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Qiu C, Yu C, Yang L, Liu S, Zhang Q, Jia S, Wang W, Jin Z, Yu D. The neutrophil-lymphocyte ratio as a risk factor for all-cause mortality among individuals with resolved HBV infection: evidence from the NHANES 1999-2018. Front Public Health 2025; 12:1493439. [PMID: 39882122 PMCID: PMC11775152 DOI: 10.3389/fpubh.2024.1493439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Accepted: 12/23/2024] [Indexed: 01/31/2025] Open
Abstract
Background Inflammation is a critical component in the process of resolved hepatitis B virus (HBV) infection. The neutrophil-to-lymphocyte ratio (NLR) serves as a sensitive indicator of systemic inflammation and immune activation. Our study aimed to investigate the correlation between elevated NLR levels and the risk of all-cause mortality in patients with resolved HBV infection. Additionally, we evaluated the potential mediating effect of diabetes mellitus (DM) on this correlation. Methods Our study enrolled 1,146 adult patients with resolved HBV infection from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018. We utilized the Restricted Cubic Splines (RCS) and Maximum Selection Rank Statistical Method (MSRSM) to analyze the relationship between the NLR and the risk of all-cause mortality. The impact of NLR was evaluated using a weighted multivariate Cox regression model, and the model's predictive accuracy was assessed using time-dependent Receiver Operating Characteristic (ROC) curves. An intermediary analysis was conducted to explore the potential influence of DM on the observed relationship. Results During follow-up period of 103.54 ± 4.90 months, we recorded 207 deaths among the study participants. The analysis using the RCS method revealed a significant positive correlation between the NLR and the risk of all-cause mortality. Those with elevated NLR levels faced a substantially higher mortality risk compared to those with lower levels, as indicated by a Hazard Ratio (HR) of 1.84, with a 95% Confidence Interval (CI) of 1.17 to 2.89 (p < 0.05). The predictive accuracy of the model was substantial, as evidenced by the Area Under the Curve (AUC) for ROC curves at 3, 5, and 10 years, which were 0.873, 0.870, and 0.862, respectively. Furthermore, mediation analysis indicated that DM significantly influenced the relationship between the NLR and mortality, with a mediation effect of 6.57% (95% Confidence Interval [CI]: 0.64 to 15%; p = 0.02). Conclusion Elevated NLR is significantly associated with an increased risk of all-cause mortality in patients with resolved HBV infection. Concurrently, DM acts as a partial mediator of this association.
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Affiliation(s)
- Chen Qiu
- Digestive Disease Center, Department of Hepatopancreatobiliary Medicine, The Second Hospital, Jilin University, Changchun, Jilin, China
| | - Chaojie Yu
- Digestive Disease Center, Department of Hepatopancreatobiliary Medicine, The Second Hospital, Jilin University, Changchun, Jilin, China
| | - Lanlan Yang
- Digestive Disease Center, Department of Hepatopancreatobiliary Medicine, The Second Hospital, Jilin University, Changchun, Jilin, China
| | - Siqi Liu
- Digestive Disease Center, Department of Hepatopancreatobiliary Medicine, The Second Hospital, Jilin University, Changchun, Jilin, China
| | - Qian Zhang
- Digestive Disease Center, Department of Hepatopancreatobiliary Medicine, The Second Hospital, Jilin University, Changchun, Jilin, China
| | - Shengnan Jia
- Digestive Disease Center, Department of Hepatopancreatobiliary Medicine, The Second Hospital, Jilin University, Changchun, Jilin, China
| | - Wenrui Wang
- Digestive Disease Center, Department of Hepatopancreatobiliary Medicine, The Second Hospital, Jilin University, Changchun, Jilin, China
| | - Zhenjing Jin
- Digestive Disease Center, Department of Hepatopancreatobiliary Medicine, The Second Hospital, Jilin University, Changchun, Jilin, China
| | - Dongdong Yu
- Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
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Kopacz A, Kubicka-Russel D, Liszewski G, Sulkowska E, Chrzanowska A, Zwolińska P, Noceń E, Potępa A, Łętowska M, Grabarczyk P. Hepatitis B Virus in Polish Blood Donors in the Period 2005-2019-Significant Changes in Epidemiology and Demographic Characteristics of Infected Donors. Viruses 2025; 17:60. [PMID: 39861849 PMCID: PMC11768870 DOI: 10.3390/v17010060] [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: 11/13/2024] [Revised: 12/20/2024] [Accepted: 12/24/2024] [Indexed: 01/27/2025] Open
Abstract
In the 1980s, Poland was a medium-endemic country, with one of the highest incidences of hepatitis B in Europe (45/105 inhabitants). Pursuant to the WHO guidelines, obligatory vaccination was introduced in 1994-1996 (as a part of hepatitis B prophylaxis for newborns), and in 2000-2011, all 14-year-olds were vaccinated. To prevent transfusion-transmitted HBV infection (TT-HBV), since the 1970s, each donation has been tested for HBsAg and, since 2005, additionally for the presence of HBV DNA. Based on the data from the Blood Transfusion Centers, changes in HBV detection in Polish blood donors were analyzed, starting from the introduction of mandatory NAT screening until 2019. During the period under analysis, a total of 11,625 HBV-infected donors were identified: 97.95% were seropositive (confirmed HBsAg) and 2.05% were seronegative (NAT yields). The detection frequency for both categories of infections was significantly (p = 0.05) higher for men than for women (Residual Risk RR = 1.4 and RR = 2.63, respectively). Seropositive infections were detected more frequently (p < 0.05) in first-time donors than in repeat donors (RR = 360), while no significant differences were observed in the category of seronegative infections. A downward trend in HBsAg detection was observed in both first-time and repeat donors (Spearman's coefficient R = -0.98 and R = -0.90, respectively). The frequency of HBsAg in first-time donors decreased 5-fold, and, in repeat donors, 30-fold. In both subpopulations, the largest decrease occurred in the age group ≤ 20 years (i.e., donors born between 1985 and 2001). The incidence of window period (WP) infections in the repeat donor group demonstrated a downward trend (R = -0.54, p < 0.05), and in the first-time donor group, no significant trend was recorded. For occult hepatitis B infection (OBI), no significant trend was observed in either donor subpopulation. WP infections were detected significantly more often in donors aged 21-50 years than in donors ≤20 years, most often in the 41-50 age group. The frequency of OBI increased with donor age and was the highest in the 51-60 age group. A spectacular decrease in the frequency of HBsAg(+) infections was observed in current study, indicating the effectiveness of the hepatitis prevention strategy applied in Poland. We expect that the improvement in the epidemiological situation among blood donors causes a reduction in the risk of TT-HBV. Confirmation of this hypothesis by the analysis of residual risk should be a subject of further studies.
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Affiliation(s)
- Aneta Kopacz
- Department of Virology, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, Poland; (D.K.-R.); (G.L.); (E.S.); (A.C.); (P.Z.); (E.N.); (A.P.); (P.G.)
| | - Dorota Kubicka-Russel
- Department of Virology, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, Poland; (D.K.-R.); (G.L.); (E.S.); (A.C.); (P.Z.); (E.N.); (A.P.); (P.G.)
| | - Grzegorz Liszewski
- Department of Virology, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, Poland; (D.K.-R.); (G.L.); (E.S.); (A.C.); (P.Z.); (E.N.); (A.P.); (P.G.)
| | - Ewa Sulkowska
- Department of Virology, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, Poland; (D.K.-R.); (G.L.); (E.S.); (A.C.); (P.Z.); (E.N.); (A.P.); (P.G.)
| | - Anna Chrzanowska
- Department of Virology, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, Poland; (D.K.-R.); (G.L.); (E.S.); (A.C.); (P.Z.); (E.N.); (A.P.); (P.G.)
| | - Paulina Zwolińska
- Department of Virology, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, Poland; (D.K.-R.); (G.L.); (E.S.); (A.C.); (P.Z.); (E.N.); (A.P.); (P.G.)
| | - Ewa Noceń
- Department of Virology, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, Poland; (D.K.-R.); (G.L.); (E.S.); (A.C.); (P.Z.); (E.N.); (A.P.); (P.G.)
| | - Anna Potępa
- Department of Virology, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, Poland; (D.K.-R.); (G.L.); (E.S.); (A.C.); (P.Z.); (E.N.); (A.P.); (P.G.)
| | - Magdalena Łętowska
- Department of Transfusion Medicine, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, Poland;
| | - Piotr Grabarczyk
- Department of Virology, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, Poland; (D.K.-R.); (G.L.); (E.S.); (A.C.); (P.Z.); (E.N.); (A.P.); (P.G.)
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Huang SW, Long H, Huang JQ. Surveillance Following Hepatitis B Surface Antigen Loss: An Issue Requiring Attention. Pathogens 2024; 14:8. [PMID: 39860969 PMCID: PMC11768139 DOI: 10.3390/pathogens14010008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 12/25/2024] [Accepted: 12/27/2024] [Indexed: 01/27/2025] Open
Abstract
Due to the lack of agents that directly target covalently closed circular DNA and integrated HBV DNA in hepatocytes, achieving a complete cure for chronic hepatitis B (CHB) remains challenging. The latest guidelines recommend (hepatitis B surface antigen) HBsAg loss as the ideal treatment target for improving liver function, histopathology, and long-term prognosis. However, even after HBsAg loss, hepatitis B virus can persist, with a risk of recurrence, reactivation, cirrhosis, and hepatocellular carcinoma. Therefore, follow-up and surveillance are still necessary. With increasing treatment options available for achieving HBsAg loss in patients with CHB, developing effective surveillance strategies has become crucial. Recent studies on outcomes following HBsAg loss provide new insights for refining current surveillance strategies, though further improvement is needed through long-term observation and follow-up.
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Affiliation(s)
- Shuai-Wen Huang
- Department of General Practice, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China;
- Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China;
- Department of Nutrition, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China
| | - Hong Long
- Department of General Practice, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China;
| | - Jia-Quan Huang
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China;
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Su CH, Chen CY, Liu CT, Yang YH, Wu PC. Hepatitis and Hepatitis B Virus Reactivation in Everolimus-Treated Solid Tumor Patients: A Focus on HBV-Endemic Areas. Cancers (Basel) 2024; 16:3997. [PMID: 39682184 DOI: 10.3390/cancers16233997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Revised: 11/06/2024] [Accepted: 11/26/2024] [Indexed: 12/18/2024] Open
Abstract
BACKGROUND Everolimus is approved for treating breast, renal, and pancreatic neuroendocrine cancers but carries the risk of hepatitis B virus (HBV) reactivation (HBVr) and hepatitis. However, data on HBVr in everolimus-treated patients are limited. This study evaluates the risk of hepatitis and HBVr in cancer patients with current or past HBV infection. METHODS This retrospective study analyzed patients prescribed everolimus between 1 January 2011 and 31 May 2022, using a private healthcare system database in Taiwan. Patients with HBsAg positivity or HBsAg negativity and anti-HBs or anti-HBc results were included. The cumulative incidence function and risk of hepatitis from a competing risk model, which estimates Fine-Gray subdistribution hazard (SDH), were analyzed across different HBV serological subgroups. The risk of hepatitis B reactivation was also calculated. RESULTS Of 377 patients, 45% (36/80) of HBsAg-positive and 0.67% (2/297) of HBsAg-negative patients received nucleos(t)ide analogues (NUCs) prophylaxis. Hepatitis occurred in 28.75% of HBsAg-positive and 17.85% of HBsAg-negative patients. Baseline HBsAg positivity and exemestane use increased hepatitis risk. HBVr occurred in 11.36% (5/44) of HBsAg-positive patients without NUCs and 5.56% (2/36) with prophylaxis. Two HBsAg-negative, anti-HBc-positive patients developed severe HBVr-related hepatitis. CONCLUSION Hepatitis occurred in 28.75% of HBsAg-positive and 17.85% of HBsAg-negative patients on everolimus. HBVr was common in HBsAg-positive patients but rare in HBsAg-negative individuals. HBV screening and liver function monitoring are critical for patients with past or current HBV infection receiving everolimus, especially in endemic areas.
