|
1
|
Izumi T, Toshima T, Itoh S, Yoshiya S, Bekki Y, Iseda N, Tsutsui Y, Toshida K, Nakayama Y, Ishikawa T, Yoshizumi T. Novel protocol for prevention from hepatitis B reactivation following living-donor liver transplantation. Hepatol Res 2024. [PMID: 39276320 DOI: 10.1111/hepr.14110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 08/06/2024] [Accepted: 08/25/2024] [Indexed: 09/16/2024]
Abstract
AIM Reactivation of hepatitis B virus (HBV) after liver transplantation (LT) remains a problem; thus, development of more effective HBV reactivation prophylaxis is desirable. We evaluated the efficacy of a combination of a long-term nucleotide analog (NA), such as entecavir (ETV) or tenofovir alafenamide (TAF), and short-term hepatitis B immunoglobulin (HBIG) in preventing HBV reactivation and compared it with conventional HBV prophylaxis. METHODS Between February 1999 and August 2023, 135 patients underwent living-donor liver transplantation for liver cirrhosis or acute liver failure caused by HBV infection or received an LT from a hepatitis B core antibody-positive donor. Recipients who had undergone LT were classified as being in the first or second era (namely until September 2017 and from October 2017), respectively, and outcomes of prophylaxis against HBV reactivation were compared between the two eras. RESULTS In the second era, recipients with HBV-related disease or who had received hepatitis B core antibody-positive liver received combination therapy with short-term HBIG and an NA such as TAF and ETV long-term. The duration of HBIG treatment was markedly shorter than in the first era in both categories of patients and HBIG could be discontinued in all cases. Surprisingly, we observed HBV reactivation in the first era, but not in the second era, in both groups. CONCLUSIONS We have established a protocol for prophylaxis against HBV reactivation using a combination of short-term HBIG and long-term NA. This protocol was found to be sufficient to prevent HBV reactivation after LT.
Collapse
Affiliation(s)
- Takuma Izumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takeo Toshima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shinji Itoh
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shohei Yoshiya
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yuki Bekki
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Norifumi Iseda
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yuriko Tsutsui
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Katsuya Toshida
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yuki Nakayama
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takuma Ishikawa
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| |
Collapse
|
|
2
|
Cholongitas E, Oikonomou T, Bafa K, Sinakos E, Papatheodoridis GV, Goulis I. Efficacy of Newer Nucleos(t)ide Analogs After Hepatitis B Immunoglobulin Discontinuation Against Hepatitis B and D Recurrence in Liver Transplant Recipients. Transplantation 2024; 108:e239-e244. [PMID: 38557857 DOI: 10.1097/tp.0000000000005027] [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: 04/04/2024]
Abstract
BACKGROUND The use of nucleos(t)ide analogs (NAs) with a high genetic barrier to resistance, namely entecavir and tenofovir, has improved the efficacy of antiviral prophylaxis against hepatitis B virus (HBV) recurrence after liver transplantation (LT). However, the optimal duration and dosage of hepatitis B immunoglobulin (HBIG) administration, particularly in patients transplanted for HBV and hepatitis D virus (HDV) coinfection, remains controversial. METHODS We evaluated 28 patients transplanted for HBV/HDV cirrhosis. After LT, each patient received a fixed scheme of low-dose HBIG plus NA for 6 mo post-LT and then continued with long-term NA prophylaxis (entecavir: 8, tenofovir: 20 patients). RESULTS During 72 mo of follow-up, reappearance of hepatitis B surface antigen at low titers was observed in 1 (3.6%) patient at 33 mo after HBIG discontinuation, which became negative after a single dose of HBIG 1000 IU/L, whereas both serum HBV DNA and HDV RNA remained persistently undetectable and without any clinical or biochemical evidence of HBV/HDV recurrence. CONCLUSIONS We showed for the first time the efficacy of a short, fixed scheme of low-dose HBIG plus NA followed by long-term NA monoprophylaxis against HBV/HDV recurrence after LT, although careful follow-up is needed after HBIG discontinuation, whereas further larger studies are needed to confirm these findings.
Collapse
Affiliation(s)
- Evangelos Cholongitas
- First Department of Internal Medicine, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - Theodora Oikonomou
- Fourth Department of Internal Medicine, Hippokratio Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Konstantina Bafa
- First Department of Internal Medicine, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - Emmanouil Sinakos
- Fourth Department of Internal Medicine, Hippokratio Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - George V Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko," Athens, Greece
| | - Ioannis Goulis
- Fourth Department of Internal Medicine, Hippokratio Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| |
Collapse
|
|
3
|
Kim DS, Yoon YI, Kim BK, Choudhury A, Kulkarni A, Park JY, Kim J, Sinn DH, Joo DJ, Choi Y, Lee JH, Choi HJ, Yoon KT, Yim SY, Park CS, Kim DG, Lee HW, Choi WM, Chon YE, Kang WH, Rhu J, Lee JG, Cho Y, Sung PS, Lee HA, Kim JH, Bae SH, Yang JM, Suh KS, Al Mahtab M, Tan SS, Abbas Z, Shresta A, Alam S, Arora A, Kumar A, Rathi P, Bhavani R, Panackel C, Lee KC, Li J, Yu ML, George J, Tanwandee T, Hsieh SY, Yong CC, Rela M, Lin HC, Omata M, Sarin SK. Asian Pacific Association for the Study of the Liver clinical practice guidelines on liver transplantation. Hepatol Int 2024; 18:299-383. [PMID: 38416312 DOI: 10.1007/s12072-023-10629-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 12/18/2023] [Indexed: 02/29/2024]
Abstract
Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.
Collapse
Affiliation(s)
- Dong-Sik Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - Young-In Yoon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | | | | | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jongman Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ho Joong Choi
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki Tae Yoon
- Department of Internal Medicine, Pusan National University College of Medicine, Yangsan, Republic of Korea
| | - Sun Young Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Cheon-Soo Park
- Department of Surgery, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Deok-Gie Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Won-Mook Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young Eun Chon
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
| | - Woo-Hyoung Kang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Ilsan, Republic of Korea
| | - Pil Soo Sung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Han Ah Lee
- Department of Internal Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Si Hyun Bae
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jin Mo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Soek Siam Tan
- Department of Medicine, Hospital Selayang, Batu Caves, Selangor, Malaysia
| | - Zaigham Abbas
- Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | - Ananta Shresta
- Department of Hepatology, Alka Hospital, Lalitpur, Nepal
| | - Shahinul Alam
- Crescent Gastroliver and General Hospital, Dhaka, Bangladesh
| | - Anil Arora
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Ashish Kumar
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Pravin Rathi
- TN Medical College and BYL Nair Hospital, Mumbai, India
| | - Ruveena Bhavani
- University of Malaya Medical Centre, Petaling Jaya, Selangor, Malaysia
| | | | - Kuei Chuan Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jun Li
- College of Medicine, Zhejiang University, Hangzhou, China
| | - Ming-Lung Yu
- Department of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | | | | | | | | | | | - H C Lin
- Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Masao Omata
- Department of Gastroenterology, Yamanashi Central Hospital, Yamanashi, Japan
- University of Tokyo, Bunkyo City, Japan
| | | |
Collapse
|
|
4
|
Sheng LP, Zhang JC, Zhong ZQ, Sheng XH, Ren J, Wang GQ. High-potency nucleos(t)ide analogues alone or plus immunoglobulin for HBV prophylaxis after liver transplantation: a meta-analysis. Hepatol Int 2023; 17:1113-1124. [PMID: 36592270 DOI: 10.1007/s12072-022-10466-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 12/01/2022] [Indexed: 01/03/2023]
Abstract
BACKGROUND The optimum prophylactic regimen against hepatitis B virus (HBV) recurrence after liver transplantation (LT) in HBV-infected patients is uncertain but of great clinical relevance. New evidence suggests that hepatitis B immunoglobulin (HBIG)-free approach would become a reasonable choice in the era of high-potency nucleos(t)ide analogues (HPNAs). We aimed to provide robust estimates for long-term survival and HBV recurrence in patients receiving different HBV-prophylaxis strategies after LT. METHODS We did a systematic review and meta-analysis using both pseudo-individual patient data recovered from included studies (IPDMA) and conventional trial-level aggregate data meta-analysis (ADMA). Hazard ratios (HRs) were calculated using different Cox proportional hazard models accounting for inter-study heterogeneity. ADMA was conducted to pool outcomes at specific time points. RESULTS A total of 16 studies involving 7897 patients and 41 studies involving 9435 were eligible for IPDMA and AMDA, respectively. Cumulative HBV recurrence rate and overall survival (OS) at 1, 3, 5 and 10 years post-LT were 0.3%, 0.9%, 1.2%, 1.7% and 95.6%, 89%, 86.4%, 86.4% in the HPNAs (i.e., entecavir and tenofovir) + HBIG combination group vs. 0.6%, 0.6%, 1.2%, 1.7% and 94.5%, 86.8%, 84.8%, 81.2% in the HPNAs monotherapy group (HR 1.20, 95% CI 0.56-2.60, p = 0.64; HR 1.09, 95% CI 0.70-1.69, p = 0.72), respectively. The results were compatible with AMDA. CONCLUSION A similar HBV recurrence and overall survival were found in patients who used HPNAs (mainly entecavir) monotherapy as in those who received a combination of HPNAs and HBIG. These findings address concerns regarding the safety and effectiveness of HPNAs monotherapy.
