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Huang SC, Cheng PN, Liu CH, Yang HC, Su TH, Tseng TC, Chen PJ, Kao JH, Liu CJ. Serum cytokine/chemokine profiles predict hepatitis B reactivation in HBV/HCV co-infected subjects receiving direct-acting antiviral agents. J Formos Med Assoc 2022; 121:920-929. [PMID: 34538552 DOI: 10.1016/j.jfma.2021.09.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 08/01/2021] [Accepted: 09/05/2021] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND/PURPOSE Direct-acting antiviral agents (DAAs) have revolutionized the paradigm for HCV treatment. However, patients with HBV and HCV co-infection receiving DAAs are at significant risk of HBV reactivation, with limited literature addressing the roles of serum chemokines/chemokines. We aimed to explore the profiles and predictive value of serum cytokines/chemokines regarding HBV reactivation in this clinical setting. METHODS From 2017 to 2019, 25 patients with HBV and HCV co-infection scheduled for DAA therapy were prospectively enrolled. At enrolment and after DAA treatment, serial serum cytokine/chemokine levels were examined. The baseline and dynamic levels were compared between those with versus without HBV virologic (defined by an increase of serum HBV DNA to >10 times) and clinical reactivation (defined by > 1.5-fold elevated ALT level than nadir and >100 U/L; or > 2-fold increase from nadir and greater than the upper normal limit, in addition to virologic reactivation). RESULTS There were 20 patients (80%) experiencing HBV virologic reactivation and 6 patients (24%) experiencing clinical reactivation. Patients with clinical reactivation had higher pre-treatment TNF-alpha (27.93 versus 18.85 pg/mL, P = 0.015), lower week-4 IFN-gamma (1.07 versus 8.74 pg/mL, P = 0.020) levels and significant declines of CCL2 and TNF-alpha (P < 0.05). Single or combination of these cytokines helped predict clinical reactivation (all P < 0.05). CONCLUSION Higher serum TNF-alpha at baseline and lower IFN-gamma at week 4 were associated with mild clinical reactivation of HBV in patients with HBV/HCV co-infection receiving DAAs. Combination of these cytokines reliably predicted HBV reactivation early.
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Affiliation(s)
- Shang-Chin Huang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan.
| | - Pin-Nan Cheng
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
| | - Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
| | - Hung-Chih Yang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan.
| | - Tung-Hung Su
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
| | - Tai-Chung Tseng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
| | - Pei-Jer Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
| | - Chun-Jen Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
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Kakisaka K, Suzuki Y, Takahashi F, Takikawa Y. Referral system has a diminished difference in the risk for hepatic encephalopathy development among each etiology in patients with acute liver injury. Hepatol Res 2022; 52:401-410. [PMID: 34989069 DOI: 10.1111/hepr.13744] [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: 11/07/2021] [Revised: 12/25/2021] [Accepted: 01/03/2022] [Indexed: 02/08/2023]
Abstract
AIM Hepatic encephalopathy (HE) development is crucial in liver transplantation for patients with acute liver injury (ALI) and failure (ALF); to predict HE development, the Japan Hepatic Encephalopathy Prediction (JHEP) model, calculated using age, etiology, prothrombin time (PT), and total bilirubin, was established in 2004, and a referral system to the liver center was implemented using the JHEP model from April 2004. METHODS The JHEP model's ability to predict HE development in 460 consecutive patients with ALI between April 2004 and January 2021 using data from the referral system was evaluated, and the JHEP model was revised. RESULTS During the observation period, 7.8% patients developed HE. There was no difference in the proportion of HE development among the etiologies. In the Hosmer-Lemeshow test for HE development prediction, the JHEP model, revised JHEP (rJHEP) model, which was calculated without etiology data, and the modified JHEP model, which used the PT international ratio instead of PT in the rJHEP model, were good fitting models. Upon 30% random sampling from the total patients 60 times, the receiver operating curve analysis of both JHEP and rJHEP models for HE development was performed in all the datasets. The area under the curve of the JHEP model was subtracted from that of the rJHEP model (95% confidential interval, 0.000516-0.01793). CONCLUSIONS The referral system using the JHEP model reduced the difference in the risk for HE development among each etiology; the rJHEP model had a better prediction ability for HE development than the JHEP model.
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Affiliation(s)
- Keisuke Kakisaka
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Yahaba, Japan
| | - Yuji Suzuki
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Yahaba, Japan
| | - Fumiaki Takahashi
- Center for Liberal Arts and Science, Iwate Medical University, Yahaba, Japan
| | - Yasuhiro Takikawa
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Yahaba, Japan
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Borojevic B, Chauhan A, Patterson S. Liver failure from delayed hepatitis B reactivation in anti-HBc-positive patient following rituximab for B-cell lymphoma. BMJ Case Rep 2021; 14:14/7/e243526. [PMID: 34244190 DOI: 10.1136/bcr-2021-243526] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
A 93-year-old man was admitted with 1 week of frank jaundice and abdominal pain. His medical history included diffuse large B-cell lymphoma treated with rituximab and cyclophosphamide, hydroxydaunomycin, oncovin and prednisolone (R-CHOP) chemotherapy 10 months prior. His investigations revealed marked hyperbilirubinemia with a total bilirubin of 355 μmol/L, along with a 17-fold elevation in alanine transaminase and impaired hepatic synthetic function. He tested hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (HBsAb) negative, hepatitis B core antibody (HBcAb) positive and had elevated hepatitis B virus DNA level at 13 691 IU/L. This was in the setting of radiological evidence of suspected cirrhosis. He was later found to have tested positive for HBcAb and negative for HBsAg and HBsAb prior to chemotherapy, but had not received antiviral prophylaxis. He was diagnosed with fulminant hepatitis secondary to delayed hepatitis B reactivation in the setting of rituximab. Hepatitis B reactivation and the role of screening and antiviral prophylaxis in isolated HBcAb-positive patients is reviewed.
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Affiliation(s)
- Branko Borojevic
- General Medicine, Austin Health, Heidelberg, Victoria, Australia
| | - Ayushi Chauhan
- General Medicine, Eastern Health, Box Hill, Victoria, Australia
| | - Scott Patterson
- Gastroenterology and General Medicine, Austin Health, Heidelberg, Victoria, Australia
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Hepatitis B Virus Reactivation Potential Risk Factors in Hepatocellular Carcinoma via Transcatheter Arterial Chemoembolization: A Retrospective Research. Can J Gastroenterol Hepatol 2021; 2021:8864655. [PMID: 33505945 PMCID: PMC7815398 DOI: 10.1155/2021/8864655] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 12/06/2020] [Accepted: 12/28/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND To explore the clinical characteristics of reactivation of hepatitis B virus (HBV) in hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). The pathological correlation of prognosis and hepatitis B virus reactivation has been given detailed analyses in our research. METHODS A total of 108 related TACE-treated HCC clinical data from January 2008 to January 2016 was gleaned and involved in this retrospective analysis. To lucubrate the nuance of survival rates between HBV reactivated group and HBV nonreactivated group, clinical data of each patient was analyzed in detail and refined the retrospective studies. RESULTS HBV reactivation occurred in 42 patients with a proportion of 38.9%. The detected HBV DNA level ≥104 in patients showed a reactivation rate of 65.8% (25/38), which was significantly higher than the HBV DNA < 104 cases (24.3%, 17/70). Research data revealed a conspicuous lower cellular immunity (P < 0.01) and better 2-year survival rate (P=0.03) in the HBV-reactivated group when compared to the nonreactivated group. CONCLUSION Some of the patients with primary hepatocellular carcinoma possibly had HBV reactivation at post-TACE-therapy. And the predominant risk factors of HBV reactivation are positive HBV test and immunosuppression. Our study suggested that HBV reactivation at post-TACE-therapy is an independent predictor of poor prognosis and low survival rate as well as a crucial reason for poor prognosis and lower survival rate, which indirectly proved that it is urgent to necessitate the antiviral therapy and immune enhancer in improving the curative effect and prognosis of HCC patients.
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Udompap P, Kim WR. Hepatitis B Virus Reactivation and Management of Patients Undergoing Immunosuppression. HEPATITIS B VIRUS AND LIVER DISEASE 2021:427-454. [DOI: 10.1007/978-981-16-3615-8_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Ekpanyapong S, Reddy KR. Hepatitis B Virus Reactivation: What Is the Issue, and How Should It Be Managed? Clin Liver Dis 2020; 24:317-333. [PMID: 32620274 DOI: 10.1016/j.cld.2020.04.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hepatitis B virus (HBV) reactivation, in the background of cleared and overt chronic HBV infection, can be seen in patients receiving immunosuppressive agents. Risk of reactivation is variably associated with HBV serologic status and types of immunosuppressive therapy. Prevention of HBV reactivation by antiviral prophylaxis is an effective strategy to reduce morbidity and mortality in those with immunocompromised states. This article defines HBV reactivation, discusses risk stratification and common medications that can induce HBV reactivation as well as guideline recommendations for prevention of HBV reactivation, and describes the prognosis and management of patients who experience HBV reactivation.
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Affiliation(s)
- Sirina Ekpanyapong
- Department of Medicine, Division of Gastroenterology and Hepatology, Vejthani Hospital, 1 Soi Lat Phrao 111, Khlong Chan, Bang Kapi District, Bangkok 10240, Thailand
| | - K Rajender Reddy
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Pennsylvania, 3400 Spruce Street, 2 Dulles HUP, Philadelphia, PA 19104, USA.
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Abstract
INTRODUCTION Hepatitis B virus (HBV) reactivation can be induced by treatments that attenuate the immunological control over HBV, leading to increased morbidity and mortality. The risk of HBV reactivation is determined by host immunity, viral factors, and the type and dose of treatments. Nevertheless, the risk of HBV reactivation for a growing number of novel therapies remains uncertain and needs to be carefully examined. Identification of patients at risk and administration of prophylactic antiviral agents are critical to prevent HBV reactivation. Early diagnosis and initiation of antiviral treatment are the keys to avoid devastating outcomes. AREA COVERED We summarized the latest evidence and recommendations for risk stratification, early diagnosis, prophylaxis, and management of HBV reactivation. EXPERT OPINION Universal screening, adequate prophylaxis, and close monitoring are essential for the prevention of HBV reactivation. Risk stratification of patients at risk with appropriate antiviral prophylaxis can prevent HBV reactivation effectively. Several emerging biomarkers have been proved to help determine the risk precisely. Early detection and timely administration of antiviral agents are crucial for management. Further studies on the precision of risk stratification as well as the optimal duration of prophylaxis and treatment are needed to establish an individualized strategy.
