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Buonomo AR, Viceconte G, Nicolini LA, Habibović S, Rajan AK, Santos L, Gherlan GS, Miron VD, Şahin GÖ, Săndulescu O. Management of hepatitis B virus (HBV) infection in multiple sclerosis patients on disease modifying therapies (DMTs). Future Virol 2025:1-10. [DOI: 10.1080/17460794.2025.2484834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 03/21/2025] [Indexed: 04/22/2025]
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Celsa C, Rizzo GEM, Di Maria G, Enea M, Vaccaro M, Rancatore G, Graceffa P, Falco G, Petta S, Cabibbo G, Calvaruso V, Craxì A, Cammà C, Di Marco V. What is the benefit of prophylaxis to prevent HBV reactivation in HBsAg-negative anti-HBc-positive patients? Meta-analysis and decision curve analysis. Liver Int 2024; 44:2890-2903. [PMID: 39206573 DOI: 10.1111/liv.16064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 07/04/2024] [Accepted: 07/29/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND AND AIMS Patients with overt or occult hepatitis B virus (HBV) infection receiving immunosuppressive treatments have a wide risk of HBV reactivation (HBVr). We performed meta-analysis with decision curve analyses (DCA) to estimate the risk of HBVr in HBsAg-negative anti-HBc-positive patients naïve to nucleos(t)ide analogues (NAs) receiving immunosuppressive treatments. APPROACH AND RESULTS Studies were identified through literature search until October 2022. Pooled estimates were obtained using random-effects model. Subgroup analyses were performed according to underlying disease and immunosuppressive treatments. DCA was used to identify the threshold probability associated with the net benefit of antiviral prophylaxis in HBsAg-negative anti-HBc-positive patients. We selected 68 studies (40 retrospective and 28 prospective), including 8034 patients with HBsAg negative anti-HBc positive. HBVr was 4% (95% CI 3%-6%) in HBsAg-negative anti-HBc-positive patients, with a significantly high heterogeneity (I2 69%; p < .01). The number-needed-to-treat (NNT) by DCA ranged from 8 to 24 for chemotherapy plus rituximab, from 12 to 24 for targeted therapies in cancer patients and from 13 to 39 for immune-mediated diseases. Net benefit was small for monoclonal antibodies. CONCLUSIONS Our DCA in HBsAg-negative anti-HBc-positive patients provided evidence that NA prophylaxis is strongly recommended in patients treated with chemotherapy combined with rituximab and could be appropriate in patients with cancer treated with targeted therapies and in patients with immune-mediated diseases. Finally, in patients with cancer treated with monoclonal antibodies or with chemotherapy without rituximab, the net benefit is even lower.
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Affiliation(s)
- Ciro Celsa
- Department of Health Promotion, Section of Gastroenterology and Hepatology, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
- Department of Surgery & Cancer, Imperial College London, London, UK
| | - Giacomo E M Rizzo
- Department of Health Promotion, Section of Gastroenterology and Hepatology, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
- Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), University of Palermo, Palermo, Italy
- Department of Diagnostic and Therapeutic Services, The Mediterranean Institute for Transplantation and Highly Specialized Therapies (ISMETT), Palermo, Italy
| | - Gabriele Di Maria
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Marco Enea
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Marco Vaccaro
- Department of Economic, Business and Statistical Sciences, University of Palermo, Palermo, Italy
| | - Gabriele Rancatore
- Department of Health Promotion, Section of Gastroenterology and Hepatology, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
- Department of Diagnostic and Therapeutic Services, The Mediterranean Institute for Transplantation and Highly Specialized Therapies (ISMETT), Palermo, Italy
| | - Pietro Graceffa
- Department of Health Promotion, Section of Gastroenterology and Hepatology, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Giuseppe Falco
- Department of Health Promotion, Section of Gastroenterology and Hepatology, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Salvatore Petta
- Department of Health Promotion, Section of Gastroenterology and Hepatology, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Giuseppe Cabibbo
- Department of Health Promotion, Section of Gastroenterology and Hepatology, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Vincenza Calvaruso
- Department of Health Promotion, Section of Gastroenterology and Hepatology, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Antonio Craxì
- Department of Health Promotion, Section of Gastroenterology and Hepatology, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Calogero Cammà
- Department of Health Promotion, Section of Gastroenterology and Hepatology, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Vito Di Marco
- Department of Health Promotion, Section of Gastroenterology and Hepatology, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
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Marty C, Adam JP, Martel-Laferrière V, Doucet S, Martel D. Impact of universal hepatitis B virus (HBV) screening using chemotherapy orders on the HBV reactivation in cancer patients. Support Care Cancer 2024; 32:541. [PMID: 39046551 DOI: 10.1007/s00520-024-08750-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Accepted: 07/18/2024] [Indexed: 07/25/2024]
Abstract
INTRODUCTION Hepatitis B virus (HBV) reactivation (HBVr) induced by chemotherapy in patients with resolved or chronic infection can lead to severe consequences. Despite recommendations, rates of HBV screening before chemotherapy are low due to poor recognition of risk factors by clinicians. The aim of the study is to assess whether routine HBV screening using universal HBV screening on chemotherapy orders (CO) could reduce HBVr incidence. METHODS This is a 1-year retrospective single-center observational study of patients who received intravenous chemotherapy post implementation of CO. We compared the incidence of HBVr in three groups of patients: those screened through CO (group 1), those screened by the medical team (group 2), and those not screened (group 3). RESULTS On a total of 1374 patients, 179 of 206 patients were screened as requested on CO (group 1) and 421 by the medical team (group 2), whereas 747 patients were not screened (group 3). Only one HBVr occurred, and no difference was seen on the incidence of HBVr between group 1 and group 3 (0% vs 0.1%; p = 1.00), probably because of a lack of follow-up after chemotherapy. Follow-up for HBVr was imperfect in group 1 and group 2 (16.7% vs 5.6%; p = 0.32). Screening was done for 92% of patients on anti-CD20 therapy. In group 3, 89 patients had ALT elevation during chemotherapy but only 17 (19%) were tested for HBVr. CONCLUSION Systematic HBV detection requested on CO is an effective way to obtain a high percentage of patients with adequate screening, particularly when chemotherapy is at high risk of HBVr. Nevertheless, this screening method do not guarantee optimal follow-up and requires improvements.
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Affiliation(s)
- Céline Marty
- Faculty of Pharmacy, Aix-Marseille Université, Marseille, France
| | - Jean-Philippe Adam
- Department of Pharmacy, Centre Hospitalier de L'Université de Montréal (CHUM), 1050 Sanguinet St, Montréal, QC, Canada.
- Centre de Recherche du Centre Hospitalier de L'Université de Montréal (CRCHUM), Montréal, QC, H2X 0C1, Canada.
| | - Valérie Martel-Laferrière
- Centre de Recherche du Centre Hospitalier de L'Université de Montréal (CRCHUM), Montréal, QC, H2X 0C1, Canada
- Division of Microbiology and Infectious Diseases, Centre Hospitalier de L'Université de Montréal, Montréal, QC, Canada
- Department of Microbiology, Infectious Diseases and Immunology, Université de Montréal, Montréal, QC, Canada
| | - Stéphane Doucet
- Centre de Recherche du Centre Hospitalier de L'Université de Montréal (CRCHUM), Montréal, QC, H2X 0C1, Canada
- Division of Medicine-Medical Oncology/Hematology, Centre Hospitalier de L'Université de Montréal, Montréal, QC, Canada
| | - Dominic Martel
- Department of Pharmacy, Centre Hospitalier de L'Université de Montréal (CHUM), 1050 Sanguinet St, Montréal, QC, Canada
- Centre de Recherche du Centre Hospitalier de L'Université de Montréal (CRCHUM), Montréal, QC, H2X 0C1, Canada
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Zhang L, Liu Y, Song S, Makamure J, Shi H, Zheng C, Liang B. Hepatitis B virus reactivation in hepatocellular carcinoma patients after hepatic arterial infusion chemotherapy combined with and without immunotherapy. Infect Agent Cancer 2024; 19:19. [PMID: 38693564 PMCID: PMC11061977 DOI: 10.1186/s13027-024-00574-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Accepted: 03/26/2024] [Indexed: 05/03/2024] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) reactivation (HBVr) is a major concern for hepatocellular carcinoma (HCC) patients undergoing hepatic arterial infusion chemotherapy (HAIC) using mFOLFOX6 regimen. There is insufficient evidence to support the routine use of HAIC combined with immunotherapy in HCC patients with HBVr. The aim of this study was to examine the adverse events (AEs) related to HBVr in HCC patients after HAIC, with or without immunotherapy, and to assess the effectiveness of antiviral prophylaxis for HBVr. METHODS Medical records of HCC patients receiving HAIC combined with and without immunotherapy between January 2021 and June 2023 were reviewed. The patients were divided into two groups based on whether they received immunotherapy or not. RESULTS Out of the 106 patients, 32 (30.2%) developed HBVr. Among these, 23 eligible patients with HBVr were included, with 14 patients (61%) receiving immunotherapy and nine patients (39%) not receiving immunotherapy. Prior to HAIC treatment, four patients in each group had detectable HBV DNA with median titre of 3.66 × 102 IU/ml (patients with immunotherapy) and 1.98 × 102 IU/ml (patients without immunotherapy), respectively. Fifteen patients did not show detectable HBV DNA. At HBVr occurrence, the median HBV DNA level was 6.95 × 102 IU/ml for all patients, 4.82 × 102 IU/ml in patients receiving immunotherapy and 1.3 × 103 IU/ml in patients not receiving immunotherapy. Grade 3 hepatitis developed in 12 cases of all patients (12/23, 48%), including five patients with immunotherapy (56%) and seven patients without immunotherapy (78%). At the 3-month follow-up, HBV DNA was detected in 10 patients, with a median HBV DNA level of 2.05 × 102 IU/ml (range, 1.5 × 102- 3.55 × 102 IU/ml) in patients (7/10) with immunotherapy and 4.28 × 102 IU/ml (range, 1.15 × 102- 5.88 × 102 IU/ml) in patients (3/10) without immunotherapy. Intensified antiviral treatment was administered to all patients. No HBVr-related fatal events occurred. CONCLUSION HBVr can occur after HAIC combined with or without immunotherapy. The degree of liver damage did not differ significantly in patients treated with or without immunotherapy. Intensified antiviral treatment was found to be crucial for HCC patients with HBVr.
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Affiliation(s)
- Lijie Zhang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, 430022, Wuhan, China
- Hubei Key Laboratory of Molecular Imaging, 430022, Wuhan, China
| | - Yiming Liu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, 430022, Wuhan, China
- Hubei Key Laboratory of Molecular Imaging, 430022, Wuhan, China
| | - Songlin Song
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, 430022, Wuhan, China
- Hubei Key Laboratory of Molecular Imaging, 430022, Wuhan, China
| | - Joyman Makamure
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, 430022, Wuhan, China
- Hubei Key Laboratory of Molecular Imaging, 430022, Wuhan, China
| | - Heshui Shi
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, 430022, Wuhan, China
- Hubei Key Laboratory of Molecular Imaging, 430022, Wuhan, China
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, 430022, Wuhan, China.
- Hubei Key Laboratory of Molecular Imaging, 430022, Wuhan, China.
| | - Bin Liang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, 430022, Wuhan, China.
- Hubei Key Laboratory of Molecular Imaging, 430022, Wuhan, China.
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Zheng Z, Wang J, Wu T, He M, Wang J, Pan Y, Chen J, Hu D, Xu L, Zhang Y, Chen M, Zhou Z. Tenofovir versus Entecavir on Outcomes of Hepatitis B Virus-Related Hepatocellular Carcinoma After FOLFOX-Hepatic Arterial Infusion Chemotherapy. J Hepatocell Carcinoma 2023; 10:2117-2132. [PMID: 38053944 PMCID: PMC10695128 DOI: 10.2147/jhc.s436062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 11/22/2023] [Indexed: 12/07/2023] Open
Abstract
Purpose The efficacy of entecavir (ETV) versus tenofovir (TDF) on the prognosis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients who underwent FOLFOX-hepatic arterial infusion chemotherapy (HAIC) remains unclear. In this study, we compared the outcomes between ETV and TDF in HBV-related advanced HCC patients who underwent FOLFOX-HAIC. Methods A total of 683 patients diagnosed with HBV-related HCC who underwent FOLFOX-HAIC and received TDF or ETV between January 2016 and December 2021 were included. Overall survival (OS), progression-free survival (PFS), HBV reactivation, and liver function of patients were compared between the ETV and TDF groups by propensity score matching (PSM). Results In the PSM cohort, for all patients and patients with ≥ 4 cycles of FOLFOX-HAIC, the median OS in the ETV group (15.2 months, 95% CI: 13.0-17.4 months; 16.6 months, 95% CI: 14.8-18.5 months; respectively) was shorter than that in the TDF group (23.0 months, 95% CI: 10.3-35.6 months; 27.3 months, 95% CI: 16.5-NA months; p=0.024, p=0.028; respectively). The median PFS in the ETV group (8.7 months, 95% CI: 7.9-9.5 months; 8.9 months, 95% CI: 8.0-9.8 months; respectively) was also shorter than that in the TDF group (11.8 months, 95% CI: 8.0-15.6 months; 12.7 months, 95% CI: 10.8-14.6 months; p=0.036, p=0.025; respectively). The rate of HBV reactivation in the ETV group was higher than that in the TDF group (12.3% vs 6.3%, p=0.040; 16.5% vs 6.2%, p=0.037, respectively). For liver function, the rate of ALBI grade that remained stable or improved in the ETV group was lower than that in the TDF group (44.6% vs 57.6%, p=0.006; 37.2% vs 53.8%, p=0.019, respectively). Conclusion Compared with ETV, TDF was associated with a better prognosis, lower proportion of HBV reactivation, and better preservation of liver function in advanced HBV-HCC patients who underwent FOLFOX-HAIC, especially those who received ≥ 4 cycles.
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Affiliation(s)
- Zhikai Zheng
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China
| | - Jiongliang Wang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China
| | - Tianqing Wu
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China
| | - Minrui He
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China
| | - Juncheng Wang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China
| | - Yangxun Pan
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China
| | - Jinbin Chen
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China
| | - Dandan Hu
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China
| | - Li Xu
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China
| | - Yaojun Zhang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China
| | - Minshan Chen
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China
| | - Zhongguo Zhou
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China
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Yang SY, Hu TH, Chou YP, Kuo YH, Tsai MC, Chang KC, Yen YH, Tseng PL. Long-term comparisons of the durability of 6 months versus 12 months antiviral therapy for hepatitis B after chemotherapy cessation. J Infect Public Health 2023; 16:1852-1859. [PMID: 37837921 DOI: 10.1016/j.jiph.2023.08.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 07/22/2023] [Accepted: 08/08/2023] [Indexed: 10/16/2023] Open
Abstract
BACKGROUND Prophylaxis antiviral therapy is recommended for patients with hepatitis B receiving chemotherapy but the ideal treatment duration after chemotherapy cessation needs more evidence for clarification. AIMS This study aimed to compare the relapse rate of short finite intervals of 6 months and 12 months of -nucleos(t)ide analogue (NA) therapy in patients stratified by low hepatitis B virus (HBV)-DNA of < 2000 IU/ml or high HBV DNA of ≥ 2000 IU/ml. METHODS Patients started tenofovir or entecavir treatment 1 week before chemotherapy and were assigned to different treatment duration groups randomly after stratified by HBV DNA pretreatment: (1) HBV DNA of < 2000 IU/ml at 6-month or 12-month duration; (2)HBV DNA of ≥ 2000 IU/ml at 6-month or 12-month duration. Virological relapse (VR) was defined as HBV DNA of > 2000 IU/ml, and clinical relapse (CR) was defined as HBV DNA of > 2000 IU/ml and alanine aminotransferase of > 80 IU/L during the follow-up period. The primary endpoint was to compare the durability between groups 1 year after antiviral therapy cessation. The secondary endpoint was VR and CR rate at long-term follow-up after antiviral therapy cessation. RESULTS This study enrolled 61 patients, and 5 patients were lost to follow-up or tumor recurrence. VR and CR rates were 46.4% and 14.3% at 1-year and 55.3% and 16.1%, at long-term follow-up, respectively. VR and CR rates demonstrated no difference between the groups. Pretreatment HBV DNA at ≥ 2000 IU/ml and end-of-treatment hepatitis B surface antigen (HBsAg) at ≥ 500 IU/ml were the predictor of VR (hazard ratio [HR]: 2.98; p = 0.010 and HR: 2.38; p = 0.037). CONCLUSIONS Prolongation from 6 months to 12 months of NA consolidation after chemotherapy cessation did not affect the VR or CR of HBV. High pretreatment HBV DNA and end-of-treatment HBsAg levels could predict VR after antiviral therapy cessation for chemotherapy.
