|
1
|
Park JS, Gayam V, Pan CQ. Review article: preventing hepatitis B graft infection in hepatitis B patients after liver transplantation: immunoglobulin vs anti-virals. Aliment Pharmacol Ther 2020; 52:944-954. [PMID: 32743822 DOI: 10.1111/apt.15999] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 03/10/2020] [Accepted: 07/05/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND A critical aspect of liver transplantation in hepatitis B patients is to prevent graft reinfection with hepatitis B virus. The use of hepatitis B immune globulin after transplant was a significant milestone, which allowed prolonged graft and patient survival by controlling hepatitis B reinfection in liver grafts. The development of anti-viral treatments with oral nucleos(t)ide analogues, led to a further reduction in graft reinfection and improvement in patient survival. The combination of the aforementioned two therapies has been widely used in hepatitis B-associated liver transplants. AIMS To address the post-transplant management of hepatitis B and provide updates on preventing graft reinfection. METHODS We performed a literature search on Ovid and PubMed for randomised controlled trials or cohort studies in English, which investigated the effectiveness of hepatitis B immune globulin and anti-viral therapy on hepatitis B-associated transplants (1/2000-1/2020). Studies that met pre-established criteria were reviewed. RESULTS Based on currently available evidence, an algorithm for post-transplant management with anti-viral therapy is proposed. Also, the management of recipients who received grafts from hepatitis B core antibody-positive donors is discussed. CONCLUSIONS The development of hepatitis B immune globulin and anti-viral treatments led to substantial improvement in graft and patient survival. The prevention of hepatitis B graft reinfection is complex and involves a broad interdisciplinary team.
Collapse
Affiliation(s)
- James S Park
- Division of Gastroenterology and Hepatology, Department of Medicine, NYU School of Medicine, NYU Langone Health, New York, NY, USA.,NYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA
| | - Vijay Gayam
- Interfaith Medical Center, SUNY Downstate University Hospital, Brooklyn, NY, USA
| | - Calvin Q Pan
- Division of Gastroenterology and Hepatology, Department of Medicine, NYU School of Medicine, NYU Langone Health, New York, NY, USA.,Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| |
Collapse
|
|
2
|
Ballarin R, Cucchetti A, Russo FP, Magistri P, Cescon M, Cillo U, Burra P, Pinna AD, Di Benedetto F. Long term follow-up and outcome of liver transplantation from hepatitis B surface antigen positive donors. World J Gastroenterol 2017; 23:2095-2105. [PMID: 28405138 PMCID: PMC5374122 DOI: 10.3748/wjg.v23.i12.2095] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2016] [Revised: 10/07/2016] [Accepted: 03/02/2017] [Indexed: 02/06/2023] Open
Abstract
Liver transplant for hepatitis B virus (HBV) currently yields excellent outcomes: it allows to rescue patients with an HBV-related advanced liver disease, resulting in a demographical modification of the waiting list for liver transplant. In an age of patient-tailored treatments, in liver transplantation as well the aim is to offer the best suitable graft to the patient who can benefit from it, also expanding the criteria for organ acceptance and allocation. With the intent of developing strategies to increase the donor pool, we set-up a multicenter study involving 3 Liver Transplant Centers in Italy: patients undergoing liver transplantation between March 03, 2004, and May 21, 2010, were retrospectively evaluated. 1408 patients underwent liver transplantation during the study period, 28 (2%) received the graft from hepatitis B surface antigen positive (HBsAg)-positive deceased donors. The average follow-up after liver transplantation was 63.7 mo [range: 0.1-119.4; SD ± 35.8]. None Primary non-function, re-liver transplantation, early or late hepatic artery thrombosis occurred. The 1-, 3- and 5-year graft and patient survival resulted of 85.7%, 82.1%, 78.4%. Our results suggest that the use of HBsAg-positive donors liver grafts is feasible, since HBV can be controlled without affecting graft stability. However, the selection of grafts and the postoperative antiviral therapy should be managed appropriately.
Collapse
|
|
3
|
Urabe A, Imamura M, Tsuge M, Kan H, Fujino H, Fukuhara T, Masaki K, Kobayashi T, Ono A, Nakahara T, Kawaoka T, Hiramatsu A, Kawakami Y, Aikata H, Hayes CN, Maki N, Ohdan H, Chayama K. The relationship between HBcrAg and HBV reinfection in HBV related post-liver transplantation patients. J Gastroenterol 2017; 52:366-375. [PMID: 27422771 DOI: 10.1007/s00535-016-1240-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2015] [Accepted: 07/02/2016] [Indexed: 02/04/2023]
Abstract
BACKGROUND Post-transplant hepatitis B virus (HBV) reinfection is one of the major problems facing patients who undergo HBV-related liver transplantation (LT). We analyzed the clinical impact of serum hepatitis B core-related antigen (HBcrAg) on HBV reinfection in post-LT patients with HBV-related liver diseases. METHODS Serum hepatitis B surface antigen (HBsAg), HBV DNA, and HBcrAg were measured over time in 32 post-LT patients. Twenty-one out of 32 patients had HCC at LT. The effects of HBcrAg, hepatocellular carcinoma (HCC) recurrence, and HBs gene mutation on HBV reinfection and withdrawal from hepatitis B immune globulin (HBIG) were analyzed. RESULTS Sixteen out of 32 patients (50 %) were positive for HBcrAg even though only six patients were thought to have experienced HBV reinfection based on reappearance of either HBV DNA or HBsAg during a median follow-up time of 75 months. Three of these six patients who became re-infected with HBV experienced HCC recurrence after LT. The HBV DNA reappearance rate was significantly higher in patients with HCC recurrence after LT (p < 0.001). Two HBV re-infected patients without HCC recurrence had HBs gene mutations G145R and G145A, respectively. Anti-HBs antibody development rate by HB vaccination was similar between HBcrAg-positive and negative patients (p = 0.325). CONCLUSIONS HBV reinfection is more common than is usually considered based on conventional measurement of HBsAg and HBV DNA. HCC recurrence and mutations in the HBV S gene were associated with HBV reinfection after LT.
Collapse
Affiliation(s)
- Ayako Urabe
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Michio Imamura
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Masataka Tsuge
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Hiromi Kan
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Hatsue Fujino
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Takayuki Fukuhara
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Keiichi Masaki
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Tomoki Kobayashi
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Atsushi Ono
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Takashi Nakahara
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Tomokazu Kawaoka
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Akira Hiramatsu
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Yoshiiku Kawakami
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Clair Nelson Hayes
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Noboru Maki
- Advanced Life Science Institute, Inc., Wako, Japan
| | - Hideaki Ohdan
- Division of Frontier Medical Science, Department of Surgery, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
| |
Collapse
|
|
4
|
Rational Basis for Optimizing Short and Long-term Hepatitis B Virus Prophylaxis Post Liver Transplantation: Role of Hepatitis B Immune Globulin. Transplantation 2016; 99:1321-34. [PMID: 26038873 PMCID: PMC4539198 DOI: 10.1097/tp.0000000000000777] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Antiviral therapy using newer nucleos(t)ide analogues with lower resistance rates, such as entecavir or tenofovir, suppress hepatitis B virus (HBV) replication, improve liver function in patients with compensated or decompensated cirrhosis, and delay or obviate the need for liver transplantation in some patients. After liver transplantation, the combination of long-term antiviral and low-dose hepatitis B Immune globulin (HBIG) can effectively prevent HBV recurrence in greater than 90% of transplant recipients. Some forms of HBV prophylaxis need to be continued indefinitely after transplantation but, in patients with a low-risk of HBV recurrence (i.e., HBV DNA levels undetectable before transplantation), it is possible to discontinue HBIG and maintain only long-term nucleos(t)ide analogue(s) therapy. A more cautious approach is necessary for those patients with high pretransplant HBV DNA levels, those with limited antiviral options if HBV recurrence occurs (i.e., HIV or hepatitis D virus coinfection, preexisting drug resistance), those with a high risk of hepatocellular carcinoma recurrence, and those at risk of noncompliance with antiviral therapy. In this group, HBIG-free prophylaxis cannot be recommended. The combination of long-term antiviral and low-dose Hepatitis B Immune globulin (HBIG) can effectively prevent HBV recurrence in > 90% of liver transplant recipients. In patients with low HBV DNA levels, nucleos(t)ide analogue(s) treatment without HBIG is possible.