Collapse
Affiliation(s)
- Li-Ping Sheng
- Department of Infectious Diseases and Center for Liver Diseases, Peking University International Hospital, Life Park Road No.1, Chang Ping District, Beijing, 102206, China
| | - Jun-Chang Zhang
- Intensive Care Unit, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Zhi-Qiang Zhong
- Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Shanghai, China
| | - Xue-Han Sheng
- The First Clinical Medical College of Harbin Medical University, Harbin, Heilongjiang, China
| | - Jing Ren
- Department of Infectious Disease, The First Affiliated Hospital of the University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Gui-Qiang Wang
- Department of Infectious Diseases and Center for Liver Diseases, Peking University International Hospital, Life Park Road No.1, Chang Ping District, Beijing, 102206, China.
- Department of Infectious Diseases, Peking University First Hospital, Beijing, China.
| |
Collapse
|
|
5
|
Mangia A, Squillante MM, Fraticelli F, Cavorsi MC, Paroni G, Zaffarano L, Piazzolla AV. HDV RNA Levels and Progression of Hepatitis Delta Infection: A 14 Year Follow Up Experience in Italy. Cells 2023; 12:1413. [PMID: 37408247 DOI: 10.3390/cells12101413] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 05/12/2023] [Accepted: 05/15/2023] [Indexed: 07/07/2023] Open
Abstract
BACKGROUND Identification of outcome predictors is one of the unmet needs in chronic HDV infection. Until recently, no reliable quantitative assays for HDV RNA were available. AIMS To evaluate the impact of baseline viremia on natural history of HDV infection in a cohort of patients whose serum samples were stored at their first visit 15 years ago. METHODS Quantitative HBsAg, HBeAg, HBeAb, HBV DNA, HDV RNA, genotypes, and liver disease severity were assessed at baseline. Patients who were no longer on active follow-up were recalled and re-evaluated in August 2022. RESULTS The majority of patients were male (64.9%); the median age was 50.1 years; and all patients were Italian, with only three born in Romania. All were HBeAg negative with HBV genotype D infection. Patients were subdivided three groups: 23 were in active follow-up (Group 1), 21 were recalled due to no longer being in follow-up (Group 2), and 11 died (Group 3). Liver cirrhosis was diagnosed in 28 subjects at the first visit; 39.3% of diagnosed patients were in Group 3, 32.1% were in Group 1 and 28.6% were in Group 2 (p = 0.001). Baseline HBV DNA IU/mL Log10 were 1.6 (1.0-5.9) in Group 1, 1.3 (1.0-4.5) in Group 2, and 4.1 (1.5-4.5) in Group 3; median baseline HDV RNA Log10 levels were 4.1 (0.7-6.7) in Group 1, 3.2 (0.7-6.2) in Group 2, and 5.2 (0.7-6.7) in Group 3, resulting significantly higher rates among patients in Group 3 compared to the other groups (p = 0.038). Eighteen patients in Group 2, as compared to 7 in Group 1, had undetectable HDV RNA at the follow-up evaluation (p = 0.001). CONCLUSIONS HDV chronic infection is a heterogeneous disease. It may not only progress but also improve over time in patients, who eventually become HDV RNA-undetectable. HDV RNA levels may help identify the subgroup of patients with less progressive liver disease.
Collapse
Affiliation(s)
- Alessandra Mangia
- Liver Unit, IRCCS Fondazione "Casa Sollievo della Sofferenza", 71013 San Giovanni Rotondo, Italy
| | | | - Filippo Fraticelli
- Liver Unit, IRCCS Fondazione "Casa Sollievo della Sofferenza", 71013 San Giovanni Rotondo, Italy
| | - Maria Chiara Cavorsi
- Liver Unit, IRCCS Fondazione "Casa Sollievo della Sofferenza", 71013 San Giovanni Rotondo, Italy
| | - Giulia Paroni
- Blood Bank, IRCCS Fondazione "Casa Sollievo della Sofferenza", 71013 San Giovanni Rotondo, Italy
| | - Lucia Zaffarano
- Blood Bank, IRCCS Fondazione "Casa Sollievo della Sofferenza", 71013 San Giovanni Rotondo, Italy
| | | |
Collapse
|
|
6
|
Zheng H, Zhu Z, Wang N, Qin J, Guo Y, Xu Z, Li X, Qi C, Yuan X, Wu W, Wang J, Liu L, Nashan B. Entecavir Combined With Short-term Hepatitis B Immunoglobulin in Preventing Hepatitis B Virus Recurrence in Liver Transplant Recipients. Transplant Proc 2023; 55:408-412. [PMID: 36907782 DOI: 10.1016/j.transproceed.2023.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 02/02/2023] [Indexed: 03/12/2023]
Abstract
BACKGROUND The combination of nucleoside analogs and long-term hepatitis B immunoglobulin (HBIG) is considered to be the standard regimen for preventing hepatitis B virus (HBV) recurrence after liver transplant (LT). However, long-term use of HBIG causes many adverse effects. The aim of this study was to evaluate the effect of nucleoside analogs entecavir combined with short-term HBIG in preventing HBV recurrence after LT. METHODS This retrospective study assessed the effect a combination of entecavir and short-term HBIG in prophylaxis of HBV recurrence among 56 LT recipients who had undergone the procedure because of HBV-associated liver disease at our center between December 2017 and December 2021. All patients received entecavir treatment combined with HBIG for the prevention of hepatitis B recurrence, and HBIG treatment was withdrawn within 1 month. The patients were followed up to determine levels of hepatitis B surface antigen, antibody to hepatitis B surface antigen (HBsAb), and HBV-DNA and the recurrence rate of HBV. RESULTS Only 1 patient appeared positive for hepatitis B surface antigen at 2 months post-LT. The overall HBV recurrence rate was 1.8%. The HBsAb titers of all patients gradually decreased over time, with a median of 376.6 IU/L at 1 month post-LT and a median of 13.47 IU/L at 12 months post-LT. During the follow-up period, the HBsAb titer of the preoperative HBV-DNA-positive patients remained at a lower level than that of HBV-DNA-negative patients. CONCLUSIONS Entecavir combined with short-term HBIG can exert a good effect for the prevention of HBV reinfection post-LT.
Collapse
Affiliation(s)
- Hao Zheng
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Zebin Zhu
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Ning Wang
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Jiwei Qin
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Yafei Guo
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Zhijun Xu
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Xuefeng Li
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Can Qi
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Xiaodong Yuan
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Wei Wu
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Jizhou Wang
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Lianxin Liu
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Björn Nashan
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China.
| |
Collapse
|
|
7
|
Liver Transplantation in Hepatitis B/Hepatitis D (Delta) Virus Coinfected Recipients. Transplantation 2022; 106:1935-1939. [DOI: 10.1097/tp.0000000000004138] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
|
|
8
|
KASL clinical practice guidelines for management of chronic hepatitis B. Clin Mol Hepatol 2022; 28:276-331. [PMID: 35430783 PMCID: PMC9013624 DOI: 10.3350/cmh.2022.0084] [Citation(s) in RCA: 69] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 04/01/2022] [Indexed: 01/10/2023] Open
|
|
9
|
Duvoux C, Belli LS, Fung J, Angelico M, Buti M, Coilly A, Cortesi P, Durand F, Féray C, Fondevila C, Lebray P, Martini S, Nevens F, Polak WG, Rizzetto M, Volpes R, Zoulim F, Samuel D, Berenguer M. 2020 position statement and recommendations of the European Liver and Intestine Transplantation Association (ELITA): management of hepatitis B virus-related infection before and after liver transplantation. Aliment Pharmacol Ther 2021; 54:583-605. [PMID: 34287994 DOI: 10.1111/apt.16374] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 11/25/2020] [Accepted: 04/01/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Prophylaxis of HBV recurrence is critical after liver transplantation in HBV patients. Despite new prophylactic schemes, most European LT centres persist on a conservative approach combining hepatitis B immunoglobulin (HBIG) and nucleos(t)ides analogues (NA). AIM This setting prompted the European Liver Intestine Transplantation Association (ELITA) to look for a consensus on the prevention of HBV recurrence. METHODS Based on a 4-round Delphi process, ELITA investigated 16 research questions and established 50 recommendations. RESULTS Prophylaxis should be driven according to 3 simplified risk groups: Low and high virological risk patients, with undetectable and detectable HBV DNA pre-LT, respectively, and special populations (HDV, HCC, poorly adherent patients). In low-risk patients, short-term (4 weeks) combination of third-generation NA+ HBIG, or third generation NA monotherapy can be considered as prophylactic options. In high-risk patients, HBIG can be discontinued once HBV DNA undetectable. Combined therapy for 1 year is advised. HBV-HCC patients should be treated according to their virological risk. In HDV/HBV patients, indefinite dual prophylaxis remains the gold standard. Full withdrawal of HBV prophylaxis following or not HBV vaccination should only be attempted in the setting of clinical trials. Organs from HBsAg+ve donors may be considered after assessment of risks, benefits, and patient consent. They should not be used if HDV is present. In poorly adherent patients, dual long-term prophylaxis is recommended. Budget impact analysis should be taken into account to drive prophylactic regimen. CONCLUSIONS These ELITA recommendations should stimulate a more rational and homogeneous approach to HBV prophylaxis across LT programs.
