and lamivudine in living donor liver transplantation. Liver Int 2005; 25(6): 1169-1174

41 Takaki A, Yagi T, Iwasaki Y, Sadamori H, Matsukawa H, Matsuda H. Short-term high-dose followed by long-term low-dose hepatitis B immunoglobulin and lamivudine therapy prevented recurrent hepatitis B after liver transplantation. Transplantation 2007; 83(2): 231-233

42 Targhetta S, Villamil F, Inturri P, Pontisso P, Fagiuoli S, Cillo U. Protocol liver biopsies in long-term management of patients transplanted for hepatitis B-related liver disease. World J Gastroenterol 2006; 12(11): 1706-712

43 Umeda M, Marusawa H, Ueda M, Takada Y, Egawa H, Uemoto S, Chiba T. Beneficial effects of short-term lamivudine treatment for de novo hepatitis B virus reactivation after liver transplantation. Am J Transplant 2006; 6(11): 2680-2685

44 Wang Z.X, Ding GS, Fu H, Zhang JJ, Chen XS, Guo WY, Shi XM, Fu ZR. Prevention of hepatitis B virus reinfection after orthotopic liver transplantation. Hepatobiliary Pancreat Dis Int 2004; 3(3): 345-348

45 Woo HY, Choi JY, Jang JW, You CR, Bae SH, Yoon SK, Yang JM, Choi SW, Han NI, Kim DG. Role of long-term lamivudine treatment of hepatitis B virus recurrence after liver transplantation. J Med Virol 2008; 80(11): 1891-1899

46 Yasunaka T, Takaki A, Yagi T, Iwasaki Y, Sadamori H, Koike K, Hirohata S, Tatsukawa M, Kawai D, Shiraha H, Miyake Y, Ikeda F, Kobashi H, Matsuda H, Shinoura S, Yoshida R, Satoh D, Utsumi M, Onishi T, Yamamoto K. Serum hepatitis B virus DNA before liver transplantation correlates with HBV reinfection rate even under successful low-dose hepatitis B immunoglobulin prophylaxis. Hepatol Int 2011.

47 Yen RD, Bonatti H, Mendez J, Aranda-Michel J, Satyanarayana R, Dickson RC. Case report of lamivudine-resistant hepatitis B virus infection post liver transplantation from a hepatitis B core antibody donor. Am J Transplant 2006; 6(5 Pt 1): 1077-1183

48 Yilmaz N, Shiffman ML, Stravitz RT,Sterling RK, Luketic VA,Sanyal AJ, Maluf D, Coterell A, Posner MP, Fisher RA. Prophylaxsis against recurrance of hepatitis B virus after liver transplantation: a retrospective analysis spanning 20 years. Liver Int 2008; 28(1): 72-78

49 Wong SN, Chu CJ, Wai CT, Howell T, Moore C, Fontana RJ, Lok ASF. Low risk of hepatitis B virus recurrence after withdrawal of long-term hepatitis B immunoglobulin in patients receiving maintenance nucleos(t)ide analogue therapy. Liver Transpl 2007; 13(3): 374-381

50 Coffin CS, Terrault NA. Management of hepatitis B in liver transplant recipients. J Viral Hepat 2007; 14 Suppl 1: 37-44

51 Angus PW, McCaughan GW, Gane EJ, Crawford DHG, Harley H. Combination low-dose hepatitis B immune globulin and lamivudine therapy provides effective prophylaxis against posttransplantation hepatitis B. Liver Transpl 2000; 6(4): 429-433

52 Deeney HN, Dusheiko GM. Lamivudine combined with hepatitis B immunoglobulin in for prophylaxis of hepatitis B recurrence after liver transplantation: time for a change? Transpl Int 2009; 22(4): 385-386

53 Steinmuller T, Seehofer D, Rayes N, Müller AR, Settmacher U, Jonas S, Neuhaus R, Berg T, Hopf U, Neuhaus P. Increasing applicability of liver transplantation for patients with hepatitis B-related liver disease. Hepatology 2002; 35(6): 1528-1535

54 Vierling JM. Management of HBV Infection in Liver Transplantation Patients. Int J Med Sci 2005; 2(1): 41-49

55 Gane EJ, Patterson S, Strasser SI, McCaughan GW, Angus PW. Combination of lamivudine and adefovir without hepatitis B immune globulin is safe and effective prophylaxis against hepatitis B virus recurrence in hepatitis B surface antigen-positive liver transplant candidates. Liver Transpl 2013; 19(3): 268-274

56 Perrella A, Lanza AG, Santaniello W, Pisaniello D, DiCostanzo G, Calise F, Amato G, Marcos A, Cuomo O. Telbivudin as prophylaxis for hepatitis B virus recurrence after liver transplantation: a case series in single-center experience. Transplant Proc 2012; 44(7): 1986-1988