Collapse
|
|
5
|
|
|
6
|
Abstract
There is an extremely high burden of liver disease owing to viral hepatitis B (HBV); about 2 billion people are infected and 350 million are chronic carriers of HBV worldwide. More effective medical therapy and liver transplantation are available for those with advancing disease. The interaction between the host immune system and the virus influences the rate of development of advanced liver disease or hepatocellular carcinoma (HCC); treatment that successfully reduces viral replication of HBV also reduces the incidence of development of advanced liver disease and HCC. Liver transplantation for HBV has yielded favorable outcomes since the institution of hepatitis B immune globulin and antiviral therapy. The ability to stabilize and rescue some patients with advanced liver disease owing to HBV has resulted in a changing demographic for patients with HBV undergoing liver transplantation. The main indications for transplant owing to HBV are now acute liver failure (both acute and acute reactivation on the background of chronic HBV) and HCC. Use of donor organs exposed to HBV with positive HBV core antibody is now routinely accepted for its good outcomes, and in selected cases with active HBV, HBV surface antigen-positive donors may be utilized to further expand the donor pool. Another indication for antiviral therapy for HBV is to reduce the risk of reactivation of latent virus in some patients previously exposed to HBV who are being treated with chemotherapy. Health care providers with HBV infection have an obligation to appropriately treat or monitor their disease closely to reduce the risk of transmission of disease from provider to patient. In the future, universal vaccination will reduce the overall burden of HBV liver disease, but until then appropriate utilization of available medical and surgical therapeutic options gives excellent clinical outcomes.
Collapse
Affiliation(s)
- M L Schilsky
- Department of Medicine and Surgery, Section of Digestive Diseases and Section of Transplantation and Immunology, Yale University School of Medicine, New Haven, Connecticut, USA.
| |
Collapse
|
|
7
|
Campsen J, Zimmerman M, Trotter J, Hong J, Freise C, Brown RS, Cameron A, Ghobrial M, Kam I, Busuttil R, Saab S, Holt C, Emond JC, Stiles JB, Lukose T, Chang MS, Klintmalm G. Multicenter review of liver transplant for hepatitis B-related liver disease: disparities in gender and ethnicity. Clin Transplant 2013; 27:829-37. [PMID: 24033475 DOI: 10.1111/ctr.12224] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/29/2013] [Indexed: 12/15/2022]
Abstract
Orthotopic liver transplantation (OLT) is the preferred treatment for selected patients with hepatitis B virus (HBV)-related liver disease. This study aimed to (i) define long-term outcomes following OLT for HBV; (ii) to quantify the incidence of HBV recurrence (rHBV) as it relates to anti-HBV treatment; and (iii) to determine outcomes for specific patient subgroups. We performed a retrospective chart review of 738 patients undergoing OLT between 1985 and 2010 at seven US transplant centers and divided the patients into 3 eras, 1985-1994, 1995-2004, and 2005-2010, based on hepatitis B immunoglobulin and antiviral therapies. In Era 3, female gender (p = 0.002), recurrent hepatocellular cancer (p < 0.001), and retransplantation (p = 0.01) were significantly associated with worse survival on multivariate analysis. Survival at three yr was poor for all ethnicities in Era 1, but significantly improved for all except black Americans by Era 3. Era 2 data showed a continued increase in rHBV from five to 10 yr (16.6%, 26.2%). In conclusion, while OLT outcomes have improved because of combination antiviral and immunoglobulin therapy, women and black Americans may not have realized an equal benefit. The rate of rHBV is significant even 10 yr post-transplant with survival affected.
Collapse
Affiliation(s)
- Jeffrey Campsen
- Baylor University Medical Center at Dallas, Dallas, TX, USA; University of Utah Health Sciences Center, Salt Lake City, UT, USA
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
8
|
Campsen J, Zimmerman M, Trotter J, Hong J, Freise C, Brown R, Cameron A, Ghobrial M, Kam I, Busuttil R, Saab S, Holt C, Emond J, Stiles J, Lukose T, Chang M, Klintmalm G. Liver transplantation for hepatitis B liver disease and concomitant hepatocellular carcinoma in the United States With hepatitis B immunoglobulin and nucleoside/nucleotide analogues. Liver Transpl 2013; 19:1020-9. [PMID: 23852663 DOI: 10.1002/lt.23703] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2012] [Accepted: 06/03/2013] [Indexed: 12/24/2022]
Abstract
Reinfection with hepatitis B virus (HBV) after liver transplantation (LT) may favor the recurrence of hepatocellular carcinoma (HCC), and combination therapy with hepatitis B immunoglobulin (HBIG) and nucleoside/nucleotide analogues may reduce HBV recurrence after LT. To test associations between HBV, HCC, and survival, we performed a retrospective chart review of patients undergoing LT for HBV between January 1985 and December 2010 at 7 US transplant centers. After we divided the patients into 3 eras based on evolving strategies in antiviral therapy (1985-1994, 1995-2004, and 2005-2010), we reviewed 16 variables to determine whether there were associations between survival and HCC recurrence. Seven hundred thirty-eight patients underwent transplantation for HBV, and 354 (48.0%) had concomitant HCC, which recurred in 58 patients (16.4%). Three-year survival was much better in era 3 versus era 1 (87% versus 40%, P = 0.001), and the incidence of HCC recurrence was lower (12% versus 29%, P = 0.009). The lungs were the most frequent first site of HCC recurrence, and they were followed by the liver. A multivariate analysis showed that HBV reinfection, HCC recurrence, and HBIG use were associated with worse survival (P < 0.001, P < 0.001, and P = 0.002, respectively); HCC recurrence and stage 3 HCC, among other factors, were associated with HBV reinfection (P < 0.001 and P = 0.004); and stage 3 HCC, vascular invasion of the explanted tumor, and post-LT chemotherapy were associated with HCC recurrence (P = 0.008, P < 0.001, and P < 0.001, respectively). Patients with HBV reinfection were 3.6 times more likely than patients without HBV to have HCC recurrence. These data suggest further study of attempts at LT for patients with HBV and HCC beyond the Milan criteria if their HBV is aggressively and successfully treated.
Collapse
Affiliation(s)
- Jeffrey Campsen
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
9
|
Roche B, Samuel D. Treatment of patients with HBV-related decompensated cirrhosis and liver transplanted patients. Clin Liver Dis 2013; 17:451-73. [PMID: 23905816 DOI: 10.1016/j.cld.2013.05.003] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Antiviral therapy using newer nucleos(t)ide analogs with lower resistance rates could suppress hepatitis B virus (HBV) replication, improve liver function in patients with compensated or decompensated cirrhosis, delay or obviate liver transplantation in some patients, and reduce the risk of HBV recurrence. Some form of HBV prophylaxis needs to be continued indefinitely posttransplant. However, in patients with a low-risk of HBV recurrence it is possible to discontinue hepatitis B immunoglobulins and maintain long-term nucleos(t)ide analog therapy. Currently, treatment of posttransplantation hepatitis B is a less important clinical problem than it was historically because effective antiviral therapies exist to rescue patients who failed initial prophylaxis.
Collapse
Affiliation(s)
- Bruno Roche
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif F-94800, France
| | | |
Collapse
|
|
10
|
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 2013; 26:E561-9. [PMID: 23061767 DOI: 10.1111/ctr.12022] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Hepatitis B immunoglobulin (HBIG), given in combination with nucleos(t)ide therapy, has reduced the rate of recurrent hepatitis B virus (HBV) following liver transplantation (LT), although the most effective protocol is unknown. We have retrospectively evaluated the use of long-term nucleos(t)ide analog in combination with one yr of low-dose HBIG. One hundred and fifty-two adults with HBV-related liver disease underwent LT in our center from January 1999 to August 2009; of these, 132 patients who received one yr of HBIG combined with long-term nucleos(t)ide analogs (largely on lamivudine [LAM] alone, n = 97) afterward were included for the purposes of this study. Median follow-up post-transplantation was 1752 d. Patient survival was 93.9%, 86.9% and 84.1% at 1, 5, and 10 yr, respectively; none of the 17 deceased patients had recurrent HBV. HBV recurrence was observed in nine patients (all received LAM+HBIG), yielding recurrence rates of 2.3%, 5.1%, and 8.6% at 1, 3, and 5/10 yr, respectively. All recurrences were successfully managed, usually with additional antiviral treatment. In conclusion, this study, with its long-term follow-up, demonstrates that short course of low-dose HBIG (without anti-HBs monitoring) combined with the use of long-term nucleos(t)ide analog is effective and less cumbersome than many protocols in current use.
Collapse
Affiliation(s)
- Tomohiro Tanaka
- Liver Transplant Unit, Multi-Organ Transplant Program, University Health Network, University of Toronto, Toronto, ON, Canada
| | | | | | | | | | | |
Collapse
|
|
11
|
Abstract
UNLABELLED The guideline on the management of chronic hepatitis B (CHB) was first developed in 2004 and revised in 2007 by the Korean Association for the Study of the Liver (KASL). Since then there have been many developments, including the introduction of new antiviral agents and the publications of many novel research results from both Korea and other countries. In particular, a large amount of knowledge on antiviral resistance--which is a serious issue in Korea--has accumulated, which has led to new strategies being suggested. This prompted the new guideline discussed herein to be developed based on recent evidence and expert opinion. TARGET POPULATION The main targets of this guideline comprise patients who are newly diagnosed with CHB and those who are followed or treated for known CHB. This guideline is also intended to provide guidance for the management of patients under the following special circumstances: malignancy, transplantation, dialysis, coinfection with other viruses, pregnancy, and children.