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Affiliation(s)
- Shih-Yu Yang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yeh-Pin Chou
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yuan-Hung Kuo
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ming-Chao Tsai
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Kuo-Chin Chang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yi-Hao Yen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Po-Lin Tseng
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
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Maqsood Q, Sumrin A, Iqbal M, Younas S, Hussain N, Mahnoor M, Wajid A. Hepatitis C virus/Hepatitis B virus coinfection: Current prospectives. Antivir Ther 2023; 28:13596535231189643. [PMID: 37489502 DOI: 10.1177/13596535231189643] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/26/2023]
Abstract
In endemic areas, hepatitis C virus (HCV)/hepatitis B virus (HBV) coinfection is common, and patients with coinfection have a higher risk of developing liver disease such as hepatocellular carcinoma, liver fibrosis and cirrhosis. In such cases, HCV predominates, and HBV replication is suppressed by HCV. HCV core proteins and interferons that are activated by HCV are responsible for the suppression of HBV. Immunosuppression is also seen in patients with HCV and HBV coinfections. A decrease in HCV-neutralizing antibody response and circulation of Th1-like Tfh cells is observed in patients with HCV and HBV coinfection. Both viruses interacted in the liver, and treatment of HCV/HBV coinfection is genotype-based and complex due to the interaction of both viruses. In HCV-dominant cases, direct-acting antiviral drugs and peg interferon plus ribavirin are used for the treatment, with continuous monitoring of AST and ALT. HBV-dominant cases are less common and are treated with peg interferon and nucleoside nucleotide analogues with monitoring of AST and ALT. The SVR rate in HCV-HBV coinfection is higher than that in monoinfection when treated with direct-acting antiviral drugs. But there is a risk of reactivation of HBV during and after therapy. The rate of reactivation is lower in patients treated with direct-acting antiviral drugs as compared to those treated with peg interferon plus ribavirin. Biomarkers of HBV such as HBcrAg, HBV DNA and HBVpg RNA are not effective in the prediction of HBV reactivation; only the hepatitis B surface antigen titre can be used as a biomarker for HBV reactivation. HCV can also be reactive, but this is found in very rare cases in which HBV is present and is treated first.
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Affiliation(s)
- Quratulain Maqsood
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Aleena Sumrin
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Maryam Iqbal
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Saima Younas
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Nazim Hussain
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Muhammada Mahnoor
- Department of Rehabilitation Science, The University of Lahore, Lahore, Pakistan
| | - Abdul Wajid
- Department of Biotechnology, Balochistan University of Information Technology, Engineering and Management Science, Quetta, Pakistan
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Dezan MGF, Cavalcante LN, Cotrim HP, Lyra AC. Hepatobiliary disease after bone marrow transplant. Expert Rev Gastroenterol Hepatol 2023; 17:129-143. [PMID: 36655915 DOI: 10.1080/17474124.2023.2169671] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 01/13/2023] [Indexed: 01/20/2023]
Abstract
INTRODUCTION Bone marrow transplantation (BMT) is the standard treatment for several hematologic pathologies. Post-BMT patients may develop hepatobiliary complications that impact morbidity and mortality. The differential diagnosis may include drug-induced liver injury (DILI), sepsis-associated liver injury (SALI), sinusoidal obstruction syndrome (SOS), graft-versus-host disease (GVHD), viral hepatitis, ischemic and fulminant hepatitis, among others. AREA COVERED Defining the etiology of hepatobiliary injury is challenging due to the overlapping symptoms. Thus, it is necessary to be aware of and understand the clinical characteristics of these hepatobiliary complications and provide adequate management with possible better outcomes. We reviewed the scientific literature focused on early hepatobiliary complications associated with BMT. We searched the PubMed database using the following descriptors: hepatic complications, drug-induced liver disease, graft-versus-host disease, cholestasis, sepsis, sinusoidal obstruction syndrome, cytomegalovirus, viral hepatitis, bone marrow transplantation, and hematopoietic stem cell transplantation. EXPERT OPINION Post-BMT hepatobiliary complications comprise several differential diagnoses and are challenges for the hepatologist's clinical practice. When evaluating these patients, it is necessary to consider the temporality between the use of certain medications, the increase in liver enzymes, and the presence of infection, in addition to applying diagnostic criteria and complementary tests for a specific diagnosis.
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Affiliation(s)
- Maria Gabriela Fernandes Dezan
- Instituto D'Or de Pesquisa e Ensino (IDOR) and Hospital São Rafael Gastro-Hepatology Service, Hospital São Rafael, Salvador, Bahia, Brazil
- Gastro-Hepatology Service - University Hospital Professor Edgard Santos (HUPES), PPGMS - Federal University of Bahia, Salvador, Bahia, Brazil
| | - Lourianne Nascimento Cavalcante
- Instituto D'Or de Pesquisa e Ensino (IDOR) and Hospital São Rafael Gastro-Hepatology Service, Hospital São Rafael, Salvador, Bahia, Brazil
- Gastro-Hepatology Service - University Hospital Professor Edgard Santos (HUPES), PPGMS - Federal University of Bahia, Salvador, Bahia, Brazil
| | - Helma Pinchemel Cotrim
- Gastro-Hepatology Service - University Hospital Professor Edgard Santos (HUPES), PPGMS - Federal University of Bahia, Salvador, Bahia, Brazil
| | - Andre Castro Lyra
- Instituto D'Or de Pesquisa e Ensino (IDOR) and Hospital São Rafael Gastro-Hepatology Service, Hospital São Rafael, Salvador, Bahia, Brazil
- Gastro-Hepatology Service - University Hospital Professor Edgard Santos (HUPES), PPGMS - Federal University of Bahia, Salvador, Bahia, Brazil
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9
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Soriano V, Moreno-Torres V, Treviño A, Barreiro P, de Jesus F, Corral O, de Mendoza C. Safety considerations in the management of hepatitis C and HIV co-infection. Expert Opin Drug Saf 2023; 22:363-372. [PMID: 37096834 DOI: 10.1080/14740338.2023.2206647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 04/20/2023] [Indexed: 04/26/2023]
Abstract
INTRODUCTION Both HCV and HIV are highly prevalent infections with current estimates of 57 and 38 million people infected worldwide, respectively. Oral antivirals can be curative for HCV and rescue HIV patients from disease progression. Dual therapy in coinfected patients requires expertise. AREAS COVERED Four major issues challenge dual HCV and HIV treatment, including overlapping drug-related side effects, hepatitis B reactivation, immune reconstitution inflammatory syndromes (IRIS), and drug-drug interactions (DDI). A search was conducted in PubMed from January 2010 to March 2023. EXPERT OPINION The advent of second-generation direct-acting antivirals (DDA) that depict higher antiviral potency, fewer side effects, pangenotypic activity and are co-formulated has expanded the indication of HCV therapy and particularly in HIV-coinfected individuals. Sequential initiation of antiretrovirals (ARV) followed by DAA is generally preferred to start dual treatment concomitantly. Close monitoring of rare episodes of HBV reactivation and IRIS is warranted. The most frequent DDI between DAA and ARV affect drug metabolism by CYP450 induction/inhibition, leading to abnormal drug exposures. Throughout this mechanism interact most HCV and HIV protease inhibitors and non-nucleoside polymerase inhibitors. Exposure to some HIV and HCV nucleos(t)ide analogues (e.g. tenofovir and sofosbuvir, respectively) is subject to induction/inhibition of drug transporters and requires special attention in patients with renal insufficiency.
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Affiliation(s)
- Vicente Soriano
- Health Sciences School & Medical Center, Universidad Internacional La Rioja (UNIR), Madrid, Spain
| | - Víctor Moreno-Torres
- Health Sciences School & Medical Center, Universidad Internacional La Rioja (UNIR), Madrid, Spain
- Department of Internal Medicine, Puerta de Hierro University Hospital & Research Institute, Majadahonda, Madrid, Spain
| | - Ana Treviño
- Health Sciences School & Medical Center, Universidad Internacional La Rioja (UNIR), Madrid, Spain
| | - Pablo Barreiro
- Health Sciences School & Medical Center, Universidad Internacional La Rioja (UNIR), Madrid, Spain
- Infctious Diseases Unit, Emergency Hospital Enfermera Isabel Zendal, Madrid, Spain
| | - Fernando de Jesus
- Health Sciences School & Medical Center, Universidad Internacional La Rioja (UNIR), Madrid, Spain
| | - Octavio Corral
- Health Sciences School & Medical Center, Universidad Internacional La Rioja (UNIR), Madrid, Spain
| | - Carmen de Mendoza
- Department of Internal Medicine, Puerta de Hierro University Hospital & Research Institute, Majadahonda, Madrid, Spain
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10
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Reactivation of Hepatitis B Virus in Lung Cancer Patients Receiving Tyrosine Kinase Inhibitor Treatment. J Clin Med 2022; 12:jcm12010231. [PMID: 36615034 PMCID: PMC9820864 DOI: 10.3390/jcm12010231] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Revised: 12/25/2022] [Accepted: 12/26/2022] [Indexed: 12/31/2022] Open
Abstract
(1) Background: We aimed to evaluate the risk of hepatitis B virus (HBV) reactivation in lung cancer patients treated with tyrosine kinase inhibitor (TKI), particularly in those with resolved HBV infection. (2) Methods: In this retrospective hospital-based cohort study, we screened all lung cancer patients with positive hepatitis B core antibodies (anti-HBc) receiving systemic antineoplastic treatment during the period from January 2011 to December 2020. Cumulative incidences of HBV reactivation, and their hazard ratios (HRs), were evaluated after adjusting patient mortality as a competing risk. (3) Results: Among 1960 anti-HBc-positive patients receiving systemic therapy, 366 were HBsAg-positive and 1594 were HBsAg-negative. In HBsAg-positive patients without prophylactic NUC, 3-year cumulative incidences of HBV reactivation were similar between patients receiving chemotherapy and patients receiving TKI (15.0%, 95% confidence interval (CI): 0−31.2% vs. 21.2%, 95% CI: 10.8−31.7%; p = 0.680). Likewise, 3-year cumulative incidences of HBV-related hepatitis were similar between the two groups (chemotherapy vs. TKI: 15.0%, 95% CI: 0−31.2% vs. 9.3%, 95% CI: 2.8−15.7%; p = 0.441). In 521 HBsAg-negative TKI users, the 3-year cumulative incidence of HBV reactivation was only 0.6% (95% CI: 0.0−1.9%). From multivariable regression analysis, we found that the only independent risk factor for HBV reactivation in TKI users was HBsAg positivity (HR 53.8, 95% CI: 7.0−412.9; p < 0.001). (4) Conclusion: Due to high risks of HBV reactivation in HBsAg-positive TKI users, NUC prophylaxis can be considered. However, in patients with resolved HBV infection, such risks are lower, and therefore regular monitoring is recommended.
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11
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The Burden of Hepatitis B, Hepatitis C, and Human Immunodeficiency Viruses in Ovarian Cancer Patients in Nairobi, Kenya. Infect Dis Rep 2022; 14:433-445. [PMID: 35735757 PMCID: PMC9222280 DOI: 10.3390/idr14030047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2022] [Revised: 05/29/2022] [Accepted: 06/01/2022] [Indexed: 12/04/2022] Open
Abstract
Ovarian cancer (OC) is a gynecological malignancy characterized by high morbidity and mortalities due to late-stage diagnosis because accurate early diagnostic biomarkers are lacking. Testing of Hepatitis B virus (HBV), Hepatitis C virus (HCV), and Human immunodeficiency virus (HIV) infections in OC patients is pertinent in light of the emerging evidence of their contribution to poor prognosis. We, for the first time, investigated the prevalence of HBV, HCV, and HIV infections in a Kenyan cohort of OC to inform optimal management. We recruited a cohort of women above 18 years of age, comprising 86 OC patients and 50 healthy controls. Participants’ blood samples were serologically screened for HBV, HCV, and HIV. We found seroprevalence rates of 29.1%, 26.7%, and 1.2% for HBV, HIV, and HCV, respectively, in OC patients. The healthy control group had HBV and HIV seroprevalence rates of 3.9% for each with no positive HCV case. HBV/HIV coinfection was noted only in the OC group with a positivity rate of 17.4%. In summary, we found higher HBV and HIV seroprevalence in Kenyan OC patients compared to the healthy control group, whereas HCV prevalence was reflective of the general population. Hence, we recommend screening for HBV and HIV among OC patients destined for anticancer treatment.
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12
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Soriano V, Edagwa B, Mendoza CD, Barreiro P, Corral O, Treviño A, Gendelman HE. Ultra-long-acting antivirals as chemical vaccines to prevent viral diseases. Future Microbiol 2022; 17:887-897. [PMID: 35658545 DOI: 10.2217/fmb-2021-0254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
For two centuries, vaccines have been successful in the fight against viruses, triggering immune protection. Indeed, the elimination of smallpox, the only infectious disease eradicated to date, was made possible through vaccination. For measles, polio and hepatitis B, vaccines are available but significant challenges exist for universal coverage. For other viruses, such as HIV and hepatitis C, vaccines have remained elusive. Recent advances in medicinal chemistry have resulted in the production of antivirals that can extend activity for months. We envision the use of ultra-long-acting antivirals for the prevention of certain viral illnesses, halting either contagions or reactivations under immunosuppression. Such 'chemical vaccines' would fill an immediate need in providing protection when classic vaccines do not exist, responses are suboptimal, escape mutants emerge or immunity wanes.
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Affiliation(s)
| | - Benson Edagwa
- Department of Pharmacology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Carmen de Mendoza
- Internal Medicine Research Laboratory, Puerta de Hierro University Hospital, Majadahonda, Madrid 28222, Spain
| | - Pablo Barreiro
- Research Laboratory, Isabel Zendal Emergency Hospital, Madrid 28055, Spain
| | | | - Ana Treviño
- UNIR Health Sciences School, Madrid 28035, Spain
| | - Howard E Gendelman
- Department of Pharmacology, University of Nebraska Medical Center, Omaha, NE 68198, USA
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13
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Wang K, Xia Y, Zhu Y, Yu W, Guo Y, Liu L. Virological breakthrough after immune checkpoint inhibitor and nucleos(t)ide analog treatment in patients with hepatitis B surface antigen positive hepatocellular carcinoma: a real-world study. J Immunother Cancer 2021. [PMCID: PMC8578995 DOI: 10.1136/jitc-2021-003195] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Background Immune checkpoint inhibitors (ICIs) have been shown to be a promising and effective treatment for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, there is a lack of evidence-based data demonstrating the impact of ICIs on HBV DNA level in HBV-HCC patients undergoing nucleos(t)ide analog (NA) therapy and of HBV DNA variation on patient survival. In this study, we aimed to investigate this issue in the real world. Methods In this single-center retrospective study, we reviewed 182 baseline hepatitis B surface antigen (HBsAg)-positive HBV-HCC patients who were treated with ICIs and pre-emptive NAs. The demographic characteristics, tumor status, treatments, HBV DNA, HBsAg, liver function, antitumor response, and patient survival were investigated. The primary endpoints were the virological breakthrough (VB) rate, HBV reactivation (HBVr) rate, and long-term HBV DNA control; the secondary endpoints were the overall survival (OS) and progression-free survival (PFS). Results (1) VB and HBVr occurred in 18.1% (33/182) and 4.4% (8/182) of patients with a median occurrence time of 3.9 months (range, 0.7–16.0) and 8.0 months (range, 3.0–16.0), respectively. The HBV DNA negative rates were 26.1% and 0 at 24 and 48 weeks in the VB group and 12.5% and 0 in the HBVr group, respectively. A baseline HBsAg level ≥200 IU/mL was the only risk factor for VB (OR 9.9, 95% CI 2.2 to 45.2, p=0.003); (2) patients with VB had much shorter median OS and median PFS than those without (12.3 months vs 18.1 months, p=0.035; 4.5 months vs 7.5 months, p=0.011). Conclusions There was a high risk of VB and a moderate risk of HBVr in HBsAg-positive HBV-HCC patients (with poor long-term HBV DNA control) undergoing ICI and pre-emptive NA therapies. The only risk factor for VB was the pretreatment HBsAg level. Further, VB might be considered as a clinical biomarker predicting inferior OS and PFS in the patients.