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Affiliation(s)
- Shang-Chin Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital , Taipei, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital , Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital , Taipei, Taiwan.,Department of Microbiology, National Taiwan University College of Medicine Taipei , Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital , Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital , Taipei, Taiwan.,Department of Medical Research, National Taiwan University Hospital , Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine , Taipei, Taiwan
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Zou X, Guo L, Gu Y, Yang Z, Huang P, Liu T, Zhao J, Wu G. Optimal timing of antiviral therapy for patients with malignant tumor who presented with hepatitis B reactivation during chemotherapy and/or immunosuppressive therapy. J Cancer 2020; 11:3559-3566. [PMID: 32284752 PMCID: PMC7150462 DOI: 10.7150/jca.40154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Accepted: 02/22/2020] [Indexed: 11/05/2022] Open
Abstract
Background: Hepatitis B virus (HBV) reactivation may occur with chemotherapy and/or immunotherapy. Antiviral prophylaxis is recommended for all patients who are hepatitis B surface antigen (HBsAg)-positive during chemotherapy and/or immunosuppressive therapy. However, the optimal timing of antiviral therapy before chemotherapy and/or immunosuppressive therapy is not fully elucidated. Patients and methods: We retrospectively evaluated 446 HBsAg-positive patients who underwent chemotherapy and/or immunosuppressive therapy. The cumulative rates of HBV reactivation were evaluated using the Kaplan-Meier method and were compared using the log-rank test. The risk factors of HBV reactivation were examined via univariate and multivariate analyses using the Cox proportional hazards model. Results: The cumulative HBV reactivation rates of patients who received antiviral therapy before chemotherapy and/or immunosuppressive therapy were significantly lower than those of patients who received antiviral therapy after chemotherapy and/or immunosuppressive therapy (P = 0.002). The incidence of HBV reactivation was significantly different between patients who received antiviral therapy at least 1 day before chemotherapy and/or immunosuppressive therapy and those who did not (P = 0.006). No significant difference was observed in the HBV reactivation rates between patients who received antiviral therapy at least 2 days (P = 0.310), 3 days (P = 0.494), and 1 week (P = 0.655) before chemotherapy and/or immunosuppressive therapy and those who did not. The multivariate Cox proportional hazards model showed that women had a lower risk of developing HBV reactivation than men (P = 0.025). The use of the prophylactic antiviral agent entecavir, compared with lamivudine and telbivudine, was associated with the decreased risk of developing HBV reactivation (P = 0.002). Conclusion: HBsAg-positive patients who received preemptive antiviral therapy after chemotherapy and/or immunosuppressive therapy had a high risk of developing HBV reactivation. However, it is not necessary for patients to receive antiviral therapy at least 1 week before chemotherapy and/or immunosuppressive therapy.
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Affiliation(s)
- Xiaofang Zou
- Department of Medical Oncology, Cancer Center, Meizhou People's Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, China
| | - Longhua Guo
- Department of Medical Oncology, Cancer Center, Meizhou People's Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, China
| | - Yinfang Gu
- Department of Medical Oncology, Cancer Center, Meizhou People's Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, China
| | - Zhijun Yang
- Department of Medical Oncology, Cancer Center, Meizhou People's Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, China
| | - Ping Huang
- Department of Medical Oncology, Cancer Center, Meizhou People's Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, China
| | - Tianhuang Liu
- Department of Hepatopathy, Meizhou People's Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, China
| | - Jingjing Zhao
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Guowu Wu
- Department of Medical Oncology, Cancer Center, Meizhou People's Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, China
- Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou, China
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Toka B, Koksal AS, İskender G, Çakmak E, Üsküdar O, Sezikli M, Şirin G, Yildirim AE, Fidan S, Acar Ş, Eminler AT, Uslan MI, Hülagü S. HBV flare associated with immunosuppressive treatments: it is still dangerous in the third-generation antivirals era. Antivir Ther 2020; 25:121-129. [PMID: 32364531 DOI: 10.3851/imp3356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/22/2020] [Indexed: 10/24/2022]
Abstract
BACKGROUND There are limited data about the mortality and morbidity of patients with HBV flare related to immunosuppressive treatments (IST) in the third-generation antivirals era. Herein, we performed a multi-centric study in patients treated with entecavir (ETV) or tenofovir disoproxil fumarate (TDF) and evaluated their clinical course. METHODS The study group included patients who were referred to gastroenterology or infectious disease specialists at eight different hospitals in Turkey. HBV flare was defined as at least a threefold elevation in alanine aminotransferase (ALT) levels above the upper limit of normal range. The demographic data, IST protocol, virological markers, liver tests, international normalized ratio (INR), HBV DNA, reactivation risk profile according to AGA guideline, MELD and MELD-Na scores were retrospectively evaluated. The primary aim of the study was to determine the liver-related mortality, including transplantation, at 12 weeks and factors predicting it. Secondary aims were to compare ETV and TDF with respect to mortality and time to ALT, bilirubin normalization and HBV DNA undetectability. RESULTS The study group included 40 patients (29 males, mean age: 57 ±12 years). Twenty-five patients (62.5%) had a high risk of reactivation. Twenty-six patients received TDF and 14 patients received ETV treatment. Eight (20%) patients developed acute liver failure and one patient (2.5%) underwent living donor liver transplantation. Seven patients died due to liver-related complications, revealing a mortality rate of 17.5%. In multivariate analysis, total bilirubin levels at the onset, ALT levels and delta-MELD score at the first week were the independent risk factors for liver related mortality (HR: 1.222, 1.003, 1.253 and 95% CI: 1.096, 1.362; 1.001, 1.004 and 1.065, 1.470, respectively). There was no significant difference between the TDF and ETV groups with respect to time to normalize ALT and bilirubin levels, HBV DNA undetectability and mortality rates (16% and 21.4%, respectively). CONCLUSIONS HBV flare associated with IST has a high mortality in the third-generation antivirals era. High total bilirubin at the onset and high ALT and delta-MELD score at the first week predict poor prognosis.
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Affiliation(s)
- Bilal Toka
- Department of Gastroenterology, University of Medical Sciences, Konya Education and Research Hospital, Konya, Turkey
| | - Aydin Seref Koksal
- Department of Gastroenterology, University Faculty of Medicine, Sakarya, Turkey
| | - Gülşen İskender
- Department of Infectious Diseases and Clinical Microbiology, Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara, Turkey
| | - Erol Çakmak
- Department of Gastroenterology, Cumhuriyet University Faculty of Medicine, Sivas, Turkey
| | - Oğuz Üsküdar
- Department of Gastroenterology, Çukurova University Faculty of Medicine, Adana, Turkey
| | - Mesut Sezikli
- Department of Gastroenterology, Hitit University Faculty of Medicine, Çorum, Turkey
| | - Göktuğ Şirin
- Department of Gastroenterology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey
| | - Abdullah Emre Yildirim
- Department of Gastroenterology, Gaziantep University Faculty of Medicine, Gaziantep, Turkey
| | - Sami Fidan
- Department of Gastroenterology, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey
| | - Şencan Acar
- Department of Gastroenterology, University Faculty of Medicine, Sakarya, Turkey
| | - Ahmet Tarik Eminler
- Department of Gastroenterology, University Faculty of Medicine, Sakarya, Turkey
| | - Mustafa Ihsan Uslan
- Department of Gastroenterology, University Faculty of Medicine, Sakarya, Turkey
| | - Sadettin Hülagü
- Department of Gastroenterology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey
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Antiviral Therapy for AECHB and Severe Hepatitis B (Liver Failure). ACUTE EXACERBATION OF CHRONIC HEPATITIS B 2019. [PMCID: PMC7498919 DOI: 10.1007/978-94-024-1603-9_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This chapter describes the principles of antiviral therapy, treatment strategies, medications and recommendations for AECHB, HBV-ACLF, HBV-related liver cirrhosis, HBV-related HCC, and liver transplantation.
Severe exacerbation of chronic hepatitis B is closely related to continuous HBV replication. Therefore, inhibiting HBV replication to reduce viral load may block disease progression and improve the quality of life of these patients. ETV or TDF has been recommend first-line drug for the treatment of AECHB. A hyperactive immune response due to continuous HBV replication is the main mechanism for development of severe hepatitis B. In addition to comprehensive treatment, early administration of potent nucleoside analogs can rapidly reduce HBV DNA concentration, relieve immune injury induced by HBV, and reduce liver inflammation and patient mortality. Antiviral agents have become important in the treatment of severe exacerbation of chronic hepatitis B. Long-term antiviral treatment with nucleoside analogs can delay or reverse the progress of liver cirrhosis. Virologic response, viral resistance and adverse drug reactions should be closely monitored during treatment. The treatment should be optimized for maximum effect based on each patient’s responses. Effective antiviral therapy can suppress HBV replication and reduce the incidence of HBV-related HCC. Patients with HBV-related HCC should receive individualized and optimal multidisciplinary comprehensive treatment. Anti-viral drugs with high efficacy, low resistance and low adverse drug reactions should be selected to improve the patient’s quality of life and prolong survival time. Methods to prevent HBV reinfection after liver transplantation include passive immunization (HBIG), antiviral treatment (nucleoside analogs) and active immunization (hepatitis B vaccine). Clinical trials involving sequential combination therapy with NUC and Peg-IFN have shown statistically significant decline in HBsAg levels on treatment and high rates of sustained post-treatment serologic response. Combination therapy with novel DAA and immunotherapeutic approach may hold promise to overcome both cccDNA persistence and immune escape, representing a critical step towards HBV cure.
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Coluccio C, Begini P, Marzano A, Pellicelli A, Imperatrice B, Anania G, Delle Fave G, Marignani M. Hepatitis B in patients with hematological diseases: An update. World J Hepatol 2017; 9:1043-1053. [PMID: 28951776 PMCID: PMC5596311 DOI: 10.4254/wjh.v9.i25.1043] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2017] [Revised: 07/13/2017] [Accepted: 08/04/2017] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) reactivation (HBVr) in patients undergoing immunosuppressive therapy is still a hot topic worldwide. Its prevention and management still represents a challenge for specialists dealing with immunosuppressed patients. Aim of this paper is to provide a critical review of the relevant information emerged in the recent literature regarding HBV reactivation following immunosuppressive treatments for oncohematological tumors. A computerized literature search in MEDLINE was performed using appropriate terms arrangement, including English-written literature only or additional relevant articles. Articles published only in abstract form and case reports not giving considerable news were excluded. Clinical manifestation of HBVr can be manifold, ranging from asymptomatic self-limiting anicteric hepatitis to life-threatening fulminant liver failure. In clusters of patients adverse outcomes are potentially predictable. Clinicians should be aware of the inherent risk of HBVr among the different virological categories (active carriers, occult HBV carriers and inactive carriers, the most intriguing category), and classes of immunosuppressive drugs. We recommend that patients undergoing immunosuppressive treatments for hematological malignancies should undergo HBV screening. In case of serological sign(s) of current or past infection with the virus, appropriate therapeutic or preventive strategies are suggested, according to both virological categories, risk of HBVr by immunosuppressive drugs and liver status. Either antiviral drug management and surveillance and pre-emptive approach are examined, commenting the current international recommendations about this debated issue.