Collapse
MESH Headings
- Acute Disease
- Adolescent
- Adult
- Aged
- Alanine Transaminase/blood
- Antiviral Agents/therapeutic use
- Asian People
- Aspartate Aminotransferases/blood
- Carcinoma, Hepatocellular/diagnosis
- Carcinoma, Hepatocellular/etiology
- Child
- Child, Preschool
- Coinfection/drug therapy
- DNA, Viral/blood
- Drug Resistance, Viral
- Drug Therapy, Combination
- Female
- Hepatitis B Surface Antigens/blood
- Hepatitis B e Antigens/blood
- Hepatitis B virus/genetics
- Hepatitis B, Chronic/complications
- Hepatitis B, Chronic/diagnosis
- Hepatitis B, Chronic/drug therapy
- Humans
- Immunosuppression Therapy
- Infectious Disease Transmission, Vertical/prevention & control
- Liver/pathology
- Liver/physiology
- Liver Cirrhosis/physiopathology
- Liver Neoplasms/diagnosis
- Liver Neoplasms/etiology
- Liver Transplantation
- Male
- Middle Aged
- Pregnancy
- Renal Dialysis
- Republic of Korea
Collapse
|
|
12
|
Laryea MA, Watt KD. Immunoprophylaxis against and prevention of recurrent viral hepatitis after liver transplantation. Liver Transpl 2012; 18:514-23. [PMID: 22315212 DOI: 10.1002/lt.23408] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
The reinfection of the hepatic allograft with hepatitis B virus and hepatitis C virus can have important sequelae that result in poor long-term patient and graft survival. Although a response to treatment with antiviral medications can improve these outcomes, not all patients tolerate these medications or experience viral eradication. Avoiding reinfection of the graft is the most effective means of improving the long-term outcomes for these patient populations. This review is focused on the prevention of viral hepatitis reinfection after liver transplantation.
Collapse
Affiliation(s)
- Marie A Laryea
- Multi-Organ Transplant Program, Dalhousie University, Halifax, Nova Scotia, Canada
| | | |
Collapse
|
|
13
|
Dindoost P, Jazayeri SM, Alavian SM. Hepatitis B immune globulin in liver transplantation prophylaxis: an update. HEPATITIS MONTHLY 2012; 12:168-76. [PMID: 22550524 PMCID: PMC3339416 DOI: 10.5812/hepatmon.832] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/11/2011] [Revised: 12/26/2011] [Accepted: 01/29/2012] [Indexed: 12/11/2022]
Abstract
CONTEXT Liver transplantation is the best treatment option for end-stage liver disease following hepatitis B (HBV) infection. However, the high rate of recurrence of HBV infection following transplantation is a disadvantage of this option. EVIDENCE ACQUISITION Over the past 2 decades, the gold standard of prophylactic treatment for the prevention of HBV re-infection following liver transplantation has been the administration of low- to high-dose hepatitis B immune globulin (HBIg) along with an antiviral agent to induce passive immunity. RESULTS The effectiveness of HBIg in preventing the recurrence of HBV depends on the dosage, route of administration, and duration of HBIg treatment, and the viremic status at the time of transplantation. There is currently no consensus on a standardized recommendation for therapeutic options that include HBIg administration. CONCLUSION This review attempts to summarize the available data on the feasibility of such options. Most recent studies support the use of long-term combination therapy of HBIg and antiviral NAs (especially new agents).
Collapse
Affiliation(s)
| | - Seyed Mohammad Jazayeri
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran
| | - Seyed Moayed Alavian
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
- Corresponding author: Seyed Moayed Alavian, Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, IR Iran. Tel.: +98-2188945186, Fax: +98-2181262072, E-mail:
| |
Collapse
|
|
14
|
Dindoost P, Jazayeri SM, Alavian SM. Hepatitis B Immune Globulin in Liver Transplantation Prophylaxis: An Update. HEPATITIS MONTHLY 2012; 12:168-176. [DOI: 10.5812/hepatmon.5124] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
15
|
Abstract
The management of hepatitis B in liver transplantation has evolved significantly over the past 2 decades. Introduction of hepatitis B immune globulin and subsequently nucleos(t)ide analogues has revolutionized transplantation for hepatitis B virus (HBV), increasing survival for patients transplanted for this indication. With the availability of new and potent antivirals for HBV, the need for liver transplant should continue to decrease in the coming years. Moreover, the newer antivirals with high resistance barriers will allow effective long-term viral prophylaxis and therefore, prevention of recurrence.
Collapse
Affiliation(s)
- Corinne Buchanan
- Center for Liver Transplantation, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | | |
Collapse
|
|
16
|
Karlas T, Hartmann J, Weimann A, Maier M, Bartels M, Jonas S, Mössner J, Berg T, Tillmann HL, Wiegand J. Prevention of lamivudine-resistant hepatitis B recurrence after liver transplantation with entecavir plus tenofovir combination therapy and perioperative hepatitis B immunoglobulin only. Transpl Infect Dis 2010; 13:299-302. [PMID: 21159112 DOI: 10.1111/j.1399-3062.2010.00591.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Combination therapy with antivirals plus hepatitis B immunoglobulin (HBIg) has become the standard treatment for prevention of post-liver transplant hepatitis B virus (HBV) recurrence. However, HBIg therapy is inconvenient and expensive. Alternative therapeutic approaches with modern nucleos(t)ide analogues are limited so far. The present case report describes prevention of HBV recurrence with entecavir and tenofovir. A 48-year-old male patient with hepatitis B-induced decompensated liver cirrhosis initially improved on lamivudine (LAM) until LAM resistance (rtL180M and rtM204V) emerged followed by renewed decompensation. Therefore, tenofovir was added to LAM leading to undetectable HBV DNA (<200 copies/mL). Six months later, low-level viremia (479 copies/mL) was detected. Treatment was escalated to tenofovir plus entecavir. HBV DNA became negative again, and the patient underwent orthotopic liver transplantation. HBIg was administered during transplantation (10,000 IU) and on the second and third postoperative days (total dose 26,000 IU). Subsequently, the anti-hepatitis B surface (HBs) titer rose to 1477 IU/L at day 4 post transplantation. Although HBIg should have been continued, the patient remained on combination therapy with tenofovir plus entecavir only. The anti-HBs titer decreased and became negative 4 months later. However, under continued combination therapy with oral antivirals, HBV DNA and hepatitis B surface antigen remained negative during the entire follow-up of 21 months after liver transplantation. Combination therapy with entecavir plus tenofovir may prevent post-liver transplant hepatitis B recurrence even without HBIg maintenance therapy. This case illustrates that combination oral antiviral therapy might substitute for HBIg as indefinite prophylactic regimen due to profound antiviral efficacy and low risk of viral resistance. Efficacy and safety must be further investigated in randomized controlled trials.
Collapse
Affiliation(s)
- T Karlas
- Department of Medicine, Dermatology and Neurology, Division of Gastroenterology and Rheumatology, University of Leipzig, Leipzig, Germany
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
17
|
Pauwelyn K, Cassiman D, Laleman W, Verslype C, Monbaliu D, Aerts R, Van Steenbergen W, Pirenne J, Nevens F. Outcomes of Long-Term Administration of Intravenous Hepatitis B Immunoglobulins for the Prevention of Recurrent Hepatitis B After Liver Transplantation. Transplant Proc 2010; 42:4399-402. [DOI: 10.1016/j.transproceed.2010.07.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
|
|
18
|
Cholongitas E, Papatheodoridis GV. Management of HBV Infection and Liver Transplantation. EVIDENCE‐BASED GASTROENTEROLOGY AND HEPATOLOGY 2010:748-761. [DOI: 10.1002/9781444314403.ch45] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
19
|
Abstract
The consequences of chronic hepatitis B virus infection include hepatocellular carcinoma and liver cirrhosis. Effective antiviral therapy in patients with hepatitis B with advanced liver disease with viral suppression and sustained HBeAg seroconversion (where applicable) may abort hepatic decompensation, diminish hepatocellular risk, and reduce the risk of viral recurrence after transplantation. Overt hepatic decompensation is an indication for referral to a transplant center.
Collapse
Affiliation(s)
- Hui-Hui Tan
- Department of Gastroenterology & Hepatology, Singapore General Hospital, Republic of Singapore.
| | | |
Collapse
|
|
20
|
Yuefeng M, Weili F, Wenxiang 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 2010; 25:517-22. [PMID: 20560989 DOI: 10.1111/j.1399-0012.2010.01290.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND The aim of this study is to examine the efficacy of long-term prophylaxis with lamivudine (LAM) after a course of post-operative hepatitis B immunoglobulin (HBIG) in patients who underwent liver transplantation (LT) for hepatitis B virus (HBV)-related disease. RESULT The medical records of HBV-infected patients who underwent a LT in our institution between July 2001 and May 2005 were reviewed. There were 15 liver transplant recipients who were administered HBIG for <18 months and used LAM as a maintenance prophylaxis regime enrolled in this study. At enrollment, all patients were hepatitis B surface antigen (HBsAg) positive and three patients were HBeAg positive. There were 13 patients who were HBV DNA positive with a mean viral load of 5.4 log copies/mL, and among them, 12 recipients were on antiviral therapy with LAM (100 mg/d orally) for 12-168 d, resulting in HBV DNA negative levels in nine patients prior to their transplant. HBV recurrence post-LT was noted in two patients who had very high-HBV DNA levels pre-LT. Both of these patients showed LAM-resistant mutation at the time of recurrence. The 11 patients who were HBV DNA negative before LT (low-risk patients) had no HBV recurrence during a follow-up at a median of 58 months post-LT. This included five patients who had intermittent low-level HBV DNA post-LT (HBsAg negative), of whom two had YMDD mutation and these two were given adefovir in addition to LAM. CONCLUSION Our retrospective study demonstrated excellent long-term outcomes in the low-risk patients treated with LAM after a short course of HBIG.