Collapse
|
|
10
|
Orfanidou A, Papatheodoridis GV, Cholongitas E. Antiviral prophylaxis against hepatitis B recurrence after liver transplantation: Current concepts. Liver Int 2021; 41:1448-1461. [PMID: 33656809 DOI: 10.1111/liv.14860] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 01/20/2021] [Accepted: 02/13/2021] [Indexed: 12/14/2022]
Abstract
The advance in treatment against hepatitis B virus (HBV) infection with the development of nucleos(t)ide analogues (NAs) with high genetic barrier to resistance, including entecavir and tenofovir, has improved clinical outcomes of patients transplanted for HBV infection, by preventing HBV recurrence after liver transplantation (LT) effectively. Currently, after LT, the combination of hepatitis B immunoglobulin (HBIG) and a high-barrier NA is considered as the standard of care for prophylaxis against HBV recurrence. However, because of the high cost of intravenous high-dose HBIG, other routes of HBIG administration, such as intramuscular or subcutaneous, have come to the foreground. In addition, several transplant centres tend to use a NA as monoprophylaxis, following a short post-LT period of HBIG and NA combination. Lately, studies using HBIG-free prophylactic regimens with entecavir or tenofovir have shown promising outcomes in preventing HBV recurrence, mostly regarding patients with undetectable HBV DNA at the time of LT. Although vaccination against HBV has been an attractive prophylactic approach, its efficacy has been controversial. Moreover, further studies are needed regarding long-term outcomes of complete withdrawal anti-HBV prophylaxis. For patients transplanted for HBV/HDV co-infection, combined regimen should be administered for a longer period post-LT. Finally, the use of grafts from hepatitis B core antibody-positive donors is safe for HBV-negative recipients, with the administration of lifelong antiviral prophylaxis.
Collapse
Affiliation(s)
- Afroditi Orfanidou
- Academic Department of Gastroenterology, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - George V Papatheodoridis
- Academic Department of Gastroenterology, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - Evangelos Cholongitas
- First Department of Internal Medicine, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| |
Collapse
|
|
11
|
Li MS, Hou ZH, Yao GZ, Tan DM. The strategy and efficacy of prophylaxis against hepatitis B virus recurrence after liver transplantation for HBV-related diseases in the era of potent nucleos(t)ide analogues: A meta-analysis. J Dig Dis 2021; 22:91-101. [PMID: 33128339 DOI: 10.1111/1751-2980.12959] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2020] [Revised: 10/04/2020] [Accepted: 10/27/2020] [Indexed: 12/11/2022]
Abstract
OBJECTIVES This meta-analysis aimed to evaluate the clinical outcome of liver transplant (LT) recipients under potent nucleoside or nucleotide analogue (NA)-based regimens and investigate different prophylactic schemes. METHODS We followed PRISMA statement to conduct this study. Two reviewers independently searched relevant literature via PubMed, Embase, Ovid MEDLINE, Web of Science and Insightmeme. Studies were included if they evaluated hepatitis B virus (HBV) recurrence under potent NA-based regimens in patients who received HBV-related LT. Primary and secondary outcomes were HBV recurrence, hepatocellular carcinoma (HCC) recurrence, all-cause and HBV recurrence-related mortality. Incidences with 95% confidence intervals were calculated and assessed by fixed and random effects models. Subgroup analyses were used to examine the impact of different treatment strategies. RESULTS Altogether 25 studies (N = 2327) were included, with a pooled HBV recurrence rate of 1.01% (95% CI 0.53%-1.59%). HBV viremia or hepatitis D virus superinfection did not influence HBV recurrence significantly (P = 0.23 and 0.71, respectively). The recurrence rate under an indefinite combination of potent NA and hepatitis B immunoglobulin (HBIG) was lower than that under potent NA monotherapy (P = 0.000) and similar to that under NA plus a finite course of HBIG (P = 0.48). The pooled HCC recurrence rate was 5.34% (95% CI 0.78%-12.48%). HBV recurrence-related mortality and all-cause mortality were 0% and 6.95% (95% CI 4.30%-10.08%), respectively. CONCLUSIONS Potent NA-based regimens provide satisfactory HBV antiviral prophylaxis and improve long-term outcomes for LT recipients. A finite combination of potent NA and HBIG is an alternative to life-long dual therapy.
Collapse
Affiliation(s)
- Ming Shu Li
- Xiangya School of Public Health, Central South University, Changsha, Hunan Province, China
| | - Zhou Hua Hou
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
| | - Guo Zhu Yao
- School of Mathematics and Statistics, Changsha University of Science and Technology, Changsha, Hunan Province, China
| | - De Ming Tan
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
| |
Collapse
|
|
12
|
Rodríguez M, Buti M, Esteban R, Lens S, Prieto M, Suárez E, García-Samaniego J. Consensus document of the Spanish Association for Study of the Liver on the treatment of hepatitis B virus infection (2020). GASTROENTEROLOGIA Y HEPATOLOGIA 2020; 43:559-587. [PMID: 32778356 DOI: 10.1016/j.gastrohep.2020.03.011] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Accepted: 03/31/2020] [Indexed: 12/14/2022]
Abstract
Hepatitis B virus (HBV) infection remains a global public health problem. HBV vaccination is the most effective tool to reduce the incidence of HBV disease. Despite there has not been new clinical developments for the treatment of chronic hepatitis B in the last few years, changing epidemiology and current insights on natural history, diagnostic tools and therapy indications make necessary an update of the former version of the consensus document of the Spanish Association for Study of the Liver on the treatment of hepatitis B infection published in 2012. The current document updates the management of chronic hepatitis B. The treatment of choice is the long-term administration of a nucleos(t)ide analogue with high barrier to resistance (entecavir, tenofovir or tenofovir alafenamide). Pegylated interferon may be an option in patients with non-advanced liver disease, but its applicability is limited due to the low efficacy and poor tolerability. All patients must be monitored for the risk of progression to advanced liver disease and development of hepatocellular carcinoma.
Collapse
Affiliation(s)
- Manuel Rodríguez
- Sección de Hepatología, Servicio de Digestivo, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, España.
| | - María Buti
- Servicio de Hepatología-Medicina Interna, Hospital Universitario Valle Hebrón, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CiBERehd), Barcelona, España
| | - Rafael Esteban
- Servicio de Hepatología-Medicina Interna, Hospital Universitario Valle Hebrón, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CiBERehd), Barcelona, España
| | - Sabela Lens
- Servicio de Hepatología, Hospital Clínic, IDIBAPS, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CiBERehd), Universidad de Barcelona, Barcelona, España
| | - Martín Prieto
- Sección de Hepatología, Servicio de Medicina Digestiva, Hospital Universitari ì Politècnic La Fe, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CiBERehd), Valencia, España
| | - Emilio Suárez
- Unidad de Enfermedades Digestivas, Hospital Universitario Virgen de Valme, Sevilla, España
| | - Javier García-Samaniego
- Unidad de Hepatología, Hospital Universitario La Paz, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CiBERehd), Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid, España.
| |
Collapse
|
|
13
|
Manini MA, Bruce M, Whitehouse G, Mazzarelli C, Considine A, Agarwal K, Suddle A, Fagiuoli S, Heaton N, Heneghan M. A Very Short Course of HBIg+NA Followed by Entecavir or Tenofovir Monotherapy Prevents HBV Recurrence in Low-Risk Liver Transplant Recipients. Transplant Proc 2020; 53:207-214. [PMID: 32605776 DOI: 10.1016/j.transproceed.2020.04.1822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2019] [Revised: 03/20/2020] [Accepted: 04/25/2020] [Indexed: 11/27/2022]
Abstract
BACKGROUND Monoprophylaxis with third-generation nucleos(t)ide analogues (NAs) can be safely adopted in hepatitis B virus (HBV)-positive, liver transplantation (LT) patients after at least 6 months of HBV immunoglobulin (HBIg)+NA. We investigated the efficacy of earlier initiation of post-LT entecavir (ETV) or tenofovir (TDF) monoprophylaxis. METHODS Between September 2011 and January 2017, all consecutive hepatitis B surface antigen (HBsAg)-positive transplanted patients were scheduled to receive HBIg with ETV or TDF for a period related to the risk for HBV reinfection: 1. low-risk patients (HBeAg-negative and HBV DNA < 12 IU/mL before LT) were due to withdraw from HBIg once HBsAg had become negative after a minimum of 7 days of HBIg+NA; 2. high-risk patients were due to receive HBIg for at least 6 months, after which they continued with third-generation NA monotherapy, only. RESULTS Twenty patients with a median interquartile range (IQR) follow-up of 46 (64-39) months were enrolled in the study (40% receiving ETV, 60% receiving TDF). Two low-risk patients refused early HBIg withdrawal and were therefore treated and analyzed along with the high-risk group. Eventually, there were 2 groups: group A, which included 12 low-risk patients, and group B, which included 8 patients (six high-risk, 2 low-risk). After transplantation, group A and B patients received HBIg+NA for a median (IQR) time of 7 (9-7) days and 9 (13-5) months, respectively. All 20 recipients demonstrated HBV DNA < 12 IU/mL and stable graft function during follow-up. Two patients (10%), 1 from each group, had HBsAg relapse. Notably, both patients who relapsed had hepatocellular carcinoma (HCC) diagnosed before LT and showed very low levels (< 0.25 IU/mL) of HBsAg after recurrence. CONCLUSION In low-risk HBsAg-positive recipients, HBIg may be safely discontinued within 2 weeks of LT and replaced by ETV or TDF monotherapy.