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Affiliation(s)
- Kunyuan Wang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ying Xia
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yun Zhu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Wenxuan Yu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yabing Guo
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Li Liu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
- Big Data Centre, Nanfang Hospital, Southern Medical University, Guangzhou, China
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14
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Sun WC, Tang PL, Chen WC, Tsay FW, Wang HM, Tsai TJ, Kao SS, Cheng JS, Tsai WL. Hepatitis B Virus Screening Before Cancer Chemotherapy in Taiwan: A Nationwide Population-Based Study. Front Med (Lausanne) 2021; 8:657109. [PMID: 34336877 PMCID: PMC8319464 DOI: 10.3389/fmed.2021.657109] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Accepted: 06/24/2021] [Indexed: 11/13/2022] Open
Abstract
Background: Reactivation of the hepatitis B virus (HBV) during cancer chemotherapy is a severe and sometimes fatal complication. In 2009, the National Health Insurance (NHI) in Taiwan recommended and reimbursed screening for HBV infection and prophylactic antiviral therapy before cancer chemotherapy. In this study, we determined the HBV screening rate in patients with cancer undergoing chemotherapy in Taiwan. Methods: We retrospectively collected data from the National Health Insurance Research Database on patients who received systemic chemotherapy for solid or hematologic cancers from January 2000 through December 2012. We defined HBV screening based on testing for serum HBsAg within 2 years of the first chemotherapy commencement. We calculated overall and annual HBV screening rates in all patients and subgroups of age, gender, cancer type, hospital level, physician's department, and implementation of NHI reimbursement for HBV screening before cancer chemotherapy. Results: We enrolled 379,639 patients. The overall HBV screening rate was 45.9%. The screening rates were higher in males, those with hematological cancer, those at non-medical centers and medical departments. The HBV screening rates before (2000–2008) and after the implementation of NHI reimbursement (2009–2012) were 38.1 and 57.5%, respectively (p < 0.0001). The most common practice pattern of HBV screening was only HBsAg (64.6%) followed by HBsAg/HBsAb (22.1%), and HBsAg/HBcAb/HBsAb (0.7%) (p < 0.0001). The annual HBV screening rate increased from 31.5 to 66.3% (p < 0.0001). The screening rates of solid and hematological cancers significantly increased by year; however, the trend was greater in solid cancer than in hematological cancer (35.9 and 26.2%, p < 0.0001). Conclusions: The HBV screening rate before cancer chemotherapy was fair but increased over time. These figures improved after implementing a government-based strategy; however, a mandatory hospital-based strategy might improve awareness of HBV screening and starting prophylactic antiviral therapy before cancer chemotherapy.
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Affiliation(s)
- Wei-Chih Sun
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Pei-Ling Tang
- Research Center of Medical Informatics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,College of Nursing, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Nursing, Meiho University, Pingtung, Taiwan
| | - Wen-Chi Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Feng-Woei Tsay
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Huay-Min Wang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Tzung-Jiun Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Sung-Shuo Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Jin-Shiung Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Wei-Lun Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
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15
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Cornberg M, Sandmann L, Protzer U, Niederau C, Tacke F, Berg T, Glebe D, Jilg W, Wedemeyer H, Wirth S, Höner Zu Siederdissen C, Lynen-Jansen P, van Leeuwen P, Petersen J. S3-Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) zur Prophylaxe, Diagnostik und Therapie der Hepatitis-B-Virusinfektion – (AWMF-Register-Nr. 021-11). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 59:691-776. [PMID: 34255317 DOI: 10.1055/a-1498-2512] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Markus Cornberg
- Deutsches Zentrum für Infektionsforschung (DZIF), Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover; Centre for individualised infection Medicine (CiiM), Hannover.,Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover
| | - Lisa Sandmann
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover
| | - Ulrike Protzer
- Institut für Virologie, Technische Universität München/Helmholtz Zentrum München, München
| | | | - Frank Tacke
- Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Charité Universitätsmedizin Berlin, Berlin
| | - Thomas Berg
- Klinik und Poliklinik für Gastroenterologie und Rheumatologie, Universitätsklinikum Leipzig, Leipzig
| | - Dieter Glebe
- Institut für Medizinische Virologie, Nationales Referenzzentrum für Hepatitis-B-Viren und Hepatitis-D-Viren, Justus-Liebig-Universität Gießen, Gießen
| | - Wolfgang Jilg
- Institut für Medizinische Mikrobiologie und Hygiene, Universität Regensberg, Regensburg
| | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover
| | - Stefan Wirth
- Zentrum für Kinder- und Jugendmedizin, Helios Universitätsklinikum Wuppertal, Wuppertal
| | | | - Petra Lynen-Jansen
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin
| | - Pia van Leeuwen
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin
| | - Jörg Petersen
- IFI Institut für Interdisziplinäre Medizin an der Asklepios Klinik St. Georg, Hamburg
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16
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Almeida PH, Matielo CEL, Curvelo LA, Rocco RA, Felga G, Della Guardia B, Boteon YL. Update on the management and treatment of viral hepatitis. World J Gastroenterol 2021; 27:3249-3261. [PMID: 34163109 PMCID: PMC8218370 DOI: 10.3748/wjg.v27.i23.3249] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 03/11/2021] [Accepted: 04/21/2021] [Indexed: 02/06/2023] Open
Abstract
This review aims to summarize the current evidence on the treatment of viral hepatitis, focusing on its clinical management. Also, future treatment options and areas of potential research interest are detailed. PubMed and Scopus databases were searched for primary studies published within the last ten years. Keywords included hepatitis A virus, hepatitis B virus (HBV), hepatitis C virus, hepatitis D virus (HDV), hepatitis E virus, and treatment. Outcomes reported in the studies were summarized, tabulated, and synthesized. Significant advances in viral hepatitis treatment were accomplished, such as the advent of curative therapies for hepatitis C and the development and improvement of hepatitis A, hepatitis B, and hepatitis E vaccination. Drugs that cure hepatitis B, going beyond viral suppression, are so far unavailable; however, targeted antiviral drugs against HBV (immunomodulatory therapies and gene silencing technologies) are promising approaches to eradicating the virus. Ultimately, high vaccination coverage and large-scale test-and-treat programmes with high screening rates may eliminate viral hepatitis and mitigate their burden on health systems. The development of curative hepatitis C treatment renewed the enthusiasm for curing hepatitis B, albeit further investigation is required. Novel therapeutic options targeting HDV life cycle are currently under clinical investigation.
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Affiliation(s)
| | - Celso E L Matielo
- Liver Unit, Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil
| | - Lilian A Curvelo
- Liver Unit, Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil
| | - Rodrigo A Rocco
- Liver Unit, Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil
| | - Guilherme Felga
- Liver Unit, Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil
| | | | - Yuri L Boteon
- Liver Unit, Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil
- Instituto Israelita de Ensino e Pesquisa Albert Einstein, Faculdade Israelita de Ciências da Saúde Albert Einstein, São Paulo 05652-900, Brazil
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17
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Wang LY, Chu SC, Lo Y, Yang YY, Chan KA. Association of Bcr-Abl Tyrosine Kinase Inhibitors With Hepatitis B Virus Reactivation Requiring Antiviral Treatment in Taiwan. JAMA Netw Open 2021; 4:e214132. [PMID: 33822067 PMCID: PMC8025118 DOI: 10.1001/jamanetworkopen.2021.4132] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
IMPORTANCE The US Food and Drug Administration (FDA) highlighted the potential risk of hepatitis B reactivation that was associated with Bcr-Abl tyrosine kinase inhibitor (TKI) treatment and has required updated product labels. OBJECTIVE To examine the association between hepatitis B flare and exposure to Bcr-Abl TKIs compared with non-Bcr-Abl TKIs. DESIGN, SETTING, AND PARTICIPANTS This nested case-control study included patients who entered a hepatitis B carrier cohort in Taiwan after January 1, 2005. Patients who received their first antiviral agents for hepatitis B flare for more than 28 days after the cohort entry date were included as case patients. For each case, a corresponding risk set was formed that included all eligible patients in the study cohort who had the same age (within 1 year), same sex, and were at risk of developing hepatitis B flare at the case date. As many as 10 control patients were randomly selected from the risk set for each case patient. TKIs were evaluated before the hepatitis B flare for case patients and before the corresponding index date for control patients. Data were collected from the Taiwan National Health Insurance research database from January 2000 to 2015. Data analysis was conducted from January to June 2019. EXPOSURE Use of Bcr-AbL TKIs. MAIN OUTCOMES AND MEASURES Conditional logistic regression was used to estimate the rate ratio for the association between hepatitis B flare and exposure to Bcr-Abl TKIs compared with non-Bcr-Abl TKIs. RESULTS Among 698 342 patients who carried incident hepatitis B virus, 66 702 patients with hepatitis B flare that required antiviral treatment (47 492 [71.2%] men; mean [SD] age at index date, 50.2 [13.8] years) were included as case patients, and 666 989 age and sex-matched patients (474 903 [71.2%] men; mean [SD] age, 50.2 [13.8] years) were included as control patients. Analysis revealed that Bcr-Abl TKI use during the previous 90 days was independently associated with a 56% higher risk of hepatitis B flare (adjusted rate ratio [aRR], 1.56; 95% CI, 1.11-2.20), and the aRR increased to 1.66 (95% CI, 1.20-2.28) for Bcr-Abl TKI use during the previous 365 days. Use of Bcr-AbL TKIs during the previous 60 days was associated with a significantly increased risk of flare among women (aRR, 3.20; 95% CI, 1.70-6.03) but not among men (aRR, 1.14; 95% CI, 0.72-1.81). CONCLUSIONS AND RELEVANCE These findings suggest that sex-specific strategies may be needed to monitor for hepatitis B reactivation among patients receiving Bcr-Abl TKIs.
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Affiliation(s)
- Ling-Yi Wang
- Epidemiology and Biostatistics Consulting Center, Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
- Department of Pharmacology, School of Medicine, College of Medicine, Tzu Chi University, Hualien, Taiwan
- Department of Pharmacy, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
| | - Sung-Chao Chu
- Department of Hematology and Oncology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
| | - Yin Lo
- Department of Pharmacy, National Taiwan University Hospital
| | - Yen-Yun Yang
- Health Data Research Center, National Taiwan University
| | - K. Arnold Chan
- Health Data Research Center, National Taiwan University
- Department of Medical Research, National Taiwan University Hospital
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18
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Zamaraev AV, Zhivotovsky B, Kopeina GS. Viral Infections: Negative Regulators of Apoptosis and Oncogenic Factors. BIOCHEMISTRY (MOSCOW) 2021. [PMID: 33202204 PMCID: PMC7590567 DOI: 10.1134/s0006297920100077] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
The disruption of apoptotic cell death process is closely associated with the etiology of various diseases, including cancer. Permanent viral infections can cause different types of cancers. Oncogenic viruses manipulate both external and internal apoptosis pathways, and inhibit the activity of proapoptotic proteins and signaling pathways, which facilitates carcinogenesis. Ineffective immune surveillance or immune response suppression can induce uncontrolled virus propagation and host cell proliferation. In this review, we discuss current data that provide insights into mechanisms of apoptotic death suppression by viruses and their role in oncogenesis.
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Affiliation(s)
- A V Zamaraev
- Faculty of Basic Medicine, Lomonosov Moscow State University, Moscow, 119192, Russia
| | - B Zhivotovsky
- Faculty of Basic Medicine, Lomonosov Moscow State University, Moscow, 119192, Russia.,Institute of Environmental Medicine, Karolinska Institute, Stockholm, SE-171 77, Sweden
| | - G S Kopeina
- Faculty of Basic Medicine, Lomonosov Moscow State University, Moscow, 119192, Russia.
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19
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Crimmin J, Fulop T, Battisti NML. Biological aspects of aging that influence response to anticancer treatments. Curr Opin Support Palliat Care 2021; 15:29-38. [PMID: 33399393 DOI: 10.1097/spc.0000000000000536] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW Cancer is a disease of older adults, where fitness and frailty are a continuum. This aspect poses unique challenges to the management of cancer in this population. In this article, we review the biological aspects influencing the efficacy and safety of systemic anticancer treatments. RECENT FINDINGS The organ function decline associated with the ageing process affects multiple systems, including liver, kidney, bone marrow, heart, muscles and central nervous system. These can have a significant impact on the pharmacokinetics and pharmacodynamics of systemic anticancer agents. Comorbidities also represent a key aspect to consider in decision-making. Renal disease, liver conditions and cardiovascular risk factors are prevalent in this age group and may impact the risk of adverse outcomes in this setting. SUMMARY The systematic integration of geriatrics principles in the routine management of older adults with cancer is a unique opportunity to address the complexity of this population and is standard of care based on a wide range of benefits. This approach should be multidisciplinary and involve careful discussion with hospital pharmacists.
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Affiliation(s)
- Jane Crimmin
- Pharmacy, The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK
| | - Tamas Fulop
- Department of Medicine, Division of Geriatrics, Research Center on Aging, University of Sherbrooke, Faculty of Medicine and Health Sciences, Québec, Quebec, Canada
| | - Nicolò Matteo Luca Battisti
- Department of Medicine - Breast Unit, The Royal Marsden NHS Foundation Trust, Breast Cancer Research Division, The Institute of Cancer Research, Sutton, Surrey, UK
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20
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Houron C, Danielou M, Mir O, Fromenty B, Perlemuter G, Voican CS. Multikinase inhibitor-induced liver injury in patients with cancer: A review for clinicians. Crit Rev Oncol Hematol 2020; 157:103127. [PMID: 33161366 DOI: 10.1016/j.critrevonc.2020.103127] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Revised: 09/29/2020] [Accepted: 10/05/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Multikinase inhibitors (MKI) are targeted molecular agents that have revolutionized cancer management. However, there is a paucity of data concerning MKI-related liver injury risk and clinical guidelines for the management of liver toxicity in patients receiving MKI for cancer are scarce. DESIGN We conducted a PubMed search of articles in English published from January 2000 to December 2018 related to hepatotoxicity of the 29 FDA-approved MKIs at doses used in clinical practice. The search terms were the international non-proprietary name of each agent cross-referenced with «hepatotoxicity», «hepatitis», «hepatic adverse event», or «liver failure», and «phase II clinical trial», «phase III clinical trial», or «case report». RESULTS Following this search, 140 relevant studies and 99 case reports were considered. Although asymptomatic elevation of aminotransferase levels has been frequently observed in MKI clinical trials, clinically significant hepatotoxicity is a rare event. In most cases, the interval between treatment initiation and the onset of liver injury is between one week and two months. Liver toxicity is often hepatocellular and less frequently mixed. Life-threatening MKI-induced hepatic injury has been described, involving fulminant liver failure or death. Starting from existing data, a description of MKI-related liver events, grading of hepatotoxicity risk, and recommendations for management are also given for various MKI molecules. CONCLUSION All MKIs can potentially cause liver injury, which is sometimes irreversible. As there is still no strategy available to prevent MKI-related hepatotoxicity, early detection remains crucial. The surveillance of liver function during treatment may help in the early detection of hepatotoxicity. Furthermore, the exclusion of potential causes of hepatic injury is essential to avoid unnecessary MKI withdrawal.