Collapse
Affiliation(s)
- M Yuefeng
- Department of Hepatobiliary Surgery, Dalian Institute of Hepatobiliary Surgery, Dalian Friendship Hospital, Dalian, China
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
21
|
Chen J, Yi L, Jia JD, Ma H, You H. Hepatitis B immunoglobulins and/or lamivudine for preventing hepatitis B recurrence after liver transplantation: a systematic review. J Gastroenterol Hepatol 2010; 25:872-9. [PMID: 20546440 DOI: 10.1111/j.1440-1746.2009.06151.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
BACKGROUND Currently, hepatitis B immunoglobulins (HBIg) and/or lamivudine have become the main options for prevention of hepatitis B recurrence after liver transplantation. AIM To assess the benefits of HBIg and/or lamivudine for prevention of hepatitis B recurrence after liver transplantation. METHODS We conducted a search of electronic databases and a manual search of bibliographical lists of relevant articles. All randomized clinical trials and non-randomized studies that meet the pre-specified criteria were included. However, results of non-randomized studies were reported under 'exploratory analyses' in the result section. The outcome measure was hepatitis B recurrence. RESULTS Two randomized and 44 non-randomized studies were included. Meta-analysis of two randomized studies shows one week HBIg combined with lamivudine regimen had equivalent effect compared with long-term high-dose HBIg regimen for preventing hepatitis B recurrence (RR 1.23; 95% CI 0.38-4.03; P = 0.73). For 44 non-randomized studies, only qualitative systematic review was performed. With long-term HBIg prophylaxis, hepatitis B recurrence rate ranged from 3.7% to 65%; with lamivudine prophylaxis, hepatitis B recurrence rate varied from 3.8% to 40.4%; Long-term high-dose HBIg plus lamivudine prophylaxis can reduce the risk of HBV recurrence to less than 10%. CONCLUSIONS Long-term HBIg prophylaxis or lamivudine prophylaxis can reduce the risk for hepatitis B virus recurrence. Long-term high-dose HBIg combined with lamivudine can further reduce HBV recurrence to less than 10%.
Collapse
Affiliation(s)
- Jie Chen
- Beijing Friendship Hospital, Capital Medical University; Municipal Key Laboratory of Beijing for Regulation of Liver Protection and Regeneration. Beijing, China
| | | | | | | | | |
Collapse
|
|
22
|
Weber NK, Forman LM, Trotter JF. HBIg discontinuation with maintenance oral anti-viral therapy and HBV vaccination in liver transplant recipients. Dig Dis Sci 2010; 55:505-9. [PMID: 19802696 DOI: 10.1007/s10620-009-0999-6] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2009] [Accepted: 09/17/2009] [Indexed: 12/20/2022]
Abstract
BACKGROUND Hepatitis B (HBV) is an uncommon indication for liver transplantation in the US accounting for approximately 5% of cases. Recurrence prophylaxis is typically long-term hepatitis B immune-globulin (HBIg) and an oral anti-HBV agent. Because of high HBIg costs and improving efficacy of new oral agents, there is increasing interest in HBIg discontinuation. AIM To describe results of a protocol at our center including HBV vaccination and HBIg discontinuation. METHODS All patients received HBIg therapy and an oral anti-viral agent from the time of transplant. Patients transplanted for HBV with a stable post-operative clinical course underwent HBV vaccination and HBIg discontinuation. After HBIg discontinuation, patients were monitored for HBV recurrence for at least one year. Recurrence was defined as either viral (HBV-DNA 10(4) copies/ml on two consecutive occasions) or hepatitis (viral recurrence with elevated liver transaminases). RESULTS Of 1182 recipients, 36 (3%) had HBV. Twenty-four were excluded from the protocol, and the remaining 12 patients underwent HBIg withdrawal. Median age at HBIg discontinuation was 56 (range, 36-70) years, median time from transplant to HBIg discontinuation was 62.8 (range, 27.5-128) months, and median time of follow-up after discontinuation was 27.4 (range, 13-69) months. Of the 12 patients vaccinated, no patients maintained HBSAb >or= 10 IU/l at last follow-up. There was no viral or hepatitis recurrence and no deaths or graft loss. CONCLUSIONS HBIg discontinuation with maintenance oral anti-viral monotherapy is safe and effective for HBV liver transplant recipients. Vaccination is not effective in this population.
Collapse
Affiliation(s)
- Nicholas K Weber
- Division of Gastroenterology and Hepatology, University of Colorado Health Sciences Center, 1635 N Ursula, Aurora, CO 80045, USA.
| | | | | |
Collapse
|
|
23
|
Mas A, Castells L, Abradelo M, Bernardos Á, Páez A, Woodward M, Sousa J. Evaluation of Anti-HBs Serum Levels and Pharmacokinetic Profile After Intravenous Administration of Niuliva, a New Hepatitis B Immunoglobulin, Following Liver Transplantation. Transplant Proc 2009; 41:4253-8. [DOI: 10.1016/j.transproceed.2009.09.083] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2009] [Accepted: 09/29/2009] [Indexed: 01/26/2023]
|
|
24
|
Katz LH, Paul M, Guy DG, Tur-Kaspa R. Prevention of recurrent hepatitis B virus infection after liver transplantation: hepatitis B immunoglobulin, antiviral drugs, or both? Systematic review and meta-analysis. Transpl Infect Dis 2009; 12:292-308. [PMID: 20002355 DOI: 10.1111/j.1399-3062.2009.00470.x] [Citation(s) in RCA: 82] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES To evaluate antiviral prophylaxis against hepatitis B virus (HBV) following liver transplantation. METHODS Systematic review and meta-analysis. Clinical trials and comparative cohort studies comparing the use of hepatitis B immunoglobulin (HBIg), antivirals, or both following liver transplantation for HBV infection were included. The primary outcome was reappearance of hepatitis B surface antigen (HBsAg). Other outcomes included all-cause and HBV-related mortality, HB-related active liver disease, and reappearance of HBV DNA after transplantation. Relative risks (RR) with 95% confidence intervals (CIs) are reported. RESULTS Twenty studies (22 comparisons) were included. Ten studies compared HBIg to combination treatment, 9 compared antivirals to combination treatment, and 3 compared lamivudine (LAM) to HBIg. Combination treatment reduced HBsAg reappearance (RR 0.28; 95% CI 0.12-0.66), and was superior to HBIg alone in all other outcome measures. Combination treatment was significantly better than antivirals in preventing reappearance of HBsAg (RR 0.31; 95% CI 0.22-0.44), even when low-dose HBIg was given. No significant difference was found between HBIg and LAM monotherapy for all measured outcomes. Major limitations with regard to comparability of the study groups in non-randomized trials were revealed. CONCLUSIONS Combination treatment with HBIg and LAM reduced HBV recurrence following liver transplantation, compared with HBIg or LAM alone, and reduced mortality compared with HBIg alone.
Collapse
Affiliation(s)
- L H Katz
- Liver Institute, Rabin Medical Center, Beilinson Hospital, Petach Tikva, Israel.
| | | | | | | |
Collapse
|
|
25
|
Papatheodoridis GV, Cholongitas E, Archimandritis AJ, Burroughs AK. Current management of hepatitis B virus infection before and after liver transplantation. Liver Int 2009; 29:1294-305. [PMID: 19619264 DOI: 10.1111/j.1478-3231.2009.02085.x] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
The progress in treatment against hepatitis B virus (HBV) has substantially improved the outcome of all HBV-infected patients. We systematically reviewed the existing data in the management of HBV transplant patients in order to assess the optimal regimen in the pretransplant setting, for post-transplant prophylaxis and for therapy of HBV recurrent infection. All data suggest that an effective pretransplant anti-HBV therapy prevents post-transplant HBV recurrence. Pretransplant therapy has been based on lamivudine with addition of adefovir upon lamivudine resistance, but the use of newer, potent high-genetic barrier agents is expected to improve long-term efficacy. Moreover, it may lead to improvement of liver function, which sometimes removes the need for transplantation, although more objective criteria for removal from waiting lists are required. After liver transplantation, the combination of HBV immunoglobulin and one nucleos(t)ide analogue, mostly lamivudine, is currently the best approach, almost eliminating the probability of HBV recurrence. Treatment of post-transplant HBV recurrence has been mainly studied with lamivudine, but it will be most effective with entecavir and tenofovir, which have a low risk of resistance. In conclusion, the newer anti-HBV agents improve the treatment of HBV both pretransplant and post-transplant. HBV immunoglobulin is still used in combination with an anti-HBV agent for post-transplant prophylaxis. Monoprophylaxis with one of the new anti-HBV agents might be possible, particularly in patients preselected as having a low risk of HBV recurrence, but further data are needed and strategies to ensure compliance must be used.
