Recurrent Hepatitis B Virus Infection Research Articles

Prevention of HBV Recurrence After Liver Transplant: Long-Term Results

Antiviral therapy with or without hepatitis B immune globulin (HBIG) is a common strategy for the prevention of hepatitis B virus (HBV) reinfection. But there is no consensus on management protocols, and long-term data are relatively rare on recurrence of HBV infection after liver transplantation using a nucleoside analogue and HBIG prophylaxis. We performed 56 liver transplants since June 2006. Among them, 32 liver recipients had liver cirrhosis associated with HBV, 9 with hepatocellular carcinoma (HCC), and 23 without HCC. Three operative mortalities, 3 deaths within 1 year related to infection, and 1 follow-up loss less than 1 year were excluded from analysis. We analyzed 25 liver transplants retrospectively. We prevented HBV reinfection with entecavir or tenofovir lifelongwith 7 days of daily intravenous HBIG, 10,000 units, including operative day, and then once a week for the next 3 weeks, and then once a month for 1 year. Afterward, 4000 or 6000 units every 2 or 3 months were given to maintain patients' serum hepatitis B antibody titer >200 mIU/mL. Mean follow-up period for HBV reinfection was 120.3 months. No patients have had reinfection. Lifelong HBIG and nucleoside is an excellent prevention strategy for HBV reinfection after liver transplant.

An Overview of the Current Hepatitis B Treatment Strategies after Liver Transplantation.

Currently, liver transplantation (LT) is considered as the only option for the treatment of patients with various causes of liver failure, including patients with chronic hepatitis B virus (HBV) infections. Overall, patients with HBV who undergo LT are at increased risk of hepatitis B infection recurrence. Although the current knowledge regarding the pathophysiology of this infection has been dramatically increased over the past few decades, it is still considered a complex disease process with varying degrees of clinical characteristics and changing patterns over time. There are various treatment strategies for preventing HBV recurrence in the LT setting. Generally, these regimens include oral nucleoside/ nucleotide analogues (NAs), hepatitis B immune globulin (HBIG), and vaccines or the combination of these drugs. The treatment strategy of choice should be based on cost-effectiveness, along with other patients underlying conditions. In this case, studies indicate that potent NAs are more cost-effective than HBIG in most case scenarios. In this article, we aimed to review the general medications used in the prophylaxis of the recurrence of HBV infection after LT.

HEPATITIS B IMMUNOGLOBULIN PROPHYLAXIS FOR PREVENTION OF DE NOVO HEPATITIS B INFECTION FROM HEPATITIS B CORE ANTIBODY-POSITIVE DONORS

Introduction: Recently, hepatitis B core antibody (anti-HBc) positive liver grafts are used as extended criteria donor organs. However, prophylaxis methods to prevent de novo hepatitis B virus (HBV) infection after liver transplantation (LT) are still controversial. Thus, the purpose of our study is to evaluate the risk and outcomes of receiving anti-HBc positive grafts with prophylactic HBIG monotherapy. Method: All adult patients who underwent LT at Samsung Medical Center in Seoul, Korea, between January 2001 and December 2018 were gathered from a prospectively maintained database and reviewed retrospectively. HBV patients received the combination treatments with antiviral prophylaxis and hepatitis B immunoglobulin (HBIG). Prophylactic HBIG monotherapy was given for patients without HBV receiving grafts from anti-HBc positive donors. Results: A total of 1355 patients underwent LT during this period. Among them, 457 (33.7%) were anti-HBc positive and 898 (66.3%) were anti-HBc negative donors, who underwent follow-up for a median time of 5.7 years. Perioperative outcomes (mortality in 30 days, complications and postoperative ICU stay period) were similar between the two groups. Also, there were no significant difference in the 1-, 5-, 10- and 15-year patient survival rates between the anti-HBc positive (87.5%, 73.5%, 67.7% and 61.2%) and the anti-HBc negative groups (88.5%, 77.7%, 70.7% and 69.6%, p = 0.080). All of the 117 recipients who were HBsAg negative and received anti-HBc positive grafts were given prophylactic HBIG monotherapy. Only one patient (0.9%, 1/117) developed de novo HBV during follow-up. There were 972 HBsAg-positive patients and 348 (35.8%) received anti-HBc positive grafts. The risk of HBV recurrence was similar between 2 groups (p = 0.308). The donor anti-HBc status did not have a significant influence on the long-term survival or the risk of de novo or recurrent HBV infection after LT.Conclusion: De novo HBV was very rare especially with HBIG prophylaxis in non-HBV patients received anti-HBc positive liver graft. There was no significant influence of anti-HBc positive grafts on the perioperative and long-term outcomes after LT.