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Affiliation(s)
- Chien-Hao Su
- School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Department of Pharmacy, Chang Gung Memorial Hospital, Chiayi 613, Taiwan
| | - Chung-Yu Chen
- School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Chien-Ting Liu
- Division of Hematology-Oncology, Department of Internal Medicine, College of Medicine, Chang Gung University, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Yi-Hsin Yang
- National Institute of Cancer Research, National Health Research Institutes, No. 367, Sheng-Li Rd., North District, Tainan 704, Taiwan
| | - Pao-Chu Wu
- School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
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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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Deepan N, Maung ST, Decharatanachart P, Chaiteerakij R. Hepatitis B Virus Reactivation in Cancer Patients Receiving Chemotherapy-A Systematic Review and Meta-Analysis. Semin Oncol 2024; 51:123-134. [PMID: 39537474 DOI: 10.1053/j.seminoncol.2024.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 07/14/2024] [Accepted: 08/04/2024] [Indexed: 11/16/2024]
Abstract
Hepatitis B virus (HBV) reactivation is a critical concern for patients with a diagnosis of cancer receiving chemotherapy worldwide. Our aim was to assess the rate of HBV reactivation during chemotherapy globally. We systematically reviewed PubMed, Embase, Scopus, and Google Scholar databases for chemotherapy-related HBV reactivation studies from inception until July 2023. A random-effects model was used to estimate the pooled reactivation rate. Total 86 studies involving 21,297 patients were included, comprising 62 and 24 studies from Eastern and Western regions. Pooled results indicated a 9% reactivation rate (95%CI: 7%-13%, I2 = 95%). Reactivation rates were 10% (95%CI: 7%-14%, I2 = 92%) for hematological malignancies and 5% (95%CI: 3%-9%, I2 = 94%) for solid tumors. Presence of HBV DNA, HBeAg, and HBsAg were correlated with reactivation rates of 29% (95%CI: 10%-60%, I2 = 91%), 23% (95%CI: 14%-36%, I2 = 78%), and 15% (95%CI: 11%-20%, I2 = 90%), respectively. For patients with positive anti-HBe Ab, anti-HBc, and anti-HBs Ab serology, pooled reactivation rates were 7% (95%CI: 3%-14%, I2 = 81%), 4% (95%CI: 3%-7%, I2 = 85%), and 3% (95%CI: 2%-6%, I2 = 80%), respectively. With antiviral prophylaxis, reactivation rates were 1% (95%CI: 0%-17%, I2 = 59%), 1% (95%CI: 0%-5%, I2 = 0%), 4% (95%CI: 2%-9%, I2 = 85%), and 6% (95%CI: 3%-12%, I2 = 32%) for patients receiving tenofovir, entecavir, lamivudine, and telbivudine, respectively. Patients with a diagnosis of cancer undergoing chemotherapy face increased risk of HBV reactivation. This analysis raises public awareness and serves as a resource for future clinical trials.
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Affiliation(s)
- Natee Deepan
- Division of Academic Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Soe Thiha Maung
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | | | - Roongruedee Chaiteerakij
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
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Salcher-Konrad M, Nguyen M, Savović J, Higgins JPT, Naci H. Treatment Effects in Randomized and Nonrandomized Studies of Pharmacological Interventions: A Meta-Analysis. JAMA Netw Open 2024; 7:e2436230. [PMID: 39331390 PMCID: PMC11437387 DOI: 10.1001/jamanetworkopen.2024.36230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Accepted: 08/04/2024] [Indexed: 09/28/2024] Open
Abstract
Importance Randomized clinical trials (RCTs) are widely regarded as the methodological benchmark for assessing clinical efficacy and safety of health interventions. There is growing interest in using nonrandomized studies to assess efficacy and safety of new drugs. Objective To determine how treatment effects for the same drug compare when evaluated in nonrandomized vs randomized studies. Data Sources Meta-analyses published between 2009 and 2018 were identified in MEDLINE via PubMed and the Cochrane Database of Systematic Reviews. Data analysis was conducted from October 2019 to July 2024. Study Selection Meta-analyses of pharmacological interventions were eligible for inclusion if both randomized and nonrandomized studies contributed to a single meta-analytic estimate. Data Extraction and Synthesis For this meta-analysis using a meta-epidemiological framework, separate summary effect size estimates were calculated for nonrandomized and randomized studies within each meta-analysis using a random-effects model and then these estimates were compared. The reporting of this study followed the Guidelines for Reporting Meta-Epidemiological Methodology Research and relevant portions of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline. Main Outcome and Measures The primary outcome was discrepancies in treatment effects obtained from nonrandomized and randomized studies, as measured by the proportion of meta-analyses where the 2 study types disagreed about the direction or magnitude of effect, disagreed beyond chance about the effect size estimate, and the summary ratio of odds ratios (ROR) obtained from nonrandomized vs randomized studies combined across all meta-analyses. Results A total of 346 meta-analyses with 2746 studies were included. Statistical conclusions about drug benefits and harms were different for 130 of 346 meta-analyses (37.6%) when focusing solely on either nonrandomized or randomized studies. Disagreements were beyond chance for 54 meta-analyses (15.6%). Across all meta-analyses, there was no strong evidence of consistent differences in treatment effects obtained from nonrandomized vs randomized studies (summary ROR, 0.95; 95% credible interval [CrI], 0.89-1.02). Compared with experimental nonrandomized studies, randomized studies produced on average a 19% smaller treatment effect (ROR, 0.81; 95% CrI, 0.68-0.97). There was increased heterogeneity in effect size estimates obtained from nonrandomized compared with randomized studies. Conclusions and Relevance In this meta-analysis of treatment effects of pharmacological interventions obtained from randomized and nonrandomized studies, there was no overall difference in effect size estimates between study types on average, but nonrandomized studies both overestimated and underestimated treatment effects observed in randomized studies and introduced additional uncertainty. These findings suggest that relying on nonrandomized studies as substitutes for RCTs may introduce additional uncertainty about the therapeutic effects of new drugs.
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Affiliation(s)
- Maximilian Salcher-Konrad
- Department of Health Policy, London School of Economics and Political Science, London, United Kingdom
- World Health Organization Collaborating Centre for Pharmaceutical Pricing and Reimbursement Policies, Pharmacoeconomics Department, Gesundheit Österreich GmbH (GÖG)/Austrian National Public Health Institute, Vienna, Austria
| | - Mary Nguyen
- Department of Health Policy, London School of Economics and Political Science, London, United Kingdom
- Department of Family and Community Medicine, University of California, San Francisco
| | - Jelena Savović
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
- National Institute for Health and Care Research Applied Research Collaboration West, University Hospitals Bristol and Weston National Health Service Foundation Trust, Bristol, United Kingdom
| | - Julian P. T. Higgins
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
- National Institute for Health and Care Research Applied Research Collaboration West, University Hospitals Bristol and Weston National Health Service Foundation Trust, Bristol, United Kingdom
| | - Huseyin Naci
- Department of Health Policy, London School of Economics and Political Science, London, United Kingdom
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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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9
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Maung ST, Deepan N, Decharatanachart P, Chaiteerakij R. Screening for viral hepatitis B infection in cancer patients before receiving chemotherapy - A systematic review and meta-analysis. Asia Pac J Clin Oncol 2024; 20:335-345. [PMID: 38512893 DOI: 10.1111/ajco.14055] [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: 12/29/2023] [Revised: 02/08/2024] [Accepted: 03/03/2024] [Indexed: 03/23/2024]
Abstract
AIM We conducted a systematic review and meta-analysis to assess the hepatitis B virus (HBV) screening rate in cancer patients before systemic chemotherapy, aiming to identify those needing antiviral prophylaxis for HBV reactivation. METHODS We searched PubMed, Embase, Scopus, and Google Scholar for relevant studies. The pooled screening rate was estimated using a random effects model. Subgroup analyses were conducted based on malignancy types, chemotherapy regimens, study period, and HBV endemic regions. RESULTS The meta-analysis included 29 studies from various endemic regions (19 low-endemic, three lower intermediate-endemic, and seven higher intermediate-endemic). These studies encompassed hematologic malignancies (n = 10), solid-organ tumors (n = 4), and combinations (n = 15). Seven studies used rituximab-containing regimens, four did not, and the remaining 11 did not specify chemotherapy regimens. The pooled screening rate was 57% (95% confidence interval [95%CI]: 46%-68%, I2 = 100%). Over time, screening rates improved from 37% (95%CI: 23%-53%) in 2006-2010 to 68% (54%-80%) in 2011-2015 and 69% (48%-84%) in 2016-2020. Screening rates were highest at 89% (74%-96%) in high endemic countries, followed by 60% (45-73%) in lower-intermediate and 49% (34-64%) in low-endemic countries. Patients with hematological malignancies had a higher screening rate than those with solid organ tumors, 65% (55%-74%) versus 37% (21%-57%), respectively. A screening rate was higher in patients receiving rituximab-containing chemotherapy than non-rituximab regimens, 68% (55%-79%) versus 45% (27%-65%). CONCLUSION Despite existing guidelines, pre-chemotherapy HBV screening rate remains unsatisfactory, with substantial heterogeneous rates globally. These findings underscore the need for effective strategies to align practices with clinical guidelines.
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Affiliation(s)
- Soe Thiha Maung
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
- Ma Har Myaing Hospital, Yangon, Myanmar
| | - Natee Deepan
- Division of Academic Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | | | - Roongruedee Chaiteerakij
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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10
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Yanagisawa Y, Imai S, Kizaki H, Hori S. A cross-sectional survey of hepatitis B virus screening in patients who received immunosuppressive therapy for rheumatoid arthritis in Japan. J Pharm Health Care Sci 2024; 10:18. [PMID: 38637884 PMCID: PMC11025209 DOI: 10.1186/s40780-024-00339-9] [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: 01/16/2024] [Accepted: 04/15/2024] [Indexed: 04/20/2024] Open
Abstract
BACKGROUND Patients with a history of hepatitis B virus (HBV) infection who are receiving immunosuppressive therapy are at risk of HBV reactivation and disease. Therefore, HBV screening is required prior to administering antirheumatic drugs with immunosuppressive effects. This study aimed to determine the status of hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), and hepatitis B surface antibody (HBsAb) screening prior to the initiation of drug therapy, including new antirheumatic drugs, in patients with rheumatoid arthritis. METHODS This retrospective cross-sectional study used data from April 2014 to August 2022 from the Japanese hospital-based administrative claims database. The inclusion criteria were rheumatoid arthritis and first prescription date of antirheumatic drugs. RESULTS A total of 82,282 patients with rheumatoid arthritis who were first prescribed antirheumatic drugs between April 2016 and August 2022 were included. Of the eligible patients, 9.7% (n=7,959) were screened for all HBV (HBsAg, HBsAb, and HbcAb) within 12 months prior to the date of initial prescription. The HBsAg test was performed in 30.0% (n=24,700), HBsAb test in 11.8% (n=9,717), and HBcAb test in 13.1% (n=10,824) of patients. The proportion of patients screened for HBV infection has been increasing since 2018; however, the proportion of patients screened for rheumatoid arthritis remains low. CONCLUSIONS Our findings suggest that HBV screening may be insufficient in patients who received antirheumatic drugs. With the increasing use of new immunosuppressive antirheumatic drugs, including biological agents, healthcare providers should understand the risk of HBV reactivation and conduct appropriate screening.
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Affiliation(s)
- Yuki Yanagisawa
- Division of Drug Informatics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan
| | - Shungo Imai
- Division of Drug Informatics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan.
| | - Hayato Kizaki
- Division of Drug Informatics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan
| | - Satoko Hori
- Division of Drug Informatics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan
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11
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Tan R, Zhu X, Sun Y, Yang S, Peng C, Feng X, Chen Z, Yimamu Y, Liao G, Yang L. The association of HBV infection and head and neck cancer: a systematic review and meta-analysis. BMC Cancer 2024; 24:225. [PMID: 38365701 PMCID: PMC10874002 DOI: 10.1186/s12885-024-11967-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Accepted: 02/06/2024] [Indexed: 02/18/2024] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) infections is an important public health problem worldwide and closely affect extrahepatic cancer. Several recent studies have investigated the relationship between HBV infection and head and neck cancer (HNC), but their findings were inconsistent.In order to address the limitations of small sample sizes, we conducted a meta-analysis to assess the association between HBV and HNC. METHODS We systematically searched PubMed, Web of Science, Embase, Scopus, Cochrane Library, and China National Knowledge Infrastructure from inception to August 2023. Original articles published as a case-control or cohort study were included. HBV infection was identified by HBsAg, HBV DNA or ICD codes. Review articles, meeting abstracts, case reports, communications, editorials and letters were excluded, as were studies in a language other than English or Chinese. According to the MOOSE guidelines, frequencies reported for all dichotomous variables were extracted by two reviewers independently. Similarly, the outcomes of OR, RR or HR, and 95% CIs after adjusting for age and gender were collected. RESULTS Thirteen relevant studies and 58,006 patients with HNC were included. Our analysis revealed a positive correlation between HBV and HNC (OR = 1.50; 95% CI: 1.28-1.77). After adjusting for age and gender, the similar result (OR = 1.30; 95% CI: 1.10-1.54) was obtained. Subgroup analysis further demonstrated a significant association between HBV infection and oral cancer (OR = 1.24; 95% CI: 1.05-1.47), as well as nasopharyngeal carcinoma (OR = 1.41; 95% CI: 1.26-1.58). However, due to the limited number of studies included, the statistical significance was not reached for cancer of the oropharynx (OR = 1.82; 95% CI: 0.66-5.05), hypopharynx (OR = 1.33; 95% CI: 0.88-2.00), and larynx (OR = 1.25; 95% CI: 0.69-2.24) after adjusting for age and gender. When excluding the interference of HIV/HCV, smoking and alcohol use, the final outcome (OR = 1.17; 95% CI: 1.01-1.35) got the same conclusion. CONCLUSIONS Our study confirmed a positive relationship between HNC, specifically oral cancer and nasopharyngeal carcinoma, and HBV infection. However, further investigation is required at the molecular level to gather additional evidence in HNC.