Collapse
Affiliation(s)
- George V Papatheodoridis
- 2nd Department of Internal Medicine, Athens University Medical School, Hippokration General Hospital, 114 Vas. Sophias avenue, Athens, Greece.
| | | | | | | |
Collapse
|
|
26
|
Post-liver transplant hepatitis B prophylaxis: the role of oral nucleos(t)ide analogues. Curr Opin Organ Transplant 2009; 14:225-30. [PMID: 19373086 DOI: 10.1097/mot.0b013e32832b1f32] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE OF REVIEW The established gold standard for prophylaxis against hepatitis B virus (HBV) recurrence post-liver transplant is combination hepatitis B immune globulin (HBIG) and lamivudine. This therapy reduces the risk of recurrence to less than 5% at 5 years; however, the cost of HBIG has led to the investigation of alternatives. This paper reviews the HBIG-sparing alternatives achieved with lamivudine and the prospects for the newer anti-HBV agents in post-liver transplant prophylaxis. RECENT FINDINGS When used with lamivudine as part of combination prophylaxis, low-dose intramuscular HBIG is equivalent to high-dose intravenous HBIG. There is recent evidence that in patients receiving HBIG/lamivudine, HBIG can be replaced with adefovir dipivoxil at 6-12 months post-liver transplant without precipitating recurrence. Furthermore, a recent study showed that primary prophylaxis with combination adefovir/lamivudine therapy without the use of long-term HBIG was effective and well tolerated as primary prophylaxis. SUMMARY Although there are few studies of potent newer anti-HBV agents such as entecavir or tenofovir being used as HBV prophylaxis, the properties of these drugs suggest that they should replace lamivudine within HBV prophylaxis regimes.
Collapse
|
|
27
|
Yamamoto M, Little G, Imagawa DK. Hepatitis B immunoglobulin in preventing reinfection following liver transplantation. Expert Rev Anti Infect Ther 2009; 7:321-8. [PMID: 19344245 DOI: 10.1586/eri.09.2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Before the availability of hepatitis B immunoglobulin (HBIG) in hepatitis B-positive transplant recipients, the acute mortality was very high, in many centers up to 50% within 60 days post-transplant. The overall reinfection rate was approximately 60% within the initial 6 months, increasing to 80-90% within the initial 12 months and, in many cases, leading to allograft loss and death or retransplantation. These recurrent infections were often more severe and more rapidly progressing than the initial infection, probably due to high-dose immunosuppressive regimens. The poor prognosis before introduction of HBIG made hepatitis B liver disease an absolute contraindication for liver transplantation, leaving these patients with very limited treatment options. This changed in the late 1980s with the introduction of HBIG, which reduced the incidence of hepatitis B in the transplanted liver to approximately 15-50%, with concomitant improvement in graft and overall survival. The prognosis was further improved by a combination of long-term HBIG and antiviral therapy, in particular lamivudine, which reduced the reinfection rate, in most cases to between 0 and 5%. Owing to the cost and relative inconvenience of HBIG, some transplant centers have experimented with early discontinuation of HBIG and replacement with antiviral monotherapy. A number of studies, however, have found significantly higher recurrence rates associated with lamivudine monotherapy (40-50%) compared with combination therapy and, hence, lamivudine monotherapy is not recommended.
Collapse
Affiliation(s)
- Maki Yamamoto
- Department of Surgery, University of California, Irvine Medical Center, Orange, CA 92868-3298, USA.
| | | | | |
Collapse
|
|
28
|
Jiang L, Jiang LS, Cheng NS, Yan LN. Current prophylactic strategies against hepatitis B virus recurrence after liver transplantation. World J Gastroenterol 2009; 15:2489-99. [PMID: 19468999 PMCID: PMC2686907 DOI: 10.3748/wjg.15.2489] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Prophylactic strategies against hepatitis B virus (HBV) recurrence after liver transplantation (LT) are essential for patients with HBV-related disease. Before LT, lamivudine (LAM) was proposed to be down-graded from first- to second-line therapy. In contrast, adefovir dipivoxil (ADV) has been approved not only as first-line therapy but also as rescue therapy for patients with LAM resistance. Furthermore, combination of ADV and LAM may result in lower risk of ADV resistance than ADV monotherapy. Other new drugs such as entecavir, telbivudine and tenofovir, are probably candidates for the treatment of hepatitis-B-surface-antigen-positive patients awaiting LT. After LT, low-dose intramuscular hepatitis B immunoglobulin (HBIG), in combination with LAM, has been regarded as the most cost-effective regimen for the prevention of post-transplant HBV recurrence in recipients without pretransplant LAM resistance and rapidly accepted in many transplant centers. With the introduction of new antiviral drugs, new hepatitis B vaccine and its new adjuvants, post-transplant HBIG-free therapeutic regimens with new oral antiviral drug combinations or active HBV vaccination combined with adjuvants will be promising, particularly in those patients with low risk of HBV recurrence.
Collapse
|
|
29
|
Abstract
Combination therapy with hepatitis B immunoglobulin (HBIG) plus nucleos(t)ide analogue have reduced the rate of hepatitis B virus (HBV) recurrence post-transplantation to less than 10% at long-term. HBV recurrence diagnosed after 3 years post-transplantation is extremely rare. Considering the cost and the constraints of HBV prophylaxis it was suggested to decrease the amount of HBIG given and possibly to discontinue HBIG administration. The additional debate was on the need to maintain or not any HBV prophylaxis at long-term or to maintain monoprophylaxis with one or two nucleos(t)ide analogues or to administer HBV vaccine: The supporters of this strategy argued that HBV recurrence can be easily controlled by administration of nucleos(t)ide analogues. However, it was shown that 50-80% of patients maintain HBV DNA in the liver, serum or peripheral mononuclear blood cells long-term after transplantation. In patients receiving monoprophylaxis with nucleos(t)ide analogues the risk of HBV reinfection increases with time due to HBV mutant strains. Vaccine protocols used to replace HBIG prophylaxis gave disappointing results. Combination protocols using low-doses of intramuscular HBIG plus nucleos(t)ide analogues have been associated with a low rate of HBV reinfection. In conclusion, long-term prophylaxis should be maintained in most patients except those with anti-HBs seroconversion.
Collapse
Affiliation(s)
- D Samuel
- Inserm, Unité 785, Villejuif, F-94804, France.
| |
Collapse
|
|
30
|
Beckebaum S, Sotiropoulos GC, Gerken G, Cicinnati VR. Hepatitis B and liver transplantation: 2008 update. Rev Med Virol 2009; 19:7-29. [DOI: 10.1002/rmv.595] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
|
|
31
|
Roche B, Samuel D. Liver transplantation in viral hepatitis: prevention of recurrence. Best Pract Res Clin Gastroenterol 2008; 22:1153-69. [PMID: 19187873 DOI: 10.1016/j.bpg.2008.12.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
End-stage liver disease caused by the hepatitis B and C viruses (HBV and HCV) are major indications for liver transplantation. Outcome depends largely on the prevention of allograft reinfection. The advent of long-term hepatitis B immune globulin administration and the introduction of new antiviral agents were a major breakthrough in the management of these patients. Today, survival after orthotopic liver transplantation (OLT) is similar to that of patients transplanted for HBsAg-negative liver disease, and the risk of recurrence is below 10%. In contrast, HCV reinfection is almost constant and significantly impairs patient and graft survival. Factors that may influence disease severity and consequently progression of HCV graft injury remain unclear. Pre-transplantation and prophylactic post-transplantation antiviral treatments are limited by low applicability and poor tolerance. Treatment of established graft lesions with combination therapy gave promising results, with sustained virological response in 25-45% of patients, but indications, modality and duration of treatment should be assessed.
Collapse
Affiliation(s)
- Bruno Roche
- Assistance Publique-Hopitaux de Paris, Hopital Paul Brousse, Centre Hepato-Biliaire, Villejuif, France
| | | |
Collapse
|
|
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; 48:1460-6. [PMID: 18925641 DOI: 10.1002/hep.22524] [Citation(s) in RCA: 135] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
UNLABELLED Prior to effective prophylaxis, liver transplantation for hepatitis B virus (HBV)-related disease was frequently complicated by recurrence, which could be severe and rapidly progressive. Combination hepatitis B immunoglobulin (HBIG) and lamivudine prophylaxis reduces this rate of recurrence to <5% at 5 years; however, HBIG administration is costly and inconvenient. We conducted a multicenter randomized study of adefovir dipivoxil substitution for low-dose intramuscular (IM) HBIG in patients without HBV recurrence at least 12 months posttransplantation for HBV-related disease. Thirty-four patients were randomized, 16 to adefovir (1 patient withdrew consent at 3 months and is not considered in the results) and 18 to continue HBIG. All continued lamivudine. Groups were well matched by age, sex, and time since transplantation (median, 4.5 years), and background virological risk for HBV recurrence (30% of patients in the adefovir group, 24% in the HBIG group having detectable HBV DNA at transplantation). All patients were alive at study completion without recurrence. One patient in the adefovir group became hepatitis B surface antigen-positive at 5 months but was persistently HBV DNA undetectable via polymerase chain reaction (sensitivity 14 IU/mL) over the following 20 months. Median creatinine was not significantly changed over the course of the study in either group. One patient in the adefovir group with a background of diabetic and hypertensive nephropathy (baseline creatinine 150 micromol/L) developed increased creatinine leading to dose reduction and ultimately cessation of adefovir at 15 months. Yearly cost of combination adefovir/lamivudine prophylaxis was $8,290 versus $13,718 IM HBIG/lamivudine. CONCLUSION Compared with combination HBIG plus lamivudine prophylaxis, combination adefovir plus lamivudine provides equivalent protection against recurrent HBV infection but with better tolerability and less cost.