Current and Potential Future Chemopreventive Strategies Against Hepatitis B Virus Reinfection in Liver Transplant Recipients

Although the availability of effective oral therapies for hepatitis B virus (HBV) infection has reduced the need for liver transplantation (LT) for decompensated cirrhosis due to chronic infection, HBV remains an important cause of hepatocellular carcinoma and acute liver failure. Recurrent HBV infection occurs almost invariably post-LT in the absence of prophylaxis if viremia was detectable pre-LT, so prophylaxis remains necessary to prevent graft reinfection. Current approaches include the use of nucleos(t)ide analogues pre- and post-LT and hepatitis B immune globulin, but several novel antiviral agents are currently under investigation in non-transplant populations and may potentially prove to be useful in the LT setting in the future.

Prevention and Treatment of Recurrent Hepatitis B after Liver Transplantation.

Chronic hepatitis B is a global health problem that leads to development of various complications, such as cirrhosis, liver cancer, and liver failure requiring liver transplantation. The recurrence of hepatitis B virus (HBV) post-liver transplantation is a major cause of allograft dysfunction, cirrhosis of the allograft, and graft failure. Patients with high viral load at the time of transplantation, hepatitis B e antigen (HBeAg) positivity, or those with a history of anti-viral drug resistance are considered as high-risk for recurrent HBV post-liver transplantation, while patients with low viral load, including HBeAg negative status, acute liver failure, and hepatitis D virus (HDV) co-infection are considered to be at low-risk for recurrent HBV post-liver transplantation. Antivirals for patients awaiting liver transplantation(LT) cause suppression of HBV replication and reduce the risk of recurrent HBV infection of the allograft and, therefore, all HBV patients with decompensated cirrhosis should be treated with potent antivirals with high genetic barrier to resistance (entecavir or tenofovir) prior to liver transplantation. Prevention of post-liver transplantation recurrence should be done using a combination of hepatitis B immunoglobulin (HBIG) and antivirals in patients at high risk of recurrence. Low dose HBIG, HBIG-free protocols, and monoprophylaxis with high potency antivirals can still be considered in patients at low risk of recurrence. Even, marginal grafts from anti-HBc positive donors can be safely used in hepatitis B surface antigen (HBsAg) negative, preferably in anti-hepatitis B core (HBc)/anti-hepatitis B surface (HBs) positive recipients. In this article, we aim to review the mechanisms and risk factors of HBV recurrence post-LT in addition to the various treatment strategies proposed for the prevention of recurrent HBV infection

Prophylactic managements of hepatitis B viral infection in liver transplantation.