Collapse
Affiliation(s)
- Matteo A Manini
- Institute of Liver Studies, King's College Hospital, London, United Kingdom; Gastroenterology, Hepatology, and Transplant Unit, Department of Specialty and Transplant Medicine, Azienda Socio Sanitaria Territoriale (ASST) Papa Giovanni XXIII, Bergamo, Italy.
| | - Matthew Bruce
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Gavin Whitehouse
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Chiara Mazzarelli
- Institute of Liver Studies, King's College Hospital, London, United Kingdom; Gastroenterology and Hepatology, ASST Ospedale Metropolitano Niguarda, Milano, Italy
| | - Aisling Considine
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Kosh Agarwal
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Abid Suddle
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Stefano Fagiuoli
- Gastroenterology, Hepatology, and Transplant Unit, Department of Specialty and Transplant Medicine, Azienda Socio Sanitaria Territoriale (ASST) Papa Giovanni XXIII, Bergamo, Italy
| | - Nigel Heaton
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Michael Heneghan
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| |
Collapse
|
|
14
|
Fernández I, Pascasio JM, Colmenero J. Prophylaxis and treatment in liver transplantation. VII Consensus Document of the Spanish Society of Liver Transplantation. GASTROENTEROLOGIA Y HEPATOLOGIA 2020; 43:169-177. [PMID: 32094045 DOI: 10.1016/j.gastrohep.2019.11.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Revised: 11/05/2019] [Accepted: 11/20/2019] [Indexed: 12/26/2022]
Abstract
Whilst prophylaxis of hepatitis B is universally accepted after liver transplantation (LT), national recommendations for the prophylaxis and treatment of hepatitis B virus (HBV) infection after LT are lacking in Spain. The aim of the VII consensus meeting organised by the Spanish Society of Liver Transplantation (SETH) was to set recommendations on the prophylaxis and treatment of hepatitis B after LT. The scientific evidence and strength of recommendations was evaluated by using the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) system. This document describes the recommendations and their level of evidence for: the definition and risk factors for hepatitis B recurrence after LT, monitoring and prophylaxis of hepatitis B recurrence at different periods after LT, treatment of hepatitis B before and after LT, and the prophylaxis of HBV infection by the recipients of LT with hepatitis B core antigen positive donors.
Collapse
Affiliation(s)
- Inmaculada Fernández
- Sociedad Española de Trasplante Hepático, Unidad de Hepatología y Trasplante Hepático, Hospital 12 de Octubre, Madrid, España
| | - Juan Manuel Pascasio
- Sociedad Española de Trasplante Hepático, Unidad de Trasplante Hepático, Hospital Virgen del Rocío, Sevilla, España
| | - Jordi Colmenero
- Unidad de Trasplante Hepático, Hospital Clínic, IDIBAPS, CIBERehd, Univ. Barcelona, Barcelona, España.
| | | | | |
Collapse
|
|
15
|
Tao Y, Wu D, Zhou L, Chen E, Liu C, Tang X, Jiang W, Han N, Li H, Tang H. Present and Future Therapies for Chronic Hepatitis B. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1179:137-186. [PMID: 31741336 DOI: 10.1007/978-981-13-9151-4_6] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Chronic hepatitis B (CHB) remains the leading cause of liver-related morbidity and mortality across the world. If left untreated, approximately one-third of these patients will progress to severe end-stage liver diseases including liver failure, cirrhosis, and hepatocellular carcinoma (HCC). High level of serum HBV DNA is strongly associated with the development of liver failure, cirrhosis, and HCC. Therefore, antiviral therapy is crucial for the clinical management of CHB. Current antiviral drugs including nucleoside/nucleotide analogues (NAs) and interferon-α (IFN-α) can suppress HBV replication and reduce the progression of liver disease, thus improving the long-term outcomes of CHB patients. This chapter will discuss the standard and optimization antiviral therapies in treatment-naïve and treatment-experienced patients, as well as in the special populations. The up-to-date advances in the development of new anti-HBV agents will be also discussed. With the combination of the current antiviral drugs and the newly developed antiviral agents targeting the different steps of the viral life cycle or the newly developed agents modulating the host immune responses, the ultimate eradication of HBV will be achieved in the future.
Collapse
Affiliation(s)
- Yachao Tao
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Dongbo Wu
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Lingyun Zhou
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Enqiang Chen
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Changhai Liu
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xiaoqiong Tang
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Wei Jiang
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Ning Han
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Hong Li
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
| | - Hong Tang
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
| |
Collapse
|
|
16
|
KASL clinical practice guidelines for management of chronic hepatitis B. Clin Mol Hepatol 2019; 25:93-159. [PMID: 31185710 PMCID: PMC6589848 DOI: 10.3350/cmh.2019.1002] [Citation(s) in RCA: 165] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Accepted: 03/25/2019] [Indexed: 02/06/2023] Open
|
|
17
|
Coffin CS, Fung SK, Alvarez F, Cooper CL, Doucette KE, Fournier C, Kelly E, Ko HH, Ma MM, Martin SR, Osiowy C, Ramji A, Tam E, Villeneuve JP. Management of Hepatitis B Virus Infection: 2018 Guidelines from the Canadian Association for the Study of Liver Disease and Association of Medical Microbiology and Infectious Disease Canada. CANADIAN LIVER JOURNAL 2018; 1:156-217. [PMID: 35992619 PMCID: PMC9202759 DOI: 10.3138/canlivj.2018-0008] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Accepted: 04/17/2018] [Indexed: 08/01/2023]
Abstract
Hepatitis B virus (HBV) infection is an important public health problem in Canada. In keeping with evolving evidence and understanding of HBV pathogenesis, the Canadian Association for the Study of Liver Disease periodically publishes HBV management guidelines. The goals of the 2018 guidelines are to (1) highlight the public health impact of HBV infection in Canada and the need to improve diagnosis and linkage to care, (2) recommend current best-practice guidelines for treatment of HBV, (3) summarize the key HBV laboratory diagnostic tests, and (4) review evidence on HBV management in special patient populations and include more detail on management of HBV in pediatric populations. An overview of novel HBV tests and therapies for HBV in development is provided to highlight the recent advances in HBV clinical research. The aim and scope of these guidelines are to serve as an up-to-date, comprehensive resource for Canadian health care providers in the management of HBV infection.
Collapse
Affiliation(s)
- Carla S. Coffin
- Cumming School of Medicine, University of Calgary, Calgary, Alberta
| | - Scott K. Fung
- Faculty of Medicine, University of Toronto, Toronto, Ontario
| | - Fernando Alvarez
- Centre hospitalier de l’université de Montréal (CHUM)—CHU Sainte-Justine, Montreal, Québec
| | - Curtis L. Cooper
- Division of Infectious Diseases, Department of Medicine, University of Ottawa, Ottawa, Ontario
| | - Karen E. Doucette
- Division of Infectious Diseases, University of Alberta, Edmonton, Alberta
| | - Claire Fournier
- Department of Medicine, Université de Montréal, Montreal, Québec
| | - Erin Kelly
- Division of Gastroenterology, Department of Medicine, University of Ottawa, Ottawa, Ontario
| | - Hin Hin Ko
- Faculty of Medicine, University of British Columbia, Vancouver, British Columbia
| | - Mang M Ma
- Division of Gastroenterology, University of Alberta, Edmonton, Alberta
| | | | - Carla Osiowy
- Viral Hepatitis and Bloodborne Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba
| | - Alnoor Ramji
- St. Paul’s Hospital, Vancouver, British Columbia
| | - Edward Tam
- LAIR Centre, Vancouver, British Columbia
| | | |
Collapse
|
|
18
|
Chien RN, Kao JH, Peng CY, Chen CH, Liu CJ, Huang YH, Hu TH, Yang HI, Lu SN, Ni YH, Chuang WL, Lee CM, Wu JC, Chen PJ, Liaw YF. Taiwan consensus statement on the management of chronic hepatitis B. J Formos Med Assoc 2018; 118:7-38. [PMID: 30527436 DOI: 10.1016/j.jfma.2018.11.008] [Citation(s) in RCA: 71] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2018] [Revised: 11/06/2018] [Accepted: 11/15/2018] [Indexed: 01/10/2023] Open
Abstract
The experts of Taiwan Association for the Study of Liver (TASL) have actively participated and led the guidelines on hepatitis B virus (HBV) management by Asian Pacific Association for the Study of Liver (APASL) which is the first international association for the study of liver to publish the statement on HBV management before. However, there are more and more new data on the natural history and treatment of HBV infection in the past decade. These include new application of an old biomarker (quantitative HBsAg), clinical significance of HBV genotype and naturally occurring mutations, the role of non-invasive examination in evaluating severity of hepatic fibrosis, clinical significance of outcome calculators, new drug or new combination strategies towards more effective therapy and organ transplantation including liver and non-liver transplantation. It is time to publish the guidelines on HBV management of Taiwan. Hence, TASL have conducted an expert meeting to review, to discuss and to debate the relevant literatures, followed by draft the manuscript of HBV management guidelines and recommendations. The guidelines include general management, indications for fibrosis assessment, time to start or stop drug therapy, choice of drug to initiate therapy, when and how to monitor the patients during and after stopping drug therapy. Recommendations on the therapy of patients in special circumstances, including women in childbearing age, patients with antiviral drug resistance, concurrent viral infection, hepatic decompensation, patient receiving immune suppression or chemotherapy and patients in the setting of liver transplantation and hepatocellular carcinoma, are also included.
Collapse
Affiliation(s)
- Rong-Nan Chien
- Liver Research Unit, Linkou Chang Gung Memorial Hospital and University College of Medicine, Taoyuan, Taiwan.