Collapse
Affiliation(s)
- Peter W Angus
- Victorian Liver Transplant Unit, Austin Health, Victoria, Australia.
| | | | | | | | | |
Collapse
|
|
33
|
Akay S, Karasu Z. Hepatitis B immune globulin and HBV-related liver transplantation. Expert Opin Biol Ther 2008; 8:1815-22. [DOI: 10.1517/14712598.8.11.1815] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
|
|
34
|
Abstract
Liver transplantation for hepatitis B represents 5-10 % of all liver transplantations performed in Europe. The prognosis after liver transplantation is related to the efficacy of prophylaxis of HBV graft reinfection. The risk of HBV reinfection is directly related to the HBV viral load at transplantation. HBV prophylaxis after transplantation with long-term administration of anti-HBS immune globulins (HBIG) or with monoprophylaxis with lamivudine can reduce significantly the risk of HBV recurrence mainly in patients without active HBV replication. Antivirals such as lamivudine, adefovir, entecavir or tenofovir can control HBV replication in patients with decompensated HBV cirrhosis waiting for transplantation. However, there is a risk of HBV viral breakthrough during nucleo (t) side antiviral treatment. The use of an antiviral alone or in combination should take into account the antiviral efficacy and the risk of viral resistance. The post-transplant combination of antiviral therapy and HBIG prophylaxis is very effective in reducing the rate of HBV reinfection to less than 10 % even in patients with HBV replication at transplantation. In the absence of active viral replication at transplantation, the possibilty to discontinue HBIG prophylaxis at long-term after transplantation with maintenance of antiviral treatment or HBV vaccination is in evaluation. The use of new antiviral therapies (nucleos(t)ide analogues) has dramatically improved the prognosis of patients with HBV reinfection of the graft. The current 5-year survival after liver transplantation for HBV related liver disease is 85 %. In conclusion, the prophylaxis of HBV reinfection combining antiviral therapy prior to transplantation, and combination of HBIG and antiviral therapy post-transplantation is effective in reducing the rate of HBV reinfection to less than 10 %.
Collapse
|
|
35
|
Buti M, Mas A, Prieto M, Casafont F, González A, Miras M, Herrero JI, Jardi R, Esteban R. Adherence to Lamivudine after an early withdrawal of hepatitis B immune globulin plays an important role in the long-term prevention of hepatitis B virus recurrence. Transplantation 2007; 84:650-4. [PMID: 17876280 DOI: 10.1097/01.tp.0000277289.23677.0a] [Citation(s) in RCA: 89] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Lamivudine combined with hepatitis B immune globulin (HBIg) is the standard of care for preventing the recurrence hepatitis B virus after liver transplant. To determine the risk of hepatitis B virus (HBV) recurrence after early withdrawal of HBIg in patients receiving lamivudine maintenance therapy, 20 patients receiving a course of HBIg and lamivudine after transplantation and long-term maintenance therapy with lamivudine and 9 patients receiving HBIg and lamivudine indefinitely were analyzed. The survival rate was 90% after a mean follow-up of 83 months. The HBV recurrence rate was 14% with a mean period of 91 months free from HBV recurrence. Both groups had similar HBV recurrence rates, 15% for the combination and 11% for lamivudine alone. Four patients, 3 of whom were noncompliant with therapy, experienced posttransplant HBV recurrence. Patients who adhere to long-term prophylaxis with lamivudine after early withdrawal of HBIg have a low risk of HBV recurrence, similar to those who receive combination prophylaxis.
Collapse
Affiliation(s)
- Maria Buti
- Hospital General Valle de Hebrón and CIBER EHD, Barcelona, Spain. mbuti@vhebronnet
| | | | | | | | | | | | | | | | | |
Collapse
|
|
36
|
Neff GW, Kemmer N, Kaiser TE, Zacharias VC, Alonzo M, Thomas M, Buell J. Combination therapy in liver transplant recipients with hepatitis B virus without hepatitis B immune globulin. Dig Dis Sci 2007; 52:2497-500. [PMID: 17404847 DOI: 10.1007/s10620-006-9658-3] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2006] [Accepted: 10/17/2006] [Indexed: 01/02/2023]
Abstract
INTRODUCTION Conventional therapy to prevent HBV recurrence in liver transplant (LTx) recipients consists of Hepatitis B Immune Globulin (HBIg). The aim of this review is to investigate the safety and efficacy of converting HBIg and LAM therapy to ADV and LAM therapy. METHODS A retrospective review involving all liver transplant patients with HBV maintained on HBIg and LAM therapy. Results collected included: gender, age, HBV serological and DNA status (COBAS AmpliScreen PCR-based testing). Serologic testing was done every three months. Patients were followed for drug reactions, therapy compliance, and immune suppression compliance. A cost benefit analysis was done for drug comparisons using United States currency values. RESULTS Patient demographics included: Male (n=6), Female (n=4), mean age 44 years (range 33 to 65). The mean length of follow up since therapy conversion (from HBIg and LMV to ADV and LMV) was 21 months (range 16 to 25 months). Serological status at time of conversion revealed that DNA status remained negative in all patients, HBsAg negative in 10/10, HB eAg (+) (5/10) and HBeAb (+)(5/10). None of the patients experienced an increase in transaminases while on dual ADV and LAM therapy. All patients were maintained on immune suppression monotherapy (tacrolimus) at 7-9 ng/mL. All patients reported compliance with the dual therapy and that they experienced no drug related side effects. Mean yearly costs for ADV and LAM was 7,235.00 United States dollars (range 6,550.00 to 8,225.00); while mean monthly costs for HBIg and LAM; 9225.00 (range 7205.00 to 12005.00). CONCLUSION The above results demonstrate beneficial effects of ADV and LAM in place of the current standard of HBIg and LAM therapy. Safety and short term results show nucleoside therapy is adequate at preventing HBV viral recurrence. Lastly, the economic benefit for ADV and LAM vastly outweighed the HBIg and LAM group.
Collapse
Affiliation(s)
- Guy W Neff
- Department of Medicine, Division of Digestive Diseases, University of Cincinnati, Cincinnati, Ohio 45267, USA.
| | | | | | | | | | | | | |
Collapse
|
|
37
|
Imvrios G, Papanikolaou V, Vrochides D, Ouzounidis N, Papagiannis A, Fouzas I, Giakoustidis D, Antoniades N, Iosifidou S, Patsiaoura K, Zafiriadou E, Takoudas D. Liver transplantation outcomes in patients with cirrhosis and hepatocellular carcinoma: experience of a single center in a viral hepatitis endemic area. Transplant Proc 2007; 39:1508-10. [PMID: 17580174 DOI: 10.1016/j.transproceed.2006.12.039] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2006] [Accepted: 12/13/2006] [Indexed: 11/23/2022]
Abstract
Our center has performed 205 orthotopic liver transplantations (OLT) in 201 patients. Hepatocellular carcinoma (HCC) was discovered in 32 (15%) patients, 5 of whom were diagnosed incidentally in recipient explants. The main underlying diagnosis was viral hepatitis (n = 28; 87.5%). Most patients (17; 53.1%) were diagnosed as having Child class B cirrhosis. Single tumors measuring <3 cm were diagnosed in 29 (90.6%) patients. Downstaging chemoembolization was performed in 7 (21.8%) patients. Preoperative aFP levels were normal in 20 (62.5%) patients. In the rest (n = 12; 37.5%), aFP levels normalized immediately after the OLT. In the latter group, 2 patients had a delayed (2 years) postoperative increase in aFP levels; both patients had tumor recurrence in the graft. All patients with hepatitis B received antiviral treatment with HBIG and lamivudine. There were 9 deaths (28.1%) in the immediate postoperative period (<30 days). One-year survival rate was 62.5% (n = 20). Actuarial 5-year survival rate was 55%, and actuarial 10-year survival rate was 40%. In conclusion, OLT has become the standard treatment for patients diagnosed with HCC in a population that shows cirrhosis most of the time to be secondary to viral hepatitis, provided that recipients are selected according to the size of the neoplasm and that they receive adequate antiviral prophylaxis.