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Affiliation(s)
- Chiara Coluccio
- Digestive and Liver Diseases Department, Sant’Andrea Hospital, School of Medicine and Psychology, Sapienza University, 00189 Rome, Italy
| | - Paola Begini
- Digestive and Liver Diseases Department, Sant’Andrea Hospital, School of Medicine and Psychology, Sapienza University, 00189 Rome, Italy
| | - Alfredo Marzano
- Division of Gastroenterology and Hepatology, San Giovanni Battista Hospital, 10126 Turin, Italy
| | | | - Barbara Imperatrice
- Digestive and Liver Diseases Department, Sant’Andrea Hospital, School of Medicine and Psychology, Sapienza University, 00189 Rome, Italy
| | - Giulia Anania
- Digestive and Liver Diseases Department, Sant’Andrea Hospital, School of Medicine and Psychology, Sapienza University, 00189 Rome, Italy
| | - Gianfranco Delle Fave
- Digestive and Liver Diseases Department, Sant’Andrea Hospital, School of Medicine and Psychology, Sapienza University, 00189 Rome, Italy
| | - Massimo Marignani
- Digestive and Liver Diseases Department, Sant’Andrea Hospital, School of Medicine and Psychology, Sapienza University, 00189 Rome, Italy
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Pattullo V. Prevention of Hepatitis B reactivation in the setting of immunosuppression. Clin Mol Hepatol 2016; 22:219-37. [PMID: 27291888 PMCID: PMC4946398 DOI: 10.3350/cmh.2016.0024] [Citation(s) in RCA: 88] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Accepted: 04/27/2016] [Indexed: 12/13/2022] Open
Abstract
Advances in the treatment of malignant and inflammatory diseases have developed over time, with increasing use of chemotherapeutic and immunosuppressive agents of a range of drug classes with varying mechanism and potency in their effects on the immune system. These advances have been met with the challenge of increased risk of hepatitis B virus (HBV) reactivation in susceptible individuals. The magnitude of risk of HBV reactivation is associated with the individual’s HBV serological status and the potency and duration of immunosuppression. Individuals with chronic hepatitis B (CHB) and previously infected but serologically cleared HBV infection are both susceptible to HBV reactivation. HBV reactivation in the setting of immunosuppression is a potentially life threatening condition leading to liver failure and death in extreme cases. It is important to recognize that HBV reactivation in the setting of immunosuppression is potentially preventable. Therefore, identification of patients at risk of HBV reactivation and institution of prophylactic antiviral therapy prior to initiation of immunosuppression is essential.
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Affiliation(s)
- Venessa Pattullo
- Department of Gastroenterology, Royal North Shore Hospital, Sydney, Australia
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Mallet V, van Bömmel F, Doerig C, Pischke S, Hermine O, Locasciulli A, Cordonnier C, Berg T, Moradpour D, Wedemeyer H, Ljungman P. Management of viral hepatitis in patients with haematological malignancy and in patients undergoing haemopoietic stem cell transplantation: recommendations of the 5th European Conference on Infections in Leukaemia (ECIL-5). THE LANCET. INFECTIOUS DISEASES 2016; 16:606-617. [PMID: 27599653 DOI: 10.1016/s1473-3099(16)00118-3] [Citation(s) in RCA: 106] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/07/2015] [Revised: 02/11/2016] [Accepted: 02/12/2016] [Indexed: 12/24/2022]
Abstract
Viral hepatitis affects millions of people worldwide, and host immunity is the key determinant of patient outcome. Viral hepatitis can be life threatening in patients with haematological malignancy, including haemopoietic stem cell transplant recipients, because of the virus itself, or through a need to decrease the dose of chemotherapy. A past or currently infected haemopoietic stem cell donor could also transmit viral hepatitis. The burden of viral hepatitis in patients with haematological malignancies and the weak evidence on which previous guidelines are based has prompted the European Conference on Infection in Leukaemia (ECIL-5) to convene a group of experts in the fields of viral hepatitis and of haematological malignancy to specifically address previously unconsidered issues and grade the available quality of evidence according to the Infectious Diseases Society of America grading system. The group recommends that all patients should be screened for hepatotropic viruses before haematological treatment and that patients or haemopoietic stem cell donors with markers of past or current viral hepatitis should be assessed by an expert. Screening, vaccination, and treatment rules are reported in this Review.
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Affiliation(s)
- Vincent Mallet
- Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Institut Pasteur, Institut National de la Santé et de la Recherche Médicale Unité 1223, Paris, France; Hepatology Service, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Cochin Port-Royal, Paris, France.
| | | | - Christopher Doerig
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
| | - Sven Pischke
- University Medical Center Hamburg-Eppendorf, First Department of Medicine, Hamburg, Germany
| | - Olivier Hermine
- Department of Haematology, Paris Descartes University, Imagine Institute, Necker Hospital, Paris, France
| | - Anna Locasciulli
- Ematologia e Trapianto di Midollo, Ospedale SanCamillo, Roma, Italia
| | - Catherine Cordonnier
- Haematology Department, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, and Paris-Est Créteil University, Créteil, France
| | - Thomas Berg
- Hepatology Section, University Hospital Leipzig, Leipzig, Germany
| | - Darius Moradpour
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
| | | | - Per Ljungman
- Karolinska University Hospital, Department of Haematology and Karolinska Institutet, Department of Medicine, Huddinge, Stockholm, Sweden
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Pattullo V. Hepatitis B reactivation in the setting of chemotherapy and immunosuppression - prevention is better than cure. World J Hepatol 2015; 7:954-967. [PMID: 25954478 PMCID: PMC4419099 DOI: 10.4254/wjh.v7.i7.954] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2014] [Revised: 01/16/2015] [Accepted: 02/12/2015] [Indexed: 02/06/2023] Open
Abstract
Due to the inherent relationship between the immune system and the hepatitis B virus (HBV) in exposed and infected individuals, immunomodulation associated with the treatment of solid tumours, haematological malignancies and inflammatory disorders has been linked to HBV reactivation (HBVr). Reactivation of HBV infection in the setting of chemotherapy and immunosuppression may lead to fulminant liver failure and death, but there is a cumulative body of evidence that these are potentially preventable adverse outcomes. As chronic hepatitis B is largely asymptomatic but also endemic worldwide, clinicians caring for patients requiring chemotherapy or immunosuppression need to be vigilant of the potential for HBVr in susceptible individuals. Serological screening and prophylactic and pre-emptive antiviral treatment with a nucleos(t)ide analogue should be considered in appropriate settings. Hepatitis B prevalence is examined in this review article, as are the risks of HBVr in patients receiving chemo- and immunosuppressive therapy. Recommendations regarding screening, monitoring and the role of antiviral prophylaxis are outlined with reference to current international associations’ guidelines and the best available evidence to date.
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Pei SN, Chen CH. Risk and prophylaxis strategy of hepatitis B virus reactivation in patients with lymphoma undergoing chemotherapy with or without rituximab. Leuk Lymphoma 2015; 56:1611-8. [PMID: 25248874 DOI: 10.3109/10428194.2014.964699] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Hepatitis B virus (HBV) reactivation is a serious but preventable complication for patients with lymphoma receiving systemic therapy. Without antiviral prophylaxis, the HBV reactivation rate is estimated to be > 50% in patients who are positive for hepatitis B surface antigen (HBsAg), and fatal hepatic failure is not uncommon. Current guidelines suggest that routine antiviral prophylaxis should be administered to all HBsAg-positive patients until 6-12 months after completion of chemotherapy. For those who are negative for HBsAg and positive for hepatitis B core antibody, HBV reactivation is uncommon when a conventional dose of chemotherapy is administered. However, with rituximab-containing immunochemotherapy, the HBV reactivation rate is 18% and the clinical course can vary from asymptomatic viremia to fulminant hepatic failure that can be potentially fatal. In this review, we discuss the risk, clinical course and prophylactic strategy of HBV reactivation in patients with lymphoma treated with chemotherapy with or without rituximab.
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Li H, Zhang HM, Chen LF, Chen YQ, Chen L, Ren H, Hu HD. Prophylactic lamivudine to improve the outcome of HBsAg-positive lymphoma patients during chemotherapy: a systematic review and meta-analysis. Clin Res Hepatol Gastroenterol 2015; 39:80-92. [PMID: 25199680 DOI: 10.1016/j.clinre.2014.07.010] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2014] [Revised: 04/23/2014] [Accepted: 07/23/2014] [Indexed: 02/04/2023]
Abstract
Hepatitis B viral (HBV) reactivation in lymphoma patients undergoing chemotherapy is associated with significant morbidity and mortality. Increasingly, lamivudine is being used to prevent hepatitis B reactivation. To assess the effects of prophylactic lamivudine on reactivation and mortality following chemotherapy in lymphoma patients who are hepatitis B surface antigen (HBsAg)-positive, we searched Medline/PubMed, Ovid MEDLINE, EMBASE, Web of Knowledge and the Cochrane Library for studies through November 2013. Statistical analysis was performed using REVMAN. Fourteen studies consisting of 636 patients were included in the analysis. The rate of HBV reactivation, incidence of hepatitis and incidence of hepatitis due to HBV reactivation in patients with lamivudine prophylaxis was significantly lower than those with no prophylaxis. Risk ratios [RRs] were 0.25 (95% confidence intervals [CI] 0.13-0.51; P=0.0001), 0.40 (95% CI 0.26-0.63; P<0.0001), and 0.21 (95% CI 0.09-0.51; P=0.0005) respectively. In addition, patients given prophylactic lamivudine had significant reductions in overall mortality and mortality attributable to HBV reactivation compared with control group. Risk ratios [RRs] were 0.45 (95% CI 0.29-0.70; P=0.0004) and 0.41 (95% CI 0.20-0.84; P=0.01) respectively. Chemotherapy disruption was not significantly different between the two groups. Risk ratios [RRs] were 0.34 (95% CI 0.09-1.26; P=0.11). Prophylactic therapy with lamivudine for HBsAg-positive lymphoma patients who are undergoing chemotherapy may reduce the risk for HBV reactivation, hepatitis due to HBV reactivation, overall mortality and mortality attributable to HBV reactivation. Additionally, patients with preventive lamivudine had a trend towards the decreased incidence of chemotherapy disruption.
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Affiliation(s)
- Hong Li
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, 76, Linjiang Road, 400010 Chongqing, China
| | - Hong-Min Zhang
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, 76, Linjiang Road, 400010 Chongqing, China
| | - Li-Fen Chen
- Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Ya-Qin Chen
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, 76, Linjiang Road, 400010 Chongqing, China
| | - Ling Chen
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, 76, Linjiang Road, 400010 Chongqing, China
| | - Hong Ren
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, 76, Linjiang Road, 400010 Chongqing, China; Institute for Viral Hepatitis of Chongqing Medical University, Chongqing, China; Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Huai-Dong Hu
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, 76, Linjiang Road, 400010 Chongqing, China; Institute for Viral Hepatitis of Chongqing Medical University, Chongqing, China; Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China.