57 Teperman LW, Poordad F, Bzowej N, Martin P, Pungpapong S, Schiano T, Flaherty J, Dinh P, Rossi S, Subramanian GM, Spivey J. Randomized trial of emtricitabine/tenofovir disoproxil fumarate after hepatitis B immunoglobulin withdrawal after liver transplantation. Liver Transpl 2013; 19(6): 594-601

58 Pan JJ, Thosani N, Machicao VI, Fallon MB. Current use of hepatitis B immune globulin for prevention of de novo hepatitis B in recipients receiving anti-HBc-positive livers. Hepatol Int 2011; 5(2): 635-43

59 Dickson RC, Terrault NA, Ishitani M, Reddy KR, Sheiner P, Luketic V, Soldevila-Pico C, Fried M, Jensen D, Jr RSB, Horwith G, Brundage R, Lok A. Protective antibody levels and dose requirements for IV 5% Nabi Hepatitis B immune globulin combined with lamivudine in liver transplantation for hepatitis B-induced end stage liver disease. Liver Transpl 2006; 12(1): 124-133

60 Jiang L, Jiang LS, Cheng NS, Yan LN. Current prophylactic strategies against hepatitis B virus recurrence after liver transplantation. World J Gastroenterol 2009; 15(20): 2489-2499

61 Hellinger WC, Bonatti H, Yao JD, Alvarez S, Brumble LM, Keating MR, Mendez JC, Kramer DJ, Dickson RC, Harnois DM, Spivey JR, Hughes CB, Nguyen JH, Steers JL. Risk stratification and targeted antifungal prophylaxis for prevention of aspergillosis and other invasive mold infections after liver transplantation. Liver Transpl 2005; 11(6): 656-662

62 Marzano A, Gaia S, Ghisetti V, Carenzi S, Premoli A, Debernardi-Venon W, Alessandria C, Franchello A, Salizzoni M, Rizzetto M. Viral load at the time of liver transplantation and risk of hepatitis B virus recurrence. Liver Transpl 2005; 11(4): 402-409

63 Han YS, Lee SK, Joh JW, Kim SJ, Kwon CHD, Park JW, Kim DJ, Park JB. Outcomes of hepatitis B virus recurrence after liver transplantation. Transplant Proc 2006; 38(7): 2123-2124

64 Jiang L, Yan L, Wen T, Zhao J, Yang J, Xu M, Wnag W. Hepatitis B Prophylaxis Using Lamivudine and Individualized Low-dose Hepatitis B Immunoglobulin in Living Donor Liver Transplantation. Transplant Proc 2013; 45(6): 2326-2330

65 Lenci I, Marcuccilli F, Tisone G, Di Paolo D, Tariciotti L, Angelico M. Total and covalently closed circular DNA detection in liver tissue of long-term survivors transplanted for HBV-related cirrhosis. Dig Liver Dis 2010; 42(8): 578-584

66 Wursthorn K, Lutgehetmann M, Dandri M, Volz T, Buggisch P, Zollner B, Longerich T, Schirmacher P, Metzler F, Zankel M, Fischer C, Currie G, Brosgart C, Petersen J. Peginterferon alpha-2b plus adefovir induce strong cccDNA decline and HBsAg reduction in patients with chronic hepatitis B. Hepatology 2006; 44(3): 675-684

67 Le Guerhier F, Pichoud C, Guerret S, Chevallier M, Jamard C, Hantz O, Li XY, Chen SH, King I, Trepo C, Cheng YC, Zoulim F. Characterization of the antiviral effect of 2’,3’-dideoxy-2’, 3’-didehydro-beta-L-5-fluorocytidine in the duck hepatitis B virus infection model. Antimicrob Agents Chemother 2000; 44(1): 111-122

68 Mason AL, Xu L, Guo L, Kuhns M, Perrillo RP. Molecular basis for persistent hepatitis B virus infection in the liver after clearance of serum hepatitis B surface antigen. Hepatology 1998; 27(6): 1736-1742

69 Mommeja-Marin H, Mondou E, Blum MR, Rousseau F. Serum HBV DNA as a marker of efficacy during therapy for chronic HBV infection: analysis and review of the literature. Hepatology 2003; 37(6): 1309-1139

70 Müller R, Gubernatis G, Farle M, Niehoff G, Klein H, Wittekind C, Tusch G, Lautz HU, Böker K, Stangel W. Liver transplantation in HBs antigen (HBsAg) carriers. Prevention of hepatitis B virus (HBV) recurrence by passive immunization. J Hepatol 1991; 13(1): 90-96

71 Sung JJ, Wong ML, Liew CT, Hui AY, Wong VWS, Leung NW, Locarnini S, Chan HLY. Intrahepatic hepatitis B virus covalently closed circular DNA can be a predictor of sustained response to therapy. Gastroenterology 2005; 128(7): 1890-1897