Collapse
Affiliation(s)
- G Imvrios
- Organ Transplant Unit, Hippokration General Hospital, 49 Konstantinoupoleos Avenue, Thessaloniki 54642, Hellas
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
38
|
Abstract
Recurrence of the original liver disease following liver transplantation is a typical complication in viral hepatitis. Recent advances, particularly the development of strategies to prevent or effectively treat hepatitis B, have led to substantial improvements in the post-transplantation outcome of hepatitis B candidates. While the efficacy of antivirals to treatrecurrent hepatitis C has improved in recent years, there is as yet no therapy to universally prevent recurrent infection, and tolerability of antivirals remains a matter of concern.
Collapse
Affiliation(s)
- Marina Berenguer
- Ciberehd and Department of Medicine, Medical University in Valencia, Spain
| |
Collapse
|
|
39
|
Eisenbach C, Sauer P, Mehrabi A, Stremmel W, Encke J. Prevention of hepatitis B virus recurrence after liver transplantation. Clin Transplant 2007; 20 Suppl 17:111-6. [PMID: 17100710 DOI: 10.1111/j.1399-0012.2006.00609.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Liver transplantation for hepatitis B virus (HBV)-related liver disease has changed from a contraindication to outcomes comparable with non-HBV-related liver transplantations during the last two decades. Mainly the implementation of immunoprophylaxis with hepatitis B immunoglobulin (HBIG) and the use of nucleoside analogs such as lamivudine and adefovir account for this dramatic change. The standard of care in most centers today consists of lamivudine treatment in replicating hepatitis B pre-orthotopic liver transplantation (OLT) and a combination regimen of lamivudine and HBIG post-OLT. With adefovir, a potent antiviral drug became available in recent years that allows for the treatment of patients with lamivudine-resistant tyrosine-methionine-aspartate-aspartate (YMDD)-mutant HBV. In the transplantation setting, first studies indicate that a triple prophylactic therapy consisting of lamivudine, adefovir, and HBIG will become the standard of care for YMDD-mutant-related hepatitis B. With new drugs emerging for the treatment of chronic HBV, there is optimism for new options also in the transplant setting.
Collapse
Affiliation(s)
- Christoph Eisenbach
- Department of Internal Medicine IV, University of Heidelberg, Heidelberg, Germany.
| | | | | | | | | |
Collapse
|
|
40
|
Prada Lobato J, Garrido López S, Catalá Pindado MA, García Pajares F. [The prophylaxis against post-liver-transplant hepatitis B re-infection]. FARMACIA HOSPITALARIA 2007; 31:30-7. [PMID: 17439311 DOI: 10.1016/s1130-6343(07)75708-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
OBJECTIVE To review the prophylaxis against post-liver transplantation hepatitis B reinfection with anti-hepatitis B immunoglobulin and nucleoside analogues. METHOD A bibliographic search was carried out using Pubmed, entering the following key words: hepatitis B and liver transplantation and (hepatitis B hyperimmune globulin and lamivudine and adefovir dipivoxil) up to June 2006. The initial search was filtered using the terms clinical trial, randomized clinical trial and review. The data contained in selected studies were reviewed. RESULTS A total of 53 works were found. Prophylaxis with anti-HB immunoglobulin and lamivudine is the best strategy for avoiding recurrence of the hepatitis B virus in patients undergoing hepatic transplants; achieving very low reinfection rates (0-10%) with follow up periods of between 1-5 years. There is a great degree of variability (dose, duration and method of HBIg administration) in the prophylactic protocols reviewed. The use of low doses of anti-HB immunoglobulin (administered intravenously followed by intramuscular administration, or administered intramuscularly from the anhepatic stage), and lamivudine in patients who receive transplants with a low risk of recurrence, shows prophylactic efficacy comparable to the use of high doses of anti-HB immunoglobulin. Furthermore, it implies a considerable reduction in costs. CONCLUSIONS The availability of suitably designed clinical trials is required to design a more cost-effective protocol and reduce variability.
Collapse
Affiliation(s)
- J Prada Lobato
- Servicio de Farmacia, Hospital Universitario Río Hortega, Valladolid.
| | | | | | | |
Collapse
|
|
41
|
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; 13:374-81. [PMID: 17318855 DOI: 10.1002/lt.21041] [Citation(s) in RCA: 88] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatitis B virus (HBV) recurrence rates of 0-16% had been reported in patients maintained on nucleoside analogues (NA) after hepatitis B immunoglobulin (HBIG) discontinuation after orthotopic liver transplantation (OLT). However, follow-up in most studies was short. We aimed to determine the long-term risk of HBV recurrence using this strategy. All HBV patients who received > or =7 doses of intravenous HBIG after OLT, with no HBV recurrence while receiving HBIG, and who eventually discontinued HBIG and were maintained on NA, were included. HBV recurrence was defined as HBsAg-positive or HBV DNA > or =5 log copies/mL on 2 consecutive occasions. Twenty-one patients met the inclusion criteria. Immediate post-OLT prophylaxis was combination HBIG and NA in 15 patients, whereas 6 patients received HBIG monotherapy for 62-109 months before NA was added. HBIG was discontinued a median of 26 (range, 0.2-121) months after OLT. Median follow-up post-HBIG discontinuation was 40 (range, 5-51) months. Only 1 patient, who had 12 months of HBIG and was noncompliant to NA therapy, had HBV recurrence, 34 months after HBIG discontinuation. One patient had HBV DNA of 3.3 log copies/mL 47 and 48 months after HBIG discontinuation but remained HBsAg-negative. Lamivudine-resistant mutations were detected in both patients. Probability of HBV recurrence was 0% and 9% at 2 and 4 years after HBIG discontinuation. Three patients had 1-2 episodes of transiently detectable HBV DNA. All were HBV DNA and HBsAg negative on repeated tests over a period of 2-36 months. Maintenance therapy with NA after discontinuation of long-term HBIG therapy is associated with a low risk of HBV recurrence after OLT in compliant HBV patients.
Collapse
Affiliation(s)
- Stephen N Wong
- Division of Gastroenterology, University of Michigan, Ann Arbor, MI 48109-0362, USA
| | | | | | | | | | | | | |
Collapse
|
|
42
|
Abstract
1. The use of low-dose immunosuppressive therapy along with pre- and posttransplantation nucleos(t)ide therapy and posttransplantation hepatitis B immunoglobulin (HBIG) has yielded marked improvements in survival. 2. Lamivudine (Epivir-HBV), adefovir (Hepsera), entecavir (Baraclude), tenofovir (Viread), emtricitabine (Emtriva), and the combination drugs tenofovir + emtricitabine (Truvada) and abacavir + lamivudine (Epzicom) are effective nucleos(t)ide antiviral agents that, in some cases, may help reverse liver disease sufficiently to avoid transplant. 3. In posttransplantation patients, virus suppression with some combination of HBIG and the nucleos(t)ide agents may prevent graft loss and death or the need for a second transplant. 4. In both the pre- and posttransplantation setting, the goal of hepatitis B virus management is complete virus suppression. 5. The use of low-dose intramuscular HBIG is evolving, with studies showing that dosing and cost can be reduced by 50-300% with a customized approach. 6. Elimination of HBIG from the treatment paradigm is currently under evaluation and may be possible with the use of newer medications that have no or low resistance rates. 7. Although there is growing evidence that some types of combination therapy may decrease the chance that drug resistance will develop and increase the likelihood of long-term success in preventing graft loss and death, additional research will be required to determine which combinations will work well in the long term, and which will not.
Collapse
Affiliation(s)
- Robert G Gish
- Department of Transplantation and Medicine, California Pacific Medical Center, San Francisco, CA, USA.
| | | |
Collapse
|
|
43
|
Abstract
The reults of orthotopic liver transplantation (OLT) for hepatitis B virus (HBV) related liver disease are significantly influenced by the HBV recurrence rate. Complete eradication of hepatitis B is rarely possible after liver transplantation and hepatic and extrahepatic reservoirs are a continuous latent source of HBV recurrence. Therefore an adequate prophylaxis is mandatory. By introduction of long term passive immunoprophylaxis the recurrence rate could be markedly reduced and survival rates significantly improved. Due to the approval of antiviral drugs, especially lamivudine as the first approved antiviral agent against HBV, new prophylactic options, including combination prophylaxis, have been introduced. This modern antiviral managemant improved the outcome of hepatitis B patients after liver transplantation. The Results after OLT are nowadays reported to be as good or in a recent UNOS database report even better than in non-HBV patients. The type of recommended prophylaxis has undergone modifications within the last years and is still subject to changes due to the ongoing development of antiviral agents. In addition, due to high costs of hepatitis immunoglobulin alternatives such as prophylaxis with nucleos(t)ide analogues or vaccination are increasingly investigated. In the following, current strategies of reinfection prophylaxis and future perspectives are reviewed.