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Cheng-Yuan Peng
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chien-Hung Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chun-Jen Liu
- Graduate Institute of Clinical Medicine, Department of Internal Medicine and Hepatitis Research Center, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Tsung-Hui Hu
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Hwa-I Yang
- Department of Genomic Research Center, Sinica Academia, Taipei, Taiwan
| | - Sheng-Nan Lu
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Yen-Hsuan Ni
- Department of Pediatrics, National Taiwan University College of Medicine and Children's Hospital, Taipei, Taiwan
| | - Won-Long Chuang
- Division of Hepatobiliary and Pancreas, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Chuan-Mo Lee
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jaw-Chin Wu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Pei-Jer Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Yun-Fan Liaw
- Liver Research Unit, Linkou Chang Gung Memorial Hospital and University College of Medicine, Taoyuan, Taiwan
| |
Collapse
|
|
19
|
Manini MA, Whitehouse G, Bruce M, Passerini M, Lim TY, Carey I, Considine A, Lampertico P, Suddle A, Heaton N, Heneghan M, Agarwal K. Entecavir or tenofovir monotherapy prevents HBV recurrence in liver transplant recipients: A 5-year follow-up study after hepatitis B immunoglobulin withdrawal. Dig Liver Dis 2018; 50:944-953. [PMID: 29735294 DOI: 10.1016/j.dld.2018.03.032] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2017] [Revised: 03/03/2018] [Accepted: 03/26/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Recent data suggest that oral third-generation nucleos(t)ide analogs (NA) monoprophylaxis following hepatitis B immunoglobulin (HBIg) withdrawal may be effective to prevent HBV reinfection after liver transplantation (LT). PATIENTS AND METHODS Between 01/2010 and 03/2012, all HBV monoinfected and HBV/HDV co-infected LT patients followed in our centre withdrew HBIg ± NA and were commenced on either ETV or TDF as monotherapy. RESULTS Seventy-seven patients were included in the study (55% TDF, 45% ETV). Group A comprised 69 HBV monoinfected patients and Group B 8 HBV/HDV co-infected patients. After HBIg withdrawal, Groups A and B patients were followed for 69 (range 13-83) months and 61 (range 31-78) months, respectively. No Group B patients had HBsAg or HBV DNA recurrence, while 6 (9%) Group A patients became HBsAg-positive after a median of 18 (range 1-40) months. The cumulative 5-year incidence of HBsAg recurrence was 9%. All 6 patients demonstrated undetectable HBV-DNA levels and stable graft function during 30 months of additional follow-up. In 3/6 patients, seroconversion was transitory, while the remaining 3 showed HBsAg levels <0.13 IU/mL over the entire period of observation. Pre-LT HCC emerged as the strongest predictor of HBsAg recurrence. CONCLUSION HBIG can be safely discontinued in HBsAgpositive LT recipients and replaced by ETV or TDF monotherapy.
Collapse
Affiliation(s)
- Matteo A Manini
- Institute of Liver Studies, King's College Hospital, London, United Kingdom; A.M. and A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
| | - Gavin Whitehouse
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Matthew Bruce
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Matteo Passerini
- A.M. and A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Tiong Y Lim
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Ivana Carey
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Aisling Considine
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Pietro Lampertico
- A.M. and A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Abid Suddle
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Nigel Heaton
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Michael Heneghan
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Kosh Agarwal
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| |
Collapse
|
|
20
|
Short Course of Postoperative Hepatitis B Immunoglobulin Plus Antivirals Prevents Reinfection of Liver Transplant Recipients. Transplantation 2017; 101:2079-2082. [PMID: 28880197 DOI: 10.1097/tp.0000000000001786] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND Hepatitis B immune globulin (HBIG) has been an integral component of prophylaxis against hepatitis B virus (HBV) recurrence in liver transplantation (LT) recipients, but HBIG is costly and inconvenient to administer, prompting consideration of alternative regimens. METHODS In this retrospective cohort, we report on the success of antiviral therapy combined with a short course (in hospital only) HBIG in liver transplant recipients with HBV DNA less than 100 IU/mL pre-LT. RESULTS A total of 42 hepatitis B surface antigen (HBsAg) positive, human immunodeficiency virus and hepatitis D virus-negative patients with pretransplant HBV DNA undetectable to 100 IU/mL who received HBIG 5000 IU in anhepatic phase and daily for 5 days together with nucleos(t)ide analogues indefinitely yielded 1- and 3-year cumulative incidences of recurrence, defined by positive serum HBsAg, of 2.9% (upper 95% confidence interval, 19%). One patient had HBV viremia 16 months post-LT without detectable HBsAg. Both patients with either HBsAg positivity or viremia had recurrent hepatocellular carcinoma diagnosed within a month of detection. Post-LT survival was 98% and 94% at 1 and 5 years, respectively. CONCLUSIONS We conclude that a very short course of HBIG combined with long-term antiviral therapy is highly effective in preventing HBV recurrence and should be the preferred strategy for LT recipients with undetectable or low-level viremia at time of LT.
Collapse
|
|
21
|
Han S, Na GH, Kim DG. A 6-month mixed-effect pharmacokinetic model for post-transplant intravenous anti-hepatitis B immunoglobulin prophylaxis. DRUG DESIGN DEVELOPMENT AND THERAPY 2017; 11:2099-2107. [PMID: 28744101 PMCID: PMC5513836 DOI: 10.2147/dddt.s134711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Background Although individualized dosage regimens for anti-hepatitis B immunoglobulin (HBIG) therapy have been suggested, the pharmacokinetic profile and factors influencing the basis for individualization have not been sufficiently assessed. We sought to evaluate the pharmacokinetic characteristics of anti-HBIG quantitatively during the first 6 months after liver transplantation. Methods Identical doses of 10,000 IU HBIG were administered to adult liver transplant recipients daily during the first week, weekly thereafter until 28 postoperative days, and monthly thereafter. Blood samples were obtained at days 1, 7, 28, 84, and 168 after transplantation. Plasma HBIG titer was quantified using 4 different immunoassay methods. The titer determined by each analytical method was used for mixed-effect modeling, and the most precise results were chosen. Simulations were performed to predict the plausible immunoglobulin maintenance dose. Results HBIG was eliminated from the body most rapidly in the immediate post-transplant period, and the elimination rate gradually decreased thereafter. In the early post-transplant period, patients with higher DNA titer tend to have lower plasma HBIG concentrations. The maintenance doses required to attain targets in 90%, 95%, and 99% of patients were ~15.3, 18.2, and 25.1 IU, respectively, multiplied by the target trough level (in IU/L). Conclusion The variability (explained and unexplained) in HBIG pharmacokinetics was relatively larger in the early post-transplant period. Dose individualization based upon patient characteristics should be adjusted focusing quantitatively on the early post-transplant period.
Collapse
Affiliation(s)
- Seunghoon Han
- Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul, South Korea.,Pharmacometrics Institute for Practical Education and Training, The Catholic University of Korea, Seocho-gu, Seoul, South Korea
| | - Gun Hyung Na
- Department of Surgery, Seoul St Mary's Hospital, The Catholic University of Korea, Seocho-gu, Seoul, South Korea
| | - Dong-Goo Kim
- Department of Surgery, Seoul St Mary's Hospital, The Catholic University of Korea, Seocho-gu, Seoul, South Korea
| |
Collapse
|
|
22
|
Zhou K, Terrault N. Management of hepatitis B in special populations. Best Pract Res Clin Gastroenterol 2017; 31:311-320. [PMID: 28774413 PMCID: PMC6548717 DOI: 10.1016/j.bpg.2017.06.002] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Revised: 06/04/2017] [Accepted: 06/05/2017] [Indexed: 01/31/2023]
Abstract
Special populations infected with chronic HBV include those with decompensated cirrhosis, coinfections (HIV, HCV, HDV), hemodialysis and renal failure, immunosuppressed including transplant patients, children and women in pregnancy. These populations differ in their natural history and risk for liver-related complications, the indications for anti-HBV therapy as well as the recommendations regarding the HBV drugs used, duration of therapy and anticipated endpoints. Reflecting the special populations with substantive changes in management in recent years, this review focuses on HBV-HIV coinfected patients, immunosuppressed patients at risk for reactivation, liver transplant recipients and pregnant women. Management of women in the context of pregnancy and post-partum requires consideration of risks to mother and fetus/infant, including the risk of mother-to-child transmission. HBV-HIV coinfected patients require initiation of treatment concurrent with their HIV therapy and the HBV drugs used must by selected to minimize HIV and HBV resistance long-term. Increasing recognition of the risk for HBV reactivation with immunosuppressive therapy has led to recommendations to use prophylactic HBV therapy in patients with moderate to high risk of reactivation. Liver transplant recipients with HBV require life-long therapy to prevent or treat HBV infection but with current therapies, graft and patient survival are excellent.
Collapse
Affiliation(s)
- Kali Zhou
- Division of Gastroenterology/Hepatology, University of California San Francisco, USA
| | - Norah Terrault
- Division of Gastroenterology/Hepatology, University of California San Francisco, USA
| |
Collapse
|
|
23
|
Zhang L, Zhang FK. Recent advances in treatment of chronic hepatitis B with entecavir. Shijie Huaren Xiaohua Zazhi 2017; 25:7-16. [DOI: 10.11569/wcjd.v25.i1.7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [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
Entecavir (ETV) is a potent hepatitis B virus inhibitor with a high barrier to resistance, and it has been recommended as one of the first-line drugs for treating chronic hepatitis B (CHB) by guidelines from several international and national societies. This paper reviews the recent advances in the treatment of CHB with ETV, in terms of treatment adherence, efficacy in the treatment of various kinds of patients with CHB, management of patients with partial virological response, viral resistance or treatment failure to ETV, treatment cessation, sequential or combination therapy with ETV and pegylated interferon, as well as the surveillance of hepatocellular carcinoma.
Collapse
|
|
24
|
Zhang L, Zhang FK. Treatment of chronic hepatitis B with tenofovir. Shijie Huaren Xiaohua Zazhi 2016; 24:4279-4287. [DOI: 10.11569/wcjd.v24.i31.4279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [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
Tenofovir (TDF) is a potent hepatitis B virus (HBV) inhibitor with a high barrier to drug resistance, and it has been recommended as one of the first-line drugs to treat chronic hepatitis B (CHB). This paper reviews the recent advances in the treatment of CHB with TDF, especially in terms of its efficacy as first-line and second-line antiviral therapies as well as its role in the prevention of mother-to-child HBV transmission.