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Affiliation(s)
- Rukeng Tan
- Hospital of Stomatology, Sun Yat-sen University, 56th Lingyuanxi Road, 510055, Guangzhou, Guangdong, China
- Guangdong Province Key Laboratory of Stomatology, No. 74, 2nd Zhongshan Road, 510080, Guangzhou, Guangdong, China
| | - Xinyu Zhu
- Hospital of Stomatology, Sun Yat-sen University, 56th Lingyuanxi Road, 510055, Guangzhou, Guangdong, China
- Guangdong Province Key Laboratory of Stomatology, No. 74, 2nd Zhongshan Road, 510080, Guangzhou, Guangdong, China
| | - Yutong Sun
- Hospital of Stomatology, Sun Yat-sen University, 56th Lingyuanxi Road, 510055, Guangzhou, Guangdong, China
- Guangdong Province Key Laboratory of Stomatology, No. 74, 2nd Zhongshan Road, 510080, Guangzhou, Guangdong, China
| | - Shihao Yang
- Hospital of Stomatology, Sun Yat-sen University, 56th Lingyuanxi Road, 510055, Guangzhou, Guangdong, China
- Guangdong Province Key Laboratory of Stomatology, No. 74, 2nd Zhongshan Road, 510080, Guangzhou, Guangdong, China
| | - Chao Peng
- Hospital of Stomatology, Sun Yat-sen University, 56th Lingyuanxi Road, 510055, Guangzhou, Guangdong, China
- Guangdong Province Key Laboratory of Stomatology, No. 74, 2nd Zhongshan Road, 510080, Guangzhou, Guangdong, China
| | - Xinkai Feng
- Hospital of Stomatology, Sun Yat-sen University, 56th Lingyuanxi Road, 510055, Guangzhou, Guangdong, China
- Guangdong Province Key Laboratory of Stomatology, No. 74, 2nd Zhongshan Road, 510080, Guangzhou, Guangdong, China
| | - Zengyu Chen
- Hospital of Stomatology, Sun Yat-sen University, 56th Lingyuanxi Road, 510055, Guangzhou, Guangdong, China
- Guangdong Province Key Laboratory of Stomatology, No. 74, 2nd Zhongshan Road, 510080, Guangzhou, Guangdong, China
| | - Yiliyaer Yimamu
- The First People's Hospital of Kashi Area, Xinjiang Uygur Autonomous Region, No.120, Yingbin Avenue, Kashi, People's Republic of China
| | - Guiqing Liao
- Hospital of Stomatology, Sun Yat-sen University, 56th Lingyuanxi Road, 510055, Guangzhou, Guangdong, China.
- Guangdong Province Key Laboratory of Stomatology, No. 74, 2nd Zhongshan Road, 510080, Guangzhou, Guangdong, China.
| | - Le Yang
- Hospital of Stomatology, Sun Yat-sen University, 56th Lingyuanxi Road, 510055, Guangzhou, Guangdong, China.
- Guangdong Province Key Laboratory of Stomatology, No. 74, 2nd Zhongshan Road, 510080, Guangzhou, Guangdong, China.
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12
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Mezzacappa C, Lim JK. Management of HBV reactivation: Challenges and opportunities. Clin Liver Dis (Hoboken) 2024; 23:e0143. [PMID: 38720793 PMCID: PMC11078521 DOI: 10.1097/cld.0000000000000143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Accepted: 01/03/2024] [Indexed: 05/12/2024] Open
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13
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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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14
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Wang YM, Luo SD, Wu CN, Wu SC, Chen WC, Yang YH, Chiu TJ. The Impact of Clinical Prognosis of Viral Hepatitis in Head and Neck Cancer Patients Receiving Concurrent Chemoradiotherapy. Biomedicines 2023; 11:2946. [PMID: 38001947 PMCID: PMC10669880 DOI: 10.3390/biomedicines11112946] [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: 09/21/2023] [Revised: 10/25/2023] [Accepted: 10/29/2023] [Indexed: 11/26/2023] Open
Abstract
This study evaluated the clinical characteristics of head and neck cancer (HNC) patients with hepatitis B (HBV) or hepatitis C (HCV) who underwent concurrent chemoradiotherapy (CCRT) and examined the prognostic impact of antiviral therapies. In a 19-year retrospective analysis of 8224 HNC patients treated with CCRT, 29.8% (2452) were diagnosed with HBV or HCV, of whom 714 received antiviral therapy. For non-metastatic HNC patients on CCRT, factors such as gender, Charlson Comorbidity Index (CCI), liver cirrhosis markers (Fibrosis-4, APRI), and initial tumor stage were significant determinants of their overall survival. However, the presence of HBV or HCV and the administration of antiviral treatments did not yield distinct survival outcomes. In summary, antiviral therapy for HBV or HCV did not affect the 5-year survival rates of non-metastatic HNC patients undergoing CCRT, while gender, tumor stage, CCI, and liver cirrhosis were notable prognostic indicators.
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Affiliation(s)
- Yu-Ming Wang
- Department of Radiation Oncology & Proton and Radiation Therapy Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan;
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; (S.-D.L.); (Y.-H.Y.)
| | - Sheng-Dean Luo
- Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; (C.-N.W.); (W.-C.C.)
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan District, Taoyuan 333, Taiwan;
| | - Ching-Nung Wu
- Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; (C.-N.W.); (W.-C.C.)
| | - Shao-Chun Wu
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan District, Taoyuan 333, Taiwan;
- Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Wei-Chih Chen
- Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; (C.-N.W.); (W.-C.C.)
| | - Yao-Hsu Yang
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; (S.-D.L.); (Y.-H.Y.)
- Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi 613, Taiwan
- Health Information and Epidemiology Laboratory of Chang Gung Memorial Hospital, Chiayi 613, Taiwan
| | - Tai-Jan Chiu
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan District, Taoyuan 333, Taiwan;
- Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
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15
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Hsu YC, Tseng CH, Kao JH. Safety considerations for withdrawal of nucleos(t)ide analogues in patients with chronic hepatitis B: First, do no harm. Clin Mol Hepatol 2023; 29:869-890. [PMID: 36916171 PMCID: PMC10577354 DOI: 10.3350/cmh.2022.0420] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Revised: 02/19/2023] [Accepted: 03/13/2023] [Indexed: 03/16/2023] Open
Abstract
Nucleos(t)ide analogues (NA) are widely used to treat hepatitis B virus (HBV) infection, but they cannot eradicate the virus and treatment duration can be lifelong if the endpoint is set at seroclearance of the hepatitis B surface antigen (HBsAg). As an alternative strategy, finite NA therapy without the prerequisite of HBsAg seroclearance has been proposed to allow treatment cessation in patients with sustained undetectable HBV viremia for two to three years. However, reactivation of viral replication almost always follows NA withdrawal. Whereas HBV reactivation might facilitate HBsAg seroclearance in some, it could lead to serious acute flare-ups in a certain proportion of patients. Occurrence and consequences of NA withdrawal flares are complicated with various factors involving the virus, host, and treatment. Accurate risk prediction for severe flares following NA cessation is essential to ensure patient safety. The risks of life-threatening flares in patients who discontinued NA according to the stopping rules of current guidelines or local reimbursement policies have recently been quantitatively estimated in large-scale studies, which also provided empirical evidence to help identify vulnerable patients at risk of devastating outcomes. Moreover, risk predictors were further explored and validated to hopefully aid in patient selection and management. In this narrative review with a focus on patient safety, we summarize and discuss current literature on the incidence of severe flares following NA cessation, risk stratification for candidate selection, rules of posttreatment monitoring, and indications for treatment resumption. We also share our thoughts on the limitations of existing knowledge and suggestions for future research.
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Affiliation(s)
- Yao-Chun Hsu
- Department of Medical Research, E-Da Hospital, Kaohsiung, Taiwan
- School of Medicine College of Medicine, I-Shou University, Kaohsiung, Taiwan
- Department of Internal Medicine, Fu-Jen Catholic University Hospital, New Taipei, Taiwan
- Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan
| | - Cheng-Hao Tseng
- School of Medicine College of Medicine, I-Shou University, Kaohsiung, Taiwan
- Division of Gastroenterology and Hepatology, E-Da Cancer Hospital, Kaohsiung, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine and Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
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16
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Xia Z, Zhang J, Chen W, Zhou H, Du D, Zhu K, Chen H, Meng J, Yang J. Hepatitis B reactivation in cancer patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis. Infect Dis Poverty 2023; 12:87. [PMID: 37736699 PMCID: PMC10515058 DOI: 10.1186/s40249-023-01128-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 08/10/2023] [Indexed: 09/23/2023] Open
Abstract
BACKGROUND Immunotherapy shows promise as a treatment option for various cancers. However, there is growing concern over potential complications from hepatitis B virus (HBV) reactivation after checkpoint blockade immunotherapy. Although most of the previous clinical trials on immune checkpoint inhibitors (ICIs) excluded patients with HBV, a few case reports and retrospective studies of HBV reactivation have been published. The aim of this study is to assess the risk of hepatitis B virus reactivation (HBVr) in patients receiving ICIs for advanced cancer. METHODS English and Chinese language literature published prior to April 30, 2023, was searched in PubMed, EMBASE, Web of Science, Cochrane, SinoMed, CNKI and Wanfang Data for studies reporting HBVr rates in cancer patients treated with ICIs. A pooled risk estimate was calculated for HBVr rates with 95% confidence intervals (CI). RESULTS Data from 34 studies including 7126 patients were retrieved and analyzed. The pooled HBVr rate in cancer patients treated with ICIs was 1.3% (I2 = 90.44%, 95% CI: 0.2-2.9%, P < 0.001). Subgroup analysis revealed that patients diagnosed with hepatocellular carcinoma (HCC), HBV carriers, and patients from Asian regions or in developing countries have a higher rate of HBVr. CONCLUSIONS Our meta-analysis demonstrated a low risk of HBVr in patients treated with ICIs for advanced cancer. ICI treatment may be safely used in patients with existing HBV infection or chronic hepatitis B, accompanied by regular monitoring and appropriate antiviral prophylaxis if necessary.
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Affiliation(s)
- Zhengzheng Xia
- Department of Pharmacy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Pharmacy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
| | - Jianyu Zhang
- Department of Pharmacy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
| | - Wenjun Chen
- Department of Pharmacy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
| | - Haiyan Zhou
- Department of Pharmacy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Di Du
- Department of Pharmacy, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Kongcai Zhu
- Department of Pharmacy, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Hui Chen
- Department of Pharmacy, Tangshan Central Hospital, Tangshan, China
| | - Jun Meng
- Department of Pharmacy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China.
| | - Jun Yang
- Department of Pharmacy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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Unger JM, Till C, Hwang JP, Arnold KB, Leblanc M, Hershman DL, Ramsey SD. Risk prediction of hepatitis B or C or HIV among newly diagnosed cancer patients. J Natl Cancer Inst 2023; 115:703-711. [PMID: 36946291 PMCID: PMC10248838 DOI: 10.1093/jnci/djad053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Revised: 03/10/2023] [Accepted: 03/16/2023] [Indexed: 03/23/2023] Open
Abstract
BACKGROUND Screening for viral infection in cancer patients is inconsistent. A mechanism to readily identify cancer patients at increased risk of existing or prior viral infection could enhance screening efforts while reducing costs. METHODS We identified factors associated with increased risk of past or chronic hepatitis virus B, hepatitis virus C, or HIV infection before initiation of systemic cancer therapy. Data were from a multicenter prospective cohort study of 3051 patients with newly diagnosed cancer (SWOG-S1204) enrolled between 2013 and 2017. Patients completed a survey with questions pertaining to personal history and behavioral, socioeconomic, and demographic risk factors for viral hepatitis or HIV. We derived a risk model to predict the presence of viral infection in a random set of 60% of participants using best subset selection. The derived model was validated in the remaining 40% of participants. Logistic regression was used. RESULTS A model with 7 risk factors was identified, and a risk score with 4 levels was constructed. In the validation cohort, each increase in risk level was associated with a nearly threefold increased risk of viral positivity (odds ratio = 2.85, 95% confidence interval = 2.26 to 3.60, P < .001). Consistent findings were observed for individual viruses. Participants in the highest risk group (with >3 risk factors), comprised of 13.4% of participants, were 18 times more likely to be viral positive compared with participants with no risk factors (odds ratio = 18.18, 95% confidence interval = 8.00 to 41.3, P < .001). CONCLUSIONS A risk-stratified screening approach using a limited set of questions could serve as an effective strategy to streamline screening for individuals at increased risk of viral infection.
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Affiliation(s)
- Joseph M Unger
- SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - Cathee Till
- SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - Jessica P Hwang
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Kathryn B Arnold
- SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - Michael Leblanc
- SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Center, Seattle, WA, USA
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Hsu YC, Huang DQ, Nguyen MH. Global burden of hepatitis B virus: current status, missed opportunities and a call for action. Nat Rev Gastroenterol Hepatol 2023:10.1038/s41575-023-00760-9. [PMID: 37024566 DOI: 10.1038/s41575-023-00760-9] [Citation(s) in RCA: 205] [Impact Index Per Article: 102.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/24/2023] [Indexed: 04/08/2023]
Abstract
Chronic hepatitis B virus (HBV) infection affects about 296 million people worldwide and is the leading aetiology of cirrhosis and liver cancer globally. Major medical complications also include acute flares and extrahepatic manifestations. In addition, people living with HBV infection also experience stigma. HBV-related cirrhosis resulted in an estimated 331,000 deaths in 2019, and it is estimated that the number of deaths from HBV-related liver cancer in 2019 was 192,000, an increase from 156,000 in 2010. Meanwhile, HBV remains severely underdiagnosed and effective measures that can prevent infection and disease progression are underutilized. Birth dose coverage for HBV vaccines remains low, particularly in low-income countries or regions where HBV burden is high. Patients with HBV infection are inadequately evaluated and linked to care and are undertreated worldwide, even in high-income countries or regions. Despite the goal of the World Health Organization to eliminate viral hepatitis as a public health problem by 2030, the annual global deaths from HBV are projected to increase by 39% from 2015 to 2030 if the status quo remains. In this Review, we discuss the current status and future projections of the global burden of HBV infection. We also discuss gaps in the current care cascade and propose future directions.