72 Germer JJ, Charlton MR, Ishitani MB, Forehand CD, Patel R. Characterization of hepatitis B virus surface antigen and polymerase mutations in liver transplant recipients pre- and post-transplant. Am J Transplant 2003; 3(6): 743-537

73 Terrault NA, Zhou S, McCory RW, Pruett TL, Lake JR, Roberts JP, Ascher NL, Wright TL., Incidence and clinical consequences of surface and polymerase gene mutations in liver transplant recipients on hepatitis B immunoglobulin. Hepatology 1998; 28(2): 555-561

74 Mutimer D, Pillay D, Dragon E, Tang H, Ahmed M, O’Donnell K, Shaw J, Burroughs N, Rand D, Cane P, Martin B, Buchan S, Boxall E, Barmat S, Gutekunst K, McMaster P, Elias E. High pre-treatment serum hepatitis B virus titre predicts failure of lamivudine prophylaxis and graft re-infection after liver transplantation. J Hepatol 1999; 30(4): 715-721

75 Perrillo RP, Wright T, Rakela J, Levy G, Schiff E, Gish R, Martin P, Dienstag J, Adams P, Dickson R, Anschuetz G, Bell S, Condreay L, Brown N. A multicenter United States-Canadian trial to assess lamivudine monotherapy before and after liver transplantation for chronic hepatitis B. Hepatology 2001; 33(2): 424-432

76 Villet, S., Pichoud C, Villeneuve JP, Trepo C, Zoulim F. Selection of a multiple drug-resistant hepatitis B virus strain in a liver-transplanted patient. Gastroenterology 2006; 131(4): 1253-1261

77 Tillmann HL, Trautwein C, Bock T, Böker KH, Jaeckel E, Glowienka M, Oldhafer KJ, Bruns I, Gauthier J, Raab HR, Manns MP. Mutational pattern of hepatitis B virus on sequential therapy with famciclovir and lamivudine in patients with hepatitis B virus reinfection occurring under HBIg immunoglobulin after liver transplantation. Hepatology 1999; 30(1): 244-256

78 Chotiyaputta W, Shawn P, Robert F, Anna L. Long-term efficacy of nucleoside monotherapy in preventing HBV infection in HBsAg-negative recipients of anti-HBc-positive donor livers. Hepatol Int 2010; 4(4): 707-715

79 Fung J, Cheung C, Chan S, CYuen MF, Chok KS, Sharr W, Dai WC, Chan AC, Cheung TT, Tsang S, Lam B, Lai CL, Lo CM. Entecavir Monotherapy is Eeffective in Suppressing Hepatitis B Virus after Liver Transplantation. Gastroenterology 2011; 141(4): 1212-1219

80 Loomba R, Rowley K, Wesley R, Smith KG, Liang TJ, Pucino F, Csako G. Hepatitis B immunoglobulin and Lamivudine improve hepatitis B-related outcomes after liver transplantation: meta-analysis. Clin Gastroenterol Hepatol 2008; 6(6): 696-700

81 Roche B, Feray C, Gigou M, Roque-Afonso AM, Arulnaden JL, Delvart V, Dussaix E, Guettier C, Bismuth H, Samuel D. HBV DNA persistence 10 years after liver transplantation despite successful anti-HBS passive immunoprophylaxis. Hepatology 2003; 38(1): 86-95

82 Terrault N. Management of hepatitis B virus infection in liver transplant recipients: prospects and challenges. Clin Transplant 2000; 14 Suppl 2: 39-43

83 Paik YH, Kim JK, Kim DY, Park JY, Ahn SH, Han KH, Chon CY, Lee KS. Clinical efficacy of a 24-months course of lamivudine therapy in patients with HBeAg negative chronic hepatitis B: a long-term prospective study. J Korean Med Sci 2010; 25(6): 882-887

84 Wai CT, Lim SG, Tan KC. Outcome of lamivudine resistant hepatitis B virus infection in liver transplant recipients in Singapore. Gut 2001; 48(4): 581

85 Lu Y, Wang B, Yu L, Liu C, Wu Z, Pan CE. Lamivudine in prevention and treatment of recurrent HBV after liver transplantation. Hepatobiliary Pancreat Dis Int 2004; 3(4): 504-507

86 Honkoop P, Niesters HGM, de Man RA, Osterhaus AD, Schalm SW. Lamivudine resistance in immunocompetent chronic hepatitis B. Incidence and patterns. J Hepatol 1997; 26(6): 1393-1395