Liver transplantation (LT) is a considerably effective treatment for patients with end-stage hepatitis B virus (HBV)-related liver disease. However, HBV infection often recurs after LT without prophylaxis. Since the 1990s, the treatment for preventing HBV reinfection after LT has greatly progressed with the introduction of hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogues (NAs), resulting in improved patient survival. The combination therapy consisting of high-dose HBIG and lamivudine is highly efficacious for preventing the recurrence of HBV infection after LT and became the standard prophylaxis for HBV recurrence. However, mainly due to the high cost of HBIG treatment, an alternative protocol for reducing the dose and duration of HBIG has been evaluated. Currently, combination therapy using low-dose HBIG and NAs is considered as the most efficacious and cost-effective prophylaxis for post-LT HBV reinfection. Recently, NA monotherapy and withdrawal of HBIG from combination therapy, along with the development of new, potent high genetic barrier NAs, have provided promising efficacy, especially for low-risk recipients. This review summarizes the prophylactic protocol and their efficacy including prophylaxis of de novo HBV infection from anti-HBc antibody-positive donors. In addition, challenging approaches such as discontinuation of all prophylaxis and active immunity through hepatitis B vaccination are discussed.

Epidemiological analysis of serological markers of hepatitis B in HIV+ patients from Curitiba and metropolitan region

Introduction: The presence of hepatitis B virus (HBV) in patients infected by the human immunodeficiency virus (HIV) leads to a higher incidence of liver disorders due to persistence and recurrence of HBV infection in addition to increased morbidity and mortality. Objective: To determine the prevalence of serological markers for hepatitis B in patients infected by HIV followed at Hospital de Clinicas da Universidade Federal do Parana (HC-UFPR). Methods: The clinical and epidemiological data were collected through a questionnaire applied to the patients, as well as a retrospective analysis of medical records. Serum levels of total hepatitis B core antibody (anti-HBc) and surface antigen of the hepatitis B virus (HBsAg) were evaluated through chemiluminescent microparticle immunoassay. Among the 297 HIV+ patients, 49.8% were seropositive only for anti-HBc, and 2.6 % were positive for both markers. Results and discussion: The prevalence of hepatitis B markers was significantly associated with HIV infection when compared with the prevalence observed in the general population from the same geographical area (anti-HBc+ HBsAg+: 0.14% vs. 2.6%, OR: 18.82, 95% CI 2.34-151.19, p = 0.00052). Concerning the associated risks to acquire HIV/HBV infection, 44.87% of the patients reported having been infected through sexual contact. A total of 16.66% HIV/HBV positive patients were in the age group 18-30 years, 62.82% were between 31-50 years and 16.66% were over 60 years old. Conclusion: The findings of the present study corroborate the need to investigate systematically the presence of markers for HBV in HIV+ patients from different regions of the country.

Prophylaxis against Recurrence in Liver Transplantation Patients with Hepatitis B Virus: What is New?

Hepatitis B virus (HBV) causes an endemic infection that affects nearly 2 billion patients worldwide. It is one of the leading causes of liver cirrhosis, hepatocellular carcinoma (HCC), and liver transplantation (LT). Recurrence of HBV infection after LT is due to specific HBV-host genome interactions. Although hepatitis B immunoglobulin treatment constituted the backbone of HBV recurrence, use of the nucleoside and nucleotide analogs (especially the ones with a higher genetic barrier to resistance), either alone or in combination, offer us new and powerful options in overcoming this serious issue.

Clinical pathology of recurrent hepatitis B after liver transplantation

To investigate the clinical pathology of recurrent hepatitis B after orthotopic liver transplantation (OLT). The clinical manifestation and hepatic pathological characteristics of 12 patients with recurrent hepatitis B after OLT were examined in this study by using hematoxylin and eosin staining,immunochemical staining of hepatitis B surface antigen and hepatitis B core antigen,tissue in situ hybridization of hepatitis B virus (HBV) DNA, and Mallory's trichrome staining.The survival rate of these OLT patients was assessed by Kaplan-Meier analysis. The early stage of recurrent HBV infection in patients with OLT was characterized by active HBV replication and mild-to-moderate inflammation in the liver. Three of the 12 patients who were treated with combination therapy group were carriers of YMDD mutants and all three showed improvement in liver function and hepatic histology after receiving adefovir dipivoxil,instead of lamivudine,in the early stage of recurrent hepatitis B after OLT. Among the patients treated with lamivudine monotherapy, four did not achieve improvement at the early stage of recurrent hepatitis B and developed fibrosing cholestatic hepatitis (FCH). Recurrent hepatitis B in patients who underwent OLT was characterized by mild-to-moderate viral hepatitis at the early stage and FCH at the later stage. Effective antiviral intervention at the early stage may reverse recurrent hepatitis B and prevent the disease progression to fatal FCH.