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Perrillo RP, Gish R, Falck-Ytter YT. American Gastroenterological Association Institute technical review on prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology 2015; 148:221-244.e3. [PMID: 25447852 DOI: 10.1053/j.gastro.2014.10.038] [Citation(s) in RCA: 389] [Impact Index Per Article: 38.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Robert P Perrillo
- Hepatology Division, Baylor University Medical Center, Department of Medicine, University of Texas Southwestern, Dallas, Texas
| | - Robert Gish
- Division of Gastroenterology and Hepatology, Department of Medicine,Stanford University, Palo Alto, California; Hepatitis B Foundation, Doylestown, Pennsylvania
| | - Yngve T Falck-Ytter
- Division of Gastroenterology and Hepatology, Department of Medicine, Case and VA Medical Center, Case Western Reserve University, Cleveland, Ohio
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Li W, Huang L, Guo H, Wei X, Liang Z. Antiviral efficacy analysis of telbivudine concurrent with the first cycle of chemotherapy in HBsAg-positive lymphoma patients. J Clin Virol 2014; 61:199-203. [PMID: 25128391 DOI: 10.1016/j.jcv.2014.07.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2013] [Revised: 05/29/2014] [Accepted: 07/10/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND HBV reactivation is a common complication in HBsAg-positive lymphoma patients with chemotherapy or immunotherapy. There is no standard antiviral treatment for these patients undergoing chemotherapy or immunotherapy. The initial time, the agent and the duration time are confused at present. OBJECTIVE This study aimed to investigate the antiviral efficacy of telbivudine concurrent with initiation of chemotherapy in HBsAg-positive patients with lymphoma. STUDY DESIGN Between April 2008 and October 2012, 359 patients with pathological diagnoses of lymphoma were admitted to the hospital. Among those, a cohort of 60 HBsAg-positive cases were included in this retrospective study, and telbivudine was taken at the same day or one day prior to the first cycle of chemotherapy. The rates of HBV reactivation, virological response, undetectable HBV DNA, the relationship between HBV reactivation and its clinical characteristics were investigated. RESULTS The rate of HBV reactivation was 11.7% (7/60), while it was 17.5% (7/40) and 75% (3/4) in patients treated with rituximab based chemotherapy and rituximab maintenance therapy, respectively. The fulminant hepatitis rate was 6.6%. The rates of virological response, undetectable HBV DNA and ALT normalization were 88.3%, 61.7% and 83.3%, respectively. HBV reactivation was associated with rituximab (P = 0.013), and HBeAg-negativity (P = 0.016), but not correlated with age, gender, clinical stages, extranodal disease, bone marrow involvement, B symptoms, HBV viral loads or serum LDH level. CONCLUSION Concurrent telbivudine treatment with initial chemotherapy can effectively reduce HBV reactivation in HBsAg-positive lymphoma patients, and the efficacy is independent of the baseline HBV viral loads.
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Affiliation(s)
- Wenyu Li
- Lymphoma Division, Cancer Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, No. 123 Huifu Road, Guangzhou 510080, China.
| | - Ling Huang
- Lymphoma Division, Cancer Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, No. 123 Huifu Road, Guangzhou 510080, China
| | - Hanguo Guo
- Lymphoma Division, Cancer Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, No. 123 Huifu Road, Guangzhou 510080, China
| | - Xiaojuan Wei
- Lymphoma Division, Cancer Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, No. 123 Huifu Road, Guangzhou 510080, China
| | - Zhanli Liang
- Lymphoma Division, Cancer Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, No. 123 Huifu Road, Guangzhou 510080, China
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Xu X, Huang P, Tian H, Chen Y, Ge N, Tang W, Yang B, Xia J. Role of lamivudine with transarterial chemoembolization in the survival of patients with hepatocellular carcinoma. J Gastroenterol Hepatol 2014; 29:1273-8. [PMID: 24955456 DOI: 10.1111/jgh.12554] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM The purpose of the present study was to determine whether lamivudine in combination with transarterial chemoembolization (TACE) could reduce hepatitis B virus (HBV) activation and improve the survival of patients with hepatocellular carcinoma (HCC). METHODS From July 2008 to October 2011, a total of 181 consecutive HBV-related HCC patients undergoing TACE were randomized to two groups (92: lamivudine, 89: control). Follow up was every 3 months. Primary and secondary end-points were time to progression (TTP) and overall survival (OS), respectively, both of which were evaluated by the Kaplan Meier technique and summarized by the hazard ratio. RESULTS The level of HBV-DNA became undetectable in 42 (45.6%) patients in the lamivudine group, compared with 10 (11.2%) in the control group (P < 0.001). The median TTP was 8.2 months in lamivudine group and 4.3 months in control group (P = 0.005), and lamivudine therapy was an independent protective factor related to TTP (P = 0.006). Moreover, 1-, 2-, and 3-year survival rates were 83%, 69%, and 58% in lamivudine group and 60%, 48%, and 48% in control group, respectively (P = 0.002). With multivariate Cox regression model, lamivudine therapy (P = 0.002) and α-fetoprotein (AFP) level (P = 0.003) were two independent predictors for OS. CONCLUSION Lamivudine therapy could reduce HBV activation and improve survival of HCC patients treated with TACE. Lamivudine therapy and AFP level are two independent factors affecting OS.
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Riedell P, Carson KR. A drug safety evaluation of rituximab and risk of hepatitis B. Expert Opin Drug Saf 2014; 13:977-87. [PMID: 24821316 DOI: 10.1517/14740338.2014.918948] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Rituximab is a widely prescribed anti-CD20 mAb for the treatment of CD20(+) B-cell non-Hodgkin Lymphoma and many other immune mediated conditions. There is a well-described association between rituximab containing chemo-immunotherapy treatment and reactivation of the hepatitis B virus (HBV). This review summarizes the current literature surrounding rituximab-associated HBV reactivation. AREAS COVERED Herein, we review the literature detailing the risk of HBV reactivation in inactive carriers and those with resolved hepatitis. The clinical presentation and management of HBV reactivation are also discussed along with a summary of clinical trials evaluating antiviral prophylaxis. Finally, clinical recommendations are detailed. Data from clinical trials, observational studies, reviews, and meta-analyses available in the Medline database were included in this narrative review. EXPERT OPINION Screening should be performed in all patients prior to the administration of any type of anti-CD20 mAb therapy. Among those with positive screening serology, testing for hepatitis B e antigen or viral load by polymerase chain reaction is appropriate. In those patients with detectable HBV DNA, the decision regarding the use of antiviral prophylaxis or observation should be individualized.
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Affiliation(s)
- Peter Riedell
- Washington University School of Medicine, Division of Oncology, Department of Medicine , 660 S. Euclid Ave, Campus Box 8056, St. Louis, MO 63110 , USA +1 314 362 0492 ; +1 314 747 5123 ;
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21
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13th Asia-Pacific Congress of Clinical Microbiology and Infection Consensus Guidelines for diagnosis and treatment of liver failure. Hepatobiliary Pancreat Dis Int 2013; 12:346-54. [PMID: 23924491 DOI: 10.1016/s1499-3872(13)60055-7] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
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- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
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22
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Idilman R, Arat M. Evaluation and management of hepatitis B virus infection in hematopoietic stem cell transplantation: before and after transplantation. Expert Rev Anti Infect Ther 2013; 9:641-52. [PMID: 21819330 DOI: 10.1586/eri.11.79] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
HBV infection remains a major global health problem and continues to be a common cause of liver-related morbidity and mortality in both immunocompetent and immunosuppressed individuals. Reactivation of HBV is a serious complication of chemotherapy/immunosuppressive therapy in patients with HBV infection. In this article, we aim to describe the diagnosis, prevention and management of HBV infection in allogeneic hematopoietic stem cell transplant candidates, from the pre- to post-transplant period. The data currently available suggest that all individuals with hemato-/onco-logical malignancies who undergo chemotherapy/immunosuppressive therapy should be screened for hepatotropic viruses such as HBV and HCV. HBV surface antigen-positive individuals who receive chemotherapy/immunosuppressive therapy are at considerable risk of HBV reactivation. Antiviral prophylaxis prevents HBV reactivation, decreases reactivation-related morbidity and mortality, and prevents interruptions in chemotherapy/immunosuppressive therapy in such individuals. The optimal duration of antiviral prophylaxis remains to be elucidated. The vaccination of HBV-naive recipients and their donors against HBV infection prior to transplantation plays an important role in preventing acquired HBV infection. The presence of hepatitis B surface antigen positivity is not an absolute contraindication for allogeneic hematopoietic stem cell transplantation.
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Affiliation(s)
- Ramazan Idilman
- Ankara University Faculty of Medicine, Department of Gastroenterology, Ibn-i Sina Hospital, Sihhiye, Ankara 06100, Turkey.
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Posthepatectomy HBV reactivation in hepatitis B-related hepatocellular carcinoma influences postoperative survival in patients with preoperative low HBV-DNA levels. Ann Surg 2013; 257:490-505. [PMID: 22868358 DOI: 10.1097/sla.0b013e318262b218] [Citation(s) in RCA: 100] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE This study aimed to clarify the incidence of hepatitis B virus (HBV) reactivation and its significance on long-term survival after partial hepatectomy in patients with HBV-related hepatocellular carcinoma (HCC), who had preoperative low HBV-DNA level of less than 2000 IU/mL. BACKGROUND HBV reactivation is a frequent complication of systemic chemotherapy in hepatitis B surface antigen-positive patients. Surgery and anesthesia result in a generalized state of immunosuppression in the immediate postoperative period. Data on HBV reactivation and its significance after partial hepatectomy are unclear. PATIENTS AND METHODS Consecutive patients from January 2006 to December 2007 were retrospectively studied. RESULTS HBV reactivation happened in 19.1% of patients in 1 year. There were 28 patients whose HBV reactivation was detected after the diagnosis of HCC recurrence. On multivariate analysis, hepatitis B e antigen (HBeAg) positivity, preoperative HBV-DNA above the lower limit of quantification (≥200 IU/mL), Ishak inflammation score of greater than 3, preoperative transarterial chemoembolization (TACE), operation time of more than 180 minutes, blood transfusion, and without prophylactic antiviral therapy were significantly associated with an increased risk of HBV reactivation. HBV reactivation negatively influenced postoperative hepatic functions. The posthepatectomy liver failure rate in patients with HBV reactivation was significantly higher than in those without reactivation (11.8% vs 6.4%; P = 0.002). The 3-year disease-free survival (DFS) rate and overall survival (OS) rates after resection in patients with HBV reactivation were significantly lower than those without reactivation (34.1% vs 46.0%; P = 0.009, and 51.6% vs 67.2%; P < 0.001, respectively). HBeAg positivity, detectable preoperative HBV-DNA level, high Ishak inflammation score, preoperative TACE, long operation time, and blood transfusion were independent risk factors for HBV reactivation, whereas prophylactic antiviral therapy was a protective factor. HBV reactivation, HBeAg positivity, HBV-DNA level of 200 IU/mL or more, tumor diameter greater than 5 cm, presence of satellite nodules, presence of portal vein tumor thrombus, blood transfusion, and resection margin less than 1.0 cm were independent risk factors for DFS. A HBV-DNA level of 200 IU/mL or more, an Ishak fibrosis score of 4 or greater, a tumor diameter greater than 5 cm, the presence of satellite nodules, the presence of portal vein tumor thrombus, a resection margin less than 1.0 cm, no prophylactic antiviral therapy, and HBV reactivation were independent risk factors for OS. CONCLUSIONS HBV reactivation was common after partial hepatectomy for HBV-related HCC with a preoperative low HBV-DNA level of less than 2000 IU/mL. Routine prophylactic antiviral treatment should be given before partial hepatectomy.
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Yeo W, Chan HLY. Hepatitis B virus reactivation associated with anti-neoplastic therapy. J Gastroenterol Hepatol 2013; 28:31-37. [PMID: 23020594 DOI: 10.1111/j.1440-1746.2012.07280.x] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/12/2012] [Indexed: 02/06/2023]
Abstract
Reactivation of hepatitis B virus (HBV) infection is a known complication during and after anti-cancer therapy. This condition can affect two patient populations: it is most commonly seen in patients who are seropositive for hepatitis B surface antigen (HBsAg), but it is also being increasingly reported among patients who are HBsAg-negative but who have prior infection, as evident by seropositive status for antibody to hepatitis B core antigen (anti-HBc), irrespective of their anti-HBs (antibody to HBsAg) status. The clinical course can vary from asymptomatic hepatitis to fulminant hepatic failure that can be potentially fatal. With the increasing use of biological agents in addition to potent cytotoxic chemotherapy in the armamentarium of anti-cancer treatments, reactivation of hepatitis B has become a common clinical situation that is faced by both oncologists and hepatologists especially in HBV endemic areas. In this review, we discuss the clinical course of reactivation in the two HBV-infected sub-populations, and the role of anti-virals in the prevention and management of HBV reactivation in association with cytotoxic chemotherapy and biological therapies.