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Affiliation(s)
- Camille Houron
- Faculté de Médecine Paris-Saclay, Université Paris-Saclay, F-94276, Le Kremlin-Bicêtre, France; INSERM U996, DHU Hepatinov, Labex LERMIT, F-92140, Clamart, France
| | - Marie Danielou
- Faculté de Médecine Paris-Saclay, Université Paris-Saclay, F-94276, Le Kremlin-Bicêtre, France; Service d'Hépato-Gastroentérologie et Nutrition, Hôpital Antoine-Béclère, AP-HP, Université Paris-Saclay, F-92140, Clamart, France
| | - Olivier Mir
- Gustave Roussy Cancer Campus, Department of Ambulatory Care, F-94805, Villejuif, France
| | - Bernard Fromenty
- INSERM, INRAE, Univ Rennes, Institut NUMECAN (Nutrition Metabolisms and Cancer), UMR_A 1341, UMR_S 1241, F-35000, Rennes, France
| | - Gabriel Perlemuter
- Faculté de Médecine Paris-Saclay, Université Paris-Saclay, F-94276, Le Kremlin-Bicêtre, France; INSERM U996, DHU Hepatinov, Labex LERMIT, F-92140, Clamart, France; Service d'Hépato-Gastroentérologie et Nutrition, Hôpital Antoine-Béclère, AP-HP, Université Paris-Saclay, F-92140, Clamart, France.
| | - Cosmin Sebastian Voican
- Faculté de Médecine Paris-Saclay, Université Paris-Saclay, F-94276, Le Kremlin-Bicêtre, France; INSERM U996, DHU Hepatinov, Labex LERMIT, F-92140, Clamart, France; Service d'Hépato-Gastroentérologie et Nutrition, Hôpital Antoine-Béclère, AP-HP, Université Paris-Saclay, F-92140, Clamart, France
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21
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Ziogas DC, Kostantinou F, Cholongitas E, Anastasopoulou A, Diamantopoulos P, Haanen J, Gogas H. Reconsidering the management of patients with cancer with viral hepatitis in the era of immunotherapy. J Immunother Cancer 2020; 8:jitc-2020-000943. [PMID: 33067316 PMCID: PMC7570225 DOI: 10.1136/jitc-2020-000943] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/10/2020] [Indexed: 12/15/2022] Open
Abstract
In the evolving immune-oncology landscape, numerous patients with cancer are constantly treated with immune checkpoint inhibitors (ICPIs) but among them, only sporadic cases with pre-existing hepatitis B virus (HBV) and hepatitis C virus (HCV) are recorded. Despite the global dissemination of HBV and HCV infections, viral hepatitis-infected patients with cancer were traditionally excluded from ICPIs containing trials and current evidence is particularly limited in case reports, retrospective cohort studies and in few clinical trials on advanced hepatocellular carcinoma. Thus, many concerns still remain about the overall oncological management of this special subpopulation, including questions about the efficacy, toxicity and reactivation risks induced by ICPIs. Here, we examine the natural course of both HBV and HCV in cancer environment, review the latest antiviral guidelines for patients undergoing systematic cancer therapies, estimating treatment-related immunosuppression and relocate immunotherapy in this therapeutic panel. Among the ICPIs-treated cases with prior viral hepatitis, we focus further on those experienced HBV or HCV reactivation and discuss their host, tumor and serological risk factors, their antiviral and immunological management as well as their hepatitis and tumor outcome. Based on a low level of evidence, immunotherapy in these specific cancer cases seems to be associated with no inferior efficacy and with a relevantly low reactivation rate. However, hepatitis reactivation and subsequent irreversible complications appeared to have poor response to deferred antiviral treatment. While, the prophylactic use of modern antiviral drugs could eliminate or diminish up front the viral load in most cases, leading to cure or long-term hepatitis control. Taking together the clinical significance of preventive therapy, the low but existing reactivation risk and the potential immune-related hepatotoxicity, a comprehensive baseline assessment of liver status, including viral hepatitis screening, before the onset of immunotherapy should be suggested as a reasonable and maybe cost-effective strategy but the decision to administer ICPIs and the necessity of prophylaxis should always be weighed at a multidisciplinary level and be individualized in each case, up to be established by future clinical trials.
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Affiliation(s)
- Dimitrios C Ziogas
- First Department of Medicine, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
| | - Frosso Kostantinou
- First Department of Medicine, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
| | - Evangelos Cholongitas
- First Department of Medicine, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
| | - Amalia Anastasopoulou
- First Department of Medicine, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
| | - Panagiotis Diamantopoulos
- First Department of Medicine, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
| | - John Haanen
- Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Helen Gogas
- First Department of Medicine, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
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22
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Konijeti GG, Grandhe S, Tincopa M, Lane JA, Shrime MG, Singh S, Loomba R. Cost-Effectiveness Analysis of Screening for Hepatitis B Virus Infection in Patients With Solid Tumors Before Initiating Chemotherapy. Clin Gastroenterol Hepatol 2020; 18:1600-1608.e4. [PMID: 31678602 DOI: 10.1016/j.cgh.2019.10.039] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2018] [Revised: 10/19/2019] [Accepted: 10/25/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Patients with solid tumors who undergo chemotherapy have an increased risk of hepatitis B virus (HBV) reactivation, but a low proportion of these patients are screened for HBV infection and guidelines make conflicting recommendations. Further, the cost-effectiveness of newer treatments for HBV prophylaxis has not been examined for this population. We aimed to analyze the cost-effectiveness of HBV screening before chemotherapy for patients with solid tumors. METHODS We compared 3 HBV screening strategies (screen all, screen only high-risk patients, or screen none) using a Markov model of a population of adults in the United States who initiated chemotherapy for a solid tumor. We modeled use of entecavir prophylaxis for HB surface antigen (HBsAg)-positive patients and surveillance for HBsAg-negative patients who are positive for HBV core antibody. The Markov cycle length was 1 year, with model simulation for up to 5 years. RESULTS The screen all strategy was the most cost effective, with an incremental cost-effectiveness ratio of $42,761 compared to screening only high-risk patients. The screen none strategy was less effective and less costly than screening all patients or only high-risk patients. The screen-all strategy was the most cost effective for all estimates of prevalence of HBsAg-positive patients and estimates of HBV reactivation in HBsAg-positive patients. Screening only high-risk patients was the most cost-effective strategy when more than 25% of high-risk patients were screened for HBV infection. CONCLUSIONS In a Markov model analysis, we found screening all patients with solid tumors for HBV infection before chemotherapy to be the most cost-effective strategy. Guidelines should consider recommending HBV tests for patients initiating chemotherapy.
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Affiliation(s)
| | - Sirisha Grandhe
- Division of Gastroenterology, University of California, Davis, Sacramento, California
| | - Monica Tincopa
- Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan
| | - Jill A Lane
- Division of Gastroenterology, Scripps Clinic, La Jolla, California
| | - Mark G Shrime
- Program in Global Surgery and Social Change, Harvard Medical School, Boston, Massachusetts
| | - Siddharth Singh
- Division of Gastroenterology, University of California, San Diego, La Jolla, California
| | - Rohit Loomba
- Division of Gastroenterology, University of California, San Diego, La Jolla, California.
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23
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Juarso AE, Kiehl M, Buchholz M, Weißinger F. [Infections as oncologic emergencies]. WIENER KLINISCHES MAGAZIN : BEILAGE ZUR WIENER KLINISCHEN WOCHENSCHRIFT 2020; 23:131-139. [PMID: 32322312 PMCID: PMC7175641 DOI: 10.1007/s00740-020-00339-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Background Patients with oncologic diseases, particularly those with hematologic malignancies, are at an increased risk of common infections and unique treatment-related complications with high mortality and morbidity. The annual incidence and prevalence of cancer in Germany is rising. Although modern treatments have generally led to improved survival, increasing age, comorbidities, and frailty of the patients require multidisciplinary strategies for handling complex therapeutic concepts and treatment of the associated complications. Methods A selective literature search and guidelines from the European Society for Medical Oncology (ESMO), the German Society of Hematology and Medical Oncology (Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie, DGHO), the Infectious Diseases Working Group of the DGHO (Arbeitsgemeinschaft Infektionen in der Hämatologie und Onkologie, AGIHO), and the American Society of Clinical Oncology (ASCO) formed the basis of this study. Conclusion Recognition of severe infections in cancer patients and their discrimination from treatment-associated complications is a challenge. Neutropenic fever is the most frequent infectious emergency in oncology. Early empiric treatment with broad-spectrum antibiotics and escalated diagnostic strategies are needed to successfully treat this vulnerable patient group. In this article, a range of potentially life-threatening infections in immunocompromised patients are discussed.
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Affiliation(s)
- Andreas Edwin Juarso
- Klinik für Innere Medizin, Hämatologie, Onkologie, Stammzelltransplantation und Palliativmedizin, Evangelisches Klinikum Bethel, Schildescher Str. 99, 33611 Bielefeld, Deutschland
| | - Malte Kiehl
- Klinik für Innere Medizin, Hämatologie, Onkologie, Stammzelltransplantation und Palliativmedizin, Evangelisches Klinikum Bethel, Schildescher Str. 99, 33611 Bielefeld, Deutschland
| | - Markus Buchholz
- Klinik für Innere Medizin, Hämatologie, Onkologie, Stammzelltransplantation und Palliativmedizin, Evangelisches Klinikum Bethel, Schildescher Str. 99, 33611 Bielefeld, Deutschland
| | - Florian Weißinger
- Klinik für Innere Medizin, Hämatologie, Onkologie, Stammzelltransplantation und Palliativmedizin, Evangelisches Klinikum Bethel, Schildescher Str. 99, 33611 Bielefeld, Deutschland
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24
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Chen CH, Hsieh HH, Wu TY. Real-world prevalence of hepatitis B virus reactivation in cancer patients in Taiwan. J Oncol Pharm Pract 2020; 27:63-70. [PMID: 32264743 DOI: 10.1177/1078155220913095] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND Hepatitis B virus carriers who receive systemic cancer chemotherapy have been found to be at a higher risk of hepatitis B virus reactivation. However, lack of standard prophylaxis protocol resulted in life-threatening adverse events. OBJECTIVE This retrospective study is to investigate prevalence and chemotherapy drug-induced hepatitis B virus reactivation in all types of cancer patients and establish an institutional clinical practice protocol.Methodology: This retrospective cohort study evaluated the incidence of hepatitis B virus infection, the pre-chemotherapy screening rate of hepatitis B surface antigen (HBsAg), and the severity of hepatitis B virus reactivation of cancer patients receiving intravenous chemotherapy between 2013 and 2014. Patients receiving local chemotherapy with intra-cavity instillation, drug- or alcohol-related hepatitis, or chemotherapy for immune diseases were excluded. RESULTS In total 784 patients, 404 patients (51.53%) underwent hepatitis B virus serum antigen (HBsAg) testing before chemotherapy, and 61 patients (7.78%) tested positive. Only 32 patients (4.08%) received prophylactic hepatitis B virus antiviral therapy. Patients receiving prophylactic antiviral drugs were significantly lower risk of hepatitis B virus reactivation than nonprophylaxis (relative risk, RR: 0.53, number needed to treat, NNT: 12). Moreover, our study found specific single or combined chemotherapy that may cause hepatitis B virus reactivation different from those of other studies conducted in Western countries. The differences may refer to enzymes, proteins and immune response of patients. CONCLUSIONS Our findings indicate that cancer patients receiving prophylactic antiviral drugs remain at risk of hepatitis B virus reactivation during chemotherapy. Therefore, the hepatitis B virus screen and chemotherapy control system was established in 2017 to reduce the risk of hepatitis B virus reactivation and improve patient safety.
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Affiliation(s)
- Chi-Hua Chen
- Department of Pharmacy, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan
| | - Hui-Hsia Hsieh
- Department of Pharmacy, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan
| | - Tien-Yuan Wu
- Department of Pharmacy, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan.,Department of Pharmacology, School of Medicine, Tzu Chi University, Hualien, Taiwan
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25
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Lee PH, Lee TY, Chang GC. Hepatitis B flare during osimertinib targeted therapy in a lung cancer patient with a resolved hepatitis B virus infection. Eur J Cancer 2020; 130:272-274. [PMID: 32204966 DOI: 10.1016/j.ejca.2020.02.026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Accepted: 02/22/2020] [Indexed: 01/06/2023]
Affiliation(s)
- Po-Hsin Lee
- Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
| | - Teng-Yu Lee
- Division of Gastroenterology & Hepatology, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Medicine, Chung Shan Medical University, Taichung, Taiwan.
| | - Gee-Chen Chang
- Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.
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26
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Antonuzzo A, Calabrò F, Quaglino P, Roila F, Sebastiani GD, Spina F, Pasqualetti G, Cortinovis D, Tagliaferri E, Peri A, Presotto EM, Egidi MF, Giacomelli L, Farroni F, Di Maio M, De Luca E, Danova M, Scottè F, Jordan K, Bossi P. Immunotherapy in Underrepresented Populations of Patients with Cancer: Do We Have Enough Evidence at Present? A Focus on Patients with Major Viral Infections and Autoimmune Disorders. Oncologist 2020; 25:e946-e954. [PMID: 32181960 DOI: 10.1634/theoncologist.2020-0035] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Accepted: 01/21/2020] [Indexed: 12/12/2022] Open
Abstract
The safety and activity of immune checkpoint inhibitors have been characterized in interventional and observational studies. However, only small studies have specifically investigated these agents in patients who are excluded or underrepresented in clinical trials, frequently referred to as "special populations" or "underrepresented populations." These include older adults, those with dysregulated immune activation, patients with a compromised immune function, and those carrying major viral infections, lymphoproliferative diseases, and major organ dysfunctions. Therefore, there remains substantial uncertainty regarding the use of immune checkpoint inhibitors in these specific settings. The Network of Italian Supportive Care in Oncology has carried out a multidisciplinary project, with the contribution of oncologists and other specialists, to retrieve the existing evidence on the use of immunotherapy in patients with solid and hematological cancers with the final aim to provide an expert guidance. The results of this effort are presented in this article, which is focused on patients with major viral infections or those with immune dysregulation/autoimmune diseases, and could be useful to guide decisions in clinical practice and to design prospective clinical trials focusing on the use of immunotherapy in these populations. IMPLICATIONS FOR PRACTICE: Substantial uncertainty remains regarding the use of immune checkpoint inhibitors in "underrepresented" patients, such as older adults, those with dysregulated immune activation, and patients with a compromised immune function, major viral infections, lymphoproliferative diseases or major organ dysfunctions. The Network of Italian Supportive Care in Oncology has carried out a multidisciplinary project to retrieve the existing evidence on the use of immunotherapy in underrepresented patients with cancer in order provide an expert guidance. The results of this effort, with a focus on patients with major viral infections or those with immune dysregulation/autoimmune diseases, are presented in this article and could be useful to guide decisions both in clinical practice and to design clinical trials.