Clinical significance of hepatitis B virus S gene mutation for recurrence of hepatitis B after liver transplantation

To examine the incidence of hepatitis B virus (HBV) S gene mutation in recipients with recurrent HBV infection after liver transplantation (LT) and to evaluate the clinical significance of these mutants. Two-hundred-and-ninety-nine patients who received LT for HBV-related liver diseases in single centre were enrolled in the study and followed up. Serum HBV DNA was amplified by fluorescence quantitative polymerase chain reaction, and HBV-S gene mutation was detected by Sanger's enzymatic method. Twelve of the 299 patients developed recurrent HBV after LT, and 2 of these 12 carried a mutant of the HBV-S gene (incidence rate of 16.67%). One of the patients had T126I and G145A mutations, and the other had a M 133L mutation. Cox regression modelling identified the risk factors of HBV recurrence after LT as HBV-YMDD mutants (P =0.01), HBV-S mutants (P =0.03) and compliance decrease (P =0.03). HBV-S mutants may contribute to recurrence of HBV after LT, and the mechanism should be addressed in future studies.

Tratamiento de la reactivación del virus de la hepatitis B en el trasplante

The indication for liver transplantation for those with hepatitis B virus (HBV) infection represents some 5%–10%, with a declining trend, due in large measure to the efficacy of antiviral drugs. Similarly, the use of nucleoside/nucleotide analogues, with or without specific gamma globulin, has helped prevent HBV infection recurrence. The posttransplantation recurrence of HBV infection can be defined as the reappearance of circulating HBsAg and HBV DNA detectable in 2 measurements. Treatment is based on the use of nucleoside/nucleotide analogues, as with patients who have not been transplanted, and is based on the same principles. Profound immunosuppression of patients with liver transplants causes the HBV DNA levels to be very high and requires rapid and effective viral replication suppression. Entecavir and tenofovir are the first-line treatments. Tenofovir is effective for treatment-naïve patients and those with lamivudine-resistance. Entecavir is highly effective for treatment-naïve patients but should be restricted in cases of prior treatment with lamivudine.

Hepatitis B and liver transplantation: molecular and clinical features that influence recurrence and outcome.

Hepatitis B virus (HBV) continues to be a major cause of morbidity and mortality worldwide. It is estimated that about 350 million people throughout the world are chronically infected with HBV. Some of these people will develop hepatic cirrhosis with decompensation and/or hepatocellular carcinoma. For such patients, liver transplantation may be the only hope for cure or real improvement in quality and quantity of life. Formerly, due to rapidity of recurrence of HBV infection after liver transplantation, usually rapidly progressive, liver transplantation was considered to be contraindicated. This changed dramatically following the demonstration that hepatitis B immune globulin (HBIG), could prevent recurrent HBV infection. HBIG has been the standard of care for the past two decades or so. Recently, with the advent of highly active inhibitors of the ribose nucleic acid polymerase of HBV (entecavir, tenofovir), there has been growing evidence that HBIG needs to be given for shorter lengths of time; indeed, it may no longer be necessary at all. In this review, we describe genetic variants of HBV and past, present, and future prophylaxis of HBV infection during and after liver transplantation. We have reviewed the extant medical literature on the subject of infection with the HBV, placing particular emphasis upon the prevention and treatment of recurrent HBV during and after liver transplantation. For the review, we searched PubMed for all papers on the subject of "hepatitis B virus AND liver transplantation". We describe some of the more clinically relevant and important genetic variations in the HBV. We also describe current practices at our medical centers, provide a summary and analysis of comparative costs for alternative strategies for prevention of recurrent HBV, and pose important still unanswered questions that are in need of answers during the next decade or two. We conclude that it is now rational and cost-effective to decrease and, perhaps, cease altogether, the routine use of HBIG during and following liver transplantation for HBV infection. Here we propose an individualized prophylaxis regimen, based on an integrated approach and risk-assessment.