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Affiliation(s)
- Winnie Yeo
- Department of Clinical Oncology, Sir Y.K. Pao Centre for Cancer, Faculty of Medicine, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
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Yang F, Zhu HL, He C, Li JJ, Xiang B, Cui X, Huang J, Ji J, Ma HB, Liu T. Effect of Antiviral Prophylaxis Strategy for Chemotherapy-Associated Hepatitis B Reactivation in Non-Hodgkin's Lymphoma Patients with Hepatitis B Virus Infection: A Retrospective Cohort Study. Indian J Hematol Blood Transfus 2012; 30:97-104. [PMID: 24839363 DOI: 10.1007/s12288-012-0195-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2012] [Accepted: 08/31/2012] [Indexed: 02/05/2023] Open
Abstract
Recent data indicates that nucleoside/nucleotide analogue (NUC) is effective in preventing and controlling hepatitis B virus (HBV) reactivation in HBV-carrying cancer patients who undergo chemotherapy, but the ideal antiviral agent and optimal application protocol still needs to be determined. Meanwhile, it is uncertain whether those with past HBV infection require antiviral prophylaxis during chemotherapy. This report retrospectively analyzed non-Hodgkin's lymphoma (NHL) patients seen from January, 2004 to June, 2009 in West China Hospital. We found that the prevalence of chronic HBV infection in our NHL patients was 20.7 % while that of past HBV infection was 21.05 %. Compared with the high rate (25.6 %) of HBV reactivation in patients with chronic HBV infection, none of those with past HBV infection in fact had occult HBV infection thus none experienced reactivation. Of the 82 patients with chronic HBV infection who received chemotherapy, antiviral prophylaxis could significantly reduce the incidence of HBV reactivation (5.0 vs. 45.2 % in the control group) and the incidence of liver function damage (32.5 vs. 73.8 % in the control group). The results of the current study confirmed previous reports that prophylactic NUCs administration can effectively prevent HBV reactivation and significantly reduce the incidence of HBV reactivation especially for patients receiving rituximab-containing regimens. Due to the fact that none of individuals who had past HBV infection developed HBV reactivation reported in our study, antiviral prophylaxis may not be required for patients with past HBV infection. Close observation of alanine aminotransferase and HBV-DNA contributes to early diagnosis and timely treatment of HBV reactivation.
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Affiliation(s)
- Fan Yang
- West China School of Clinical Medicine, Sichuan University, No. 37 Guoxue Alley, Chengdu, China
| | - Huan-Ling Zhu
- Department of Haematology, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Chengdu, China
| | - Chuan He
- Department of Haematology, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Chengdu, China
| | - Jian-Jun Li
- Department of Haematology, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Chengdu, China
| | - Bing Xiang
- Department of Haematology, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Chengdu, China
| | - Xu Cui
- Department of Haematology, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Chengdu, China
| | - Jie Huang
- Department of Haematology, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Chengdu, China
| | - Jie Ji
- Department of Haematology, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Chengdu, China
| | - Hong-Bing Ma
- Department of Haematology, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Chengdu, China
| | - Ting Liu
- Department of Haematology, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Chengdu, China
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Huang L, Li J, Lau WY, Yan J, Zhou F, Liu C, Zhang X, Shen J, Wu M, Yan Y. Perioperative reactivation of hepatitis B virus replication in patients undergoing partial hepatectomy for hepatocellular carcinoma. J Gastroenterol Hepatol 2012; 27:158-64. [PMID: 21871026 DOI: 10.1111/j.1440-1746.2011.06888.x] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIM Reactivation of hepatitis B virus (HBV) replication happens in patients who receive transarterial chemoembolization or systemic chemotherapy for hepatocellular carcinoma (HCC). The incidence and risk factors of HBV reactivation during the perioperative period in HCC patients receiving hepatic resection is unknown. METHODS Between May 2009 and November 2010, 164 consecutive patients with HBV-related HCC who underwent hepatic resection were prospectively enrolled in the study. Among these, 126 patients received antiviral treatment before the operation (the antiviral group) and 38 patients did not receive any antiviral treatment (the non-antiviral group). RESULTS Ten patients (6.1%) developed HBV reactivation perioperatively (within 1 month after hepatectomy). The incidence of HBV reactivation in the antiviral group and non-antiviral group were 1.6% (2/126) and 21.1% (8/38), respectively (P < 0.001). On univariate analysis, preoperative HBV DNA < 1.0 × 10(3) copies/mL and non-antiviral therapy were significantly correlated with the occurrence of HBV reactivation (P = 0.044 and P < 0.001, respectively). Only non-antiviral therapy remained as a predictive factor on multivariate analysis (odds ratio, 15.46; 95% confidence interval, 2.80-85.46, P = 0.002). The recovery of liver function (defined as a decrease of alanine aminotransferase back to normal) was achieved in 86.8% (132/152) patients without HBV reactivation and in 37.5% (3/8) patients with HBV reactivation when evaluated on day 30 after hepatectomy (P < 0.001). CONCLUSION Hepatectomy could reactivate HBV replication during the perioperative period, especially in patients who did not receive any antiviral therapy. A close monitoring of HBV DNA during the perioperative period was necessary irrespective of the preoperative HBV DNA level. Once HBV was reactivated, antiviral therapy should be given.
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Affiliation(s)
- Liang Huang
- Department of Hepatic Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
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27
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Liu CJ, Chen PJ, Chen DS, Kao JH. Hepatitis B virus reactivation in patients receiving cancer chemotherapy: natural history, pathogenesis, and management. Hepatol Int 2011; 7:316-26. [DOI: 10.1007/s12072-011-9279-6] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2011] [Accepted: 05/27/2011] [Indexed: 12/13/2022]
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28
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Chen XQ, Peng JW, Lin GN, Li M, Xia ZJ. The effect of prophylactic lamivudine on hepatitis B virus reactivation in HBsAg-positive patients with diffuse large B-cell lymphoma undergoing prolonged rituximab therapy. Med Oncol 2011; 29:1237-41. [PMID: 21556931 DOI: 10.1007/s12032-011-9974-0] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2011] [Accepted: 04/29/2011] [Indexed: 12/19/2022]
Abstract
The association of prolonged rituximab therapy and hepatitis B virus (HBV) reactivation in diffuse large B-cell lymphoma (DLBCL) and the role of lamivudine prophylaxis remain undefined. The prevalence and mortality of HBV reactivation in HBsAg-positive patients with DLBCL undergoing rituximab-based treatment, who received prophylactic treatment with or without lamivudine, were retrospectively analyzed. From January 2003 to December 2009, there were 50 patients enrolled in the study, among of which 30 received the prophylactic treatment of lamivudine and 20 without prophylactic treatment of lamivudine. Among of the 50 patients, seven patients received further rituximab maintenance, once every 3 months for 2 years. Compared with lamivudine treatment group, it showed that there was significantly higher prevalence of HBV reactivation (60.0% vs 13.3%, P = .001), severe hepatitis (45.0% vs 6.7%, P = .004), and mortality (25.0% vs 3.3%, P = .032) in non-lamivudine prophylactic group; however, there was no statistically significant difference in the HBV DNA levels at reactivation (3.94 × 10(6) vs 8.30 × 10(5) copies/ml, P = .47) and the time from first dose of rituximab to HBV reactivation(207 vs 386 days, P = .28). For patients undergoing further rituximab maintanence treatment, the prevalence and mortality of HBV reactivation were 71.4 and 28.6%, respectively. The prevalence and mortality of HBV reactivation are 66.7% vs 75.0% (P = 1.00) and 0 vs 50.0% (P = .43) in lamivudine prophylactic and non-lamivudine prophylactic groups, respectively. The effect of lamivudine prophylaxis on preventing HBV reactivation was found to be less in patients undergoing longer duration of rituximab treatment. A longer duration of rituximab treatment contributed to higher morbidity and mortality of HBV reactivation in HbsAg-positive patients with DLBCL. Further study is warranted for the optimal management of hepatitis caused by HBV reactivation.
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Affiliation(s)
- Xiao-Qin Chen
- Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, People's Republic of China
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29
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Abstract
Reactivation of hepatitis B is characterized by a sudden increase in hepatitis B virus (HBV) replication in a patient with prior evidence of resolved or inactive HBV infection. Although HBV reactivation can occur spontaneously, it usually occurs after chemotherapy, immunosuppression (organ transplantation) or an alteration in immune function (therapy for autoimmune disease, human immunodeficiency virus infection). The clinical presentation cases can vary, ranging from a subclinical, asymptomatic course to severe acute hepatitis and even death. Although reactivation of HBV is mainly found in HBsAg-positive patients, it can be observed in serologically recovered anti-hepatitis B core antibody (HBc)-positive, HBsAg-negative patients. Serum HBV DNA typically increases during immune suppression, followed by a disease flare and HBV DNA clearance following immune restoration after immune suppression is stopped. In organ transplant recipients, without immune reconstitution, high HBV DNA levels can lead to fibrosing cholestatic hepatitis related to the direct cytopathic effect of HBV. Several randomized, controlled trials and meta-analyses have shown that reactivation can be prevented by lamivudine prophylaxis. Screening for HBsAg and anti-HBc should be performed before beginning immunosuppressive treatment and routine prophylaxis is recommended in HBsAg-positive patients. The optimal duration of prophylaxis remains to be determined. In anti-HBc-positive patients with or without anti-hepatitis B surface antigen, alanine transaminase and HBV DNA levels should be closely monitored and antiviral therapy should be started when HBV reactivation is confirmed. The use of new more potent nucleos(t)ides analogues with lower resistance rates would seem to be logical; however, experience with these drugs in the prophylaxis and treatment of severe HBV reactivation is limited.
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Affiliation(s)
- Bruno Roche
- AP-HP, Hopital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France
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30
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Sun Z, Li G, Ai X, Luo B, Wen Y, Zhao Z, Dong S, Guan J. Hepatic and biliary damage after transarterial chemoembolization for malignant hepatic tumors: incidence, diagnosis, treatment, outcome and mechanism. Crit Rev Oncol Hematol 2010; 79:164-74. [PMID: 20719529 DOI: 10.1016/j.critrevonc.2010.07.019] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2009] [Revised: 03/19/2010] [Accepted: 07/19/2010] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVE To provide an overview of recent studies on transarterial chemoembolization-related hepatic and biliary damage (TRHBD) in patients with malignant hepatic tumors (MHT) and to explore the reasons for TRHBD. METHODS Literature on the treatments for MHT by TACE was sought in PubMed and the related information was summarized. RESULTS TRHBD is found to occur in the hepatic parenchymal cells, biliary tree and blood-vascular system. The damage is mainly due to ischemia resulting from embolic materials such as gelatin sponge and lipiodol. In addition, clinicians' skill levels in non-superselective catheterization, the health condition of the patients, and the chemical agents used may also be related to the damage. Most of the deterioration can be reversed if the patients are diagnosed and treated properly and promptly. CONCLUSIONS Understanding the mechanisms of TRHBD more comprehensively is helpful in developing effective methods for prevention and treatment.