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Affiliation(s)
- Andrea Antonuzzo
- UO Oncologia 1 SSN Polo Oncologico, Ambulatorio Terapie di Supporto, Pisa, Italy
| | | | - Pietro Quaglino
- Dermatologic Clinic, Department of Medical Sciences, Turin, Italy
| | - Fausto Roila
- Department of Medical Oncology, Azienda Ospedaliera, Universitaria Perugia, Italy
| | - Gian Domenico Sebastiani
- Unità Operativa Complessa di Reumatologia, Ospedale di Alta Specializzazione "San Camillo,", Rome, Italy
| | - Francesco Spina
- Division of Hematology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale Tumori, Milan, Italy
| | | | | | | | - Alessandro Peri
- Sodium Unit, Endocrinology, Department of Experimental and Clinical Biomedical Sciences, Mario Serio, University of Florence, Careggi Hospital, Florence, Italy
| | - Elena Margherita Presotto
- Sodium Unit, Endocrinology, Department of Experimental and Clinical Biomedical Sciences, Mario Serio, University of Florence, Careggi Hospital, Florence, Italy
| | | | - Luca Giacomelli
- Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy
- Polistudium SRL, Milan, Italy
| | - Ferruccio Farroni
- Gastroenterology Department, Foligno Hospital, Unità Sanitaria Locale Umbria 2, Foligno, Italy
| | - Massimo Di Maio
- Department of Oncology, University of Turin, Turin, Italy
- Division of Medical Oncology, Azienda Ospedaliero Ordine Mauriziano Hospital, Turin, Italy
| | - Emmanuele De Luca
- Department of Oncology, University of Turin, Turin, Italy
- Division of Medical Oncology, Azienda Ospedaliero Ordine Mauriziano Hospital, Turin, Italy
| | - Marco Danova
- Department of Internal Medicine and Medical Oncology, Vigevano Civic Hospital, Azienda Socio Sanitaria Territoriale (ASST) of Pavia, Pavia, Italy
| | - Florian Scottè
- Medical Oncology and Supportive Care Department, Hôpital Foch, Suresnes, France
| | - Karin Jordan
- Leitende Oberärztin, Klinik für Hämatologie, Onkologie und Rheumatologie, Innere Medizin V, Universitätsklinikum Heidelberg, Heidelberg, Germany
| | - Paolo Bossi
- Medical Oncology, University of Brescia, ASST-Spedali Civili, Brescia, Italy
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27
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Park SK, Choi CH, Chun J, Lee H, Kim ES, Park JJ, Park CH, Lee BI, Jung Y, Park DI, Kim DY, Park H, Jeen YT. Prevention and management of viral hepatitis in inflammatory bowel disease: a clinical practice guideline by the Korean Association for the Study of Intestinal Diseases. Intest Res 2020; 18:18-33. [PMID: 32013312 PMCID: PMC7000641 DOI: 10.5217/ir.2019.09155] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Accepted: 12/27/2019] [Indexed: 02/06/2023] Open
Abstract
The treatment of inflammatory bowel disease (IBD) has been revolutionized for the last 10 years by the increasing use of immunomodulators and biologics. With immunosuppression of this kind, opportunistic infection is an important safety concern for patients with IBD. In particular, viral hepatitis is determined by the interaction between the virus and the host's immunity, and the risk of reactivation increases if immunity is compromised by immunosuppression therapy. Parts of Asia, including Korea, still show intermediate endemicity for the hepatitis A virus and hepatitis B virus compared with the United States and Western Europe. Thus, members of IBD research group of the Korean Association for the Study of Intestinal Diseases have produced a guideline on the prevention and management of viral hepatitis in IBD.
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Affiliation(s)
- Soo-Kyung Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Chang Hwan Choi
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Jaeyoung Chun
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Heeyoung Lee
- Center for Preventive Medicine and Public Health, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Eun Sun Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Jae Jun Park
- Department of Internal Medicine, Institute of Gastroenterology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Chan Hyuk Park
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Bo-In Lee
- Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yunho Jung
- Division of Gastroenterology, Department of Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Dong-Il Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Do Young Kim
- Department of Internal Medicine, Institute of Gastroenterology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hana Park
- Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yoon Tae Jeen
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
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- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
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28
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Juarso E, Kiehl M, Buchholz M, Weißinger F. [Infections as oncologic emergencies]. ONKOLOGE 2019; 26:129-138. [PMID: 32288312 PMCID: PMC7102394 DOI: 10.1007/s00761-019-00691-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
Hintergrund Patienten mit onkologischen Erkrankungen, insbesondere mit hämatologischen Neoplasien, haben ein erhöhtes Risiko für allgemeine Infektionen und spezielle therapieassoziierte Komplikationen mit hoher Morbidität und Mortalität. Die jährliche Inzidenz und Prävalenz für Krebserkrankungen steigt in Deutschland. Moderne Therapieverfahren haben zu einem verbesserten Überleben geführt, jedoch erfordern steigendes Alter, Komorbiditäten und Gebrechlichkeit der Patienten multidisziplinäre Strategien zur Durchführung komplexer Therapiekonzepte und zur Behandlung von deren Komplikationen. Methode Eine selektive Literaturrecherche sowie die Leitlinien der European Society for Medical Oncology (ESMO), der Deutschen Gesellschaft für Hämatologie und Medizinische Onkologie (DGHO), der Arbeitsgemeinschaft Infektionen in der Hämatologie und Onkologie der DGHO (AGIHO) und der American Society of Clinical Oncology (ASCO) sind die Grundlage für den vorliegenden Artikel. Schlussfolgerungen Das Erkennen schwerer Infektionen bei Krebspatienten und deren Unterscheidung von therapieassoziierten Komplikationen stellt eine Herausforderung für den behandelnden Arzt dar. Neutropenisches Fieber ist der häufigste infektiologische Notfall in der Onkologie. Frühzeitige empirische Therapie mit Breitspektrumantibiotika und eskalierende diagnostische Maßnahmen sind notwendig für die erfolgreiche Therapie dieser Risikogruppe. In diesem Beitrag wird eine Reihe von lebensbedrohlichen Infektionen bei immunkompromittierten Patienten diskutiert.
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Affiliation(s)
- Edwin Juarso
- Klinik für Innere Medizin, Hämatologie, Onkologie, Stammzelltransplantation und Palliativmedizin, Evangelisches Klinikum Bethel, Schildescher Str. 99, 33611 Bielefeld, Deutschland
| | - Malte Kiehl
- Klinik für Innere Medizin, Hämatologie, Onkologie, Stammzelltransplantation und Palliativmedizin, Evangelisches Klinikum Bethel, Schildescher Str. 99, 33611 Bielefeld, Deutschland
| | - Markus Buchholz
- Klinik für Innere Medizin, Hämatologie, Onkologie, Stammzelltransplantation und Palliativmedizin, Evangelisches Klinikum Bethel, Schildescher Str. 99, 33611 Bielefeld, Deutschland
| | - Florian Weißinger
- Klinik für Innere Medizin, Hämatologie, Onkologie, Stammzelltransplantation und Palliativmedizin, Evangelisches Klinikum Bethel, Schildescher Str. 99, 33611 Bielefeld, Deutschland
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29
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Toka B, Eminler AT, Gönüllü E, Tozlu M, Uslan MI, Parlak E, Karabay O, Koksal AS. Rheumatologists’ awareness of hepatitis B reactivation before immunosuppressive therapy. Rheumatol Int 2019; 39:2077-2085. [DOI: 10.1007/s00296-019-04437-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Accepted: 08/28/2019] [Indexed: 12/19/2022]
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30
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Reactivation of Hepatitis B Virus in Patients with Multiple Myeloma. Cancers (Basel) 2019; 11:cancers11111819. [PMID: 31752356 PMCID: PMC6895787 DOI: 10.3390/cancers11111819] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2019] [Revised: 11/16/2019] [Accepted: 11/17/2019] [Indexed: 12/11/2022] Open
Abstract
Reactivation of hepatitis B virus (HBV) is a well-known complication in patients with hematological malignancies during or after cytotoxic chemotherapy. If the initiation of antiviral therapy is delayed in patients with HBV reactivation, these patients can develop severe hepatitis and may die of fulminant hepatitis. The preventive strategy for HBV reactivation in patients with malignant lymphoma has already been established based on some prospective studies. As there was an increased number of novel agents being approved for the treatment of multiple myeloma (MM), the number of reported cases of HBV reactivation among MM patients has gradually increased. We conducted a Japanese nationwide retrospective study and revealed that HBV reactivation in MM patients is not rare and that autologous stem cell transplantation is a significant risk factor. In this study, around 20% of all patients with HBV reactivation developed HBV reactivation after 2 years from the initiation of therapy, unlike malignant lymphoma. This might be due to the fact that almost all of the patients received chemotherapy for a long duration. Therefore, a new strategy for the prevention of HBV reactivation in MM patients is required.
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Abstract
PURPOSE OF REVIEW To provide an update on recent studies of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in cancer patients with an emphasis on viral reactivation after cancer treatment, new antiviral therapies, and safety concerns. RECENT FINDINGS The diagnostic criteria for HBV reactivation in patients receiving cancer therapy were revised in 2018. HBV reactivation in these patients is preventable, even with the use of new cancer therapies. HCV reactivation also has been reported in cancer patients, particularly those with hematologic malignancies, and is not a virologic condition usually associated with poor outcome. Prophylaxis to prevent HCV reactivation is not recommended because therapy with direct-acting antivirals eradicates the infection in the majority of cancer patients. SUMMARY Cancer patients with HBV or HCV infection are at risk for viral reactivation, with many similarities between these two infections. Patients at high risk for reactivation will benefit significantly from taking oral antivirals, which will reduce the risk of HBV reactivation or prevent development of HCV reactivation following its virologic cure.
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Kotake T, Satake H, Okita Y, Hatachi Y, Hamada M, Omiya M, Yasui H, Hashida T, Kaihara S, Inokuma T, Tsuji A. Prevalence and risk factors of hepatitis B virus reactivation in patients with solid tumors with resolved HBV infection. Asia Pac J Clin Oncol 2019; 15:63-68. [PMID: 29984542 PMCID: PMC7379615 DOI: 10.1111/ajco.13050] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Accepted: 06/18/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND Reports of hepatitis B virus (HBV) reactivation in solid tumors are very limited, and their frequencies and risk factors were previously unknown. AIM To evaluate the prevalence and risk factors of HBV reactivation in patients with solid tumors with resolved HBV infection. METHODS All 1088 patients with solid tumors were assessed for eligibility; 251 patients had resolved HBV infection (negative for HBs antigen and positive for anti-HBc antibody and/or positive for anti-HBs antibody), and HBV-DNA was assessed for 243 of these patients in whom we analyzed the prevalence of HBV reactivation. Risk factors for HBV reactivation were exploratorily evaluated by analysis of a case-control study. RESULTS The prevalence of HBV-DNA reactivation was 2.1% (95% confidence interval [CI], 0.3-3.9%). We did not observe any exacerbation of HBV-DNA by early intervention. A low anti-HBs antibody titer (<10.0 mIU/mL) and high average daily dexamethasone dose (>1.0 mg/day) were high risk factors, with odds ratios of 5.94 (95% CI, 1.15-30.6, P = 0.03) and 8.69 (95% CI, 1.27-58.8, P = 0.02), respectively. CONCLUSION HBV reactivation in solid tumor patients was relatively rare. Therefore, risk factors that can identify targets for HBV screening must be determined in future studies.
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Affiliation(s)
- Takeshi Kotake
- Department of Medical OncologyKobe City Medical Center General HospitalKobeJapan
| | - Hironaga Satake
- Department of Medical OncologyKobe City Medical Center General HospitalKobeJapan
| | - Yoshihiro Okita
- Department of Clinical OncologyFaculty of MedicineKagawa UniversityKagawaJapan
| | - Yukimasa Hatachi
- Department of Medical OncologyKobe City Medical Center General HospitalKobeJapan
| | - Mamiko Hamada
- Department of NursingKobe City Medical Center General HospitalKobeJapan
| | - Masatomo Omiya
- Clinical & Translational Research CenterKobe University HospitalKobeJapan
| | - Hisateru Yasui
- Department of Medical OncologyKobe City Medical Center General HospitalKobeJapan
| | - Toru Hashida
- Department of PharmacyKobe City Medical Center General HospitalKobeJapan
| | - Satoshi Kaihara
- Department of General and Transplant SurgeryKobe City Medical Center General HospitalKobeJapan
| | - Tetsuro Inokuma
- Department of GastroenterologyKobe City Medical Center General HospitalKobeJapan
| | - Akihito Tsuji
- Department of Clinical OncologyFaculty of MedicineKagawa UniversityKagawaJapan
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Li J, Wang M, Zhang B, Wu X, Lin TL, Liu XF, Zhou Y, Zhang XH, Xu H, Shen LJ, Zou J, Lu P, Zhang D, Gu WJ, Zhang MX, Pan J, Cao H. Chinese consensus on management of tyrosine kinase inhibitor-associated side effects in gastrointestinal stromal tumors. World J Gastroenterol 2018; 24:5189-5202. [PMID: 30581268 PMCID: PMC6295840 DOI: 10.3748/wjg.v24.i46.5189] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2018] [Revised: 11/04/2018] [Accepted: 11/07/2018] [Indexed: 02/06/2023] Open
Abstract
Tyrosine kinase inhibitors (TKIs) have improved the overall survival of patients with gastrointestinal stromal tumors (GISTs), but their side effects can impact dose intensity and, consequently, the clinical benefit. To date, no guideline or consensus has been published on the TKI-associated adverse reactions. Therefore, the Chinese Society of Surgeons for Gastrointestinal Stromal Tumor of the Chinese Medical Doctor Association organized an expert panel discussion involving representatives from gastrointestinal surgery, medical oncology, cardiology, dermatology, nephrology, endocrinology, and ophthalmology to consider the systemic clinical symptoms, molecular and cellular mechanisms, and treatment recommendations of GISTs. Here, we present the resultant evidence- and experience-based consensus to guide the management of TKI-associated side events in clinical practice.
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Affiliation(s)
- Jian Li
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Ming Wang
- Department of Gastrointestinal Surgery, Reiji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China
| | - Bo Zhang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xin Wu
- Department of General Surgery, the General Hospital of the People’s Liberation Army, Beijing 100853, China
| | - Tian-Long Lin
- Department of Gastrointestinal Surgery, Reiji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China
| | - Xiu-Feng Liu
- Department of Oncology, The Chinese People’s Liberation Army 81st Hospital, Nanjing 210031, Jiangsu Province, China
| | - Ye Zhou
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
| | - Xin-Hua Zhang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Hao Xu
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 320100, Jiangsu Province, China
| | - Li-Jing Shen
- Department of Hematology, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200240, China
| | - Jing Zou
- Department of Respirology, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200240, China
| | - Ping Lu
- Department of Dermatology, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200240, China
| | - Dong Zhang
- Department of Nephrology, The General Hospital of the People’s Liberation Army, Beijing 100853, China
| | - Wei-Jun Gu
- Department of Endocrinology, The General Hospital of the People’s Liberation Army, Beijing 100853, China
| | - Mei-Xia Zhang
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jian Pan
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Hui Cao
- Department of Gastrointestinal Surgery, Reiji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China
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Arora A, Anand AC, Kumar A, Singh SP, Aggarwal R, Dhiman RK, Aggarwal S, Alam S, Bhaumik P, Dixit VK, Goel A, Goswami B, Kumar A, Kumar M, Madan K, Murugan N, Nagral A, Puri AS, Rao PN, Saraf N, Saraswat VA, Sehgal S, Sharma P, Shenoy KT, Wadhawan M. INASL Guidelines on Management of Hepatitis B Virus Infection in Patients receiving Chemotherapy, Biologicals, Immunosupressants, or Corticosteroids. J Clin Exp Hepatol 2018; 8:403-431. [PMID: 30568345 PMCID: PMC6286881 DOI: 10.1016/j.jceh.2018.06.010] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Accepted: 06/10/2018] [Indexed: 02/09/2023] Open
Abstract
Hepatitis B Virus (HBV) reactivation in patients receiving chemotherapy, biologicals, immunosupressants, or corticosteroids is emerging to be an important cause of morbidity and mortality in patients with current or prior exposure to HBV infection. These patients suffer a dual onslaught of illness: one from the primary disease for which they are receiving the culprit drug that led to HBV reactivation, and the other from HBV reactivation itself. The HBV reactivation not only leads to a compromised liver function, which may culminate into hepatic failure; it also adversely impacts the treatment outcome of the primary illness. Hence, identification of patients at risk of reactivation before starting these drugs, and starting treatment aimed at prevention of HBV reactivation is the best strategy of managing these patients. There are no Indian guidelines on management of HBV infection in patients receiving chemotherapy, biologicals, immunosupressants, or corticosteroids for the treatment of rheumatologic conditions, malignancies, inflammatory bowel disease, dermatologic conditions, or solid-organ or bone marrow transplantation. The Indian National Association for Study of the Liver (INASL) had set up a taskforce on HBV in 2016, with a mandate to develop consensus guidelines for management of various aspects of HBV infection, relevant to India. In 2017 the taskforce had published the first INASL guidelines on management of HBV infection in India. In the present guidelines, which are in continuation with the previous guidelines, the issues on management of HBV infection in patients receiving chemotherapy, biologicals, immunosupressants, or corticosteroids are addressed.