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Affiliation(s)
- Yao-Chun Hsu
- Center for Liver Diseases, E-Da Hospital, Kaohsiung, Taiwan.
- School of Medicine, I-Shou University, Kaohsiung, Taiwan.
- Division of Gastroenterology, Fu-Jen Catholic University Hospital, New Taipei, Taiwan.
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, New Taipei, Taiwan.
| | - Daniel Q Huang
- Division of Gastroenterology and Hepatology, National University Health System, Singapore, Singapore
- Department of Medicine, National University of Singapore, Singapore, Singapore
| | - Mindie H Nguyen
- Department of Medicine, Stanford University Medical Centre, Palo Alto, CA, USA.
- Department of Epidemiology and Population Health, Stanford University Medical Centre, Palo Alto, CA, USA.
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19
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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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20
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Zhao Y, Song Y, Zhang H, Qu T, Axinbai M, Yang Y, Zhang L. Efficacy of nucleos(t)ide analogues(NAs) in preventing virus reactivation in oncology patients with HBV infection after chemotherapy or surgery: A network meta-analysis. Front Oncol 2023; 12:1050714. [PMID: 36727050 PMCID: PMC9885183 DOI: 10.3389/fonc.2022.1050714] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 12/23/2022] [Indexed: 01/18/2023] Open
Abstract
Objective In this study, we aimed to perform a network meta-analysis to compare the effectiveness of NAs in decreasing the reactivation of HBV, reducing chemotherapy disruption, and improving survival in oncology patients. Methods Relevant randomized controlled trials (RCT) evaluating the impact of NAs in HBV infected-related oncology patients were retrieved from electronic databases. The outcome indicators included reactivation rate, survival rate of 1 to 3 years after treatment, and chemotherapy disruption rate. The studies were evaluated for bias using the RCT risk of bias assessment tool recommended in the Cochrane Handbook. The risk ratio (RR) was used to compare the outcome indicators for the anti-viral treatment, and the surface under the cumulative ranking curves (SUCRA) was used to identify the optimal therapeutic regime. Results A total of 67 trials containing 5722 patients were included in this study. Regarding the reduction of reactivation rate, entecavir, lamivudine, adefovir alone were less effective than the combination of lamivudine and entecavir (94.9%), with RR values ranging from 3.16 to 3.73. However, based on SUCRA, the efficacy of telbivudine (80.3%) and the combination of lamivudine and adefovir dipivoxil (58.8%) were also acceptable. Entecavir (RR values ranging from 1.25 to 1.50) and lamivudine (RR values ranging from 1.27 to 1.35) can prolong the survival rate of patients at 1-3 years, and were better than adefovir dipivoxil in the comparison of 1-year survival rate. The RR values were 1.18 and 1.19, respectively. And entecavir 's ranking in SUCRA was more stable. Entecavir, lamivudine, and tenofovir all reduced chemotherapy interruption rates compared with no antiviral therapy, especially for tenofovir. Conclusions Current evidence shows that lamivudine combined with entecavir, telbivudine, and lamivudine combined with adefovir dipivoxil were the most effective in preventing virus reactivation in HBV infected-related cancer patients treated with chemotherapy. Entecavir had the most stable effect on survival, while tenofovir had the best impact on reducing the chemotherapy disruption rate. Due to limited quality and quantity of the included studies, more high-quality studies are required to verify the above conclusions. Systematic review registration PROSPEROI [https://www.crd.york.ac.uk/PROSPERO/index.php], identifier CRD4202250685.
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Affiliation(s)
- Yuqing Zhao
- Graduate School, Beijing University of Chinese Medicine, Beijing, China,Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Yingying Song
- Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Huan Zhang
- Graduate School, Beijing University of Chinese Medicine, Beijing, China,Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Tongshuo Qu
- Graduate School, Beijing University of Chinese Medicine, Beijing, China,Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Malina Axinbai
- Graduate School, Beijing University of Chinese Medicine, Beijing, China,Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Yidian Yang
- Graduate School, Beijing University of Chinese Medicine, Beijing, China,Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Liping Zhang
- Graduate School, Beijing University of Chinese Medicine, Beijing, China,Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China,*Correspondence: Liping Zhang,
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Wang P, Li B, Zhou S, Xin Y, Zhu Z, Duan S, Bai D, Yuan H, Xu W, Xiao J. Efficacy and safety of COVID-19 vaccines for patients with spinal tumors receiving denosumab treatment: An initial real-clinical experience study. Front Oncol 2023; 13:1034466. [PMID: 37035168 PMCID: PMC10073434 DOI: 10.3389/fonc.2023.1034466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 02/28/2023] [Indexed: 04/11/2023] Open
Abstract
Background Even if COVID-19 vaccine has gradually been adopted in the world, information of side effects and crosstalk in patients with spinal tumors is absent due to the exclusion from clinical research. In this research, we aimed to investigate the efficacy and safety for the patients with spinal tumors treated by denosumab. Methods In this retrospective research, 400 patients under treatment of denosumab against spinal tumors in real-clinical experience were grouped into two cohorts according to the treatment of COVID-19 vaccine. And linked hospital data, serum samples and unsolicited related adverse events had been collected from January 22nd 2021 to June 1st 2021 respectively. Results 233 patients of all participants who received regular treatment of denosumab were vaccinated by mRNA or inactivated vaccine. Patients of metastatic disease and primary osseous spinal tumor showed similar distribution in both two groups. Over the study period, within 176 patients tested the status of serologic response of vaccine, 88(81.48%) and 41(87.23%) individuals injected one or two inactivated vaccines had effective antibody against SARS-CoV-2 infections. As 21 patients (85.71%) treated by mRNA vaccine did. Considering of the safety of vaccine, most common systemic adverse events were nausea or vomiting (45 events vs 23events). Interestingly, fewer participants in the vaccine group were statistically recorded in local adverse events than in the placebo group (16 events vs 33 events). Conclusions Our initial real-clinical experience suggests that COVID-19 vaccines are likely safe and effective in in patients with spinal tumors receiving denosumab treatment.
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Affiliation(s)
- Pengru Wang
- Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Bo Li
- Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Shangbin Zhou
- Naval Medical Center, Naval Military Medical University, Shanghai, China
| | - Yingye Xin
- Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Zhipeng Zhu
- Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Shujie Duan
- Department of Orthopedic, Changning County People's Hospital, Yunnan, China
| | - Danyang Bai
- Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Hao Yuan
- Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Wei Xu
- Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, China
- *Correspondence: Jianru Xiao, ; Wei Xu,
| | - Jianru Xiao
- Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, China
- *Correspondence: Jianru Xiao, ; Wei Xu,
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22
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Hwang JP, Arnold KB, Unger JM, Chugh R, Tincopa MA, Loomba R, Hershman D, Ramsey SD. Antiviral therapy use and related outcomes in patients with cancer and viral infections: results from SWOG S1204. Support Care Cancer 2022; 31:93. [PMID: 36585488 PMCID: PMC9803880 DOI: 10.1007/s00520-022-07525-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 11/16/2022] [Indexed: 01/01/2023]
Abstract
PURPOSE Information is limited about adherence to practice guidelines in patients with hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV infection receiving anticancer treatment. METHODS Newly diagnosed adult cancer patients were enrolled in a multicenter, prospective cohort study (SWOG S1204) during 2013-2017 to evaluate the prevalence of HBV, HCV, or HIV in patients initiating anticancer treatment. At 6 months, records of virus-positive patients were reviewed for antiviral therapy use; anticancer treatment dose reduction; and HBV reactivation (elevated viral load). Categorical variables were compared using chi-square or Fisher's exact test. RESULTS Of 3055 enrolled patients with viral testing, 230 had chronic or past HBV, HCV, or HIV with 6-month follow-up data (chronic HBV, 15 patients; past HBV, 158; HCV, 49; HIV, 30). Twenty percent (3/15) of chronic HBV and 11% (17/158) of past HBV patients were co-infected with HCV and/or HIV. Rates of antiviral therapy use by 6 months were as follows: chronic HBV, 85% (11/13); past HBV receiving anti-B cell therapy, 60% (3/5); past HBV receiving systemic anticancer therapy without anti-B cell therapy, 8% (8/105); HCV, 6% (2/35); and HIV, 90% (19/21). Among patients with available data, anticancer treatment dose was reduced in 1 of 145 patients with past HBV and 1 of 42 with HCV. HBV reactivation occurred in 1 of 15 patients with chronic HBV; this patient was not receiving antiviral therapy. CONCLUSION Many patients with cancer and viral infections either do not receive guideline-recommended antiviral treatment or receive antiviral treatment that is not recommended in guidelines. Further education is needed to improve adherence to guidelines.
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Affiliation(s)
- Jessica P Hwang
- Department of General Internal Medicine, Unit 1465, The University of Texas MD Anderson Cancer Center, P.O. Box 301402, Houston, TX, 77230-1402, USA.
| | - Kathryn B Arnold
- SWOG Statistics and Data Management Center, Seattle, WA, USA
- Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - Joseph M Unger
- SWOG Statistics and Data Management Center, Seattle, WA, USA
- Fred Hutchinson Cancer Center, Seattle, WA, USA
| | | | | | - Rohit Loomba
- Division of Gastroenterology, Department of Medicine, and Wertheim School of Public Health, University of California at San Diego, La Jolla, CA, USA
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23
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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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24
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Tagliamento M, Remon J, Giaj Levra M, De Maria A, Bironzo P, Besse B, Novello S, Mezquita L. Immune Checkpoint Inhibitors in Patients With Cancer and Infection by Hepatitis B or C Virus: A Perspective Through the Results of a European Survey. JTO Clin Res Rep 2022; 4:100446. [PMID: 36687558 PMCID: PMC9853354 DOI: 10.1016/j.jtocrr.2022.100446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 11/09/2022] [Accepted: 12/02/2022] [Indexed: 12/16/2022] Open
Abstract
Introduction Patients with cancer and hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are underrepresented in several clinical trials testing immune checkpoint inhibitors (ICIs). Consequently, safety and efficacy of ICI therapy in this population have not been completely defined. We aimed to evaluate the attitudes of oncologists on this topic. Methods We conducted a 14-item European anonymous online survey. Results Physicians from 56 oncology departments (26 from Italy, 15 from France, and 15 from Spain) took part in the survey. They mainly used to prescribe ICIs for treating patients with lung cancer, melanoma, and renal cell carcinoma. Of them, 95% recognized the need for specific guidelines addressing the management of patients with cancer and HBV or HCV treated with ICIs. Just 63% of the respondents screened patients for HBV and HCV status before ICIs initiation, although the risk of immune-related hepatotoxicity or viral reactivation was a major concern for most of them. Only 9% of the surveyed oncologists considered HBV and HCV infection a major exclusion criterion for receiving ICIs. Furthermore, 29% of the respondents would start a prophylactic treatment of active infection at ICIs initiation. Conclusions ICIs administration in patients with cancer and HBV or HCV infection is of concern for most of the surveyed European oncologists. Nonetheless, active screening and treatment of viral hepatitis should be improved. Data in this specific setting are needed for an evidence-based management and should be generated by broadening inclusion criteria of clinical trials to allow the enrollment of patients with HBV and HCV.
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Affiliation(s)
- Marco Tagliamento
- Cancer Medicine Department, Gustave Roussy, Villejuif, France,Department of Internal Medicine and Medical Specialties (Di.M.I.), University of Genova, Genova, Italy,Corresponding author. Address for correspondence: Marco Tagliamento, MD, Cancer Medicine Department, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
| | - Jordi Remon
- Department of Medical Oncology, Centro Integral Oncológico Clara Campal (HM-CIOCC), Hospital HM Delfos, Barcelona, Spain
| | | | - Andrea De Maria
- Division of Infectious Diseases, IRCCS Ospedale Policlinico San Martino, DISSAL, University of Genova, Genova, Italy
| | - Paolo Bironzo
- Thoracic Oncology Unit, Department of Oncology, San Luigi Hospital, University of Torino, Orbassano, Italy
| | - Benjamin Besse
- Cancer Medicine Department, Gustave Roussy, Villejuif, France
| | - Silvia Novello
- Thoracic Oncology Unit, Department of Oncology, San Luigi Hospital, University of Torino, Orbassano, Italy
| | - Laura Mezquita
- Division of Medical Oncology, Hospital Clínic, Barcelona, Spain,Laboratory of Translational Genomic and Targeted Therapies in Solid Tumors, IDIBAPS, Barcelona, Spain
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25
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Spera AM. Hepatitis B virus infection reactivation in patients under immunosuppressive therapies: Pathogenesis, screening, prevention and treatment. World J Virol 2022; 11:275-282. [PMID: 36188738 PMCID: PMC9523324 DOI: 10.5501/wjv.v11.i5.275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 05/20/2022] [Accepted: 07/26/2022] [Indexed: 02/05/2023] Open
Abstract
With a 5.3% of the global population involved, hepatitis B virus (HBV) is a major public health challenge requiring an urgent response. After a possible acute phase, the natural history of HBV infection can progress in chronicity. Patients with overt or occult HBV infection can undergo HBV reactivation (HBVr) in course of immunosuppressive treatments that, apart from oncological and hem-atological diseases, are also used in rheumatologic, gastrointestinal, neurological and dermatological settings, as well as to treat severe acute respiratory syndrome coronavirus 2 infection. The risk of HBV reactivation is related to the immune status of the patient and the baseline HBV infection condition. The aim of the present paper is to investigate the risk of HBVr in those not oncological settings in order to suggest strategies for preventing and treating this occurrence. The main studies about HBVr for patients with occult hepatitis B infection and chronic HBV infection affected by non-oncologic diseases eligible for immunosuppressive treatment have been analyzed. The occurrence of this challenging event can be reduced screening the population eligible for immunosuppressant to assess the best strategies according to any virological status. Further prospective studies are needed to increase data on the risk of HBVr related to newer immunomodulant agents employed in non-oncological setting.