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Affiliation(s)
- Zhengang Sun
- Department of Hepatobiliary Surgery, Jingzhou Central Hospital, JingZhou 4343100, Hubei Province, China
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31
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Abstract
Chronic hepatitis B virus (HBV) is estimated to be present in 350 million people worldwide. One of its major complications is reactivation of dormant HBV, which is associated with significant morbidity and mortality. Although reactivation can occur spontaneously, the most common risk factor is initiation of immunosuppression. As the use of immunosuppressive therapy increases, the incidence of HBV reactivation is expected to rise. Screening with serologic markers for hepatitis B is recommended before initiating immunosuppressive therapy. In patients with no evidence of HBV infection, immunization is recommended. In chronic carriers, prophylactic antiviral treatment has been shown to decrease overall morbidity and mortality. Patients with inactive HBV should be monitored closely during immunosuppressive treatment with alanine transaminase and serum HBV-DNA levels and treated promptly if they develop HBV reactivation. Although HBV reactivation is a serious complication, it can be prevented with screening and prophylactic treatment.
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32
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Lubel JS, Angus PW. Hepatitis B reactivation in patients receiving cytotoxic chemotherapy: diagnosis and management. J Gastroenterol Hepatol 2010; 25:864-71. [PMID: 20546439 DOI: 10.1111/j.1440-1746.2010.06243.x] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Nearly one third of the world's population have been infected with hepatitis B and the virus is endemic in many Asian countries. With increasing life expectancy and the expected global increase in cancer, chemotherapy induced reactivation of hepatitis B is likely to become an increasing problem. Patients with significant levels of hepatitis B virus (HBV) DNA in serum prior to chemotherapy and patients receiving intensive chemotherapy for hematological malignancies appear particularly at risk. Most patients who suffer reactivation of hepatitis B are positive for hepatitis B surface antigen (HBsAg) prior to chemotherapy and are therefore easily identifiable by routine screening. In addition, the very large population of patients who have been exposed to the virus and have apparently cleared the virus as assessed by serological testing (HBsAg negative/hepatitis B core antibody [HBcAb] positive) may also be at risk of reactivation. These patients should be monitored and in some cases receive prophylaxis during chemotherapy. Published experience with antiviral prophylaxis has largely been limited to the nucleoside analogue, lamivudine. The commencement of antiviral prophylaxis prior to chemotherapy and its continuation until restitution of normal host immunity is the cornerstone to effective prevention of hepatitis B reactivation. This review summarizes the important issues related to HBV reactivation and suggests an algorithm for managing these patients in the clinical setting.
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Affiliation(s)
- John S Lubel
- Department of Hepatology, Box Hill Hospital, Box Hill, Melbourne, Victoria, Australia.
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33
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Muñoz Bertrán E, Pérez Ceballos E, Gómez Espín R, Ortega González I. [Hepatitis B reactivation in an HbsAg-negative/anti-HBc-positive patient with B-cell non-Hodgkin lymphoma receiving chemotherapy with rituximab]. GASTROENTEROLOGIA Y HEPATOLOGIA 2010; 33:377-81. [PMID: 20363054 DOI: 10.1016/j.gastrohep.2010.01.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Subscribe] [Scholar Register] [Received: 12/01/2009] [Revised: 01/21/2010] [Accepted: 01/22/2010] [Indexed: 01/29/2023]
Abstract
Reactivation of hepatitis B virus infection in patients with resolved infection is rare and is usually associated with immunosuppressive therapy. Morbidity and mortality are high. Some cases of hepatitis B reactivation associated with the use of rituximab have previously been published. We present the case of a patient with B-cell non-Hodgkin lymphoma receiving combination chemotherapy with rituximab who showed hepatitis B reactivation followed by liver failure. The most recent literature on this topic is reviewed and discussed.
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MESH Headings
- Adenine/analogs & derivatives
- Adenine/therapeutic use
- Aged, 80 and over
- Antibodies, Monoclonal/administration & dosage
- Antibodies, Monoclonal/adverse effects
- Antibodies, Monoclonal, Murine-Derived
- Antibody Specificity
- Antineoplastic Combined Chemotherapy Protocols/administration & dosage
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Comorbidity
- Cyclophosphamide/administration & dosage
- Fatal Outcome
- Hepatitis B Antibodies/blood
- Hepatitis B Antibodies/immunology
- Hepatitis B Core Antigens/immunology
- Hepatitis B Surface Antigens/blood
- Hepatitis B virus/physiology
- Hepatitis B, Chronic/complications
- Hepatitis B, Chronic/drug therapy
- Hepatitis B, Chronic/virology
- Humans
- Immunologic Factors/administration & dosage
- Immunologic Factors/adverse effects
- Immunotherapy/adverse effects
- Liver Failure/etiology
- Lymphoma, B-Cell, Marginal Zone/complications
- Lymphoma, B-Cell, Marginal Zone/drug therapy
- Male
- Organophosphonates/therapeutic use
- Prednisone/administration & dosage
- Recurrence
- Rituximab
- Tenofovir
- Vincristine/administration & dosage
- Virus Activation/drug effects
- Virus Activation/immunology
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Aomatsu T, Komatsu H, Yoden A, Hosomi A, Miyazaki H, Sogo T, Inui A, Fujisawa T, Tamai H. Fulminant hepatitis B and acute hepatitis B due to intrafamilial transmission of HBV after chemotherapy for non-Hodgkin's lymphoma in an HBV carrier. Eur J Pediatr 2010; 169:167-71. [PMID: 19466454 DOI: 10.1007/s00431-009-1000-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2009] [Accepted: 05/11/2009] [Indexed: 01/22/2023]
Abstract
Hepatitis B virus (HBV) reactivation after chemotherapy has been investigated, but little is known about the risk of horizontal transmission from an immunocompromised host with HBV reactivation. We treated two children with fulminant hepatitis B and acute hepatitis B, respectively, whose grandmother, an HBV carrier, had been undergoing rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R+CHOP) therapy for lymphoma. The grandmother was also suffering from fulminant hepatitis when both children became ill. The complete HBV DNA sequences of the three family members were identical. The full genome sequence analysis of HBV provided strong evidence of intrafamilial transmission of HBV. Treatments that cause immunosuppression, such as R+CHOP therapy for lymphoma, can increase the levels of serum HBV DNA and the risk of intrafamilial HBV infection when given to HBV carriers. In conclusion, specific antiviral prophylaxis is indispensable for preventing horizontal transmission as well as reactivation of HBV in chemotherapy-treated HBV carriers.
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Affiliation(s)
- Tomoki Aomatsu
- Department of Pediatrics, Osaka Medical College, Takatsuki, Japan
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35
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Fatal lactic acidosis associated with the use of combination oral medications to treat reactivation of hepatitis B. J Clin Gastroenterol 2009; 43:1008-10. [PMID: 19461528 DOI: 10.1097/mcg.0b013e31819c3945] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Oral nucleos(t)ide analogs for the treatment of hepatitis B virus (HBV) infection are well tolerated with minimal side effects. These agents do carry a Food and Drug Administration "black box" warning about the development of fatal lactic acidosis on the basis of data from the human immunodeficiency virus literature. However, no previously published cases of this lethal side effect have been reported in patients undergoing HBV treatment using the current Food and Drug Administration-approved HBV medications. We report a case of HBV reactivation after chemotherapy for leukemia, and the development of fatal lactic acidosis attributed to the use of combination oral HBV medications.
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36
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Pei SN, Chen CH, Lee CM, Wang MC, Ma MC, Hu TH, Kuo CY. Reactivation of hepatitis B virus following rituximab-based regimens: a serious complication in both HBsAg-positive and HBsAg-negative patients. Ann Hematol 2009; 89:255-62. [DOI: 10.1007/s00277-009-0806-7] [Citation(s) in RCA: 163] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2009] [Accepted: 07/31/2009] [Indexed: 12/13/2022]
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37
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Negreanu L, Baty G, Dubois F, de Muret A, Bacq Y. Hepatitis B virus reactivation after a resolutive acute hepatitis leading to a diagnosis of T cell lymphoma. Dig Liver Dis 2009; 41:e39-e41. [PMID: 18819852 DOI: 10.1016/j.dld.2008.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2008] [Revised: 05/30/2008] [Accepted: 06/05/2008] [Indexed: 12/11/2022]
Abstract
A case of hepatitis B virus reactivation leading to the diagnosis of a T cell lymphoma is reported. A 66-year-old woman with a past history (10 years before) of spontaneously recovered acute hepatitis B (with disappearance of serum hepatitis B surface antigen and appearance of anti-HBs), has been referred for hepatologic consultation for acute hepatitis. The patient was found positive again for hepatitis B surface antigen as well HBeAg and hepatitis B virus DNA. No other cause of liver disease was identified and a diagnosis of spontaneous hepatitis B virus reactivation was made. Five months later a peripheral T cell lymphoma was diagnosed. This unusual case confirms that natural immunity is not protective against hepatitis B virus reactivation and shows that such hepatitis B virus reactivation may precede the usual clinical manifestations of a peripheral T cell lymphoma.
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Affiliation(s)
- L Negreanu
- Department of Hepato-gastro-enterology, Trousseau Hospital, Tours Regional University Hospital, Tours, France
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38
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Coiffier B. Hepatitis B Virus Reactivation in Patients Receiving Chemotherapy for Cancer Treatment: Role of Lamivudine Prophylaxis. Cancer Invest 2009; 24:548-52. [PMID: 16939967 DOI: 10.1080/07357900600815232] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatitis B virus (HBV) reactivation is a frequent complication in inactive HBV carriers at time of chemotherapy or following this chemotherapy. This complication appeared during or after chemotherapy and was not increased by the use of rituximab alone or combined with chemotherapy. This is a severe complication most frequently seen in lymphoma patients. Lamivudine have efficacy to treat the patients once the clinical disease is present. However, lamivudine prophylaxis beginning before chemotherapy and until at least 6 months after the end of chemotherapy is recommended for all HBV carriers. Hepatitis C virus is usually not associated with reactivation and prophylaxis should not be used.
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39
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Ziakas PD, Karsaliakos P, Mylonakis E. Effect of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in lymphoma: a meta-analysis of published clinical trials and a decision tree addressing prolonged prophylaxis and maintenance. Haematologica 2009; 94:998-1005. [PMID: 19454492 DOI: 10.3324/haematol.2009.005819] [Citation(s) in RCA: 62] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Lamivudine prophylaxis is an effective strategy in HbSAg-positive patients receiving cancer chemotherapy. Recent data indicate that a lamividune-prophylaxis strategy results in a decrease of hepatitis B virus (HBV) reactivation rates, though its effect on HBV-mortality remains equivocal. This report evaluates the benefits from this strategy among lymphoma patients and develops a management approach for patients with prolonged immunosuppression. A Medline search was conducted to retrieve published trials on HBsAg-positive lymphoma patients receiving prophylactic lamivudine during chemotherapy. Basic inclusion criterion was to report HBV-reactivation rates with and without lamivudine prophylaxis. A meta-analysis of the risk of HBV-reactivation and HBV-related mortality was conducted, and the pooled effect was calculated as risk ratio (RR). We found that lamivudine prophylaxis is associated with a significant reduction in hepatitis B virus reactivation (RR 0.21, 95%CI 0.13-0.35) and a trend in reducing HBV-related mortality (RR 0.68, 95%CI 0.19-2.49). In order to study the long-term effects of anti-HBV prophylaxis when prolonged immunosuppression is needed, we used our findings to model a decision tree. Overall survival was the main outcome used in the analysis. Rituximab maintenance in B-cell lymphomas was used as a paradigm of prolonged immunosuppression. We found that extended anti-HBV prophylaxis can improve survival rates by 2.4% in HBsAg-positive patients. If 1,000 HBsAg-positive lymphoma patients receive prophylaxis, one will die from hepatitis B virus reactivation versus 25/1,000 if no prophylaxis is administered. This effect is probably mediated through a reduction of hepatitis B virus reactivation and HBV-related mortality. The ideal antiviral agent needs to be determined.