87 Schiff E, Lai CL, Hadziyannis S, Nuehaus P, Terrault N, Colombo M, Tillmann H, Samuel D, Zuezem S, Villenueve JP,Arteburn S, BorrotoEsoda K, Brosgart C, Chuck S, Shakil AO, Fung J, Alberti A, Lok A, Picciotto A, Torre F, Riely C, Trepo C, Bizollon T, BottaaFridlund D, Gerolami R, Douglas D, Ranjan D, Faust D, Trojan J, Gane E, Villa E, Boarino M, Sokal E, Starkel P, Bonino F, Maurizio B, Gordon F, Pratt J, Berr F, Schiefke I, McCaughan G, Strasser S, Dusheiko G, Pageaux GP, Larrey D, Pastore G, Santantonio T, Alexander G, Woodall T, Van Vlierberghe H, Colle I, Harley H, Guggenheim J, MyxStaccini A, Metreau JM, Mavier P, Vierling J, Tran T, Girgrah N, Nyberg L, Yuen MF, Ma M, Balnco MD, Merli M, Tanzilli P, Angelico M, Di Paolo D, Rizzetto M, Marzano A, Lampertico P, Prieto M, Berenguer M, Felder M, Sterneck M, Willems M, Charlton M, Gunneson T, Ritter M, Voight M, Swift J, Shiffman M, Tassopoulos N, Klissas I, Naourmov N, Chamouard P, Marcellin P, Durand F, Angus P, Nathan C, Toniutto P, Fumo E, Andreone P, Cursaro C, Barcena R, Hoz FG, Zachoval R, Christina M, De Man RA, Metselaar H. Adefovir dipivoxil for wait-listed and post-liver transplantation patients with lamivudine-resistant hepatitis B: final long-term results. Liver Transpl 2007; 13(3): 349-360

88 Genzini T, dos Santos RG, Pedrosa C, Lo LAC, Noujaim HM, Crescentini F, Mota LT, Guirro TG, Ferreira FY, Salomao P, Pereira JRB, de Miranda MP. Liver transplantation in bearers of hepatitis B associated or not with delta hepatitis in the age of the new antiviral drugs: is hyperimmune globulin still necessary? Transplant Proc 2010; 42(2): 496-497

89 Fung J, Chan SC, Cheung C, Yuen MF, Chok KSH, Sharr W, Chan ACY, Cheung TT, Seto WK, Fan ST, Lai CL, Lo CM. Oral nucleoside/nucleotide analogs without hepatitis B immune globulin after liver transplantation for hepatitis B. Am J Gastroenterol 2013; 108(6): 942-948

90 Wadhawan M, Gupta S, Goyal N, Taneja S, Kumar A. Living related liver Transplant in hepatitis B related liver disease without Hepatitis B Immunoglobulin prophylaxis. Liver Transpl 2013; 19(9)

91 Fung J, Cheung C, Chan SC, Yuen MF, Chok KSH, Sharr W, Dai WC, Chan ACY, Cheung TT, Tsang S, Lam B, Lai CL, Lo CM. Entecavir monotherapy is effective in suppressing hepatitis B virus after liver transplantation. Gastroenterology 2011 141(4): 1212-1219

92 Donataccio D, Roggen F, De Reyck C, Verbaandert C, Bodeus M, Lerut J. Use of anti-HBc positive allografts in adult liver transplantation: toward a safer way to expand the donor pool. Transpl Int 2006; 19(1): 38-43

93 Jimenez-Perez M, Saez-Gomez AB, Poce LM, Lozano-Rey JM, de la Cruz-Lombardo J, Rodrigo-Lopez JM. Efficacy and safety of entecavir and/or tenofovir for prophylaxis and treatment of hepatitis B recurrence post-liver transplant. Transplant Proc 2010; 42(8): 3167-3168

94 Schiff ER, Ching-Lung Lai, Stefanos Hadziyannis, Peter Neuhaus, Norah Terrault, Massimo Colombo, Hans L. Tillmann, Didier Samuel, Stefan Zeuzem, Leslie Lilly, Maria Rendina, Jean-Pierre Villeneuve, Nicole Lama, Craig James, Michael. Wulfsohn, Hamid Namini, Christopher Westland, Shelly Xiong, Gavin S. Choy, Sally Van Doren, John Fry, Carol L. Brosgart. Adefovir dipivoxil therapy for lamivudine-resistant hepatitis B in pre- and post-liver transplantation patients. Hepatology 2003; 38(6): 1419-1427

95 Xie SB, Zhu JY, Ying Z, Zeng LJ, Chao M, Lu MQ. Prevention and risk factors of the HBV recurrence after orthotopic liver transplantation: 160 cases follow-up study. Transplantation 2010; 90(7): 786-790

96 Perrakis A, Fortsch T, Del Medico A, Croner RS, Muller V. Liver transplantation for hepatitis B-induced liver disease: long-term outcome and effectiveness of antiviral therapy for prevention of recurrent hepatitis B infection. Transplant Proc 2013; 45(5): 1953-1956

97 Hwang S, Ahn CS, Song GW, Kim KH, Moon DB, Oh HB, Lim YS, Lee HC, Ha TY, Jung DH, Chung YH, Lee SG. Posttransplantation prophylaxis with primary high-dose hepatitis B immunoglobulin monotherapy and complementary preemptive antiviral add-on. Liver Transpl 2011; 17(4): 456-465