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Key Words
- ACLF, Acute-on-Chronic Liver Failure
- AFP, Alphafetoprotein
- ALT, Alanine Aminotransferase
- Anti-HBc, Antibodies to Hepatitis B Core Antigen
- Anti-HBs, Antibodies to Hepatitis B Surface Antigen
- CHB, Chronic Hepatitis B
- CHOP, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone
- CKD, Chronic Kidney Disease
- DILI, Drug-Induced Liver Injury
- DNA, Deoxyribonucleic Acid
- ETV, Entecavir
- GRADE, Grading of Recommendations, Assessment, Development and Evaluation
- HAV, Hepatitis A Virus
- HBIG, Hepatitis B Immune Globulin
- HBV DNA, Hepatitis B Virus Deoxyribonucleic Acid
- HBV, Hepatitis B Virus
- HBcAg, Hepatitis B Core Antigen
- HBeAg, Hepatitis B Envelope Antigen
- HBsAg, Hepatitis B Surface Antigen
- HDV, Hepatitis D Virus
- HEV, Hepatitis E Virus
- HLA, Human Leukocyte Antigen Class I
- INASL, Indian National Association for Study of the Liver
- LAM, Lamivudine
- NAs, Nucleos(t)ide Analogs
- NHL, Non-Hodgkin’s Lymphoma
- NK, Natural Killer
- PegIFN-α, Pegylated Interferon Alpha
- RA, Rheumatoid Arthritis
- SLE, Systemic Lupus Erythematosus
- TAF, Tenofovir Alafenamide
- TDF, Tenofovir Disoproxil Fumarate
- TLC, Total Leucocyte Count
- ULN, Upper Limit of Normal
- cancer
- cccDNA, Covalently Closed Circular Deoxyribonucleic Acid
- chemotherapy
- hepatitis B
- immunosupressants
- liver failure
- rcDNA, Relaxed-Circular Deoxyribonucleic Acid
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Affiliation(s)
- Anil Arora
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | | | - Ashish Kumar
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Shivaram P. Singh
- Department of Gastroenterology, S.C.B. Medical College, Cuttack, India
| | - Rakesh Aggarwal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Radha K. Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Shyam Aggarwal
- Department of Medical Oncology, Sir Ganga Ram Hospital, New Delhi, India
| | - Seema Alam
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Pradeep Bhaumik
- Department of Medicine, Agartala Govt. Medical College (AGMC), Agartala, India
| | - Vinod K. Dixit
- Department of Gastroenterology, Institute of Medical Sciences Banaras Hindu University, Varanasi, India
| | - Ashish Goel
- Department of Hepatology, Christian Medical College, Vellore, India
| | - Bhabadev Goswami
- Department of Gastoenterology, Gauhati Medical College, Guwahati, India
| | - Ashok Kumar
- Department of Rheumatology, Fortis Flt Lt Rajan Dhall Hospital, New Delhi, India
| | - Manoj Kumar
- Department of Hepatology and Liver Transplantation, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Kaushal Madan
- Gastroenterology & Hepatology, Max Smart Super Speciality Hospital, New Delhi, India
| | | | - Aabha Nagral
- Department of Gastroenterology, Jaslok and Apollo Hospitals, Mumbai, India
| | - Amarender S. Puri
- Department of Gastroenterology, G.B. Pant Hospital, New Delhi, India
| | - Padaki N. Rao
- Hepatology, Asian Institute Of Gastroenterology, Hyderabad, India
| | - Neeraj Saraf
- Hepatology, Medanta - The Medicity, Gurugram, India
| | - Vivek A. Saraswat
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Sanjeev Sehgal
- Institute of Liver Transplantation and Regenerative Medicine, Medanta - The Medicity, Gurugram, India
| | - Praveen Sharma
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | | | - Manav Wadhawan
- Hepatology & Liver Transplant (Medicine), Fortis Escorts Liver & Digestive Diseases Institute (FELDI), Fortis Escorts Hospital, Delhi, India
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Grant MJ, DeVito N, Salama AKS. Checkpoint inhibitor use in two heart transplant patients with metastatic melanoma and review of high-risk populations. Melanoma Manag 2018; 5:MMT10. [PMID: 30459942 PMCID: PMC6240846 DOI: 10.2217/mmt-2018-0004] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2018] [Accepted: 08/03/2018] [Indexed: 12/12/2022] Open
Abstract
Due to the unique side-effect profile of immune checkpoint inhibitors (ICIs), groups of patients deemed to be at high risk of complications were excluded from trials that proved the efficacy and safety of these agents in patients with various malignancies. Among these excluded patients were those with prior solid organ transplantation, chronic viral infections and pre-existing autoimmune diseases including paraneoplastic syndromes. We present follow-up on a patient from a previously published case report with an orthotopic heart transplantation who was treated with both cytotoxic T-lymphocyte antigen 4 and PD-1 inhibition safely, without organ rejection. Additionally, we describe the case of a patient with a cardiac allograft who also did not experience organ rejection after treatment with pembrolizumab. Through smaller trials, retrospective analyses, case series and individual case reports, we are accumulating initial data on how these agents are tolerated by the aforementioned groups. Our survey of the literature has found more evidence of organ transplant rejection in patients treated with PD-1 inhibitors than those treated with inhibitors of cytotoxic T-lymphocyte antigen 4. Patients with chronic viral infections, especially hepatitis C, seem to have little to no risk of treatment-related increase in serum RNA levels. The literature contains few documented cases of devastating exacerbations of pre-existing autoimmune disease during treatment with ICIs, and flares seem to be easily controlled by immunosuppression in the vast majority of cases. Last, several cases allude to a promising role for disease-specific antibodies and other serum biomarkers in identifying patients at high risk of developing certain immune-related adverse events, detecting subclinical immune-related adverse event onset, and monitoring treatment response to immunosuppressive therapy in patients treated with ICIs. Though these excluded populations have not been well studied in randomized placebo-controlled trials, we may be able to learn and derive hypotheses from the existing observational data in the literature.
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Affiliation(s)
- Michael J Grant
- Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.,Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
| | - Nicholas DeVito
- Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.,Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA
| | - April K S Salama
- Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.,Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA
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A Rare Case of Pembrolizumab-Induced Reactivation of Hepatitis B. Case Rep Oncol Med 2018; 2018:5985131. [PMID: 30416833 PMCID: PMC6207901 DOI: 10.1155/2018/5985131] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2018] [Revised: 09/06/2018] [Accepted: 09/27/2018] [Indexed: 02/07/2023] Open
Abstract
Hepatitis B virus (HBV) infection is common across the world, especially in Asia, Africa, Southern Europe, and Latin America. The association of HBV infection in patients suffering from different oncological conditions is well established. Many cases of HBV reactivation have been reported in patients on immunosuppressive chemotherapy and in patients undergoing hematopoietic bone marrow transplantations. Only one case has been reported so far of HBV reactivation in a patient treated with programmed cell death receptor 1 (PD-1) checkpoint inhibitors in the setting of HIV status. We report a case of a 51-year-old male, former smoker, diagnosed with stage IV poorly differentiated adenocarcinoma of the lung, and started on pembrolizumab, who developed reactivation of chronic hepatitis requiring antiviral therapy.
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Inayat F, Song F, Ali NS, Aslam MH, Aloma A, Hachem H, Saif MW. Hepatitis B virus reactivation following imatinib therapy: A comparative review of 9 cases. J Oncol Pharm Pract 2018; 25:1500-1508. [PMID: 30079802 DOI: 10.1177/1078155218790337] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Patients undergoing cytotoxic or immunosuppressive therapy for cancer have an established predilection for hepatitis B virus reactivation; however, the risk associated with newer molecularly targeted agents has not been well investigated. Imatinib, a small molecule tyrosine kinase inhibitor, induces rapid and sustained clinical benefit by inhibiting a number of signaling pathways, including BCR-ABL and c-KIT. We report the case of a patient who developed hepatitis B virus reactivation while receiving imatinib therapy for gastrointestinal stromal tumor. Furthermore, a structured literature search of the medical databases consisting of MEDLINE and PubMed was performed using the terms "hepatitis B", "reactivation", and "imatinib". The search identified nine case reports only. The data on patients' characteristics, epidemiology, clinical features, comorbid conditions, diagnosis, and management are summarized. Imatinib-associated hepatitis B virus reactivation was reported in seven patients with chronic myeloid leukemia, one with desmoid tumor, and one with gastrointestinal stromal tumor. This review serves to outline our current understanding of the epidemiology, risk factors, and pathophysiology of chronic hepatitis B virus reactivation secondary to imatinib therapy as well as the current approaches to diagnosis and management of this condition. We aim to increase awareness about this possible association and advocate for hepatitis B virus screening prior to imatinib therapy, especially in patients who are at increased risk for chronic hepatitis B virus infection.
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Affiliation(s)
| | - Fei Song
- 2 Tufts Medical Center, Boston, USA
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Epstein DJ, Dunn J, Deresinski S. Infectious Complications of Multiple Sclerosis Therapies: Implications for Screening, Prophylaxis, and Management. Open Forum Infect Dis 2018; 5:ofy174. [PMID: 30094293 PMCID: PMC6080056 DOI: 10.1093/ofid/ofy174] [Citation(s) in RCA: 103] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Accepted: 07/12/2018] [Indexed: 12/12/2022] Open
Abstract
Multiple sclerosis therapies include interferons, glatiramer, and multiple immunosuppressive drugs. Discerning infectious risks of immunosuppressive drugs requires understanding their mechanisms of action and analyzing interventional studies and postmarketing observational data. Though identical immunosuppressive therapies are sometimes used in non-neurologic conditions, infectious risks may differ in this population. Screening for and treatment of latent tuberculosis (TB) infection should be prioritized for patients receiving alemtuzumab; ocrelizumab is likely not associated with an increased risk of TB. Hepatitis B virus (HBV) reactivation can be devastating for patients treated with ocrelizumab and alemtuzumab, whereas the small molecule oral agents do not likely pose substantial risk of HBV. Progressive multifocal leukoencephalopathy is a particular concern with natalizumab. Alemtuzumab, and possibly natalizumab and fingolimod, risks herpes virus reactivation and may warrant prophylaxis. Unusual opportunistic infections have been described. Vaccination is an important tool in preventing infections, though vaccine timing and contraindications can be complex.
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Affiliation(s)
- David J Epstein
- Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University, Stanford, California
| | - Jeffrey Dunn
- Department of Neurology and Neurological Sciences, Stanford University, Stanford, California
| | - Stan Deresinski
- Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University, Stanford, California
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Blackard JT, Sherman KE. Hepatitis B virus (HBV) reactivation-The potential role of direct-acting agents for hepatitis C virus (HCV). Rev Med Virol 2018; 28:e1984. [PMID: 29761585 PMCID: PMC6233878 DOI: 10.1002/rmv.1984] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2017] [Revised: 04/04/2018] [Accepted: 04/05/2018] [Indexed: 12/16/2022]
Abstract
Hepatitis C virus (HCV) is known to inhibit hepatitis B virus (HBV) replication in patients with HBV/HCV coinfection. Reactivation of HBV in patients treated for HCV with direct-acting agents (DAAs) has emerged recently as an important clinical consideration. A growing number of case reports and case series support the association between new HCV treatments and HBV reactivation. Yet, very little is known about the specific viral characteristics that facilitate reactivation as functional characterization of the reactivated HBV has been conducted only rarely. This review provides the most recent data on HBV reactivation in the context of DAA initiation and highlights the existing viral genomic data from reactivating viruses. Current functional studies of HBV reactivation are largely limited by the retrospective identification of cases, no standardization of genomic regions that are studied with respect to HBV reactivation, and the lack of inclusion of nonreactivating controls to establish specific viral mutations that are associated with HBV reactivation. Importantly, none of these sequencing studies included cases of HBV reactivation after initiation of DAAs. While new HCV treatments have revolutionized care for HCV infected patients, HBV reactivation will likely increase in frequency, as DAAs are more commonly prescribed. Pretreatment determination of HBV status and thoughtful management of HBV coinfections will be necessary and lead to improved patient safety and yield optimal treatment results.
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Affiliation(s)
- Jason T Blackard
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | - Kenneth E Sherman
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
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Abstract
Hepatitis B virus (HBV) is a hepatotropic virus that can establish a persistent and chronic infection in humans through immune anergy. Currently, 3.5% of the global population is chronically infected with HBV, although the incidence of HBV infections is decreasing owing to vaccination and, to a lesser extent, the use of antiviral therapy to reduce the viral load of chronically infected individuals. The course of chronic HBV infection typically comprises different clinical phases, each of which potentially lasts for decades. Well-defined and verified serum and liver biopsy diagnostic markers enable the assessment of disease severity, viral replication status, patient risk stratification and treatment decisions. Current therapy includes antiviral agents that directly act on viral replication and immunomodulators, such as interferon therapy. Antiviral agents for HBV include reverse transcriptase inhibitors, which are nucleoside or nucleotide analogues that can profoundly suppress HBV replication but require long-term maintenance therapy. Novel compounds are being actively investigated to achieve the goal of HBV surface antigen seroclearance (functional cure), a serological state that is associated with a higher remission rate (thus, no viral rebound) after treatment cessation and a lower rate of cirrhosis and hepatocellular carcinoma. This Primer addresses several aspects of HBV infection, including epidemiology, immune pathophysiology, diagnosis, prevention and management.
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Aygen B, Demir AM, Gümüş M, Karabay O, Kaymakoğlu S, Köksal AŞ, Köksal İ, Örmeci N, Tabak F. Immunosuppressive therapy and the risk of hepatitis B reactivation: Consensus report. THE TURKISH JOURNAL OF GASTROENTEROLOGY : THE OFFICIAL JOURNAL OF TURKISH SOCIETY OF GASTROENTEROLOGY 2018; 29:259-269. [PMID: 29755010 PMCID: PMC6284666 DOI: 10.5152/tjg.2018.18263] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/30/2018] [Accepted: 04/07/2018] [Indexed: 12/12/2022]
Abstract
This consensus report includes expert opinions and recommendations regarding the screening, and if necessary, the follow-up, prophylaxis, and treatment of hepatitis B before the treatment in patients who will undergo immunosuppressive therapy due to an emergency risk of hepatitis B reactivation. To increase awareness regarding the risk of hepatitis B reactivation in immunosuppressive patients, academicians from several university health research and training centers across Turkey came together and discussed the importance of the subject, current status, and issues in accordance with the current literature data and presented solutions.
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Affiliation(s)
- Bilgehan Aygen
- Department of Infectious Diseases and Clinical Microbiology, Erciyes University School of Medicine, Kayseri, Turkey
| | - Ahmet Muzaffer Demir
- Division of Hematology, Department of Internal Diseases, Trakya University School of Medicine, Edirne, Turkey
| | - Mahmut Gümüş
- Division of Oncology, Department of Internal Diseases, İstanbul Medeniyet University School of Medicine, İstanbul, Turkey
| | - Oğuz Karabay
- Department of Infectious Diseases and Clinical Microbiology, Sakarya University School of Medicine, Sakarya, Turkey
| | - Sabahattin Kaymakoğlu
- Division of Gastroenterology, Department of Internal Diseases, İstanbul University İstanbul School of Medicine, İstanbul, Turkey
| | - Aydın Şeref Köksal
- Division of Gastroenterology, Department of Internal Diseases, Sakarya University School of Medicine, Sakarya, Turkey
| | - İftihar Köksal
- Department of Infectious Diseases and Clinical Microbiology, Karadeniz Technical University School of Medicine, Trabzon, Turkey
| | - Necati Örmeci
- Division of Gastroenterology, Department of Internal Diseases, Ankara University School of Medicine, Ankara, Turkey
| | - Fehmi Tabak
- Department of Infectious Diseases and Clinical Microbiology, İstanbul University Cerrahpaşa School of Medicine, İstanbul, Turkey
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Hwang JP, Lok AS, Fisch MJ, Cantor SB, Barbo A, Lin HY, Foreman JT, Vierling JM, Torres HA, Granwehr BP, Miller E, Eng C, Simon GR, Ahmed S, Ferrajoli A, Romaguera J, Suarez-Almazor ME. Models to Predict Hepatitis B Virus Infection Among Patients With Cancer Undergoing Systemic Anticancer Therapy: A Prospective Cohort Study. J Clin Oncol 2018; 36:959-967. [PMID: 29447061 PMCID: PMC7351320 DOI: 10.1200/jco.2017.75.6387] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
PURPOSE Most patients with cancer are not screened for hepatitis B virus (HBV) infection before undergoing anticancer therapy, and optimal screening strategies are unknown. We sought to develop selective HBV screening strategies for patients who require systemic anticancer therapy. METHODS This prospective cohort study included adults age ≥ 18 years with solid or hematologic malignancies who received systemic anticancer therapy at a comprehensive cancer center during 2013 and 2014. Patients underwent hepatitis B surface antigen, hepatitis B core antibody, and hepatitis B surface antibody testing, and completed a 19-question modified Centers for Disease Control and Prevention (CDC) HBV survey. Multivariable models that predict chronic or past HBV infection were developed and validated using bootstrapping. RESULTS A total of 2,124 patients (mean age, 58 ± 13 years) completed the risk survey and HBV testing. Of these, 54% were women; 77% were non-Hispanic white, 11% Hispanic, 8% black, and 4% Asian; and 20% had a hematologic malignancy and 80% a solid tumor. Almost 12% were born outside the United States. The prevalence was 0.3% for chronic HBV infection and 6% for past HBV infection. Significant predictors of positive hepatitis B surface antigen or hepatitis B core antibody tests were as follows: men who had sex with men, black or Asian race, birthplace outside the United States, parent's birthplace outside the United States, household exposure to HBV, age ≥ 50 years, and history of injection drug use. The area under the receiver operating characteristic curve of the model on the basis of these seven predictors was 0.79 (95% CI, 0.73 to 0.82). The modified CDC survey and brief tools with fewer than seven questions yielded similar false-negative rates (0% and 0% to 0.7%, respectively). CONCLUSION An internally validated risk tool performed as well as the modified CDC survey; however, more than 90% of patients who completed the tool would still require HBV testing. Universal HBV testing is more efficient than risk-based screening.