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Affiliation(s)
- Panayiotis D Ziakas
- Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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40
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Katz LH, Fraser A, Leibovici L, Tur-Kaspa R. Lamivudine for preventing reactivation of hepatitis B infection in patients planned to undergo immunosuppressive therapy. Hippokratia 2009. [DOI: 10.1002/14651858.cd005264.pub2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Affiliation(s)
- Lior H Katz
- Sheba Medical Center; Gastroenterology Department; Tel-Hashomer Ramat-Gan Israel 52621
| | - Abigail Fraser
- University of Bristol, Oakfield House; Department of Social Medicine, MRC Centre for Causal Analysis in Translational Epidemiology; Oakfield Road Bristol UK BS8 2BN
| | - Leonard Leibovici
- Beilinson Campus, Rabin Medical Center; Department of Medicine E; 39 Jabotinsky Street Petah-Tiqva Israel 49100
| | - Rani Tur-Kaspa
- Rabin Medical Center - Beilison Campus; Department of Internal Medicine D; - Beilinson Campus Petah Tigva Israel 49100
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41
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Sarin SK, Kumar A, Almeida JA, Chawla YK, Fan ST, Garg H, de Silva HJ, Hamid SS, Jalan R, Komolmit P, Lau GK, Liu Q, Madan K, Mohamed R, Ning Q, Rahman S, Rastogi A, Riordan SM, Sakhuja P, Samuel D, Shah S, Sharma BC, Sharma P, Takikawa Y, Thapa BR, Wai CT, Yuen MF. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the study of the liver (APASL). Hepatol Int 2009; 3:269-82. [PMID: 19669378 PMCID: PMC2712314 DOI: 10.1007/s12072-008-9106-x] [Citation(s) in RCA: 642] [Impact Index Per Article: 40.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2008] [Accepted: 09/26/2008] [Indexed: 02/06/2023]
Abstract
The Asian Pacific Association for the Study of the Liver (APASL) set up a working party on acute-on-chronic liver failure (ACLF) in 2004, with a mandate to develop consensus guidelines on various aspects of ACLF relevant to disease patterns and clinical practice in the Asia-Pacific region. Experts predominantly from the Asia-Pacific region constituted this working party and were requested to identify different issues of ACLF and develop the consensus guidelines. A 2-day meeting of the working party was held on January 22-23, 2008, at New Delhi, India, to discuss and finalize the consensus statements. Only those statements that were unanimously approved by the experts were accepted. These statements were circulated to all the experts and subsequently presented at the Annual Conference of the APASL at Seoul, Korea, in March 2008. The consensus statements along with relevant background information are presented in this review.
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Affiliation(s)
- Shiv Kumar Sarin
- Department of Gastroenterology, G. B. Pant Hospital, Affiliated to University of Delhi, Jawahar Lal Nehru Road, New Delhi, 110 002 India
| | - Ashish Kumar
- Department of Hepatology, Institute of Liver & Biliary Sciences (ILBS), D-1 Vasant Kunj, New Delhi, 110 070 India
| | - John A. Almeida
- Gastrointestinal and Liver Unit, The Prince of Wales Hospital and University of New South Wales, Barker Street, Randwick 2031, New South Wales, Australia
| | - Yogesh Kumar Chawla
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Sheung Tat Fan
- Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong SAR, China
| | - Hitendra Garg
- Department of Gastroenterology, G. B. Pant Hospital, Affiliated to University of Delhi, Jawahar Lal Nehru Road, New Delhi, 110 002 India
| | - H. Janaka de Silva
- Department of Medicine, Faculty of Medicine, University of Kelaniya, P.O. Box 6, Thalagolla Road, Ragama, Sri Lanka
| | - Saeed Sadiq Hamid
- Section of Gastroenterology, Department of Medicine, The Aga Khan University Hospital, Stadium Road, P.O. Box 3500, Karachi , 74800 Pakistan
| | - Rajiv Jalan
- The University College London (UCL) Institute of Hepatology, Division of Medicine, University College London, 69-75 Chenies Mews, London, WC1E 6HX UK
| | - Piyawat Komolmit
- Department of Medicine, Faculty and Medicine, Chulalongkorn University, Bangkok , 10330 Thailand
| | - George K. Lau
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong SAR, China
| | - Qing Liu
- Beijing Youan Hospital, Capital University of Medical Sciences, Beijing, China
| | - Kaushal Madan
- Department of Hepatology, Institute of Liver & Biliary Sciences (ILBS), D-1 Vasant Kunj, New Delhi, 110 070 India
| | - Rosmawati Mohamed
- Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, 50603 Malaysia
| | - Qin Ning
- Laboratory of Infectious Immunology, Department of Infectious Disease, Institute of Immunology, Huazhong University of Science and Technology, Wuhan, China
| | - Salimur Rahman
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Archana Rastogi
- Department of Pathology, Institute of Liver & Biliary Sciences (ILBS), D-1 Vasant Kunj, New Delhi, 110 070 India
| | - Stephen M. Riordan
- Gastrointestinal and Liver Unit, The Prince of Wales Hospital and University of New South Wales, Barker Street, Randwick 2031, New South Wales, Australia
| | - Puja Sakhuja
- Department of Pathology, G. B. Pant Hospital, Affiliated to University of Delhi, Jawahar Lal Nehru Road, New Delhi, 110 002 India
| | - Didier Samuel
- INSERM Unité 785, AP-HP Hôpital Paul Brousse, Villejuif, 94800 France
| | - Samir Shah
- Department of Gastroenterology, Jaslok Hospital and Research Center, 15 - Dr. Deshmukh Marg, Pedder Road, Mumbai, 400 026 India
| | - Barjesh Chander Sharma
- Department of Gastroenterology, G. B. Pant Hospital, Affiliated to University of Delhi, Jawahar Lal Nehru Road, New Delhi, 110 002 India
| | - Praveen Sharma
- Department of Gastroenterology, G. B. Pant Hospital, Affiliated to University of Delhi, Jawahar Lal Nehru Road, New Delhi, 110 002 India
| | - Yasuhiro Takikawa
- Department of Gastroenterology and Hepatology, Iwate Medical University, 19-1 Uchimaru, Morioka, 020-8505 Japan
| | - Babu Ram Thapa
- Division of Pediatric Gastroenterology, Department of Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Chun-Tao Wai
- Asian Center for Liver Diseases and Transplantation, Gleneagles Hospital, Annexe Block #02-37, 6A Gleneagles Hospital, Singapore, 258500 Singapore
| | - Man-Fung Yuen
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong SAR, China
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42
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Lau GKK. Hepatitis B reactivation after chemotherapy: two decades of clinical research. Hepatol Int 2008; 2:152-62. [PMID: 19669300 PMCID: PMC2716860 DOI: 10.1007/s12072-008-9056-3] [Citation(s) in RCA: 75] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2007] [Accepted: 01/23/2008] [Indexed: 02/06/2023]
Abstract
Hepatitis due to hepatitis B virus reactivation after cytotoxic or immunosuppressive therapy is a serious cause of liver-related morbidity and mortality. With the characterization of the underlying pathogenesis, much progress in the management of this important clinical problem has been made in the past 2 decades. By year 2008, it is mandatory to screen for hepatitis B surface antigen status before initiating intensive chemotherapy or immunosuppressive therapy. All those who are hepatitis B surface antigen positive should be started on preemptive nucleos(t)ide analogues. However, there remains important issues, such as the type and duration of nucleos(t)ide analogue therapy, which need to be understood. As not all hepatitis B surface antigen-positive patients will suffer from HBV reactivation, it is therefore useful to identify risk factors related to HBV reactivation so that patients will not be treated unnecessarily with nucleos(t)ide analogues. To date, a high baseline level of viral replication, as reflected by high serum HBV DNA level, positive serum hepatitis B e antigen, and a high intrahepatic covalently closed circular DNA level, is the most important predictor for HBV reactivation. Recently, there has been an increased awareness of reactivation of occult hepatitis B virus, especially in hepatitis B virus endemic area, such as the Asia-Pacific region. Careful epidemiological study will be needed to clarify the impact of occult hepatitis B infection in patients treated with cytotoxic or immunosuppressive therapy.
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Affiliation(s)
- George K K Lau
- Department of Medicine, The University of Hong Kong, Room 1838, Block K, Queen Mary Hospital, 102 Pokfulum Road, Hong Kong, Hong Kong SAR China,
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43
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Hsu C, Hsiung CA, Su IJ, Hwang WS, Wang MC, Lin SF, Lin TH, Hsiao HH, Young JH, Chang MC, Liao YM, Li CC, Wu HB, Tien HF, Chao TY, Liu TW, Cheng AL, Chen PJ. A revisit of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in non-Hodgkin's lymphoma: a randomized trial. Hepatology 2008; 47:844-53. [PMID: 18302293 DOI: 10.1002/hep.22106] [Citation(s) in RCA: 243] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
UNLABELLED Lamivudine is effective to control hepatitis B virus (HBV) reactivation in HBV-carrying cancer patients who undergo chemotherapy, but the optimal treatment protocol remains undetermined. In this study, HBV carriers with newly diagnosed non-Hodgkin's lymphoma (NHL) who underwent chemotherapy were randomized to either prophylactic (P) or therapeutic (T) lamivudine treatment groups. Group P patients started lamivudine from day 1 of the first course of chemotherapy and continued treatment until 2 months after completion of chemotherapy. Group T patients received chemotherapy alone and started lamivudine treatment only if serum alanine aminotransferase (ALT) levels elevated to greater than 1.5-fold of the upper normal limit (ULN). The primary endpoint was incidence of HBV reactivation during the 12 months after starting chemotherapy. During chemotherapy, fewer group P patients had HBV reactivation (11.5% versus 56%, P = 0.001), HBV-related hepatitis (7.7% versus 48%, P = 0.001), or severe hepatitis (ALT more than 10-fold ULN) (0 versus 36%, P < 0.001). No hepatitis-related deaths occurred during protocol treatment. Prophylactic lamivudine use was the only independent predictor of HBV reactivation. After completion of chemotherapy, the incidence of HBV reactivation did not differ between the 2 groups. Two patients, both in group P, died of HBV reactivation-related hepatitis, 173 and 182 days, respectively, after completion of protocol treatment. When compared with an equivalent group of lamivudine-naïve lymphoma patients who underwent chemotherapy, therapeutic use of lamivudine neither reduced the severity of HBV-related hepatitis nor changed the patterns of HBV reactivation. CONCLUSION Prophylactic lamivudine use, but not therapeutic use, reduces the incidence and severity of chemotherapy-related HBV reactivation in NHL patients.