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Affiliation(s)
- Anna Maria Spera
- Infectious Disease Unit, Universitary Hospital OORR San Giovanni di Dio e Ruggi d'Aragona, Salerno 84131, Italy
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26
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Hwang JP, Artz AS, Shah P, Symington B, Feld JJ, Hammond SP, Ludwig E, Pai A, Ramsey SD, Schlam I, Suga JM, Wang SH, Somerfield MR. Practical Implementation of Universal Hepatitis B Virus Screening for Patients With Cancer. JCO Oncol Pract 2022; 18:636-644. [DOI: 10.1200/op.22.00074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Affiliation(s)
| | - Andy S. Artz
- City of Hope Comprehensive Cancer Center, Duarte, CA
| | - Parth Shah
- Fred Hutchinson Cancer Research Center, Seattle, WA
| | - Banu Symington
- Memorial Hospital of Sweetwater County, Rock Springs, WY
| | - Jordan J. Feld
- Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Sarah P. Hammond
- Massachusetts General Hospital and Dana-Farber Cancer Institute, Boston, MA
| | - Emmy Ludwig
- Memorial Sloan Kettering Cancer Center, New York, NY
| | - Amy Pai
- The University of Texas MD Anderson Cancer Center, Houston, TX
| | | | | | | | - Su H. Wang
- Saint Barnabas Medical Center, Florham Park, NJ
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27
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Nagai Y, Sata M, Ohta H, Onuki T, Saito T, Uchiyama A, Kurosaki A, Yoshizumi N, Takigami A, Nakazawa S, Nakayama M, Yamaguchi H, Hagiwara K. Herpes zoster in patients with lung cancer treated with PD-1/PD-L1 antibodies. Immunotherapy 2022; 14:1211-1217. [PMID: 36039980 DOI: 10.2217/imt-2021-0318] [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
Background: There are no available clinical data on immunotherapy and the risk of herpes zoster. Materials & methods: This retrospective study included patients with recurrent or advanced lung cancer who were inoperable and ineligible for radiotherapy and were treated with either a PD-1/PD-L1 antibody (136 patients) or an EGFR tyrosine kinase inhibitor (149 patients) at Jichi Medical University Hospital between January 2016 and December 2018. Results: Herpes zoster-free survival was significantly shorter in the PD-1/PD-L1 antibody-treated group compared with the EGFR tyrosine kinase inhibitor-treated group (hazard ratio: 0.20; 95% CI: 0.048-0.84; p = 0.016). PD-1/PD-L1 antibody administration was independently and significantly associated with herpes zoster occurrence. Conclusion: Clinicians should anticipate herpes zoster in patients with lung cancer during treatment with PD-1/PD-L1 antibodies.
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Affiliation(s)
- Yoshiaki Nagai
- Division of Respiratory Medicine, Department of Internal Medicine, Jichi Medical University Hospital, 3311-1 Yakushi-ji, Shimotsuke-shi, Tochigi-ken, 329-0431, Japan
| | - Masafumi Sata
- Division of Respiratory Medicine, Department of Internal Medicine, Jichi Medical University Hospital, 3311-1 Yakushi-ji, Shimotsuke-shi, Tochigi-ken, 329-0431, Japan
| | - Hiromitsu Ohta
- Department of Respiratory Medicine, Jichi Medical University Saitama Medical Center, Saitama, Japan
| | - Tsugitoshi Onuki
- Division of Respiratory Medicine, Department of Internal Medicine, Jichi Medical University Hospital, 3311-1 Yakushi-ji, Shimotsuke-shi, Tochigi-ken, 329-0431, Japan
| | - Tatsuya Saito
- Division of Respiratory Medicine, Department of Internal Medicine, Jichi Medical University Hospital, 3311-1 Yakushi-ji, Shimotsuke-shi, Tochigi-ken, 329-0431, Japan
| | - Ayumi Uchiyama
- Division of Respiratory Medicine, Department of Internal Medicine, Jichi Medical University Hospital, 3311-1 Yakushi-ji, Shimotsuke-shi, Tochigi-ken, 329-0431, Japan
| | - Ayako Kurosaki
- Division of Respiratory Medicine, Department of Internal Medicine, Jichi Medical University Hospital, 3311-1 Yakushi-ji, Shimotsuke-shi, Tochigi-ken, 329-0431, Japan
| | - Naoko Yoshizumi
- Division of Respiratory Medicine, Department of Internal Medicine, Jichi Medical University Hospital, 3311-1 Yakushi-ji, Shimotsuke-shi, Tochigi-ken, 329-0431, Japan
| | - Ayako Takigami
- Division of Respiratory Medicine, Department of Internal Medicine, Jichi Medical University Hospital, 3311-1 Yakushi-ji, Shimotsuke-shi, Tochigi-ken, 329-0431, Japan
| | - Shoko Nakazawa
- Division of Respiratory Medicine, Department of Internal Medicine, Jichi Medical University Hospital, 3311-1 Yakushi-ji, Shimotsuke-shi, Tochigi-ken, 329-0431, Japan
| | - Masayuki Nakayama
- Division of Respiratory Medicine, Department of Internal Medicine, Jichi Medical University Hospital, 3311-1 Yakushi-ji, Shimotsuke-shi, Tochigi-ken, 329-0431, Japan
| | - Hironori Yamaguchi
- Department of Clinical Oncology, Jichi Medical University Hospital, 3311-1 Yakushi-ji, Shimotsuke-shi, Tochigi-ken, 329-0431, Japan
| | - Koichi Hagiwara
- Division of Respiratory Medicine, Department of Internal Medicine, Jichi Medical University Hospital, 3311-1 Yakushi-ji, Shimotsuke-shi, Tochigi-ken, 329-0431, Japan
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Interaction between baseline HBV loads and the prognosis of patients with HCC receiving anti-PD-1 in combination with antiangiogenic therapy undergoing concurrent TAF prophylaxis. BMC Infect Dis 2022; 22:614. [PMID: 35836207 PMCID: PMC9284788 DOI: 10.1186/s12879-022-07602-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Accepted: 07/07/2022] [Indexed: 12/24/2022] Open
Abstract
Background A high baseline hepatitis B virus (HBV) load has always been listed as an exclusion criterion for programmed cell death-1 (PD-1) inhibitor-associated therapy in clinical trials, as the interaction between HBV load and anti-PD-1/PD-L1 therapy with anti HBV therapy remains controversial. Methods We retrospectively enrolled 70 unresectable HCC patients who were seropositive for HBsAg and accepted tenofovir alafenamide fumarate (TAF) therapy before anti-PD-1 in combination with an antiangiogenic treatment. Patients were divided into a low HBV DNA group (≤ 2000 IU/ml) and a high HBV DNA group (> 2000 IU/ml) according to the baseline HBV DNA levels. Tumour response and progression-free survival (PFS) were compared, and univariate and multivariate Cox analyses were performed to identify potential risk factors for PFS. The incidences of HBV reactivation and HBV-associated hepatitis were also recorded. Results 48 patients were assigned to the low group and the remaining 22 patients were assigned to the high group. The objective response rates (ORRs), disease control rates (DCRs), and PFS between the two groups showed no significant difference (P = 0.761, 0.552, and 0.784, respectively). The results of Cox analyses revealed that there was no relationship between baseline HBV load and PFS. Additionally, HBV reactivation occurred in only 2 patients (2.9%), and no patient experienced HBV-related hepatic impairment when given a continuous TAF treatment. Conclusions Baseline HBV loads do not affect the prognosis of HCC patients receiving anti-PD-1 in combination with an antiangiogenic therapy, while PD-1 inhibitors do not aggravate HBV reactivation and hepatic impairment in patients simultaneously subjected to TAF prophylaxis. Baseline HBV loads do not affect the prognosis of HCC patients receiving anti-PD-1 in combination with antiangiogenic therapy. Besides, PD-1 inhibitors do not aggravate HBV reactivation and hepatic impairment undergoing concurrent TAF prophylaxis.
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Saitta C, Pollicino T, Raimondo G. Occult Hepatitis B Virus Infection: An Update. Viruses 2022; 14:v14071504. [PMID: 35891484 PMCID: PMC9318873 DOI: 10.3390/v14071504] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Revised: 06/28/2022] [Accepted: 06/29/2022] [Indexed: 11/16/2022] Open
Abstract
Occult hepatitis B virus (HBV) infection (OBI) refers to a condition in which replication-competent viral DNA is present in the liver (with detectable or undetectable HBV DNA in the serum) of individuals testing negative for the HBV surface antigen (HBsAg). In this peculiar phase of HBV infection, the covalently closed circular DNA (cccDNA) is in a low state of replication. Many advances have been made in clarifying the mechanisms involved in such a suppression of viral activity, which seems to be mainly related to the host's immune control and epigenetic factors. OBI is diffused worldwide, but its prevalence is highly variable among patient populations. This depends on different geographic areas, risk factors for parenteral infections, and assays used for HBsAg and HBV DNA detection. OBI has an impact in several clinical contexts: (a) it can be transmitted, causing a classic form of hepatitis B, through blood transfusion or liver transplantation; (b) it may reactivate in the case of immunosuppression, leading to the possible development of even fulminant hepatitis; (c) it may accelerate the progression of chronic liver disease due to different causes toward cirrhosis; (d) it maintains the pro-oncogenic properties of the "overt" infection, favoring the development of hepatocellular carcinoma.
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Affiliation(s)
- Carlo Saitta
- Division of Medicine and Hepatology, University Hospital of Messina, 98124 Messina, Italy;
- Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy
| | - Teresa Pollicino
- Department of Human Pathology, University Hospital of Messina, 98124 Messina, Italy;
| | - Giovanni Raimondo
- Division of Medicine and Hepatology, University Hospital of Messina, 98124 Messina, Italy;
- Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy
- Correspondence: ; Tel.: +39-(0)-902212392
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Zhu Y, Li H, Wang X, Zheng X, Huang Y, Chen J, Meng Z, Gao Y, Qian Z, Liu F, Lu X, Shi Y, Shang J, Yan H, Zheng Y, Qiao L, Zhang Y, Xiang X, Dan Y, Sun S, Hou Y, Zhang Q, Xiong Y, Li S, Chen J, Huang Z, Li B, Jiang X, Luo S, Chen Y, Gao N, Liu C, Ji L, Yuan W, Li J, Li T, Zheng R, Zhou X, Ren H, Zhou Y, Xu B, Yu R, Tan W, Deng G. Hepatitis B Virus Reactivation Increased the Risk of Developing Hepatic Failure and Mortality in Cirrhosis With Acute Exacerbation. Front Microbiol 2022; 13:910549. [PMID: 35875559 PMCID: PMC9300993 DOI: 10.3389/fmicb.2022.910549] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 06/10/2022] [Indexed: 11/13/2022] Open
Abstract
Background and AimsHepatitis B virus (HBV) reactivation is a serious condition and has been extensively described in chemotherapeutic immunosuppressive population. However, little is known about HBV reactivation in immunocompetent patients with chronic hepatitis B (CHB). In this study, we evaluated the prevalence and the clinical significance of HBV reactivation in CHB patients with acute exacerbations.MethodPatients were screened from two prospective multicenter observational cohorts (CATCH-LIFE cohort). A total of 1,020 CHB patients with previous antiviral treatment history were included to assess the prevalence, risk factors, clinical characteristics of HBV reactivation, and its influence on the progression of chronic liver disease.ResultsThe prevalence of HBV reactivation was 51.9% in CHB patients with acute exacerbations who had antiviral treatment history in our study. Among the 529 patients with HBV reactivation, 70.9% of them were triggered by discontinued antiviral treatment and 5.9% by nucleos(t)ide analogs (NUCs) resistance. The prevalence of antiviral treatment disruption and NUCs resistance in patients with HBV reactivation is much higher than that in the patients without (70.9% vs. 0.2%, and 5.9% vs. 0, respectively, both p < 0.001). Stratified and interaction analysis showed that HBV reactivation was correlated with high short-term mortality in cirrhosis subgroup (HR = 2.1, p < 0.001). Cirrhotic patients with HBV reactivation had a significantly higher proportion of developing hepatic failure (45.0% vs. 20.3%, p < 0.001), acute-on-chronic liver failure (ACLF; 31.4% vs. 21.8%, p = 0.005), and short-term death (14.0% vs. 5.9% for 28-day, and 23.3% vs. 12.4% for 90-day, both p < 0.001) than those without. HBV reactivation is an independent risk factor of 90-day mortality for cirrhosis patients (OR = 1.70, p = 0.005), as well as hepatic encephalopathy, ascites, and bacterial infection.ConclusionThis study clearly demonstrated that there was a high prevalence of HBV reactivation in CHB patients, which was mainly triggered by discontinued antiviral treatment. The HBV reactivation strongly increased the risk of developing hepatic failure, ACLF and short-term death in HBV-related cirrhotic patients, which may suggest that HBV reactivation would be a new challenge in achieving the WHO target of 65% reduction in mortality from hepatitis B by 2030.