Collapse
Affiliation(s)
- Daniel Seehofer
- Department of General, Visceral, and Transplantation Surgery, Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany
| | | |
Collapse
|
|
44
|
Roche B, Samuel D. [Liver transplantation for complications of hepatitis B]. Presse Med 2006; 35:335-45. [PMID: 16493338 DOI: 10.1016/s0755-4982(06)74579-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
In the absence of prophylaxis, there is an elevated risk of virus recurrence after liver transplantation required because of chronic hepatitis B. Regardless of prophylaxis, the risk of recurrence is associated with pre-graft viral load. Long-term prophylaxis by hepatitis B immune globulin (HBIG) significantly reduces the risk of recurrence, especially if there was no pre-graft viral replication. Use of antiviral agents such as lamivudine, adefovir, tenofovir, and entecavir, control HBV replication in patients with decompensation of cirrhosis while awaiting transplantation and in patients with HBV recurrence post-graft. The risk of emergence of resistant strains limits the use of these antiviral agents. The choice of one or several combined antiviral agents depends on their resistance profiles. Combining antiviral agents and HBIG after transplantation can reduce the risk of HBV recurrence to less than 10%, even in patients with viral replication pre-graft. If there was no detectable viral load pre-graft, withdrawal of HBIG should be considered at some point, while continuing an antiviral agent or after anti-HBV vaccination.
Collapse
Affiliation(s)
- Bruno Roche
- Centre hépatobiliaire, Hôpital Paul Brousse, Villejuif.
| | | |
Collapse
|
|
45
|
Zheng S, Chen Y, Liang T, Lu A, Wang W, 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; 12:253-8. [PMID: 16447195 DOI: 10.1002/lt.20701] [Citation(s) in RCA: 126] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The aim of our study was to determine the outcomes of liver transplant recipients receiving either lamivudine (LAM) monotherapy or LAM combined with low-dose intramuscular (IM) hepatitis B Immunoglobulin (HBIG) therapy. We performed a retrospective review of the medical records of patients that had had liver transplantation in a single center for HBV-related liver diseases from December 1999 to June 2004. A total of 165 patients received LAM monotherapy (51 patients) or combined prophylaxis (114 patients) post-liver transplantation (LT) with a mean follow-up of 20.13 months. Hepatitis B relapsed in 21 patients of the hepatitis B surface antigen (HBsAg) carriers who received LAM monotherapy, with a 1- and 2-yr actuarial risk of 27.4% and 39.7%. Recurrence occurred in 16 patients of 114 patients receiving the combined prophylaxis, with a 1- and 2-yr recurrence rate of 13.5% and 15.2% (P = 0.024). A total of 25 cases (67.6%) with YMDD mutants were detected in all the 37 patients, 14 cases (66.7%) in the monotherapy group and 11 cases (68.8%) in the combination group. In conclusion, LAM and low-dose intramuscular HBIG treatment demonstrates a better result than LAM monotherapy, as prophylaxis against post-LT reinfection of the graft, but the safety and efficacy as a substitution for high-dose intravenous HBIG with LAM needs to be investigated further.
Collapse
Affiliation(s)
- Shusen Zheng
- Department of Hepatobiliary Pancreatic Surgery, Key Lab of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital of Medical College, Zhejiang University, Hang Zhou, PR China
| | | | | | | | | | | | | |
Collapse
|
|
46
|
Suehiro T, Shimada M, Kishikawa K, Shimura T, Soejima Y, Yoshizumi T, Hashimoto K, Mochida Y, Maehara Y, Kuwano H. 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; 25:1169-74. [PMID: 16343068 DOI: 10.1111/j.1478-3231.2005.01165.x] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND Hepatic grafts from hepatitis B surface antigen-negative and anti-core antibody (HBcAb)-positive donors have been shown to transmit hepatitis B virus (HBV) infection. Recently, it has been reported that combined hepatitis B immune globulin (HBIG) and lamivudine therapy is effective in the prevention of hepatitis B recurrence after living donor liver transplantation (LDLT). In this report, we assessed the efficacy of combined HBIG and lamivudine therapy in preventing HBV transmission by graft with HBcAb-positive donors. METHODS We studied 22 patients who had undergone LDLT with allografts from HBcAb-positive living donors at Gunma University Hospital and Kyushu University Hospital. Long-term combined HBIG and lamivudine therapy were administrated to all recipients. Serum samples from the donor and recipient were tested for HBcAb, HBV DNA, and hepatitis B surface antibody. Liver biopsies from grafts were tested for HBV DNA. RESULTS All recipients were HBcAb negative before LDLT. All of the donor livers were HBV DNA positive at the time of LDLT. All of the recipients had HBsAb titers greater than 300 mIU/ml 4 weeks after LDLT, and remained 100 mIU/ml thereafter. None of the recipients have become infected with HBV with a follow-up of 25-86 months. CONCLUSIONS Perioperative combined HBIG and lamivudine therapy can prevent HBV infection in recipients who receive liver grafts from HBcAb-positive donors.
Collapse
Affiliation(s)
- Taketoshi Suehiro
- Department of General Surgical Science and the 21 Century COE Program, Graduate School of Medicine, Gunma University, Maebashi, Japan.
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
47
|
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; 11:716-732. [PMID: 15973718 DOI: 10.1002/lt.20492] [Citation(s) in RCA: 127] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Affiliation(s)
- Norah Terrault
- University of California at San Francisco, San Francisco, CA
| | - Bruno Roche
- Centre Hépatobiliaire, Hôpital Paul Brousse, Villejuif, France
| | - Didier Samuel
- Centre Hépatobiliaire, Hôpital Paul Brousse, Villejuif, France
| |
Collapse
|
|
48
|
Roche B, Samuel D. [Prevention and treatment of hepatitis B virus infection after liver transplantation]. ACTA ACUST UNITED AC 2005; 29:393-404. [PMID: 15864201 DOI: 10.1016/s0399-8320(05)80787-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Affiliation(s)
- Bruno Roche
- Centre Hépatobiliaire, EA 3541, Université Paris-Sud, Villejuif, France
| | | |
Collapse
|
|
49
|
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; 11:402-9. [PMID: 15776431 DOI: 10.1002/lt.20402] [Citation(s) in RCA: 123] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatitis B virus (HBV) recurrence after liver transplantation is significantly reduced by prophylaxis with hepatitis B immune globulins (HBIG) or antiviral drugs in nonreplicating patients and by the combination of both drugs in replicating patients. However, the load of HBV DNA, which defines replicating status in patients undergoing liver transplantation, remains unclear. This study analyzes the correlation between the viral load, tested with a single amplified assay, at the time of liver transplantation, and the risk of hepatitis B recurrence in 177 HBV carriers who underwent transplantation in a single center from 1990 to 2002. Overall, HBV relapsed after surgery in 15 patients (8.5%) with a 5- and 8-year actuarial rate of recurrence of 8% and 21%, respectively. After liver transplantation hepatitis B recurred in 9% of 98 selected subjects treated only with immune globulins and in 8% of 79 viremic patients who received immune globulins and lamivudine (P = NS). A linear correlation was observed between recurrence and viral load at the time of surgery. In transplant patients with HBV DNA higher than 100,000 copies/mL, 200-99,999 copies/mL, and DNA undetectable by amplified assay, hepatitis B recurred in 50%, 7.5%, and 0% of patients, respectively. Overall, a viral load higher than 100,000 copies/mL at the time of liver transplantation was significantly associated with hepatitis B recurrence (P = .0003). In conclusion, spontaneous or antiviral-induced HBV DNA viral load at the time of surgery classifies the risk of HBV recurrence after liver transplantation and indicates the best prophylaxis strategy.
Collapse
Affiliation(s)
- Alfredo Marzano
- Department of Gastroenterology, San Giovanni Battista Hospital, Turin, Italy.
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
50
|
Roche B, Samuel D. Treatment of hepatitis B and C after liver transplantation. Part 1, hepatitis B. Transpl Int 2005; 17:746-58. [PMID: 15688165 DOI: 10.1007/s00147-004-0797-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2002] [Revised: 11/25/2003] [Accepted: 01/05/2004] [Indexed: 12/19/2022]
Abstract
The outcome of OLT for HBV-related liver disease is dependent on the prevention of allograft re-infection. Over the past decade, major advances have been made in the management of HBV transplant candidates. The advent of long-term hepatitis B immune globulin (HBIG) administration as a prophylaxis against HBV recurrence, and the introduction of new antiviral agents against HBV infection, such as lamivudine (LAM), were a major breakthrough in the management of these patients. Results of OLT for HBV infection are similar to those achieved with other indications. Pre-OLT antiviral treatment such as LAM can suppress HBV replication before OLT and thus decrease the risk of re-infection of the graft. Combination prophylaxis with LAM and HBIG after transplantation highly effectively reduces the rate of HBV re-infection, even in HBV replicative cirrhotic patients. The optimal HBIG protocol in the LAM era is yet to be defined: dosing of HBIG, routes of administration, and possibility of stopping HBIG. Several antiviral drugs have been developed for the management of HBV infection on the graft, so outcome is currently good.
Collapse
Affiliation(s)
- Bruno Roche
- Centre Hepatobiliaire, UPRES 3541, EPI 99-41, Universite Paris-Sud, Hôpital Paul Brousse, 14 Ave. P.V. Couturier, 94800 Villejuif, France
| | | |
Collapse
|