Collapse
|
|
25
|
Wranke A, Wedemeyer H. Antiviral therapy of hepatitis delta virus infection - progress and challenges towards cure. Curr Opin Virol 2016; 20:112-118. [PMID: 27792905 DOI: 10.1016/j.coviro.2016.10.002] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2016] [Revised: 10/03/2016] [Accepted: 10/10/2016] [Indexed: 12/14/2022]
Abstract
Hepatitis B-/D-virus co-infection causes the most severe form of viral hepatitis, frequently leading to liver cirrhosis, hepatic decompensation and consecutive liver-related mortality. Treatment options for hepatitis delta are limited. The only recommended therapy is pegylated interferon alpha which leads to virological responses in about 25-30% of patients. However, interferon therapy is associated with frequent side-effects and late HDV RNA relapses have been described during long-term follow even in patients who were HDV RNA negative 24 weeks after the end of therapy. Thus, alternative treatment options are urgently needed. Clinical studies have been performed exploring prenylation inhibitors, viral entry inhibitors and nucleic acid polymers to block particle release. We here summarize the progress and challenges towards cure of HDV infection.
Collapse
Affiliation(s)
- Anika Wranke
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; German Center for Infection Research (DZIF), Partner Side HepNet Study-House, Hannover, Germany; HepNet Study-House, Hannover, Germany; Integrated Research and Treatment Center Transplantation, Hannover Medical School, Germany.
| |
Collapse
|
|
26
|
Cholongitas E, Goulis I, Antoniadis N, Fouzas I, Imvrios G, Giakoustidis D, Giouleme O, Papanikolaou V, Akriviadis E, Vasiliadis T. Nucleos(t)ide analog(s) prophylaxis after hepatitis B immunoglobulin withdrawal against hepatitis B and D recurrence after liver transplantation. Transpl Infect Dis 2016; 18:667-673. [PMID: 27421122 DOI: 10.1111/tid.12575] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2016] [Revised: 03/22/2016] [Accepted: 05/05/2016] [Indexed: 12/23/2022]
Abstract
BACKGROUND/AIMS Nucleos(t)ide analogs (NAs) have made a hepatitis B immunoglobulin (HBIG)-sparing protocol an attractive approach against hepatitis B virus (HBV) recurrence after liver transplantation (LT). However, this approach is considered controversial in patients transplanted for HBV and hepatitis D (HDV) co-infection. MATERIAL/METHODS All patients transplanted for HBV/HDV cirrhosis were evaluated. After LT, each patient received HBIG + NAs and then continued with NAs prophylaxis. All patients were followed up with HBV serum markers and HBV DNA, while anti-HDV/HDV RNA was performed in those with HBV recurrence. RESULTS A total of 34 recipients were included (22 men, age: 46.7 ± 16 years). After HBIG discontinuation, NAs were received as monoprophylaxis (lamivudine [LAM]: 2, adefovir [AFV]: 1, entecavir: 9, tenofovir [TDF]: 12) or dual prophylaxis (LAM + AFV [or TDF]: 10 patients). Two (5.8%) of the 34 patients had HBV/HDV recurrence after HBIG withdrawal (median follow-up: 28 [range, 12-58] months). These 2 patients had undetectable HBV DNA at LT. Statistical analysis revealed that those with recurrence had received HBIG for shorter period, compared to those without recurrence (median: 9 vs. 28 months, P = 0.008). CONCLUSIONS We showed for the first time, to our knowledge, that maintenance therapy with NAs prophylaxis after HBIG discontinuation was effective against HBV/HDV recurrence, but it seems that a longer period of HBIG administration might be needed before it is withdrawn after LT.
Collapse
Affiliation(s)
- E Cholongitas
- 4th Department of Internal Medicine, Medical School of Aristotle University, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece.
| | - I Goulis
- 4th Department of Internal Medicine, Medical School of Aristotle University, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece
| | - N Antoniadis
- Department of Transplant Surgery, Medical School of Aristotle University, Thessaloniki, Greece
| | - I Fouzas
- Department of Transplant Surgery, Medical School of Aristotle University, Thessaloniki, Greece
| | - G Imvrios
- Department of Transplant Surgery, Medical School of Aristotle University, Thessaloniki, Greece
| | - D Giakoustidis
- Department of Transplant Surgery, Medical School of Aristotle University, Thessaloniki, Greece
| | - O Giouleme
- Department of Transplant Surgery, Medical School of Aristotle University, Thessaloniki, Greece
| | - V Papanikolaou
- Department of Transplant Surgery, Medical School of Aristotle University, Thessaloniki, Greece
| | - E Akriviadis
- 4th Department of Internal Medicine, Medical School of Aristotle University, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece
| | - T Vasiliadis
- 3rd Department of Internal Medicine, Medical School of Aristotle University Papageorgiou General Hospital of Thessaloniki, Thessaloniki, Greece
| |
Collapse
|
|
27
|
Lenci I, Baiocchi L, Tariciotti L, Di Paolo D, Milana M, Santopaolo F, Manzia TM, Toti L, Svicher V, Tisone G, Perno CF, Angelico M. Complete hepatitis B virus prophylaxis withdrawal in hepatitis B surface antigen-positive liver transplant recipients after longterm minimal immunosuppression. Liver Transpl 2016; 22:1205-1213. [PMID: 27272189 DOI: 10.1002/lt.24493] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Revised: 05/03/2016] [Accepted: 05/05/2016] [Indexed: 02/05/2023]
Abstract
Tailored approaches have been attempted to prevent hepatitis B virus (HBV) reinfection in antibodies against hepatitis B surface antigen (HBsAg)-positive liver transplantation (LT) recipients in order to minimize the use of hepatitis B immune globulin (HBIG) and nucleoside analogues (NAs). We report the results of complete HBV prophylaxis withdrawal after a follow-up of at least 6 years in LT recipients with undetectable serum HBV DNA and intrahepatic total HBV DNA and covalently closed circular DNA at LT. We included 30 HBsAg positive, hepatitis B e antigen-negative recipients, 6 with hepatitis C virus and 7 with hepatitis D virus coinfection, who had received HBIG plus NA for at least 5 years after LT. Stepwise HBIG and NA withdrawal was performed in two 6-month periods under strict monitoring of HBV virology. All patients underwent a clinical, biochemical, and virological follow-up at 3-6 month intervals. HBV recurrence (HBsAg seroreversion ± detectable HBV DNA) occurred in 6 patients: in 1 patient after HBIG interruption and in 5 after both HBIG and NA cessation. Only 3 patients required reinstitution of HBV prophylaxis because of persistent HBV replication, and all achieved optimal control of HBV infection and did not experience clinical events. The other who recurred showed only short-lasting HBsAg positivity, with undetectable HBV DNA, followed by spontaneous anti-HBs seroconversion. An additional 15 patients mounted an anti-HBs titer, without previous serum HBsAg detectability. At the end of follow-up, 90% of patients were still prophylaxis-free, 93.3% were HBsAg negative, and 100% were HBV DNA negative; 60% had anti-HBs titers >10 IU/L (median, 143; range, 13-1000). This small series shows that complete prophylaxis withdrawal is safe in patients transplanted for HBV-related disease at low risk of recurrence and is often followed by spontaneous anti-HBs seroconversion. Further studies are needed to confirm this finding. Liver Transplantation 22 1205-1213 2016 AASLD.
Collapse
Affiliation(s)
- Ilaria Lenci
- Hepatology Unit, Tor Vergata University, Rome, Italy
| | | | | | | | | | | | | | - Luca Toti
- Liver Transplant Unit, Tor Vergata University, Rome, Italy
| | - Valentina Svicher
- Laboratory of Molecular Virology, Tor Vergata University, Rome, Italy
| | | | | | | |
Collapse
|
|
28
|
Zheng JN, Zou TT, Zou H, Zhu GQ, Ruan LY, Cheng Z, Van Poucke S, Zheng MH. Comparative efficacy of oral nucleotide analogues for the prophylaxis of hepatitis B virus recurrence after liver transplantation: a network meta-analysis. Expert Rev Anti Infect Ther 2016; 14:979-87. [PMID: 27491868 DOI: 10.1080/14787210.2016.1220831] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Prophylactic nucleos(t)ide anologues against hepatitis B virus (HBV) recurrence after liver transplantation (LT) include lamivudine, entecavir, tenofovir, adefovir. Since the most effective strategies for post-LT remain inconclusive, we aimed to compare 6 different treatment options (lamivudine, entecavir, tenofovir, adefovir, lamivudine plus adefovir, lamivudine plus tenofovir) in terms of HBV recurrence after LT using network meta-analysis. METHODS The search identified seventeen studies involving 6 different prophylactic regimens covering 7274 patients. RESULTS Compared with entecavir, lamivudine plus tenofovir (OR 2.00, 95%CI 0.02-183.29), lamivudine plus adefovir, (OR 2.83, 95%CI 0.18-33.57), tenofovir (OR 1.11, 95%CI 0.22-5.80), adefovir (OR 3.78, 95%CI 0.59-22.16), lamivudine (OR 4.62, 95%CI 1.75-11.39) were associated with an increased risk of HBV recurrence. CONCLUSION Entecavir resulted with the highest probability (31%) as the best prophylactic option on reducing the risk of HBV recurrence. Entecavir is the preferred oral NAs treatment compared to other five different prophylactic regimens in the prevention of HBV recurrence after LT.