98 Hwang S, Lee SG, Ahn CS, Kim KH, Moon DB, Ha TY, Song GW, Jung DH, Park JI, Ryu JH, Lee HJ, Suh DJ, Lim YS. Prevention of hepatitis B recurrence after living donor liver transplantation: primary high-dose hepatitis B immunoglobulin monotherapy and rescue antiviral therapy. Liver Transpl 2008; 14(6): 770-778

99 Freshwater DA, Dudley T, Cane P, Mutimer DJ. Viral persistence after liver transplantation for hepatitis B virus: a cross-sectional study. Transplantation 2008; 85(8): 1105-1111

100 Xi ZF, Xia Q, Zhang JJ, Chen XS, Han LZ, Wang X, Shen CH, Luo Y, Xin TY, Wang SY, Qiu de K. The role of entecavir in preventing hepatitis B recurrence after liver transplantation. J Dig Dis 2009; 10(4): 321-327

101 McGonigal KH, Bajjoka IE, Abouljoud MS. Tenofovir-Emtricitabine Therapy for the Prevention of Hepatitis B Recurrence in Four Patients After Liver Transplantation. Pharmacotherapy Article first published online: 6 JUN 2013, DOI: 10.1002/phar.1306

102 Tanaka T, Benmousa A, Marquez M, Therapondos G, Renner EL, Lilly LB. The long-term efficacy of nucleos(t)ide analog plus a year of low-dose HBIG to prevent HBV recurrence post-liver transplantation. Clin Transplant 2012; 26(5): E561-9

103 Gao YJ, Zhang M, Jin B, Meng FP, Liu ZW, Su HB, Ma XM, Zhao JM, Li HW. A clinical-pathological analysis of hepatitis B virus recurrence after liver transplantation in Chinese patients. J Gastroenterol Hepatol 2014; 29(3): 554-560

104 Kim YK, Kim SH, Lee SD, Park SJ. Clinical outcomes and risk factors of hepatitis B virus recurrence in patients who received prophylaxis with entecavir and hepatitis B immunoglobulin following liver transplantation. Transplant Proc 2013; 45(8): 3052-3056

105 Varghese J, Reddy MS, Cherian T, Vijaya S, Jayanthi V, Rela M. Anti-HBs response to hepatitis B immunoglobulin prophylaxis in liver transplant recipients. Indian J Gastroenterol 2014; 33(3): 226-230

106 Avolio AW, Nure E. Liver transplantation for hepatitis B virus patients: long-term results of three therapeutic approaches. Transplant Proc 2008; 40(6): 1961-1964

107 Anderson RD, Chinnakotla S, Guo LS, Perrillo RP, Klintmalm GB, Davis GL. Intramuscular hepatitis B immunoglobulin (HBIG) and nucleosides for prevention of recurrent hepatitis B following liver transplantation: comparison with other HBIG regimens. Clin Transplant 2007. 21(4): p. 510-7.

108 Alonso I, HERREROS DE TEJADA A, MORENO J M, RUBIO E, LUCENA J L, DE LA REVILLA J, SANCHEZ TURRION V, GOMEZ A, LOPEZ J, CUERVAS-MONS V Effectiveness of low-dose intramuscular anti-VHB immune globulin in the prophylaxis of viral B hepatitis reinfection after liver transplantation: preliminary report. Transplant Proc 2003; 35(5): 1850-1851

109 Brock GN, Mostajabi F, Ferguson N, Carrubba CJ, Eng M, Buell JF, Marvin MR. Prophylaxis against de novo hepatitis B for liver transplantation utilizing hep B core (+) donors: does hepatitis B immunoglobulin provide a survival advantage? Transpl Int Article first published online: 15 MAR 2011. DOI: 10.1111/j.1432-2277.2011.01236.x

110 Marıia Buti, Antoni Mas, Martıin Prieto, Fernando Casafont, Antonio González, Manuel Miras, Jose-Ignacio Herrero, Rossendo Jardı, Eva Cruz de Castro, César Garcıa-Rey. A randomized study comparing lamivudine monotherapy after a short course of hepatitis B immune globulin (HBIg) and lamivudine with long-term lamivudine plus HBIg in the prevention of hepatitis B virus recurrence after liver transplantation. J Hepatol 2003; 38(6): 811-817

111 Ben-Ari Z, Yaffa Ashur, Nili Daudi, Hemda Shmilovitz-Wiess, Marius Brown, Jaqueline Sulkes, Athalia Klein, Eytan Mor, Ran Tur-Kaspa1 andDaniel Shouval. Genotype prevalence, viral load and outcome of hepatitis B virus precore mutant infection in stable patients and in patients after liver transplantation. Clin Transplant 2004; 18(4): 415-422