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Affiliation(s)
- Ying Zhu
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Hai Li
- Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Xianbo Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xin Zheng
- Department of Infectious Diseases, Institute of Infection and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yan Huang
- Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, China
| | - Jinjun Chen
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Zhongji Meng
- Department of Infectious Diseases, Hubei Clinical Research Center for Precise Diagnosis and Therapy of Liver Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Yanhang Gao
- Department of Hepatology, The First Hospital of Jilin University, Changchun, China
| | - Zhiping Qian
- Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China
| | - Feng Liu
- Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University, Jinan, China
| | - Xiaobo Lu
- Infectious Disease Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Yu Shi
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jia Shang
- Department of Infectious Diseases, Henan Provincial People’s Hospital, Zhengzhou, China
| | - Huadong Yan
- Department of Hepatology, Hwamei Hospital, Ningbo No.2 Hospital, University of Chinese Academy of Sciences, Ningbo, China
| | - Yubao Zheng
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Liang Qiao
- Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yan Zhang
- Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Xiaomei Xiang
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
- Chongqing Key Laboratory for Research of Infectious Disease, Chongqing, China
| | - Yunjie Dan
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
- Chongqing Key Laboratory for Research of Infectious Disease, Chongqing, China
| | - Shuning Sun
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Yixin Hou
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Qun Zhang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yan Xiong
- Department of Infectious Diseases, Institute of Infection and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Sumeng Li
- Department of Infectious Diseases, Institute of Infection and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jun Chen
- Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, China
| | - Zebing Huang
- Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, China
| | - Beiling Li
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xiuhua Jiang
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Sen Luo
- Department of Infectious Diseases, Hubei Clinical Research Center for Precise Diagnosis and Therapy of Liver Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Yuanyuan Chen
- Department of Infectious Diseases, Hubei Clinical Research Center for Precise Diagnosis and Therapy of Liver Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Na Gao
- Department of Hepatology, The First Hospital of Jilin University, Changchun, China
| | - Chunyan Liu
- Department of Hepatology, The First Hospital of Jilin University, Changchun, China
| | - Liujuan Ji
- Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China
| | - Wei Yuan
- Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China
| | - Jing Li
- Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University, Jinan, China
| | - Tao Li
- Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University, Jinan, China
| | - Rongjiong Zheng
- Infectious Disease Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Xinyi Zhou
- Infectious Disease Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Haotang Ren
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yi Zhou
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
- Chongqing Key Laboratory for Research of Infectious Disease, Chongqing, China
| | - Baoyan Xu
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
- Chongqing Key Laboratory for Research of Infectious Disease, Chongqing, China
| | - Rentao Yu
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Wenting Tan
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
- Chongqing Key Laboratory for Research of Infectious Disease, Chongqing, China
- Wenting Tan,
| | - Guohong Deng
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
- Chongqing Key Laboratory for Research of Infectious Disease, Chongqing, China
- *Correspondence: Guohong Deng,
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31
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Franzè MS, Pollicino T, Raimondo G, Squadrito G. Occult hepatitis B virus infection in hepatitis C virus negative chronic liver diseases. Liver Int 2022; 42:963-972. [PMID: 35246933 PMCID: PMC9310828 DOI: 10.1111/liv.15233] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 01/09/2022] [Accepted: 02/16/2022] [Indexed: 01/26/2023]
Abstract
Data concerning the prevalence of hepatitis B virus (HBV) occult infection (OBI) varies greatly in the different studies according to the sensitivity and specificity of the diagnostic approaches and the HBV prevalence in the different populations examined. The clinical implications of OBI are still debated. While the impact of OBI in HBV transmission as well as in HBV reactivation under immunosuppression are well established, the role of OBI in liver disease and hepatocellular carcinoma (HCC) development are still not definitively elucidated. It has been hypothesized that OBI might contribute to worsening the liver disease course when other causes of liver damage co-exist. Furthermore, much evidence suggests a role of OBI in the hepato-carcinogenesis processes through both indirect and direct oncogenic mechanisms that might favour HCC development. Data on the OBI clinical implications mainly come from studies performed in patients with hepatitis C virus (HCV) infection. However, HCV prevalence has dramatically fallen in the past years also because of the advent of specific and highly effective direct acting antivirals, with a consequent abrupt change of the worldwide scenario of chronic liver disease. Information about OBI prevalence and possible clinical impact in non-HCV-related liver disease are fragmentary, and the objective of this review is to critically summarize the available data in this field.
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Affiliation(s)
- Maria Stella Franzè
- Department of Clinical and Experimental MedicineMessina UniversityMessinaItaly,Division of Medicine and HepatologyMessina University HospitalMessinaItaly
| | - Teresa Pollicino
- Department of Human PathologyMessina UniversityMessinaItaly,Division of Advanced Diagnostic LaboratoriesMessina University HospitalMessinaItaly
| | - Giovanni Raimondo
- Department of Clinical and Experimental MedicineMessina UniversityMessinaItaly,Division of Medicine and HepatologyMessina University HospitalMessinaItaly
| | - Giovanni Squadrito
- Department of Clinical and Experimental MedicineMessina UniversityMessinaItaly,Division of Internal MedicineMessina University HospitalMessinaItaly
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32
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Ji DZ, Pang XY, Shen DT, Liu SN, Goyal H, Xu HG. Global prevalence of occult hepatitis B: A systematic review and meta-analysis. J Viral Hepat 2022; 29:317-329. [PMID: 35253969 DOI: 10.1111/jvh.13660] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Revised: 11/30/2021] [Accepted: 02/05/2022] [Indexed: 12/13/2022]
Abstract
The study aimed to investigate the prevalence and risk factors associated with occult hepatitis B virus (HBV) infection (OBI) in the global population. We searched PubMed, Embase, CINAHL, Cochrane and Web of Science from database inception through 27 Dec, 2018. Studies reporting HBV-DNA serological data in previously undiagnosed hepatitis B patients were included. The data were further categorized according to the presence of risk factors. After an initial screening of 2,325 records, we finally included 98 articles about the prevalence of OBI from 34 countries and regions. The OBI prevalence was 0.82% (95% CI:0.69-0.96) in the general population, 16.26% (95% CI:10.97-22.34) in HIV patients, 13.99% (95% CI:8.33-20.79) in patients with other liver diseases, 4.25% (95% CI:1.64-7.87) in haemodialysis patients and 5.14% (95% CI:2.26-9.01) patients with other risk factors. In conclusion, OBI prevalence varies significantly across different populations and nations, which deserve attention from the public health authorities. Our results generate further epidemiological data to identify the population with OBI, which has important clinical implications in finding these high-risk populations to design preventive and management strategies.
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Affiliation(s)
- Dong-Ze Ji
- Department of Pathology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Xiao-Yu Pang
- Department of Laboratory Medicine, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Dan-Ting Shen
- Department of Laboratory Medicine, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Shu-Na Liu
- Department of Laboratory Medicine, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Hemant Goyal
- Department of Medicine, The Wright Center of Graduate Medical Education, Scranton, Pennsylvania, USA
| | - Hua-Guo Xu
- Department of Laboratory Medicine, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
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33
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Echavarria I, Carrión Galindo JR, Corral J, Diz Taín MP, Henao Carrasco F, Iranzo González-Cruz V, Mielgo-Rubio X, Quintanar T, Rivas Corredor C, Pérez Segura P. SEOM clinical guidelines for the prophylaxis of infectious diseases in cancer patients (2021). Clin Transl Oncol 2022; 24:724-732. [PMID: 35230619 PMCID: PMC8886704 DOI: 10.1007/s12094-022-02800-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/31/2022] [Indexed: 12/14/2022]
Abstract
Infections are still a major cause of morbi-mortality in patients with cancer. Some of these infections are preventable through specific measures, such as vaccination or prophylaxis. This guideline aims to summarize the evidence and recommendations for the prevention of infections in cancer patients, devoting special attention to the most prevalent preventable infectious disease. All the evidences will be graded according to The Infectious Diseases Society of America grading system.
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Affiliation(s)
- Isabel Echavarria
- Department of Medical Oncology, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañon (IiSGM), CIBERONC, C/ Dr. Esquerdo, 46, 28007 Madrid, Spain
| | | | - Jesús Corral
- Department of Medical Oncology, Clínica Universidad de Navarra, Madrid, Spain
| | | | | | - Vega Iranzo González-Cruz
- Department of Medical Oncology, Hospital General Universitario de Valencia, Valencia, Spain
- Department of Medicine, Universitat de València, Valencia, Spain
- Centro de Investigación Biomédica en Red en Cáncer (CIBERONC), Valencia, Spain
| | - Xabier Mielgo-Rubio
- Department of Medical Oncology, Hospital Universitario Fundación Alcorcón, Madrid, Spain
| | - Teresa Quintanar
- Department of Medical Oncology, Hospital General Universitario de Elche, Elche, Spain
| | | | - Pedro Pérez Segura
- Department of Medical Oncology, Hospital Clínico San Carlos, Madrid, Spain
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Hepatitis B virus and hepatitis C virus reactivation in cancer patients receiving novel anticancer therapies. Clin Microbiol Infect 2022; 28:1321-1327. [DOI: 10.1016/j.cmi.2022.02.042] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 01/06/2022] [Accepted: 02/27/2022] [Indexed: 12/21/2022]
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Chang Y, Jeong SW, Jang JY. Hepatitis B Virus Reactivation Associated With Therapeutic Interventions. Front Med (Lausanne) 2022; 8:770124. [PMID: 35096867 PMCID: PMC8795508 DOI: 10.3389/fmed.2021.770124] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 12/20/2021] [Indexed: 12/14/2022] Open
Abstract
Hepatitis B virus (HBV) reactivation associated with various therapeutic interventions is an important cause of morbidity and mortality in patients with current or resolved HBV infection. Because no curative treatment for HBV infection is yet available, there are many individuals at risk for HBV reactivation in the general population. Populations at risk for HBV reactivation include patients who are currently infected with HBV or who have been exposed to HBV in the past. HBV reactivation and its potential consequences is a concern when these populations are exposed to anti-cancer chemotherapy, immunosuppressive or immunomodulatory therapies for the management of various malignancies, rheumatologic diseases, inflammatory bowel disease, or solid-organ or hematologic stem cell transplantation. Accordingly, it has become important to understand the basics of HBV reactivation and the mechanisms by which certain therapies are more susceptible to HBV reactivation. This review aims to raise the awareness of HBV reactivation and to understand the mechanisms and the risks of HBV reactivation in various clinical settings.
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Affiliation(s)
- Young Chang
- Department of Internal Medicine, Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul, South Korea
| | - Soung Won Jeong
- Department of Internal Medicine, Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul, South Korea
| | - Jae Young Jang
- Department of Internal Medicine, Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul, South Korea
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36
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Mohareb AM, Patel NJ, Fu X, Kim AY, Wallace ZS, Hyle EP. Screening for Hepatitis B Virus Prior to Initiating Tocilizumab and Tofacitinib in Patients With Rheumatic Diseases: A Cross-sectional Study. J Rheumatol 2022; 49:104-109. [PMID: 34334359 PMCID: PMC8724454 DOI: 10.3899/jrheum.210257] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/16/2021] [Indexed: 01/03/2023]
Abstract
OBJECTIVE Hepatitis B virus (HBV) can reactivate among rheumatology patients initiating tocilizumab (TCZ) or tofacitinib (TOF). HBV screening is recommended by the Centers for Disease Control and Prevention (CDC), the American Association for the Study of Liver Diseases (AASLD), and the Canadian Rheumatology Association, but it is not explicitly recommended by the American College of Rheumatology. METHODS We conducted a cross-sectional study to characterize HBV screening practices for adult rheumatology patients initiating TCZ or TOF before December 31, 2018, in the Greater Boston area. We classified appropriate HBV screening patterns prior to TCZ or TOF (i.e., HBV surface antigen [HBsAg], total core antibody [anti-HBcAb], and surface antibody [HBsAb]) as follows: complete (all 3 tested), partial (any 1 or 2 tests), or none. We determined the frequency of inappropriate HBV testing (HBV e-antigen, anti-HBcAb IgM, or HBV DNA without a positive HBsAg or total anti-HBcAb) and used multivariable regression to assess factors associated with complete HBV screening. RESULTS Among 678 subjects initiating TCZ, 194 (29%) completed appropriate HBV screening, 307 (45%) had partial screening, and 177 (26%) had none. Among 391 subjects initiating TOF, 94 (24%) completed appropriate HBV screening, 195 (50%) had partial screening, and 102 (26%) had none. Inappropriate testing was performed in 22% of subjects. Race was associated with complete HBV screening (White vs non-White: OR 0.74, 95% CI 0.57-0.95), whereas prior immunosuppression was not (conventional synthetic disease-modifying antirheumatic drugs [DMARDs]: OR 1.05, 95% CI 0.72-1.55; biologic DMARDs: OR 0.73, 95% CI 0.48-1.12). CONCLUSION Patients initiating TCZ or TOF are infrequently screened for HBV despite recommendations from the AASLD and CDC.