One Year of Hepatitis B Immunoglobulin Plus Tenofovir Therapy is Safe and Effective in Preventing Recurrent Hepatitis B Infection Post-Liver Transplantation

Hepatitis B immunoglobulin (HBIG) given in combination with a nucleos(t)ide analogue has reduced the rate of recurrent hepatitis B virus (HBV) infection following liver transplantation (LT); however, the most effective protocol remains unclear. To evaluate the use of tenofovir disoproxil fumarate (TDF) in combination with one year of low-dose HBIG. Twenty-four adults who underwent LT for HBV-related liver disease at the University Health Network (Toronto, Ontario) and received TDF (± lamivudine) and one year of HBIG to prevent recurrent HBV infection from June 2005 to June 2011 were evaluated. The median length of follow-up post-LT was 29.1 months. Three patients died during the follow-up period. Patient survival was 100% and 84.1% at one and five years, respectively. None of the patients developed recurrent HBV infection. No significant adverse event was observed due to TDF administration; renal function pre- and post-LT were also acceptably preserved. The present study demonstrated that a short, finite course of low-dose HBIG combined with maintenance of long-term TDF staring before LT is cost-effective and safe. However, further prospective study involving a larger patient cohort with a longer follow-up period is required to confirm the results.

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

Without effective prophylaxis, liver transplantation for hepatitis B virus (HBV)-related liver disease is frequently complicated by severe and rapidly progressive HBV recurrence. Combination prophylaxis with hepatitis B immune globulin (HBIG) and lamivudine (LAM) reduces long-term recurrence rates below 10%; however, HBIG is costly and inconvenient to administer. We, therefore, conducted a multicenter, prospective study of outcomes with an HBIG-sparing regimen of LAM plus adefovir dipivoxil (ADV) initiated at the time of listing for liver transplantation and continued after transplantation. Twenty-six patients were recruited into this study at the time of listing for transplantation, and 20 subsequently underwent transplantation. Twelve of the 26 patients had LAM exposure before the study baseline, but none had LAM resistance. The median HBV viral load before the institution of antiviral therapy was approximately 4.0 log(10) IU/mL (range=2.3-7.5 log(10) IU/mL). To the 20 patients who underwent transplantation, 800 IU of intramuscular HBIG was given immediately after transplantation and daily for 7 days only (total HBIG dose=6400 IU). All transplant patients remained alive without HBV recurrence (they were negative for hepatitis B surface antigen, and HBV DNA was undetectable) after a median follow-up of 57 months after transplantation (range=27-83 months). The median serum creatinine level in these patients rose from 81 to 119 μmol/L over the course of the study. No patient required dose reduction or cessation. After the completion of this prospective study, the regimen was modified so that no perioperative HBIG was administered if the pretransplant serum HBV DNA level was suppressed below 3 log(10) IU/mL. Another 28 patients with HBV-related liver disease underwent transplantation (18 without HBIG). All remained alive and well without HBV recurrence after a median follow-up of 22 months after transplantation (range=10-58 months). In conclusion, a combination of LAM and ADV initiated at the time of wait listing provides safe and effective protection against recurrent HBV infection without the high costs and inconvenience associated with long-term HBIG therapy.