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Affiliation(s)
- Chiun Hsu
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
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Katz LH, Fraser A, Gafter-Gvili A, Leibovici L, Tur-Kaspa R. Lamivudine prevents reactivation of hepatitis B and reduces mortality in immunosuppressed patients: systematic review and meta-analysis. J Viral Hepat 2008; 15:89-102. [PMID: 18184191 DOI: 10.1111/j.1365-2893.2007.00902.x] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
To assess the effects of prophylactic lamivudine on reactivation and mortality following immunosuppressive therapy in hepatitis B surface antigen (HBsAg)-positive patients, we performed a meta-analysis. Systematic review and meta-analysis of randomized and nonrandomized prospective controlled trials and retrospective comparative case series were identified through The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and LILACS. The primary outcomes were virological reactivation, clinical reactivation and mortality. Secondary outcomes included hepatitis B virus (HBV)-related mortality, liver histology, discontinuation or disruption of immunosuppressive therapy, lamivudine-resistant HBV strains and adverse events. A total of 21 studies were included, two of which were randomized controlled trials. Clinical and virological reactivation were significantly reduced in the lamivudine group [odds ratio (OR) 0.09; 95% confidence interval (CI) 0.05-0.15 and OR 0.04; 95% CI 0.01-0.14 respectively]. All-cause mortality was significantly reduced in the lamivudine group (OR 0.36; 95% CI 0.23-0.56) which translates to only 11 patients who need to be treated to prevent one death. Lamivudine significantly reduced HBV-related mortality, and discontinuations or disruptions of the immunosuppressive treatment. No adverse effects of lamivudine were recorded, and resistance to lamivudine occurred in low rates. We demonstrated a clear benefit of lamivudine in terms of clinical and virological HBV reactivation, overall mortality, HBV-related mortality and interruptions or discontinuations in the immunosuppressive treatment. Lamivudine should be administered prophylactically to HBsAg-positive patients who are about to receive immunosuppressive therapy.
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Affiliation(s)
- L H Katz
- Department of Medicine D and Liver Institute, Beilinson Campus, Rabin Medical Center, Petah-Tiqva, Israel.
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45
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Lubel JS, Testro AG, Angus PW. Hepatitis B virus reactivation following immunosuppressive therapy: guidelines for prevention and management. Intern Med J 2007; 37:705-12. [PMID: 17894766 DOI: 10.1111/j.1445-5994.2007.01479.x] [Citation(s) in RCA: 73] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
It is well known that immunosuppressive drugs or cancer chemotherapy can stimulate replication of hepatitis B virus (HBV) and precipitate severe flares of HBV infection. The risk of this syndrome of 'reactivation hepatitis B' is highest in haematopoietic stem cell or solid organ transplant recipients and in those undergoing chemotherapy for haematological malignancies; however, it has been described following almost any form of immunosuppressive treatment. Fortunately, it can be largely prevented by prophylactic therapy with oral anti-HBV nucleoside/nucleotide analogues. Importantly, chronic HBV infection is usually asymptomatic, and most patients at risk are likely to be unaware that they carry the infection. Thus, the key to avoiding this potentially fatal complication of immunosuppressive treatment is to ensure that all patients at risk of chronic HBV infection are screened for the disease before commencing immunosuppressive treatment or chemotherapy.
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Affiliation(s)
- J S Lubel
- Victorian Liver Transplant Unit, Department of Gastroenterology, Austin Health, Heidelberg, Victoria, Australia
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46
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Antiviral prophylaxis for chemotherapy-induced reactivation of chronic hepatitis B virus infection. Clin Liver Dis 2007; 11:965-91, x. [PMID: 17981237 DOI: 10.1016/j.cld.2007.08.006] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Chronic hepatitis B virus (HBV) carriers are at considerable risk of reactivation of HBV infection when undergoing chemotherapy or immunosuppressive therapy. Complications of HBV reactivation, including asymptomatic elevation of HBV DNA levels, acute hepatitis, acute liver failure, and delays or dose reductions in chemotherapy, are avoidable with appropriate prophylactic oral antiviral therapy. This article reviews evidence for and presents a grade A recommendation supporting primary prophylaxis among HBV carriers with lamivudine. The dose and duration of prophylaxis, risk of lamivudine resistance, and future directions of prophylactic therapy for HBV reactivation during chemotherapy are discussed. Recommendations are suggested based on expert opinion for prophylaxis with the combination of lamivudine plus adefovir or with entecavir as alternative antiviral strategies that substantially reduce or avoid the risk of HBV antiviral drug resistance.
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47
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Shim SJ, Seong J, Lee IJ, Han KH, Chon CY, Ahn SH. Radiation-induced hepatic toxicity after radiotherapy combined with chemotherapy for hepatocellular carcinoma. Hepatol Res 2007; 37:906-13. [PMID: 17610506 DOI: 10.1111/j.1872-034x.2007.00149.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
AIM The purpose of the present study was to analyze hepatic toxicity following radiotherapy combined with regional chemotherapy for hepatocellular carcinoma (HCC). METHODS From 2001 to 2003, a total of 132 patients with HCC received 3-D conformal radiation therapy (3D-CRT) combined with chemotherapy. Patients were divided into two groups based on drug localization: the transcatheter arterial chemoembolization (TACE) group, where the chemotherapeutic drug (adriamycin) was localized within the tumor, and the non-TACE group, where the drugs (adriamycin, cisplatin, 5-fluorouracil) were diffusely spread over the entire liver. RESULTS Patients were evaluated by biochemical parameters for any hepatic toxicity prior to, during, and until 12 months after 3D-CRT. Hepatic toxicity was defined as radiation-induced liver disease (RILD) or combined modality-induced liver disease (CMILD), which is defined as RILD with abnormal elevation of total bilirubin levels. In the TACE group, three patients developed RILD (5.6%) and none developed CMILD. In the non-TACE group, three patients (3.7%) and seven patients (8.8%) developed RILD and CMILD, respectively. CONCLUSION Hepatic toxicity following radiotherapy combined with regional chemotherapy for HCC might be influenced by the distribution of the chemotherapeutic drugs. A more precise understanding of hepatic toxicity from chemoradiotherapy will help design optimal treatments for HCC.
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Affiliation(s)
- Su J Shim
- Departments of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
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48
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Saab S, Dong MH, Joseph TA, Tong MJ. Hepatitis B prophylaxis in patients undergoing chemotherapy for lymphoma: a decision analysis model. Hepatology 2007; 46:1049-56. [PMID: 17680650 DOI: 10.1002/hep.21783] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
UNLABELLED Hepatitis B reactivation is a major cause of morbidity and mortality in patients undergoing chemotherapy for lymphomas. These patients may experience direct liver-related complications or reduced cancer survival because of interruptions in chemotherapy. Our aim was to compare the costs and outcomes of 2 different chronic hepatitis B management strategies. In hepatitis B carriers undergoing chemotherapy, we pursued a decision analysis model to compare the costs and clinical outcomes of using lamivudine prophylaxis versus initiating lamivudine only when clinically overt hepatitis occurred. Our results indicate that the use of lamivudine prophylaxis is cost-effective. Even though the use of lamivudine prophylaxis was associated with an incremental cost of $1530 per patient ($18,707 versus $17,177), both the number and severity of hepatitis B reactivations were reduced. None of the patients in the prophylaxis group had liver-related deaths versus 20 who died in the no-prophylaxis group. Cancer deaths were also reduced from 47-39 with lamivudine prophylaxis, presumably because of the increased need for cessation or modification of chemotherapy in patients who had severe hepatitis B virus flares. The incremental cost-effectiveness ratio of using lamivudine prophylaxis was $33,514 per life year saved. CONCLUSION Our results provide pharmacoeconomic support for the use of lamivudine prophylaxis in patients undergoing chemotherapy for lymphoma treatment.
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Affiliation(s)
- Sammy Saab
- Department of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
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Lalazar G, Rund D, Shouval D. Screening, prevention and treatment of viral hepatitis B reactivation in patients with haematological malignancies. Br J Haematol 2007; 136:699-712. [PMID: 17338776 DOI: 10.1111/j.1365-2141.2006.06465.x] [Citation(s) in RCA: 222] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The prevalence of hepatitis B virus (HBV) infection in patients with haematological malignancies is increased compared with the general population worldwide. HBV reactivation is common following chemotherapy and is associated with a high mortality despite prompt anti-viral treatment. HBV reactivation may necessitate interruption of chemotherapy with adverse prognostic consequences for the haematological disease. Chemotherapy-induced immune suppression may lead to increased HBV replication. Immune reconstitution within the weeks and months following recovery from chemotherapy may be associated with a flare of hepatitis B manifested by hepatocellular injury. Risk factors associated with HBV reactivation include detectable hepatitis B surface antigen (HBsAg), HBV DNA, Hepatitis B e (HBeAg) antigen, antibodies to hepatitis B core antigen (anti-HBc), treatment with corticosteroids, young age and male gender. Lamivudine is effective during HBV reactivation due to immune suppression. Clinical trials have demonstrated that pre-emptive antiviral treatment with lamivudine is superior to deferred treatment. Current recommendations emphasise screening for HBV infection in all haematology patients, particularly prior to chemotherapy. Patients who are HBsAg positive or HBV DNA positive should receive pre-emptive treatment with lamivudine before chemotherapy. The duration of lamivudine treatment may be prolonged commensurate with the degree of immunosuppression. HBV naïve patients should be immunised against hepatitis B, as should haematopoietic stem cell donors. In summary, overt and occult HBV pose a serious, but preventable, threat. Pre-treatment screening of patients at risk should be practiced diligently by all clinicians that treat patients with malignancies.
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Affiliation(s)
- Gadi Lalazar
- Liver Unit, Departments of Medicine, Hadassah-Hebrew University Hospital, Jerusalem, Israel
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50
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Yağci M, Yağci M, Acar K, Acar K, Sucak GT, Aki Z, Bozdayi G, Haznedar R. A prospective study on chemotherapy-induced hepatitis B virus reactivation in chronic HBs Ag carriers with hematologic malignancies and pre-emptive therapy with nucleoside analogues. Leuk Lymphoma 2006; 47:1608-12. [PMID: 16966273 DOI: 10.1080/10428190500472974] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Chemotherapy-induced hepatitis B virus (HBV) reactivation is a serious problem in chronic HBV carriers with hematologic malignancies. In 12 patients with hematologic malignancies, we performed a prospective study to determine the effectiveness of nucleoside analogues in the pre-emptive therapy of chemotherapy-induced HBV reactivation. HBV reactivation occurred in seven patients (58.3%) whereas five of the seven patients (71%) responded to nucleoside analogue therapy. HBV reactivation-related acute liver failure and death was not observed in the present study. All five patients with chronic lymphocytic leukemia (CLL) experienced chemotherapy-induced HBV reactivation regardless of the chemotherapy regimen. Therefore, we suggest that CLL carries a significant risk of chemotherapy-induced HBV reactivation. The pre-emptive therapy of chemotherapy-induced HBV reactivation appears to be safe, based on the results of this pilot study. Pre-emptive therapy enables the definition of high-risk patients who cannot be identified by primary prophylaxis.
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Affiliation(s)
- Münci Yağci
- Department of Haematology, Gazi Medical School, Ankara, Turkey.
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