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Affiliation(s)
- Jessica P. Hwang
- Jessica P. Hwang, Scott B. Cantor, Andrea Barbo, Heather Y. Lin, Jessica T. Foreman, Harrys A. Torres, Bruno P. Granwehr, Ethan Miller, Cathy Eng, George R. Simon, Sairah Ahmed, Alessandra Ferrajoli, Jorge Romaguera, and Maria E. Suarez-Almazor, The University of Texas MD Anderson Cancer Center; John M. Vierling, Baylor College of Medicine, Houston, TX; Anna S. Lok, University of Michigan, Ann Arbor, MI; and Michael J. Fisch, Aim Specialty Health, Chicago, IL
| | - Anna S. Lok
- Jessica P. Hwang, Scott B. Cantor, Andrea Barbo, Heather Y. Lin, Jessica T. Foreman, Harrys A. Torres, Bruno P. Granwehr, Ethan Miller, Cathy Eng, George R. Simon, Sairah Ahmed, Alessandra Ferrajoli, Jorge Romaguera, and Maria E. Suarez-Almazor, The University of Texas MD Anderson Cancer Center; John M. Vierling, Baylor College of Medicine, Houston, TX; Anna S. Lok, University of Michigan, Ann Arbor, MI; and Michael J. Fisch, Aim Specialty Health, Chicago, IL
| | - Michael J. Fisch
- Jessica P. Hwang, Scott B. Cantor, Andrea Barbo, Heather Y. Lin, Jessica T. Foreman, Harrys A. Torres, Bruno P. Granwehr, Ethan Miller, Cathy Eng, George R. Simon, Sairah Ahmed, Alessandra Ferrajoli, Jorge Romaguera, and Maria E. Suarez-Almazor, The University of Texas MD Anderson Cancer Center; John M. Vierling, Baylor College of Medicine, Houston, TX; Anna S. Lok, University of Michigan, Ann Arbor, MI; and Michael J. Fisch, Aim Specialty Health, Chicago, IL
| | - Scott B. Cantor
- Jessica P. Hwang, Scott B. Cantor, Andrea Barbo, Heather Y. Lin, Jessica T. Foreman, Harrys A. Torres, Bruno P. Granwehr, Ethan Miller, Cathy Eng, George R. Simon, Sairah Ahmed, Alessandra Ferrajoli, Jorge Romaguera, and Maria E. Suarez-Almazor, The University of Texas MD Anderson Cancer Center; John M. Vierling, Baylor College of Medicine, Houston, TX; Anna S. Lok, University of Michigan, Ann Arbor, MI; and Michael J. Fisch, Aim Specialty Health, Chicago, IL
| | - Andrea Barbo
- Jessica P. Hwang, Scott B. Cantor, Andrea Barbo, Heather Y. Lin, Jessica T. Foreman, Harrys A. Torres, Bruno P. Granwehr, Ethan Miller, Cathy Eng, George R. Simon, Sairah Ahmed, Alessandra Ferrajoli, Jorge Romaguera, and Maria E. Suarez-Almazor, The University of Texas MD Anderson Cancer Center; John M. Vierling, Baylor College of Medicine, Houston, TX; Anna S. Lok, University of Michigan, Ann Arbor, MI; and Michael J. Fisch, Aim Specialty Health, Chicago, IL
| | - Heather Y. Lin
- Jessica P. Hwang, Scott B. Cantor, Andrea Barbo, Heather Y. Lin, Jessica T. Foreman, Harrys A. Torres, Bruno P. Granwehr, Ethan Miller, Cathy Eng, George R. Simon, Sairah Ahmed, Alessandra Ferrajoli, Jorge Romaguera, and Maria E. Suarez-Almazor, The University of Texas MD Anderson Cancer Center; John M. Vierling, Baylor College of Medicine, Houston, TX; Anna S. Lok, University of Michigan, Ann Arbor, MI; and Michael J. Fisch, Aim Specialty Health, Chicago, IL
| | - Jessica T. Foreman
- Jessica P. Hwang, Scott B. Cantor, Andrea Barbo, Heather Y. Lin, Jessica T. Foreman, Harrys A. Torres, Bruno P. Granwehr, Ethan Miller, Cathy Eng, George R. Simon, Sairah Ahmed, Alessandra Ferrajoli, Jorge Romaguera, and Maria E. Suarez-Almazor, The University of Texas MD Anderson Cancer Center; John M. Vierling, Baylor College of Medicine, Houston, TX; Anna S. Lok, University of Michigan, Ann Arbor, MI; and Michael J. Fisch, Aim Specialty Health, Chicago, IL
| | - John M. Vierling
- Jessica P. Hwang, Scott B. Cantor, Andrea Barbo, Heather Y. Lin, Jessica T. Foreman, Harrys A. Torres, Bruno P. Granwehr, Ethan Miller, Cathy Eng, George R. Simon, Sairah Ahmed, Alessandra Ferrajoli, Jorge Romaguera, and Maria E. Suarez-Almazor, The University of Texas MD Anderson Cancer Center; John M. Vierling, Baylor College of Medicine, Houston, TX; Anna S. Lok, University of Michigan, Ann Arbor, MI; and Michael J. Fisch, Aim Specialty Health, Chicago, IL
| | - Harrys A. Torres
- Jessica P. Hwang, Scott B. Cantor, Andrea Barbo, Heather Y. Lin, Jessica T. Foreman, Harrys A. Torres, Bruno P. Granwehr, Ethan Miller, Cathy Eng, George R. Simon, Sairah Ahmed, Alessandra Ferrajoli, Jorge Romaguera, and Maria E. Suarez-Almazor, The University of Texas MD Anderson Cancer Center; John M. Vierling, Baylor College of Medicine, Houston, TX; Anna S. Lok, University of Michigan, Ann Arbor, MI; and Michael J. Fisch, Aim Specialty Health, Chicago, IL
| | - Bruno P. Granwehr
- Jessica P. Hwang, Scott B. Cantor, Andrea Barbo, Heather Y. Lin, Jessica T. Foreman, Harrys A. Torres, Bruno P. Granwehr, Ethan Miller, Cathy Eng, George R. Simon, Sairah Ahmed, Alessandra Ferrajoli, Jorge Romaguera, and Maria E. Suarez-Almazor, The University of Texas MD Anderson Cancer Center; John M. Vierling, Baylor College of Medicine, Houston, TX; Anna S. Lok, University of Michigan, Ann Arbor, MI; and Michael J. Fisch, Aim Specialty Health, Chicago, IL
| | - Ethan Miller
- Jessica P. Hwang, Scott B. Cantor, Andrea Barbo, Heather Y. Lin, Jessica T. Foreman, Harrys A. Torres, Bruno P. Granwehr, Ethan Miller, Cathy Eng, George R. Simon, Sairah Ahmed, Alessandra Ferrajoli, Jorge Romaguera, and Maria E. Suarez-Almazor, The University of Texas MD Anderson Cancer Center; John M. Vierling, Baylor College of Medicine, Houston, TX; Anna S. Lok, University of Michigan, Ann Arbor, MI; and Michael J. Fisch, Aim Specialty Health, Chicago, IL
| | - Cathy Eng
- Jessica P. Hwang, Scott B. Cantor, Andrea Barbo, Heather Y. Lin, Jessica T. Foreman, Harrys A. Torres, Bruno P. Granwehr, Ethan Miller, Cathy Eng, George R. Simon, Sairah Ahmed, Alessandra Ferrajoli, Jorge Romaguera, and Maria E. Suarez-Almazor, The University of Texas MD Anderson Cancer Center; John M. Vierling, Baylor College of Medicine, Houston, TX; Anna S. Lok, University of Michigan, Ann Arbor, MI; and Michael J. Fisch, Aim Specialty Health, Chicago, IL
| | - George R. Simon
- Jessica P. Hwang, Scott B. Cantor, Andrea Barbo, Heather Y. Lin, Jessica T. Foreman, Harrys A. Torres, Bruno P. Granwehr, Ethan Miller, Cathy Eng, George R. Simon, Sairah Ahmed, Alessandra Ferrajoli, Jorge Romaguera, and Maria E. Suarez-Almazor, The University of Texas MD Anderson Cancer Center; John M. Vierling, Baylor College of Medicine, Houston, TX; Anna S. Lok, University of Michigan, Ann Arbor, MI; and Michael J. Fisch, Aim Specialty Health, Chicago, IL
| | - Sairah Ahmed
- Jessica P. Hwang, Scott B. Cantor, Andrea Barbo, Heather Y. Lin, Jessica T. Foreman, Harrys A. Torres, Bruno P. Granwehr, Ethan Miller, Cathy Eng, George R. Simon, Sairah Ahmed, Alessandra Ferrajoli, Jorge Romaguera, and Maria E. Suarez-Almazor, The University of Texas MD Anderson Cancer Center; John M. Vierling, Baylor College of Medicine, Houston, TX; Anna S. Lok, University of Michigan, Ann Arbor, MI; and Michael J. Fisch, Aim Specialty Health, Chicago, IL
| | - Alessandra Ferrajoli
- Jessica P. Hwang, Scott B. Cantor, Andrea Barbo, Heather Y. Lin, Jessica T. Foreman, Harrys A. Torres, Bruno P. Granwehr, Ethan Miller, Cathy Eng, George R. Simon, Sairah Ahmed, Alessandra Ferrajoli, Jorge Romaguera, and Maria E. Suarez-Almazor, The University of Texas MD Anderson Cancer Center; John M. Vierling, Baylor College of Medicine, Houston, TX; Anna S. Lok, University of Michigan, Ann Arbor, MI; and Michael J. Fisch, Aim Specialty Health, Chicago, IL
| | - Jorge Romaguera
- Jessica P. Hwang, Scott B. Cantor, Andrea Barbo, Heather Y. Lin, Jessica T. Foreman, Harrys A. Torres, Bruno P. Granwehr, Ethan Miller, Cathy Eng, George R. Simon, Sairah Ahmed, Alessandra Ferrajoli, Jorge Romaguera, and Maria E. Suarez-Almazor, The University of Texas MD Anderson Cancer Center; John M. Vierling, Baylor College of Medicine, Houston, TX; Anna S. Lok, University of Michigan, Ann Arbor, MI; and Michael J. Fisch, Aim Specialty Health, Chicago, IL
| | - Maria E. Suarez-Almazor
- Jessica P. Hwang, Scott B. Cantor, Andrea Barbo, Heather Y. Lin, Jessica T. Foreman, Harrys A. Torres, Bruno P. Granwehr, Ethan Miller, Cathy Eng, George R. Simon, Sairah Ahmed, Alessandra Ferrajoli, Jorge Romaguera, and Maria E. Suarez-Almazor, The University of Texas MD Anderson Cancer Center; John M. Vierling, Baylor College of Medicine, Houston, TX; Anna S. Lok, University of Michigan, Ann Arbor, MI; and Michael J. Fisch, Aim Specialty Health, Chicago, IL
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Artz AS, Paul S. Screening for Hepatitis B Virus Infection: Are We Asking the Right Questions? J Clin Oncol 2018; 36:935-936. [DOI: 10.1200/jco.2018.77.7128] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- Andrew S. Artz
- Andrew S. Artz and Sonali Paul, University of Chicago, Chicago, IL
| | - Sonali Paul
- Andrew S. Artz and Sonali Paul, University of Chicago, Chicago, IL
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44
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Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, Brown RS, Bzowej NH, Wong JB. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 2018; 67:1560-1599. [PMID: 29405329 PMCID: PMC5975958 DOI: 10.1002/hep.29800] [Citation(s) in RCA: 2746] [Impact Index Per Article: 392.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Accepted: 01/11/2018] [Indexed: 12/11/2022]
Affiliation(s)
- Norah A Terrault
- Division of Gastroenterology/Hepatology, University of California San Francisco, San Francisco, CA
| | - Anna S F Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI
| | - Brian J McMahon
- Liver Diseases and Hepatitis Program, Alaska NativeTribal Health Consortium, Anchorage, AK
| | - Kyong-Mi Chang
- Division of Gastroenterology, Corporal Michael J. Crescenz VA Medical Center & University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Jessica P Hwang
- Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Maureen M Jonas
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA
| | - Robert S Brown
- Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY
| | | | - John B Wong
- Division of Clinical Decision Making, Tufts Medical Center, Tufts University School of Medicine, Boston, MA
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45
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Wang J, Jia J, Chen R, Ding S, Xu Q, Zhang T, Chen X, Liu S, Lu F. RFX1 participates in doxorubicin-induced hepatitis B virus reactivation. Cancer Med 2018; 7:2021-2033. [PMID: 29601674 PMCID: PMC5943424 DOI: 10.1002/cam4.1468] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Revised: 02/02/2018] [Accepted: 03/01/2018] [Indexed: 12/18/2022] Open
Abstract
Cytotoxic chemotherapy drugs, including doxorubicin, can directly promote hepatitis B virus (HBV) replication, but the mechanism has not been fully clarified. This study investigated the potential mechanism underlying the cytotoxic chemotherapy‐mediated direct promotion of HBV replication. We found that HBV replication and regulatory factor X box 1 gene (RFX1) expression were simultaneously promoted by doxorubicin treatment. The amount of RFX1 bound to the HBV enhancer I was significantly increased under doxorubicin treatment. Furthermore, the activity of doxorubicin in promoting HBV replication was significantly attenuated when the expression of endogenous RFX1 was knocked down, and the EP element of HBV enhancer I, an element that mediated the binding of RFX1 and HBV enhancer I, was mutated. In addition, two different sequences of the conserved EP element were found among HBV genotypes A‐D, and doxorubicin could promote the replication of HBV harboring either of the conserved EP elements. Here, a novel pathway in which doxorubicin promoted HBV replication via RFX1 was identified, and it might participate in doxorubicin‐induced HBV reactivation. These findings would be helpful in preventing HBV reactivation during anticancer chemotherapy.