112 Chun J, Kim W, Kim BG, Lee KL, Suh KS, Yi NJ, Park KU, Kim YJ, Yoon JH, Lee HS. High viremia, prolonged Lamivudine therapy and recurrent hepatocellular carcinoma predict posttransplant hepatitis B recurrence. Am J Transplant 2010; 10(7): 1649-1659

113 Dodson SF, de Vera ME, Bonham CA, Geller DA, Rakela J, Fung JJ. Lamivudine after hepatitis B immune globulin is effective in preventing hepatitis B recurrence after liver transplantation. Liver Transpl 2000; 6(4): 434-439

114 Dehghani SM, Taghavi SA, Geramizadeh B, Nikeghbalian S, Derakhshan N, Malekpour A, Malek-Hosseini SA. Hepatitis B recurrence after liver transplantation: a single center experiences and review the literature. Hepat Mon 2013; 13(1): e6609

115 Dumortier J, Chevallier P, Scoazec JY, Berger F, Boillot O. Combined lamivudine and hepatitis B immunoglobulin for the prevention of hepatitis B recurrence after liver transplantation: long-term results. Am J Transplant 2003; 3(8): 999-1002

116 Degertekin B, Steven-Huy B. Han, Emmet B. Keeffe, Eugene R. Schiff, Velimir A. Luketic, Robert S. Brown, Jr., Sukru Emre, Consuelo Soldevila-Pico, K. Rajender Reddy, Michael B. Ishitani, Tram T. Tran, Timothy L. Pruett, Anna S. F. Lok, and the NIH HBV-OLT Study Group. Impact of virologic breakthrough and HBIG regimen on hepatitis B recurrence after liver transplantation. Am J Transplant 2010; 10(8): 1823-1833

117 Di Paolo D, Giuseppe T, Paola P, Ilaria L, Settimio Z, Mario A. Low-dose hepatitis B immunoglobulin given “on demand” in combination with lamivudine: a highly cost-effective approach to prevent recurrent hepatitis B virus infection in the long-term follow-up after liver transplantation. Transplantation 2004; 77(8): 1203-1208

118 Faust D, Rabenau HF, Allwinn R, Caspary WF, Zeuzem S. Cost-effective and safe ambulatory long-term immunoprophylaxis with intramuscular instead of intravenous hepatitis B immunoglobulin to prevent reinfection after orthotopic liver transplantation. Clin Transplant 2003; 17(3): 254-258

119 Fábrega E, García-Suarez C, Guerra A, Orive A, Casafont F, Crespo J, Pons-Romero F. Liver transplantation with allografts from hepatitis B core antibody-positive donors: a new approach. Liver Transpl 2003; 9(9): 916-920

120 Emilio Fábrega, Covadonga García-Suarez, Armando Guerra, Aitor Orive, Fernando Casafont, Javier Crespo andFernando Pons-Romero. Low-dose intramuscular hepatitis B immune globulin and lamivudine for long-term prophylaxis of hepatitis B recurrence after liver transplantation. Transplant Proc 2004; 36(3): 535-538

121 Filipponi F, Franchello A, Carrai P, Romagnoli R, De Simone P, Woodward MK, Páez A, Salizzoni M. Efficacy, safety, and pharmacokinetics of intramuscular hepatitis B immune globulin, Igantibe, for the prophylaxis of viral B hepatitis after liver transplantation. Dig Liver Dis 2010; 42(7): 509-514

122 Han SH, Martin P, Edelstein M. Hu R, Kunder G, Holt C, Saab S, Durazo F, Goldstein L, Farmer D, Ghobrial RM. Busuttil RW. Conversion from intravenous to intramuscular hepatitis B immune globulin in combination with lamivudine is safe and cost-effective in patients receiving long-term prophylaxis to prevent hepatitis B recurrence after liver transplantation. Liver Transpl 2003; 9(2): 182-187

123 Honaker MR, Shokouh-Amiri MH, Vera SR, Alloway RR, Grewal HP, Hardinger KL, Kizilisik AT, Bagous T, Trofe J, Stratta RJ, Egidi MF, Gaber AO. Evolving experience of hepatitis B virus prophylaxis in liver transplantation. Transpl Infect Dis 2002; 4(3): 137-143

124 Iacob, S., et al., Costs and efficacy of “on demand” low-dose immunoprophylaxis in HBV transplanted patients: experience in the Romanian program of liver transplantation. J Gastrointestin Liver Dis 2008; 17(4): 383-388

125 Jiang L, Yan L, Li B, Wen T, Zhao J, Jiang L, Cheng N, Wei Y, YangJ, Xu M, Wang W. Prophylaxis against hepatitis B recurrence posttransplantation using lamivudine and individualized low-dose hepatitis B immunoglobulin. Am J Transplant 2010; 10(8): 1861-1869