Collapse
Affiliation(s)
- Ji-Na Zheng
- a Department of Hepatology, Liver Research Center , the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.,b School of the First Clinical Medical Sciences , Wenzhou Medical University , Wenzhou , China
| | - Tian-Tian Zou
- a Department of Hepatology, Liver Research Center , the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.,c School of the Second Clinical Medical Sciences , Wenzhou Medical University , Wenzhou , China
| | - Hai Zou
- d Department of Infection Diseases , Zhejiang Provincial People's Hospital , Hangzhou , China
| | - Gui-Qi Zhu
- a Department of Hepatology, Liver Research Center , the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.,b School of the First Clinical Medical Sciences , Wenzhou Medical University , Wenzhou , China
| | - Lu-Yi Ruan
- a Department of Hepatology, Liver Research Center , the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.,b School of the First Clinical Medical Sciences , Wenzhou Medical University , Wenzhou , China
| | - Zhang Cheng
- a Department of Hepatology, Liver Research Center , the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.,b School of the First Clinical Medical Sciences , Wenzhou Medical University , Wenzhou , China
| | - Sven Van Poucke
- e Department of Anesthesiology, Intensive Care, Emergency Medicine and Pain Therapy , Ziekenhuis Oost-Limburg , Genk , Belgium
| | - Ming-Hua Zheng
- a Department of Hepatology, Liver Research Center , the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.,f Institute of Hepatology , Wenzhou Medical University , Wenzhou , China
| |
Collapse
|
|
29
|
Sinakos E, Antoniadis N, Goulis I, Cholongitas E, Kiapidou S, Tsakni E, Vasiliadis T, Papanikolaou V, Akriviadis E. Nucleos(t)ide analogues for the prevention of hepatitis B recurrence after liver transplantation do not affect serum phosphorus levels. Ann Gastroenterol 2016; 29:208-213. [PMID: 27065734 PMCID: PMC4805742 DOI: 10.20524/aog.2016.0014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2015] [Accepted: 02/15/2016] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND Nucleos(t)ide analogues (NAs) constitute the backbone of treatment for the prevention of hepatitis B virus recurrence after liver transplantation (LT). Decline in serum phosphorus levels is a common side effect of nucleotide therapy. Our aim was to assess the impact of nucleotide treatment on the occurrence of hypophosphatemia after LT and determine possible predictors. METHODS We retrospectively analyzed data from liver transplant recipients who had been transplanted for various indications. All patients were evaluated every 3 months. Each patient was considered to be having hypophosphatemia when at least one value of serum phosphorus ≤2.5 mg/dL was detected. RESULTS In total, 109 patients [83 males (76%)] with a mean age of 55±10 years were included. 46/67 (67%) patients with hepatitis B received a nucleotide. The rate of hypophosphatemia (55%) was not different between patients with hepatitis B and those transplanted for other indications (62%). Patients receiving a nucleotide did not run a greater risk of hypophosphatemia than patients receiving only nucleosides (59% vs. 48%, P=0.39). Male gender and everolimus use were associated with the occurrence of hypophosphatemia in patients with hepatitis B. In multivariate analysis only gender was associated with hypophosphatemia (odds ratio 11.43, 95%CI -2.11 to -0.49; P=0.0025). CONCLUSIONS Hypophosphatemia occurs in more than half of liver transplant recipients regardless of the indication for LT. Male gender and everolimus use seem to predispose to hypophosphatemia, whereas the type of antiviral agent does not.
Collapse
Affiliation(s)
- Emmanouil Sinakos
- 4 Department of Internal Medicine (Emmanouil Sinakos, Ioannis Goulis, Evangelos Cholongitas, Stefania Kiapidou, Evangelos Akriviadis), Thessaloniki, Greece
| | - Nikolaos Antoniadis
- Department of Transplant Surgery (Nikolaos Antoniadis, Ekaterini Tsakni, Vassilios Papanikolaou), Thessaloniki, Greece
| | - Ioannis Goulis
- 4 Department of Internal Medicine (Emmanouil Sinakos, Ioannis Goulis, Evangelos Cholongitas, Stefania Kiapidou, Evangelos Akriviadis), Thessaloniki, Greece
| | - Evangelos Cholongitas
- 4 Department of Internal Medicine (Emmanouil Sinakos, Ioannis Goulis, Evangelos Cholongitas, Stefania Kiapidou, Evangelos Akriviadis), Thessaloniki, Greece
| | - Stefania Kiapidou
- 4 Department of Internal Medicine (Emmanouil Sinakos, Ioannis Goulis, Evangelos Cholongitas, Stefania Kiapidou, Evangelos Akriviadis), Thessaloniki, Greece
| | - Ekaterini Tsakni
- Department of Transplant Surgery (Nikolaos Antoniadis, Ekaterini Tsakni, Vassilios Papanikolaou), Thessaloniki, Greece
| | - Themistoklis Vasiliadis
- 3 Pr. Department of Internal Medicine (Themistoklis Vasiliadis), Aristotle University of Thessaloniki, Greece
| | - Vassilios Papanikolaou
- Department of Transplant Surgery (Nikolaos Antoniadis, Ekaterini Tsakni, Vassilios Papanikolaou), Thessaloniki, Greece
| | - Evangelos Akriviadis
- 4 Department of Internal Medicine (Emmanouil Sinakos, Ioannis Goulis, Evangelos Cholongitas, Stefania Kiapidou, Evangelos Akriviadis), Thessaloniki, Greece
| |
Collapse
|
|
30
|
|
|
31
|
Ferrarese A, Zanetto A, Gambato M, Bortoluzzi I, Nadal E, Germani G, Senzolo M, Burra P, Russo FP. Liver transplantation for viral hepatitis in 2015. World J Gastroenterol 2016; 22:1570-1581. [PMID: 26819523 PMCID: PMC4721989 DOI: 10.3748/wjg.v22.i4.1570] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2015] [Revised: 09/20/2015] [Accepted: 11/19/2015] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation (LT) is a life-saving treatment for patients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis viruses are between the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. Before the availability of antiviral prophylaxis, hepatitis B virus (HBV) recurrence was universal in patients who were HBV DNA-positive before transplantation. The natural history of recurrent HBV was accelerated by immunosuppression, and it progressed rapidly to graft failure and death. Introduction of post-transplant prophylaxis with immunoglobulin alone first, and associated to antiviral drugs later, drastically reduced HBV recurrence, resulting in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Overall, patient and graft survival after LT for hepatitis C virus (HCV)-associated cirrhosis is inferior compared with other indications. However, successful pretransplant or post transplant antiviral therapy has been associated with increased graft and overall survival. Until recently, the combination of pegylated interferon and ribavirin was the standard of care for the treatment of patients with chronic hepatitis C. Highly active antiviral compounds have been developed over the past decade, thanks to new in vitro systems to study HCV entry, replication, assembly, and release.
Collapse
|
|
32
|
Ku W, Wang U, Nguyen MH. Efficacy and effectiveness of anti-HBV therapy with early withdrawal of HBIG prophylaxis to prevent HBV recurrence following liver transplantation. Expert Opin Biol Ther 2015; 15:665-77. [PMID: 25865452 DOI: 10.1517/14712598.2015.1025045] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
INTRODUCTION The traditional regimen for prophylaxis of hepatitis B recurrence post-liver transplantation is to use hepatitis B immune globulin (HBIG) along with oral antiviral therapy; however, it is unclear when it is safe to discontinue HBIG after certain time point and to maintain patients with only oral antiviral therapy. Several studies have suggested that maintenance with oral anti-hepatitis B virus (HBV) therapy following short-term or no HBIG following the immediate post-transplantation period may also be safe and effective in prevention of HBV recurrence. AREAS COVERED We reviewed relevant literature to determine the effectiveness of early withdrawal of HBIG after liver transplantation and its effect on prevention of HBV recurrence. We used PubMed to search for any studies that used HBIG-free or short-term HBIG protocols with continued anti-HBV therapy. Short-term is defined as 12 months or less, and it is an evolving concept as new data on shorter and shorter duration becomes available. Additionally, a mini-quantitative analysis of the studies was performed using studies that involved the use of entecavir and tenofovir as anti-HBV therapy with or without HBIG. EXPERT OPINION Patients who are considered low risk for HBV recurrence at the time of liver transplant may safely be able to utilize a short-term duration of HBIG with indefinite antiviral maintenance therapy afterwards, whereas high-risk patients will likely need long-term HBIG in combination with antiviral therapy.
Collapse
Affiliation(s)
- Winston Ku
- Stanford University Medical Center, Division of Gastroenterology and Hepatology , 750 Welch Rd, Suite #210, Palo Alto, CA 94304 , USA
| | | | | |
Collapse
|
|
33
|
Song ZL, Cui YJ, Zheng WP, Teng DH, Zheng H. Application of nucleoside analogues to liver transplant recipients with hepatitis B. World J Gastroenterol 2015; 21:12091-12100. [PMID: 26576094 PMCID: PMC4641127 DOI: 10.3748/wjg.v21.i42.12091] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Revised: 08/22/2015] [Accepted: 09/30/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B is a common yet serious infectious disease of the liver, affecting millions of people worldwide. Liver transplantation is the only possible treatment for those who advance to end-stage liver disease. Donors positive for hepatitis B virus (HBV) core antibody (HBcAb) have previously been considered unsuitable for transplants. However, those who test negative for the more serious hepatitis B surface antigen can now be used as liver donors, thereby reducing organ shortages. Remarkable improvements have been made in the treatment against HBV, most notably with the development of nucleoside analogues (NAs), which markedly lessen cirrhosis and reduce post-transplantation HBV recurrence. However, HBV recurrence still occurs in many patients following liver transplantation due to the development of drug resistance and poor compliance with therapy. Optimized prophylactic treatment with appropriate NA usage is crucial prior to liver transplantation, and undetectable HBV DNA at the time of transplantation should be achieved. NA-based and hepatitis B immune globulin-based treatment regimens can differ between patients depending on the patients' condition, virus status, and presence of drug resistance. This review focuses on the current progress in applying NAs during the perioperative period of liver transplantation and the prophylactic strategies using NAs to prevent de novo HBV infection in recipients of HBcAb-positive liver grafts.