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Affiliation(s)
- Jie Wang
- State Key Laboratory of Natural and Biomimetic Drugs, Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Junqiao Jia
- State Key Laboratory of Natural and Biomimetic Drugs, Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Ran Chen
- State Key Laboratory of Natural and Biomimetic Drugs, Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Shanlong Ding
- State Key Laboratory of Natural and Biomimetic Drugs, Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Qiang Xu
- State Key Laboratory of Natural and Biomimetic Drugs, Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Ting Zhang
- State Key Laboratory of Natural and Biomimetic Drugs, Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Xiangmei Chen
- State Key Laboratory of Natural and Biomimetic Drugs, Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Shuang Liu
- Beijing Artificial Liver Treatment & Training Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Fengmin Lu
- State Key Laboratory of Natural and Biomimetic Drugs, Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
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Arora A, Singh SP, Kumar A, Saraswat VA, Aggarwal R, Bangar M, Bhaumik P, Devarbhavi H, Dhiman RK, Dixit VK, Goel A, Goswami B, Kapoor D, Madan K, Narayan J, Nijhawan S, Pandey G, Rai RR, Sahu MK, Saraf N, Shalimar, Shenoy T, Thomas V, Wadhawan M. INASL Position Statements on Prevention, Diagnosis and Management of Hepatitis B Virus Infection in India: The Andaman Statements. J Clin Exp Hepatol 2018; 8:58-80. [PMID: 29743798 PMCID: PMC5938334 DOI: 10.1016/j.jceh.2017.12.001] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Accepted: 12/09/2017] [Indexed: 12/12/2022] Open
Abstract
Hepatitis B Virus (HBV) infection is one of the major causes of morbidity, mortality and healthcare expenditure in India. There are no Indian consensus guidelines on prevention, diagnosis and management of HBV infection. The Indian National Association for Study of the Liver (INASL) set up a taskforce on HBV in 2016, with a mandate to develop consensus guidelines for diagnosis and management of HBV infection, relevant to disease patterns and clinical practices in India. The taskforce first identified contentious issues on various aspects of HBV management, which were allotted to individual members of the taskforce who reviewed them in detail. A 2-day round table discussion was held on 11th and 12th February 2017 at Port Blair, Andaman & Nicobar Islands, to discuss, debate, and finalize the consensus statements. The members of the taskforce reviewed and discussed the existing literature threadbare at this meeting and formulated the 'INASL position statements' on each of the issues. The evidence and recommendations in these guidelines have been graded according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) system with minor modifications. The strength of recommendations (strong: 1, weak: 2) thus reflects the quality (grade) of underlying evidence (A, B, C, D). We present here the INASL position statements on prevention, diagnosis and management of HBV in India.
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Key Words
- AASLD, American Association for the Study of Liver Diseases
- ADV, adefovir dipivoxil
- ALT, alanine aminotransferase
- APASL, Asian Pacific Association for the Study of the Liver
- ART, antiretroviral therapy
- AST, aspartate aminotransferase
- Anti-HBe, antibodies to hepatitis B envelope antigen
- CBC, complete blood count
- CDC, Center for Disease Control
- CHB, chronic hepatitis B
- CU-HCC, Chinese University-Hepatocellular Carcinoma
- DAA, direct-acting antiviral
- DILI, drug induced liver injury
- DNA, deoxyribonucleic acid
- EASL, European Association for the Study of the Liver
- ETV, entecavir
- GAG-HCC, Guide with Age, Gender, HBV DNA, Core Promoter Mutations and Cirrhosis-Hepatocellular Carcinoma
- GGT, gamma-glutamyl transferase
- GRADE, Grading of Recommendations Assessment Development and Evaluation
- HBIG, hepatitis B immune globulin
- HBV, hepatitis B virus
- HBeAg, hepatitis B envelope antigen
- HCC, hepatocellular carcinoma
- HCV, hepatitis C virus
- HDV, hepatitis D virus
- HIV, human immunodeficiency virus
- IFN-α, interferon alpha
- INASL, Indian National Association for Study of the Liver
- INR, international normalized ratio
- KASL, Korean Association for the Study of the Liver
- LAM, lamivudine
- NA, nucleos(t)ide analogue
- PAGE-B, platelets, age, gender—hepatitis B
- PVNR, primary virological non-response
- PVR, partial virological response
- PegIFN-α, pegylated interferon alpha
- RCT, randomized controlled trial
- REACH-B, risk estimation for hepatocellular carcinoma in chronic hepatitis B
- SOVR, sustained off-therapy virological response
- TAF, tenofovir alafenamide
- TDF, tenofovir disoproxil fumarate
- TDV, telbivudine
- TSH, thyroid-stimulating hormone
- VR, virologic response
- WHO, World Health Organization
- anti-HBs, antibody to hepatitis B surface antigen
- cccDNA, covalently closed circular DNA
- chronic hepatitis
- cirrhosis
- eGFR, estimated glomerular filtration rate
- hepatitis B
- jaundice
- liver failure
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Affiliation(s)
- Anil Arora
- Director, Institute of Liver, Gastroenterology, and Pancreatico-Biliary Sciences, Ganga Ram Institute for Postgraduate Medical Education & Research (GRIPMER), Sir Ganga Ram Hospital, New Delhi, India
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Kwak YE, Stein SM, Lim JK. Practice Patterns in Hepatitis B Virus Screening Before Cancer Chemotherapy in a Major US Hospital Network. Dig Dis Sci 2018; 63:61-71. [PMID: 29177849 DOI: 10.1007/s10620-017-4850-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2017] [Accepted: 11/14/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND Cancer patients receiving chemotherapy face an increased risk of reactivation of chronic hepatitis B virus infection. AIM To determine the HBV screening rate in patients receiving cancer chemotherapy in various clinical settings. METHOD We identified 11,959 adult cancer patients (age ≥ 18 years) receiving parenteral chemotherapy between 2012 and 2015 within a major US hospital network, including a large university hospital, community teaching hospitals, and community oncology clinics. RESULT Two thousand and forty-five patients (17.1%) were screened for either HBV surface antigen (HBsAg) or HBV core antibody (HBcAb) before chemotherapy, and 1850 patients (15.5%) had both HBsAg and HBcAb tested before chemotherapy. 8.4% were exposed to HBV, and 0.9% had chronic HBV infection (both HBsAg/HBcAb positive). Patients with hematologic tumor were more often screened than with solid tumor (55.6 vs. 8.3%, p < 0.001). Patients receiving chemotherapy with higher HBV reactivation risk had higher yet suboptimal HBV screening rate (41.1% B-depleting agents, 21.5% anthracycline, 14.9% steroid, 64.7% anti-TNF alpha and 18.6% other chemotherapy, p < 0.001). Patients with age ≥ 50 years (old 16.2% vs. young 23.9%, p < 0.001) and Asian ethnicity (Asian 13.6 vs. Caucasian 16.6%, p < 0.001) were screened less for HBV despite higher prevalence of HBV exposure (old 9.3% vs. young 4.3%, p < 0.001 and Asian 27.8% vs. Caucasian 6.4%, p < 0.001). Patients receiving chemotherapy in community oncology clinics were less screened versus community teaching hospitals or university hospital (12.7 vs. 19.1 vs. 19.7%, p < 0.001), despite similar prevalence of HBV infection. On multivariate analysis, receiving chemotherapy at a community oncology clinic [odds ratio (OR) 0.57, 95% confidence interval (CI) 0.45-0.72, p < 0.001] was independently associated with less HBV screening compared to receiving chemotherapy at a university or community teaching hospital. CONCLUSION HBV screening among patients undergoing cancer chemotherapy was suboptimal and less commonly performed in community oncology clinics compared to teaching hospitals.
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Affiliation(s)
- Ye Eun Kwak
- Department of Internal Medicine, Yale New Haven Health, Bridgeport Hospital, 267 Grant St, Bridgeport, CT, 06614, USA
| | - Stacy M Stein
- Department of Internal Medicine, Section of Medical Oncology and Smilow Cancer Center, Yale University School of Medicine, 35 Park St, Ste North Pavillion 8, New Haven, CT, 06511, USA
| | - Joseph K Lim
- Department of Internal Medicine, Section of Digestive Diseases and Yale Liver Center, Yale University School of Medicine, 333 Cedar Street, LMP 1080, New Haven, CT, 06520-8019, USA.
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48
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Ogawa E, Furusyo N, Murata M, Toyoda K, Hayashi T, Ura K. Potential risk of HBV reactivation in patients with resolved HBV infection undergoing direct-acting antiviral treatment for HCV. Liver Int 2018; 38:76-83. [PMID: 28618152 DOI: 10.1111/liv.13496] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2017] [Accepted: 06/07/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS Despite a known risk of hepatitis B virus (HBV) reactivation during direct-acting antiviral (DAA) treatment for patients with hepatitis C virus (HCV)-HBV coinfection, it remains unclear whether patients with past HBV infection are at risk for reactivation. This study evaluated the risk of HBV reactivation during treatment with sofosbuvir (SOF)-based regimens, focusing on patients with resolved HBV infection. METHODS This study analyzes the data of 183 consecutive patients treated with SOF-based regimens. From these patients, 63 with resolved HBV infection (negative for hepatitis B surface antigen [HBsAg] and undetectable HBV DNA but positive for hepatitis B core antibody) were eligible for this study. HBV reactivation was defined as a quantifiable HBV DNA level >20 IU/mL. RESULTS Among the patients antibody to HBsAg (anti-HBs) positive (10-500 mIU/mL) (n = 30), the titre of anti-HBs was significantly decreased with time, as shown by the results of repeated-measures analysis of variance (P = .0029). Overall, four patients (6.3%) with resolved HBV infection came to have detectable HBV DNA during treatment, including one who had HBV reactivation at week 4 (HBV DNA 80 IU/mL). However, none developed hepatic failure. Among four patients who had detectable HBV DNA during treatment, all were negative or had very low-titre (<20 mIU/mL) anti-HBs at baseline. CONCLUSIONS The titre of anti-HBs was significantly decreased from the early stage of DAA treatment. Chronic hepatitis C patients with resolved HBV infection and negative or very low-titre anti-HBs at baseline are at risk for having detectable HBV DNA transiently during treatment.
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Affiliation(s)
- Eiichi Ogawa
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Norihiro Furusyo
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Masayuki Murata
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Kazuhiro Toyoda
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Takeo Hayashi
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Kazuya Ura
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
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Long KR, Lomonosova E, Li Q, Ponzar NL, Villa JA, Touchette E, Rapp S, Liley RM, Murelli RP, Grigoryan A, Buller RM, Wilson L, Bial J, Sagartz JE, Tavis JE. Efficacy of hepatitis B virus ribonuclease H inhibitors, a new class of replication antagonists, in FRG human liver chimeric mice. Antiviral Res 2018; 149:41-47. [PMID: 29129708 PMCID: PMC5743599 DOI: 10.1016/j.antiviral.2017.11.008] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2017] [Revised: 09/11/2017] [Accepted: 11/07/2017] [Indexed: 12/20/2022]
Abstract
Chronic hepatitis B virus infection cannot be cured by current therapies, so new treatments are urgently needed. We recently identified novel inhibitors of the hepatitis B virus ribonuclease H that suppress viral replication in cell culture. Here, we employed immunodeficient FRG KO mice whose livers had been engrafted with primary human hepatocytes to ask whether ribonuclease H inhibitors can suppress hepatitis B virus replication in vivo. Humanized FRG KO mice infected with hepatitis B virus were treated for two weeks with the ribonuclease H inhibitors #110, an α-hydroxytropolone, and #208, an N-hydroxypyridinedione. Hepatitis B virus viral titers and S and e antigen plasma levels were measured. Treatment with #110 and #208 caused significant reductions in plasma viremia without affecting hepatitis B virus S or e antigen levels, and viral titers rebounded following treatment cessation. This is the expected pattern for inhibitors of viral DNA synthesis. Compound #208 suppressed viral titers of both hepatitis B virus genotype A and C isolates. These data indicate that Hepatitis B virus replication can be suppressed during infection in an animal by inhibiting the viral ribonuclease H, validating the ribonuclease H as a novel target for antiviral drug development.
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Affiliation(s)
- Kelly R Long
- Seventh Wave Laboratories LLC, 19 Worthington Access Drive, Maryland Heights, MO 63043, USA.
| | - Elena Lomonosova
- Department of Molecular Microbiology and Immunology & the Saint Louis University Liver Center, Saint Louis University School of Medicine, 1100 S. Grand Blvd., St. Louis, MO 63104, USA.
| | - Qilan Li
- Department of Molecular Microbiology and Immunology & the Saint Louis University Liver Center, Saint Louis University School of Medicine, 1100 S. Grand Blvd., St. Louis, MO 63104, USA.
| | - Nathan L Ponzar
- Department of Molecular Microbiology and Immunology & the Saint Louis University Liver Center, Saint Louis University School of Medicine, 1100 S. Grand Blvd., St. Louis, MO 63104, USA.
| | - Juan A Villa
- Department of Molecular Microbiology and Immunology & the Saint Louis University Liver Center, Saint Louis University School of Medicine, 1100 S. Grand Blvd., St. Louis, MO 63104, USA.
| | - Erin Touchette
- Seventh Wave Laboratories LLC, 19 Worthington Access Drive, Maryland Heights, MO 63043, USA.
| | - Stephen Rapp
- Seventh Wave Laboratories LLC, 19 Worthington Access Drive, Maryland Heights, MO 63043, USA.
| | - R Matt Liley
- Seventh Wave Laboratories LLC, 19 Worthington Access Drive, Maryland Heights, MO 63043, USA.
| | - Ryan P Murelli
- Brookyln College & PhD Program in Chemistry at the Graduate Center of the City University of New York, NY 11210, USA.
| | - Alexandre Grigoryan
- Brookyln College & PhD Program in Chemistry at the Graduate Center of the City University of New York, NY 11210, USA.
| | - R Mark Buller
- Department of Molecular Microbiology and Immunology & the Saint Louis University Liver Center, Saint Louis University School of Medicine, 1100 S. Grand Blvd., St. Louis, MO 63104, USA
| | - Lisa Wilson
- Yecuris Corporation, P.O. Box 4645, Tualatin, OR 97062, USA.
| | - John Bial
- Yecuris Corporation, P.O. Box 4645, Tualatin, OR 97062, USA.
| | - John E Sagartz
- Seventh Wave Laboratories LLC, 19 Worthington Access Drive, Maryland Heights, MO 63043, USA.
| | - John E Tavis
- Department of Molecular Microbiology and Immunology & the Saint Louis University Liver Center, Saint Louis University School of Medicine, 1100 S. Grand Blvd., St. Louis, MO 63104, USA.
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Xu Z, Dai W, Wu YT, Arshad B, Li X, Wu H, Chen HR, Wu KN, Kong LQ. Prophylactic effect of lamivudine on chemotherapy-induced hepatitis B virus reactivation in patients with solid tumour: A meta-analysis. Eur J Cancer Care (Engl) 2017; 27:e12799. [PMID: 29265535 DOI: 10.1111/ecc.12799] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/21/2017] [Indexed: 01/03/2023]
Abstract
Hepatitis B virus (HBV) reactivation is a remarkable risk during the chemotherapy for solid tumour patients. Nucleos(t)ide analogues (NAs) are recommended as prophylaxis for the reactivation of HBV infection in some cancer patients prior to systemic chemotherapy. Therefore, we performed a meta-analysis aiming to determine the efficacy of prophylactic lamivudine on prevention of HBV reactivation and its related negative outcomes among solid tumour patients with chronic HBV infection receiving systemic chemotherapy. The primary outcome was HBV reactivation, and the secondary outcomes were HBV-related hepatitis, chemotherapy disruption, mortality and tyrosine-methio-nine-aspartate-aspartate (YMDD) mutations. Twelve original researches involving 1,101 patients were analysed in this study. The relative risk of HBV reactivation in patients with lamivudine prophylaxis was significantly lower than that without prophylaxis (RR = 0.17, 95% CL: 0.10-0.29, p < .00001). Lamivudine prophylaxis reduced the relative risk of hepatitis (p < .00001), chemotherapy disruptions (p = .01) and mortality (p = .08) due to HBV reactivation. Lamivudine prophylaxis is effective in reducing HBV reactivation and its related negative outcomes, such as hepatitis and chemotherapy disruption and mortality among chemotherapeutic solid tumour patients with chronic HBV infection. Future studies should lay more emphasis on the early HBV screening, mode of treatment and duration of NAs prophylaxis among solid tumour patients receiving chemotherapy.
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Affiliation(s)
- Z Xu
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - W Dai
- Department of Orthopaedics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Y-T Wu
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - B Arshad
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - X Li
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - H Wu
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - H-R Chen
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - K-N Wu
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - L-Q Kong
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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