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Affiliation(s)
- Amir M. Mohareb
- Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA,Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA,Harvard Medical School, Boston MA USA
| | - Naomi J. Patel
- Harvard Medical School, Boston MA USA,Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, MA, USA
| | - Xiaoqing Fu
- Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA
| | - Arthur Y. Kim
- Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA,Harvard Medical School, Boston MA USA
| | - Zachary S. Wallace
- Harvard Medical School, Boston MA USA,Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, MA, USA,Clinical Epidemiology Program, Mongan Institute, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Emily P. Hyle
- Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA,Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA,Harvard Medical School, Boston MA USA
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37
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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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Onorato L, Pisaturo M, Camaioni C, Grimaldi P, Codella AV, Calò F, Coppola N. Risk and Prevention of Hepatitis B Virus Reactivation during Immunosuppression for Non-Oncological Diseases. J Clin Med 2021; 10:5201. [PMID: 34768721 PMCID: PMC8584565 DOI: 10.3390/jcm10215201] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 10/30/2021] [Accepted: 11/03/2021] [Indexed: 12/31/2022] Open
Abstract
Reactivation of overt or occult HBV infection (HBVr) is a well-known, potentially life-threatening event which can occur during the course of immunosuppressive treatments. Although it has been described mainly in subjects receiving therapy for oncological or hematological diseases, the increasing use of immunosuppressant agents in non-oncological patients observed in recent years has raised concerns about the risk of reactivation in several other settings. However, few data can be found in the literature on the occurrence of HBVr in these populations, and few clear recommendations on its management have been defined. The present paper was written to provide an overview of the risk of HBV reactivation in non-neoplastic patients treated with immunosuppressive drugs, particularly for rheumatological, gastrointestinal, dermatological and neurological diseases, and for COVID-19 patients receiving immunomodulating agents; and to discuss the potential strategies for prevention and treatment of HBVr in these settings.
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Affiliation(s)
- Lorenzo Onorato
- Department of Mental Health and Public Medicine, Faculty of Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80138 Naples, Italy; (L.O.); (M.P.); (C.C.); (P.G.)
- Infectious Diseases Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Via Pansini 5, 80138 Naples, Italy; (A.V.C.); (F.C.)
| | - Mariantonietta Pisaturo
- Department of Mental Health and Public Medicine, Faculty of Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80138 Naples, Italy; (L.O.); (M.P.); (C.C.); (P.G.)
| | - Clarissa Camaioni
- Department of Mental Health and Public Medicine, Faculty of Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80138 Naples, Italy; (L.O.); (M.P.); (C.C.); (P.G.)
| | - Pierantonio Grimaldi
- Department of Mental Health and Public Medicine, Faculty of Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80138 Naples, Italy; (L.O.); (M.P.); (C.C.); (P.G.)
| | - Alessio Vinicio Codella
- Infectious Diseases Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Via Pansini 5, 80138 Naples, Italy; (A.V.C.); (F.C.)
| | - Federica Calò
- Infectious Diseases Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Via Pansini 5, 80138 Naples, Italy; (A.V.C.); (F.C.)
| | - Nicola Coppola
- Department of Mental Health and Public Medicine, Faculty of Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80138 Naples, Italy; (L.O.); (M.P.); (C.C.); (P.G.)
- Infectious Diseases Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Via Pansini 5, 80138 Naples, Italy; (A.V.C.); (F.C.)
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Hepatitis B Virus Infection in Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation. J Pers Med 2021; 11:jpm11111108. [PMID: 34834460 PMCID: PMC8619006 DOI: 10.3390/jpm11111108] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 10/20/2021] [Accepted: 10/25/2021] [Indexed: 01/12/2023] Open
Abstract
Considering a steady increase in the number of allogeneic hematopoietic stem cell transplantations (allo-HSCT) worldwide and the significant proportion of the world’s population that has been exposed to hepatitis B virus (HBV) infection, HBV reactivation following allo-HSCT remains an important issue for post-transplant morbidity and mortality. Antiviral prophylaxis can reduce HBV replication, severity of HBV-related hepatitis, and mortality; therefore, identification of patients at risk is crucial. It is recommended that all recipients and donors should be screened for active or prior HBV infection, including HBsAg, antiHBc, and antiHBs. Adoptive immunity transfer from the donor seems to have protective effects against HBV reactivation. Antiviral prophylaxis should be initiated in all HBsAg-positive patients. HBsAg-negative, antiHBc-positive patients remain at risk; therefore, antiviral prophylaxis should be considered if baseline serum HBV DNA is detectable. In HBsAg-negative, antiHBc-positive patients without detectable HBV DNA, close monitoring of viral load with an on-demand therapy is necessary. Entecavir or tenofovir rather than lamivudine are more appropriate for the emergence of lamivudine resistance. The treatment duration remains unclear, with 6- to 12-month therapy after cessation of immunosuppressive therapy commonly recommended. Here we review the updated evidence and recent recommendations regarding HBV reactivation in patients undergoing allo-HSCT for individualized therapy.
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Lau G, Yu ML, Wong G, Thompson A, Ghazinian H, Hou JL, Piratvisuth T, Jia JD, Mizokami M, Cheng G, Chen GF, Liu ZW, Baatarkhuu O, Cheng AL, Ng WL, Lau P, Mok T, Chang JM, Hamid S, Dokmeci AK, Gani RA, Payawal DA, Chow P, Park JW, Strasser SI, Mohamed R, Win KM, Tawesak T, Sarin SK, Omata M. APASL clinical practice guideline on hepatitis B reactivation related to the use of immunosuppressive therapy. Hepatol Int 2021; 15:1031-1048. [PMID: 34427860 PMCID: PMC8382940 DOI: 10.1007/s12072-021-10239-x] [Citation(s) in RCA: 85] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 07/20/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIM Hepatitis B reactivation related to the use of immunosuppressive therapy remains a major cause of liver-related morbidity and mortality in hepatitis B endemic Asia-Pacific region. This clinical practice guidelines aim to assist clinicians in all disciplines involved in the use of immunosuppressive therapy to effectively prevent and manage hepatitis B reactivation. METHODS All publications related to hepatitis B reactivation with the use of immunosuppressive therapy since 1975 were reviewed. Advice from key opinion leaders in member countries/administrative regions of Asian-Pacific Association for the study of the liver was collected and synchronized. Immunosuppressive therapy was risk-stratified according to its reported rate of hepatitis B reactivation. RECOMMENDATIONS We recommend the necessity to screen all patients for hepatitis B prior to the initiation of immunosuppressive therapy and to administer pre-emptive nucleos(t)ide analogues to those patients with a substantial risk of hepatitis and acute-on-chronic liver failure due to hepatitis B reactivation.
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Affiliation(s)
- George Lau
- Humanity and Health Clinical Trial Center, Humanity and Health Medical Group, Hong Kong SAR, China.
- The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, 100039, China.
| | - Ming-Lung Yu
- Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tz-You 1st Rd, Chinese Taipei, Kaohsiung, Taiwan.
| | - Grace Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | | | - Hasmik Ghazinian
- Department of Hepatology, Nork Clinical Hospital of Infectious Diseases, Yerevan, Armenia
| | - Jin-Lin Hou
- Department of Infectious Diseases, Institute of Hepatology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Teerha Piratvisuth
- Department of Medicine, NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand
| | - Ji-Dong Jia
- Liver Research Center, Beijing Friendship Hospital, Beijing, China
| | - Masashi Mizokami
- Genome Medical Science Project, National Center for Global Health and Medicine, Ichikawa, Japan
| | - Gregory Cheng
- The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, 100039, China
- Faculty of Health Science, Macau University, Macau SAR, China
| | - Guo-Feng Chen
- Department of Liver Diseases, Fifth Medical Center of Chinese, PLA General Hospital, Beijing, China
| | - Zhen-Wen Liu
- Research Center for Liver Transplantation, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Oidov Baatarkhuu
- Department of Infectious Diseases, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
| | - Ann Lii Cheng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Woon Leung Ng
- Department of Medicine, United Christian Hospital, Hong Kong SAR, China
| | - Patrick Lau
- Humanity and Health Clinical Trial Center, Humanity and Health Medical Group, Hong Kong SAR, China
| | - Tony Mok
- Department of Clinical Oncology, State Key Laboratory of South China, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Jer-Ming Chang
- Division of Nephrology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Saeed Hamid
- Department of Medicine, Aga Khan University and Hospital, Stadium Road, Karachi, 74800, Pakistan
| | - A Kadir Dokmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Rino A Gani
- Liver Transplantation Team, Ciptomangunkusumo Hospital, Jakarta, Indonesia
| | - Diana A Payawal
- Department of Medicine, Cardinal Santos Medical Center, Mandaluyong, Metro, Manila, Philippines
| | - Pierce Chow
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore, Singapore
| | - Joong-Won Park
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Simone I Strasser
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, Australia
| | - Rosmawaiti Mohamed
- Department of Medicine, University Malaya Medical Centre, Kuala Lumpur, Malaysia
| | - Khin Maung Win
- Yangon Gastroenterology and Liver Centre, Yangon, Myanmar
| | - Tanwandee Tawesak
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Masao Omata
- Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu-shi, Yamanashi, 400-8506, Japan
- The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
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Shih CA, Chen WC. Prevention of hepatitis B reactivation in patients requiring chemotherapy and immunosuppressive therapy. World J Clin Cases 2021; 9:5769-5781. [PMID: 34368296 PMCID: PMC8316946 DOI: 10.12998/wjcc.v9.i21.5769] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 04/12/2021] [Accepted: 06/02/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) reactivation can lead to severe acute hepatic failure and death in patients with HBV infection. HBV reactivation (HBVr) most commonly develops in patients undergoing cancer chemotherapy, especially B cell-depleting agent therapy such as rituximab and ofatumumab for hematological or solid organ malignancies and that receiving hematopoietic stem cell transplantation without antiviral prophylaxis. In addition, the potential consequences of HBVr is particularly a concern when patients are exposed to either immunosuppressive or biologic therapies for the management of rheumatologic diseases, inflammatory bowel disease and dermatologic diseases. Thus, screening with HBV serological markers and prophylactic or pre-emptive antiviral treatment with nucleos(t)ide analogues should be considered in these patients to diminish the risk of HBVr. This review discusses the clinical manifestation, prognosis and management of HBVr, risk stratifications of cancer chemotherapy and immunosuppressive therapy and international guideline recommendations for the prevention of HBVr in patients with HBV infection and resolved hepatitis B.
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Affiliation(s)
- Chih-An Shih
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Antai Medical Care Corporation, Antai Tian-Sheng Memorial Hospital, Pingtung County 928, Taiwan
- Department of Nursing, Meiho University, Pingtung County 928, Taiwan
| | - Wen-Chi Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
- Institute of Biomedical Sciences, College of Science, National Sun Yat-sen University, Kaohsiung 8424, Taiwan
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Duan MH, Cao XX, Chang L, Zhou DB. Risk of hepatitis B virus reactivation following ruxolitinib treatment in patients with myeloproliferative neoplasms. ACTA ACUST UNITED AC 2021; 26:460-464. [PMID: 34184610 DOI: 10.1080/16078454.2021.1945234] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Objectives The aim of this retrospective analysis was to assess the incidence of hepatitis B virus (HBV) reactivation among patients with myeloproliferative neoplasms (MPN) during and after ruxolitinib treatment. Methods Between February 2013 and February 2020, 224 patients with MPN were treated using ruxolitinib at Peking Union Medical College Hospital. Of these, 6 had chronic, and 56 had resolved HBV infection, including 43 patients who received combination treatment with thalidomide, prednisone, and stanozolol (TSP) during ruxolitinib treatment. Results Two patients with chronic HBV infection who did not take any antiviral prophylaxis developed HBV reactivation and hepatitis flare. The other four patients with chronic HBV infection, who took antiviral prophylaxis before ruxolitinib treatment, did not develop HBV reactivation. Also, no patients with resolved HBV infection received antiviral prophylaxis and developed HBV reactivation. Conclusion This study demonstrated that HBV reactivation and hepatitis flare might commonly occur a few months after initiating ruxolitinib treatment in patients with chronic HBV infection who did not take antiviral prophylaxis, especially in combination with TSP. Still, it was extremely rare in patients with resolved HBV infection.