Viral Hepatitis in Liver Transplantation

Liver transplantation is the only alternative for patients with end-stage liver disease. Viral hepatitis B and C are among the most common causes of cirrhosis and hepatocellular carcinoma and a frequent indication for liver transplantation. Hepatitis B virus immunoglobulin and nucleot(s)ide analogues have facilitated the management of patients with hepatitis B who have received liver transplants and resulted in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Current therapeutic approaches are far from optimal, because sustained virologic responses are only achieved in one-third of treated patients, and adverse effects are common and severe. However, the rapid development of direct-acting antivirals against hepatitis C virus will change the management of this disease and in a few years prevent graft infection with this virus.

Management of Patients with Chronic Hepatitis B Before and After Liver Transplantation: An Update

The use of newer and more potent antiviral agents against hepatitis B virus (HBV) results in greater viral suppression; however, liver transplantation is still required for complications of HBV infection. Post-transplant outcomes for HBV-related disorders are currently comparable to or slightly better than for other indications for liver transplantation in adults in the United States. In the absence of prophylactic antiviral therapy, recurrent HBV infection occurs invariably in patients with detectable serum HBV-deoxyribonucleic acid (DNA) at the time of transplantation, leading to poorer outcomes with severe graft injury, reduced patient and allograft survival. Therefore, anti-HBV therapy is indicated in all patients with detectable serum HBV-DNA pre-transplantation and prophylactic therapy to prevent recurrent HBV infection is standard-of-care. This review summarizes available evidence for the use of different antiviral agents before liver transplantation, the effectiveness of prophylactic agents in preventing recurrent HBV infection post-liver transplantation, and the efficacy of several regimens for treating recurrent HBV infection post-liver transplantation.

Long-Term Recurrence-Free Survival After Liver Transplantation from an ABO-Incompatible Living Donor for Treatment of Hepatocellular Carcinoma Exceeding Milano Criteria in a Patient With Hepatitis B Virus Cirrhosis: A Case Report

The early results of liver transplantations (OLT) in patients with advanced hepatocellular carcinoma (HCC) were poor because of frequent tumor recurrence. However, OLT has significant, theoretical advantage that it removes both the tumor and the organ that is at a risk of malignancy. The Japanese law on organ transplantation limited the availability of cadaveric liver donors until its revision on July 17, 2011. ABO-incompatible OLT was formerly contraindicated because performed anti-A/B antibodies on recipient endothelial cells raised the risk of antibody-mediated humoral graft rejection. We have herein described four successful cases of steroid withdrawal among adult patients who underwent living donor OLT from ABO-incompatible donors. In addition, we transplanted a liver from a living donor into an ABO-incompatible recipient on August 9, 2004. The 55-year-old man with HCC due to hepatitis B virus (HBV) a cirrhosis had a Child-Pugh score of C, and Model for End-stage Liver Disease score of 22. Two tumors greater than 5 cm, exceeded the Milan criteria. His des-gamma-carboxy prothrombin level was 6 mAu/mL, and alpha-fetoprotein, 18.78 ng/mL. Antirejection therapy included multiple perioperative plasmaphereses and splenectomy; with an immunosuppressive regimen consisting of tacrolimus, methylprednisolone, and mycophenolate mofetil. The maintenance dose of immunosuppression did not differ from that of ABO-identical cases. After transplantation, we used intrahepatic arterial infusion therapy with prostaglandin E1 (PG E1). The patient had complications of portal vein thrombosis, hepatic artery thrombosis, and acute myocardial infarction, which were treated by interventional radiology in the posttransplantation period. We controlled the HBsAb titer by administering hepatitis B immunoglobulin and lamivudine (200 IU/L doses) for 1 year after OLT and 100 IU/L doses thereafter. As a result, the patient achieved long-term, disease-free graft survival without steroids. He currently has good liver function and leads a normal lifestyle. Our results suggested the feasibility of controlling antibody-mediated humoral rejection and other complications in living donor liver transplantations into ABO-incompatible adults via intrahepatic arterial PG E1 infusion splenectomy, and plasmapheresis with regular immunosuppression. Withdrawal of steroids, HBV vaccination, and lamivudine, an nucleoside analog reverse transcriptase inhibitor, have achieved long-term (7 years) survival without recurrent HBV infection or tumor.