126 Jain A, Orloff M, Abt P, Kashyap R, Mohanka R, Lansing K, Kelley M, Bozorgzadeh A. Use of hepatitis B core antibody-positive liver allograft in hepatitis C virus-positive and -negative recipients with use of short course of hepatitis B immunoglobulin and Lamivudine. Transplant Proc 2005; 37(7): 3187-3189

127 Jiao ZY, Yan LN, Li B, Zeng Y, Wen TF, Lu SC, Zhao JC, Wang WT, Xu MQ, Yang JY, Li ZH, Ma YK, Zhang ZW, Chen ZY. Liver transplantation for chronic hepatitis B patients with lamivudine monotherapy or lamivudine combined with individualized low-dose hepatitis B immunoglobulin treatment. Zhonghua Gan Zang Bing Za Zhi 2007; 15(11): 804-808

128 Karademir S, Astarcioğlu H, Akarsu M, Ozkardesler S, Ozzeybek D, Sayiner A, Akan M, Tankurt E, Astarcioğlu I. Prophylactic use of low-dose, on-demand, intramuscular hepatitis B immunoglobulin and lamivudine after liver transplantation. Transplant Proc 2006; 38(2): 579-583

129 Kwon CH, Suh KS, Cho JY, Yi NJ, Jang JJ, Lee KU. Change of hepatitis B virus DNA status in anti-HBc positive liver graft. Korean J Hepatol 2006; 12(2): 191-200

130 Lee SK, Park JH, Joh JW, Kim SJ, Choi IS, Choi SH. Prophylaxis against hepatitis B recurrence following liver transplantation in HBs Ag(+) patients. Transplant Proc 2000; 32(7): 2248-2249

131 Lee KW, Lee DS, Lee HH, Kim SJ, Joh JW, Seo JM, Choe YH, Lee SK. Prevention of de novo hepatitis B infection from HbcAb-positive donors in living donor liver transplantation. Transplant Proc 2004; 36(8): 2311-2312

132 Loss GE Jr, Mason AL, Nair S, Blazek J, Farr G, Guo L, Cohen AJ, Eason JD. Does lamivudine prophylaxis eradicate persistent HBV DNA from allografts derived from anti-HBc-positive donors? Liver Transpl 2003; 9(12): 1258-1264

133 Manzarbeitia C, Reich DJ, Ortiz JA, Rothstein KD, Araya VR, Munoz SJ. Safe use of livers from donors with positive hepatitis B core antibody. Liver Transpl 2002; 8(6): 556-61.

134 Park SJ, Paik SW, Choi MS, Lee JH, Koh KC, Kim SJ, Joh JW, Lee SK. Is lamivudine with 1-week HBlg as effective as long-term high-dose HBlg in HBV prophylaxis after liver transplantation? Transplant Proc 2002; 34(4): 1252-1254

135 Prakoso E, Strasser SI, Koorey DJ, Verran D, McCaughan GW. Long-term lamivudine monotherapy prevents development of hepatitis B virus infection in hepatitis B surface-antigen negative liver transplant recipients from hepatitis B core-antibody-positive donors. Clin Transplant 2006; 20(3): 369-373

136 Roque-Afonso AM, Feray C, Samuel D, Simoneau D, Roche B, Emile JF, Gigou M, Shouva D, Dussaix E. Antibodies to hepatitis B surface antigen prevent viral reactivation in recipients of liver grafts from anti-HBC positive donors. Gut 2002; 50(1): 95-99

137 Jens Rosenau, Matthias J. Bahr, Hans L. Tillmann, Christian Trautwein, Jürgen Klempnauer, Michael P. Manns, Klaus H. W. Böker. Lamivudine and low-dose hepatitis B immune globulin for prophylaxis of hepatitis B reinfection after liver transplantation possible role of mutations in the YMDD motif prior to transplantation as a risk factor for reinfection. J Hepatol 2001; 34(6): 895-902

138 Seehofer D, Rayes N, Steinmüller T, Müller AR, Jonas S, Settmacher U, Neuhaus R, Berg T, Neuhaus P. Combination prophylaxis with Hepatitis B immunoglobulin and lamivudine after liver transplantation minimizes HBV recurrence rates unless evolution of pretransplant lamivudine resistance. Z Gastroenterol 2002; 40(9): 795-799

139 Sousa JM, Pareja F, Serrano J, Gómez MA, García I, Tamayo MJ, Díaz C, Martín C, Pascasio JM, Hinojosa R, Pérez-Bernal JB, Cañas E, Sayago M, Bernardos A. Comparison between levels of anti-HBS with a fixed administration dose of HBIG and a combination of HBIG and lamivudine for the prophylaxis of hepatitis B after liver transplantation. Transplant Proc 2003; 35(2): 723-724

140 Yasuhiko Sugawara, Masatoshi Makuuchi, Junichi Kaneko, Nobuhisa Akamatsu, Hiroshi Imamura andNorihiro Kokudo. Living donor liver transplantation for hepatitis B cirrhosis. Liver Transpl 2003; 9(11): 1181-1184