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Affiliation(s)
- Ming-Hui Duan
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Xin-Xin Cao
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Long Chang
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Dao-Bin Zhou
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
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Cao X, Wang Y, Li P, Huang W, Lu X, Lu H. HBV Reactivation During the Treatment of Non-Hodgkin Lymphoma and Management Strategies. Front Oncol 2021; 11:685706. [PMID: 34277431 PMCID: PMC8281013 DOI: 10.3389/fonc.2021.685706] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 06/16/2021] [Indexed: 12/14/2022] Open
Abstract
Hepatitis B virus reactivation (HBV-R), which can lead to HBV-related morbidity and mortality, is a common and well-known complication that occurs during the treatment of non-Hodgkin lymphoma (NHL) patients with current or past exposure to HBV infection. HBV-R is thought to be closely associated with chemotherapeutic or immunosuppressive therapies. However, immunosuppressive agents such as anti-CD20 antibodies (e.g., rituximab and ofatumumab), glucocorticoids, and hematopoietic stem cell transplantation (HSCT) administered to NHL patients during treatment can cause deep immunodepression and place them at high risk of HBV-R. In this review, we explore the current evidence, the guidelines of several national and international organizations, and the recommendations of expert panels relating to the definition, risk factors, screening and monitoring strategies, whether to use prophylaxis or pre-emptive therapy, and the optimal antiviral agent and duration of antiviral therapy for HBV-R.
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Affiliation(s)
- Xing Cao
- Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yafei Wang
- Department of Respiratory and Critical Care Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Panyun Li
- Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wei Huang
- Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaojuan Lu
- Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hongda Lu
- Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Yonezawa H, Tanaka S, Furuya M, Yamada K, Asanuma K, Fujiya Y, Miyanishi K, Takahashi S, Kato J. Determination of reactivation rate and risk factors for Hepatitis B virus reactivation in low-positive cases: A retrospective cohort study. J Infect Chemother 2021; 27:1454-1458. [PMID: 34176717 DOI: 10.1016/j.jiac.2021.06.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 05/01/2021] [Accepted: 06/06/2021] [Indexed: 11/29/2022]
Abstract
INTRODUCTION In quantitative assays for hepatitis B virus (HBV) DNA, although the amplification reaction signal is detected for low-positive cases, quantification remains challenging. HBV reactivation has been reported in many studies, but only a few have focused on HBV low-positive cases. This study aimed to determine the reactivation rate and risk factors for HBV reactivation in low-positive cases. METHODS In this retrospective cohort study, we analyzed 7498 patients who had their HBV DNA measured at Sapporo Medical University Hospital between April 2008 and November 2020. Patient selection criteria were defined as follows: hepatitis B surface antigen was negative; HBV DNA was detectable but not quantifiable at least once. HBV DNA was monitored according to the guidelines for HBV reactivation. RESULTS In total, 49,086 HBV DNA quantitative tests were performed. HBV DNA levels of 2578 tests were detectable but not quantifiable. Eighty patients met the criteria in this study. The median observation period was 497 days, and the 2-year reactivation rate was 15%. Ten patients had low HBV DNA positivity at baseline. Malignant lymphoma was observed in 15 patients; chemotherapy was used to treat other solid tumors in 35 patients, and immunosuppressive therapy was used in 30 patients. Multivariate analysis revealed that HBV DNA detected below the quantification level at baseline was an independent risk factor for HBV reactivation (adjusted hazard ratio 5.82; P = 0.010). CONCLUSIONS Patients with low HBV DNA positivity, especially at baseline, are at high risk for HBV reactivation and therefore require closer monitoring.
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Affiliation(s)
- Hitoshi Yonezawa
- Division of Laboratory Medicine, Sapporo Medical University Hospital, Sapporo, Japan
| | - Shingo Tanaka
- Division of Laboratory Medicine, Sapporo Medical University Hospital, Sapporo, Japan; Department of Infection Control and Laboratory Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan; Department of Medical Oncology, Sapporo Medical University School of Medicine, Sapporo, Japan.
| | - Momoko Furuya
- Division of Laboratory Medicine, Sapporo Medical University Hospital, Sapporo, Japan
| | - Koji Yamada
- Division of Laboratory Medicine, Sapporo Medical University Hospital, Sapporo, Japan
| | - Koichi Asanuma
- Division of Laboratory Medicine, Sapporo Medical University Hospital, Sapporo, Japan
| | - Yoshihiro Fujiya
- Division of Laboratory Medicine, Sapporo Medical University Hospital, Sapporo, Japan; Department of Infection Control and Laboratory Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Koji Miyanishi
- Department of Medical Oncology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Satoshi Takahashi
- Division of Laboratory Medicine, Sapporo Medical University Hospital, Sapporo, Japan; Department of Infection Control and Laboratory Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Junji Kato
- Department of Medical Oncology, Sapporo Medical University School of Medicine, Sapporo, Japan
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Novotny LA, Evans JG, Su L, Guo H, Meissner EG. Review of Lambda Interferons in Hepatitis B Virus Infection: Outcomes and Therapeutic Strategies. Viruses 2021; 13:1090. [PMID: 34207487 PMCID: PMC8230240 DOI: 10.3390/v13061090] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 05/27/2021] [Accepted: 06/01/2021] [Indexed: 12/27/2022] Open
Abstract
Hepatitis B virus (HBV) chronically infects over 250 million people worldwide and causes nearly 1 million deaths per year due to cirrhosis and liver cancer. Approved treatments for chronic infection include injectable type-I interferons and nucleos(t)ide reverse transcriptase inhibitors. A small minority of patients achieve seroclearance after treatment with type-I interferons, defined as sustained absence of detectable HBV DNA and surface antigen (HBsAg) antigenemia. However, type-I interferons cause significant side effects, are costly, must be administered for months, and most patients have viral rebound or non-response. Nucleos(t)ide reverse transcriptase inhibitors reduce HBV viral load and improve liver-related outcomes, but do not lower HBsAg levels or impart seroclearance. Thus, new therapeutics are urgently needed. Lambda interferons (IFNLs) have been tested as an alternative strategy to stimulate host antiviral pathways to treat HBV infection. IFNLs comprise an evolutionarily conserved innate immune pathway and have cell-type specific activity on hepatocytes, other epithelial cells found at mucosal surfaces, and some immune cells due to restricted cellular expression of the IFNL receptor. This article will review work that examined expression of IFNLs during acute and chronic HBV infection, the impact of IFNLs on HBV replication in vitro and in vivo, the association of polymorphisms in IFNL genes with clinical outcomes, and the therapeutic evaluation of IFNLs for the treatment of chronic HBV infection.
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Affiliation(s)
- Laura A. Novotny
- Division of Infectious Diseases, Medical University of South Carolina, Charleston, SC 29525, USA; (L.A.N.); (J.G.E.)
| | - John Grayson Evans
- Division of Infectious Diseases, Medical University of South Carolina, Charleston, SC 29525, USA; (L.A.N.); (J.G.E.)
| | - Lishan Su
- Division of Virology, Pathogenesis, and Cancer, Institute of Human Virology, Departments of Pharmacology, Microbiology, and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA;
| | - Haitao Guo
- Department of Microbiology and Molecular Genetics, Cancer Virology Program, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA;
| | - Eric G. Meissner
- Division of Infectious Diseases, Medical University of South Carolina, Charleston, SC 29525, USA; (L.A.N.); (J.G.E.)
- Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA
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Abstract
Hepatitis B virus reactivation (HBVr) can occur spontaneously, but more often occurs when a patient is in an immunocompromised state or on immunosuppressive therapy. HBVr can lead to clinical hepatitis, acute liver failure, and even death. HBVr is preventable with screening of at-risk patients and initiation of prophylactic antiviral therapy for appropriate candidates. Screening for hepatitis B virus is recommended for all patients who plan to initiate immunosuppressive therapy. An individual's serological profile, underlying disease, and planned type of immunosuppression contribute to their risk of HBVr. This review serves to summarize the major society guidelines regarding screening, management of, and monitoring for HBVr in individuals on anticancer therapy and immunosuppressive therapy.
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Affiliation(s)
- Yun Wang
- Vatche and Tamar Manoukian Division of Digestive Diseases
| | - Steven-Huy B Han
- Pfleger Liver Institute, David Geffen School of Medicine at the University of California, Los Angeles, CA
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Management of Hepatitis-B Virus Infection in Immunocompromised Children: A Single Center Experience. J Pediatr Gastroenterol Nutr 2021; 72:597-602. [PMID: 33399328 DOI: 10.1097/mpg.0000000000003042] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
OBJECTIVES The aims of the study was to expand the pediatric experience on hepatitis-B virus (HBV) reactivation, a known complication in patients with hematologic malignancies or on immunosuppression. METHODS Retrospective appraisal of HBV therapy/prophylaxis in immunocompromised children, studied from April 2006 to March 2020. RESULTS Eighteen HBV-positive patients, 5 girls, median age 11.1 (4.1--17.9) years were included. Seventeen of 18 were immunosuppressed at HBV-infection diagnosis. Seventeen were at high risk of reactivation, 1 at moderate risk. Five of 18 had acute hepatitis B as first infection or reactivation, 6 had HBeAg-positive infection, 1 an HBeAg-negative infection and 6 HBsAg-negative infection. Median follow-up was 2.7 (0.7--12.5) years. No HBV-related mortality was observed. Prophylaxis had to be repeated in 1. Lamivudine was used in 6/12 viremic patients and HBV-DNA negativization obtained in 2/6 (33%). Tenofovir-DF was used in 2/12 and entecavir in 4/12: 100% attained HBV-DNA negativization. Therapy had to be switched from tenofovir-DF to entecavir in 1 patient because of renal impairment. Virological breakthroughs were observed in 1 lamivudine-treated patient, leading to a hepatitis flare; 1 patient on entecavir had a hepatitis flare at immunoreconstitution. Mortality was 33% in the HBsAg-positive group. Seven prophylactic treatments were administered to 6 patients with HBsAg-negative infection: tenofovir-DF in 2 HBV-DNA-positive, lamivudine in 5 HBV-DNA-negative, without reverse HBsAg seroconversion, morbidity or mortality. CONCLUSIONS There is a residual risk of acute hepatitis B in immunocompromised children, mortality rate was substantial, potentially related to the delays in commencing chemotherapy caused by liver dysfunction. Tenofovir-DF or entecavir are the drugs of choice for HBV treatment in immunocompromised children.
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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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Lasagna A, Zuccaro V, Sacchi P, Chiellino S, Bruno R, Pedrazzoli P. Risk of reactivation of occult hepatitis B during immunotherapy in cancer treatment: myth, reality or new horizons? Future Oncol 2021; 17:1577-1580. [PMID: 33590770 DOI: 10.2217/fon-2020-1196] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Affiliation(s)
- Angioletta Lasagna
- Medical Oncology Unit, Fondazione IRCCS Policlinico San Matteo, Viale Camillo Golgi 19, Pavia, Italy
| | - Valentina Zuccaro
- Division of Infectious Diseases I, Fondazione IRCCS Policlinico San Matteo, Viale Camillo Golgi 19, Pavia, Italy
| | - Paolo Sacchi
- Division of Infectious Diseases I, Fondazione IRCCS Policlinico San Matteo, Viale Camillo Golgi 19, Pavia, Italy
| | - Silvia Chiellino
- Medical Oncology Unit, Fondazione IRCCS Policlinico San Matteo, Viale Camillo Golgi 19, Pavia, Italy
| | - Raffaele Bruno
- Division of Infectious Diseases I, Fondazione IRCCS Policlinico San Matteo, Viale Camillo Golgi 19, Pavia, Italy.,Department of Clinical, Surgical, Diagnostic & Pediatric Sciences, University of Pavia, Viale Camillo Golgi 19, Pavia, Italy
| | - Paolo Pedrazzoli
- Medical Oncology Unit, Fondazione IRCCS Policlinico San Matteo, Viale Camillo Golgi 19, Pavia, Italy.,Department of Internal Medicine & Medical Therapy, University of Pavia, Viale Camillo Golgi 19, Pavia, Italy
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Pisaturo M, Onorato L, Russo A, Coppola N. Prevalence of occult HBV infection in Western countries. J Med Virol 2020; 92:2917-2929. [PMID: 32275083 DOI: 10.1002/jmv.25867] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Accepted: 03/19/2020] [Indexed: 12/11/2022]
Abstract
Due to a lack of standardized tests, it is difficult to obtain prevalence data and define the real impact of occult HBV infection (OBI) in Western countries. The present review article addresses the prevalence of OBI, defined as presence of hepatitis B virus (HBV) DNA in liver tissue or plasma in HBsAg-negative subjects, in Western countries. This varies in different studies according to the different methodologies used (based on serology vs virology), to the sample analyzed for the diagnosis (liver tissue vs plasma), to the different populations studied, to the different geographical variations in the HBV spread, to the host characteristics (age, gender, risk factors for acquiring HBV infection) and to the presence of other parenteral infections (hepatitis C virus and/or human immunodeficiency virus [HIV] infections). Considering the different liver diseases analyzed, that is in patients with cryptogenic cirrhosis or advanced liver fibrosis, the prevalence of OBI ranges 4% to 38%. Considering the different populations studied, in the case of parenteral blood exposure it is about 45%, in patients with chronic hepatitis C it is estimated at about 52%, in HIV-infected patients it ranges from 0% to 45%, in blood donors from 0% to 22.7% and in hemodialysis patients it ranges from 0% to 54%. In conclusion, OBI is a virological entity to be considered when performing the patient's evaluation for immunosuppressive diseases, liver pathologies, or for blood transfusions. Knowing the prevalence and clinical impact of OBI will allow better patient management.
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Affiliation(s)
- Mariantonietta Pisaturo
- Department of Mental Health and Public Medicine-Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Lorenzo Onorato
- Department of Mental Health and Public Medicine-Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Antonio Russo
- Department of Mental Health and Public Medicine-Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Nicola Coppola
- Department of Mental Health and Public Medicine-Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
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