Collapse
|
|
34
|
Pipili C, Cholongitas E. Pharmaceutical management of hepatitis B and C in liver and kidney transplant recipients. World J Gastrointest Pharmacol Ther 2015; 6:105-10. [PMID: 26558143 PMCID: PMC4635149 DOI: 10.4292/wjgpt.v6.i4.105] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2015] [Revised: 07/05/2015] [Accepted: 07/29/2015] [Indexed: 02/06/2023] Open
Abstract
The combination of hepatitis B immune globulin with entecavir or tenofovir (at least for a certain period of time) seems to be the most reasonable prophylaxis against recurrent hepatitis B after liver transplantation. Entecavir represents an attractive option for treatment of naïve kidney transplant recipients, because of its high efficacy and the low rates of resistance. However antiviral treatment should be individualized in the view of kidney function and the previous resistance. To date, new captivating therapeutic strategies could make interferon-free regimens viable for treatment of hepatitis C virus positive liver transplant recipients. The recent combinations of sofosbuvir with simeprevir or daclatasvir or ledipasvir plus/minus ribavirin have boosted the on treatment and sustained virological response to rates approaching 100% within liver transplant recipients with recurrent chronic hepatitis C (CHC). Preliminary data showed that the second generation direct oral antivirals could result to high treatment rates of recurrent CHC in kidney transplant recipients as well. Ongoing studies will clarify the optimal treatment of recurrent CHC in kidney transplant recipients.
Collapse
|
|
35
|
Khemichian S, Hsieh MJ, Zhang SR, Limurti J, Kim J, Fong TL. Nucleoside-Nucleotide Analog Combination Therapy Is Effective in Preventing Recurrent Hepatitis B After Liver Transplantation. Dig Dis Sci 2015; 60:2807-12. [PMID: 25939541 DOI: 10.1007/s10620-015-3671-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2015] [Accepted: 04/15/2015] [Indexed: 01/19/2023]
Abstract
BACKGROUND Hepatitis B immune globulin (HBIg) in combination with a nucleos(t)ide analog is the mainstay of prophylactic regimen to prevent recurrence of hepatitis B following orthotopic liver transplantation (OLT). HBIg therapy is costly and inconvenient for the patients. There is a growing experience converting HBIg/nucleos(t)ide to combination nucleotide/nucleoside analogs from. METHODS Twenty-six patients that underwent OLT between March 2001 and July 2011 who had received at least 12 months of HBIg and single nucleos(t)ide were enrolled. HBsAg and HBV DNA were undetectable, and anti-HBs were detectable at the time of switch. HBV DNA and HBsAg were measured every 3 months following discontinuation of HBIg and addition of nucleos(t)ide. RESULTS Patients included 23 Asians/3 Caucasian, 21 males/5 females. Mean time of conversion from HBIg/nucleos(t)ide to nucleoside/nucleotide combination was 77.5 (range 11-132) months after OLT. Mean duration of follow-up after conversion was 31.9 (range 14-70) months. All patients had undetectable HBV DNA, and 24 patients remained HBsAg negative during follow-up. Two patients recurred 7 and 9 months later, respectively, with detectable HBsAg. Both patients continued to have undetectable HBV DNA and normal ALT. HBsAg was neutralized by reinfusion of HBIg. CONCLUSION Nucleoside/nucleotide combination is an effective alternative to HBIg/nucleos(t)ide to prevent recurrence of hepatitis B after OLT.
Collapse
Affiliation(s)
- Saro Khemichian
- Liver Transplantation Program, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA,
| | | | | | | | | | | |
Collapse
|
|
36
|
Kornberg A. Intravenous immunoglobulins in liver transplant patients: Perspectives of clinical immune modulation. World J Hepatol 2015; 7:1494-1508. [PMID: 26085909 PMCID: PMC4462688 DOI: 10.4254/wjh.v7.i11.1494] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2015] [Revised: 04/19/2015] [Accepted: 05/08/2015] [Indexed: 02/06/2023] Open
Abstract
Shortage of appropriate donor grafts is the foremost current problem in organ transplantation. As a logical consequence, waiting times have extended and pretransplant mortality rates were significantly increasing. The implementation of a priority-based liver allocation system using the model of end-stage liver disease (MELD) score helped to reduce waiting list mortality in liver transplantation (LT). However, due to an escalating organ scarcity, pre-LT MELD scores have significantly increased and liver recipients became more complex in recent years. This has finally led to posttransplant decreasing survival rates, attributed mainly to elevated rates of infectious and immunologic complications. To meet this challenging development, an increasing number of extended criteria donor grafts are currently accepted, which may, however, aggravate the patients’ infectious and immunologic risk profiles. The administration of intravenous immunoglobulins (IVIg) is an established treatment in patients with immune deficiencies and other antibody-mediated diseases. In addition, IVIg was shown to be useful in treatment of several disorders caused by deterioration of the cellular immune system. It proved to be effective in preventing hyperacute rejection in highly sensitized kidney and heart transplants. In the liver transplant setting, the administration of specific Ig against hepatitis B virus is current standard in post-LT antiviral prophylaxis. The mechanisms of action of IVIg are complex and not fully understood. However, there is increasing experimental and clinical evidence that IVIg has an immuno-balancing impact by a combination of immuno-supporting and immuno-suppressive properties. It may be suggested that, especially in the context of a worsening organ shortage with all resulting clinical implications, liver transplant patients should benefit from immuno-regulatory capabilities of IVIg. In this review, perspectives of immune modulation by IVIg and impact on outcome in liver transplant patients are described.
Collapse
|
|
37
|
Cholongitas E, Tziomalos K, Pipili C. Management of patients with hepatitis B in special populations. World J Gastroenterol 2015; 21:1738-1748. [PMID: 25684938 PMCID: PMC4323449 DOI: 10.3748/wjg.v21.i6.1738] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2014] [Revised: 10/27/2014] [Accepted: 11/19/2014] [Indexed: 02/06/2023] Open
Abstract
The development of effective nucleos(t)ide analogs (NAs) against hepatitis B virus (HBV) has improved the outcome of patients with chronic hepatitis B (CHB). This review updates issues related to the management of CHB patients included in special populations. Entecavir (ETV) and tenofovir (TDF) represent the currently recommended first-line NAs in patients with HBV decompensated cirrhosis. The combination of HBV immunoglobulin (usually for a finite duration) and NA is considered the standard of care for prophylaxis against HBV recurrence after liver transplantation. TDF is the best choice for hemodialysis patients and in patients with chronic kidney disease with nucleoside resistance. ETV and telbivudine are the preferred options in naïve renal transplant recipients and with low viremia levels, respectively. All hepatitis B surface antigen (HBsAg)-positive candidates should be treated with NAs before renal transplantation to achieve undetectable HBV DNA at the time of transplantation. Conventional interferon or NAs can also be used in children, on the basis of well-established therapeutic indication. Pregnant women at high risk of perinatal transmission could be treated with lamivudine, telbivudine or TDF in the last trimester of pregnancy. HBsAg-positive patients under immunosuppression should receive NA pre-emptively (regardless of HBV DNA levels) up to 12 mo after its cessation. In HBsAg negative, anti-HBc positive patients under immunosuppression, further studies are needed to form a final conclusion; however, it seems that anti-HBV prophylaxis is justified in such patients with hematological diseases and/or for those receiving rituximab-containing regimens, regardless of their anti-HBs or serum HBV DNA status.
Collapse
|
|
38
|
Xi ZF, Xia Q. Recent advances in prevention of hepatitis B recurrence after liver transplantation. World J Gastroenterol 2015; 21:829-835. [PMID: 25624716 PMCID: PMC4299335 DOI: 10.3748/wjg.v21.i3.829] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2014] [Revised: 08/31/2014] [Accepted: 12/08/2014] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation is the only effective treatment for hepatitis B virus (HBV)-related end-stage liver disease. However, without antiviral prophylaxis, the recurrence rate of hepatitis B is as high as 80%-100%, which leads to a 50% mortality rate in the first 2 years after liver transplantation. Combination therapy of hepatitis B immunoglobulin (HBIG) and lamivudine demonstrated a higher efficacy of prophylaxis and further reduced the rate of recurrence to < 10%. The strategy of HBIG combined with lamivudine has been the standard treatment in many centers. However, the high rate of lamivudine resistance and the many disadvantages of HBIG have compelled surgeons to reconsider the long-term efficacy of this strategy for the prevention of HBV reinfection. Recently, new nucleos(t)ide analogues, such as entecavir and tenofovir, have been approved as first-line monotherapies for the treatment of chronic hepatitis B infection. These antiviral medicines have replaced lamivudine as the first choice in the prevention of HBV recurrence after liver transplantation. Various therapies that are composed of entecavir, tenofovir, and lamivudine plus adefovir, with or without HBIG have been adopted in several liver transplant centers. This article reviews the recent advances in prophylaxis for the recurrence of hepatitis B after liver transplantation.
Collapse
|
|
39
|
Harmancı Ö, Selçuk H, Haberal M. Prophylaxis against Recurrence in Liver Transplantation Patients with Hepatitis B Virus: What is New? J Clin Transl Hepatol 2014; 2:259-65. [PMID: 26356785 PMCID: PMC4521236 DOI: 10.14218/jcth.2014.00023] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2014] [Revised: 09/17/2014] [Accepted: 09/18/2014] [Indexed: 12/18/2022] Open
Abstract
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.
Collapse
Affiliation(s)
- Özgür Harmancı
- Department of Gastroenterology, Başkent University Medical School, Ankara, Turkey
- Correspondence to: Özgür Harmancı, Department of Gastroenterology, Başkent University Medical School, Mareşal Fevzi çakmak Cad. No:45 Bahçelievler, 06490, Ankara, Turkey. Tel: +90-312-212-6868, Fax: +90-312-215-0835. E-mail:
| | - Haldun Selçuk
- Department of Gastroenterology, Başkent University Medical School, Ankara, Turkey
| | - Mehmet Haberal
- Department of General Surgery, Başkent University Medical School, Ankara, Turkey
| |
Collapse
|