141 Yi NJ, Suh KS, Cho JY, Kwon CH, Lee KW, Joh JW, Lee SK, Kim SI, Lee KU. Recurrence of hepatitis B is associated with cumulative corticosteroid dose and chemotherapy against hepatocellular carcinoma recurrence after liver transplantation. Liver Transpl 2007; 13(3): 451-458

142 Mao-Lin Yan, Lu-Nan Yan, Bo Li, Yong Zeng, Tian-Fu Wen, Wen-Tao Wang, Jia-Yin Yang, Ming-Qing Xu, Zhi-Hui Li, Yong-Bing Chen. Intramuscular hepatitis B immune globulin combined with lamivudine in prevention of hepatitis B recurrence after liver transplantation. Hepatobiliary Pancreat Dis Int 2006; 5(3): 360-363

143 YANG Yang, ZHANG Qi, CAI Chang-jie, LU Ming-qiang, LI Xi, JIANG Nan, JIANG Hua, XU Chi, LI Hua, WANG Gen-shu, YI Shu-hong, ZHANG Jian, ZHANG Jun-feng, YI Hui-min, ZHANG Ying-cai. Prophylaxis of hepatitis B recurrence in post-liver transplantation patients with lamivudine-resistant YMDD mutant. Chin Med J (Engl) 2007; 120(16): 1400-1403

144 Andy S. Yu, John M. Vierling, Steven D. Colquhoun, Walid S. Arnaout, Chuek-Kee Chan, Elham Khanafshar, Stephen A. Geller, W. Stephen Nichols, Tse-Ling Fong. Transmission of hepatitis B infection from hepatitis B core antibody--positive liver allografts is prevented by lamivudine therapy. Liver Transpl 2001; 7(6): 513-517

145 Yuefeng M, Weili F, Wengxiang T, Ligang X, Guiling L, Hongwei G, Wencai L, Xiaoguang W, Wei M, Zhongyi F. Long-term outcome of patients with lamivudine after early cessation of hepatitis B immunoglobulin for prevention of recurrent hepatitis B following liver transplantation. Clin Transplant Article first published online: 15 JUN 2010; DOI: 10.1111/j.1399-0012.2010.01290.x

146 Zhu JP, Zhang TL, Li L, Yuan J, Song SB, Xiu DR, Hou KY, Li T, Zhuang H. Prevention and treatment of hepatitis B recurrence after liver transplantation. Hepatobiliary Pancreat Dis Int 2003; 2(4): 500-503

147 Cai CJ, L, MQ, Chen YH, Zhao H, Li MR, Chen GH. Clinical study on prevention of HBV re-infection by entecavir after liver transplantation. Clin Transplant 2012; 26(2): 208-215

148 Hu TH, Chen CL, Wang CC, Chiu KW, Eng HL, Cheng YF, Pre-transplant HBV viral resistance is not a risk factor for HBV recurrence after liver transplantation. Liver Transpl 2012; 18(Suppl. 1): 1

149 Masatoshi Ishigami, Yasuharu Onishi, Takashi Ito, Yoshiaki Katano, Akihiro Ito, Yoshiki Hirooka, Tetsuya Kiuchi, Hidemi Goto. Anti-hepatitis B surface immunoglobulin reduction in early postoperative period after liver transplantation in hepatitis B virus-positive patients. Hepatol Res 2011; 41(12): 1189-1198

150 Robert Perrillo, Maria Buti, Francois Durand, Michael Charlton, Adrian Gadano, Guido Cantisani, Che-Chuan Loong, Kimberly Brown, Wenhua Hu, Juan Carlos Lopez-Talavera, Cyril Llamoso. Entecavir and HBIg in patients receiving liver transplant for chronic hepatitis B. Liver Transpl 2013; 19(8). DOI: 10.1002/lt.23690

151 Yoshihide Ueda, Hiroyuki Marusawa, Toshimi Kaido, Yasuhiro Ogura, Kohei Ogawa, Atsushi Yoshizawa, Koichiro Hata, Yasuhiro Fujimoto, Norihiro Nishijima, Tsutomu Chiba, Shinji Uemoto. Efficacy and safety of prophylaxis with entecavir and hepatitis B immunoglobulin in preventing hepatitis B recurrence after living-donor liver transplantation. Hepatol Res 2013; 43(1): 67-71

152 Holt D, Thomas R, Van Thiel D, Brems JJ. Use of hepatitis B core antibody-positive donors in orthotopic liver transplantation. Arch Surg 2002; 137(5): 572-575; discussion 575-576

Peer reviewers: Jinyang Gu, PhD, Department of Hepatobiliary Surgery, Affiliated DrumTower Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, 210008, China; Nermine A Ehsan, Professor, Department of pathology, National Liver Institute, Menoufiya University, Shebin ElKom, Menoufiya, Egypt.


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