The option of HBIG-free prophylaxis against recurrent HBV

Since the early 1990's, hepatitis B immune globulin (HBIG) has been central to the prevention of hepatitis B virus (HBV) recurrence after liver transplantation. When used in combination with oral nucleos(t)ide analogues, HBIG prevents reinfection with HBV in ⩾90% of transplant recipients. While HBIG is highly efficacious, its use is undermined by its high cost. Because of this limitation, there have been many studies of alternative regimens seeking to minimize the dose or duration of HBIG without sacrificing low HBV recurrence rates. Toward that goal, lower dose intramuscular HBIG in combination with oral nucleos(t)ide analogues has been shown to be highly efficacious in preventing disease recurrence and represents a significant cost savings when compared with high dose intravenous administration. The withdrawal of HBIG after a defined course of combination HBIG and oral antivirals has also been shown to be effective, particularly if combination antiviral therapy is used. The ability to achieve undetectable HBV DNA levels pre-transplantation in the majority of patients may contribute to the high efficacy of these HBIG "light" regimens. Additionally, the success of antiviral rescue therapy for those patients who fail prophylaxis and develop recurrent HBV infection post-transplant has provided the impetus to move increasingly towards HBIG-free approaches. New techniques to detect occult HBV in hepatic and extrahepatic sites may allow clinicians to define a subgroup of patients in whom withdrawal of HBIG or all prophylaxis may be applicable.

The role of HBIg as hepatitis B reinfection prophylaxis following liver transplantation

Without adequate prophylaxis, liver transplantation (LTx) is frequently followed by hepatitis B virus (HBV) reinfection, which results in rapidly progressing liver disease and significantly decreased overall survival. In the last two decades, significant progress has been made in the prophylaxis and treatment of HBV. We present an overview of different protocols and regimens used for prophylaxis of HBV reinfection after LTx and describe the protocol implemented at our center. Following LTx, HBV reinfection can be effectively prevented by administration of anti-hepatitis B immunoglobulin (HBIg) alone or more recently in combination with antiviral nucleoside/nucleotide analogs (NUCs). Several studies reported good results with the use of HBIg alone, but combination treatment with HBIg and NUCs has proven to be a superior prophylactic regimen for HBV recurrence. At present, combination therapy (HBIg and a nucleoside or nucleotide analog) is the gold standard used in many transplantation centers. This preventive regimen reduces the risk of a recurrence of HBV infection and thereby the need for re-transplantation. Future and ongoing studies will show how long HBIg must be given after transplantation, especially when used in combination with potent antivirals, such as entecavir or tenofovir.

Posttransplantation Hepatitis B Prophylaxis with Combination Oral Nucleoside and Nucleotide Analog Therapy

Liver transplant recipients are at risk of developing recurrent hepatitis B after liver transplantation for hepatitis B virus (HBV)-related liver disease. We evaluated the efficacy of a new hepatitis B prophylaxis regimen involving conversion from at least 12 months of HBIg with lamivudine to combination therapy with an oral nucleoside and nucleotide analog. Between June 2008 and May 2010, a total of 61 liver transplant recipients were converted to a combination of a nucleoside and nucleotide analog. The mean (±standard deviation) follow-up time after conversion was 15.0 (±6.1) months. Recurrent HBV occurred in two (3.3%) patients at 3.1 and 16.6 months after HBIg cessation. The overall person time incidence rate for HBV recurrence after HBIg cessation was 2.7 cases per 100 person-years. The estimate of HBV recurrence was 1.7% at 1 year after HBIg cessation. HBIg cessation a minimum of 12 months after liver transplantation with subsequent combination therapy with a nucleoside and nucleotide analog provides effective prophylaxis against recurrent HBV infection. The clinical implications of HBsAg detection without clinical, biochemical or molecular manifestations of recurrent hepatitis B require further study.