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Lu JL, Cheng Y, Xu ZL, Qian GX, Wei MT, Jia WD. Immune checkpoint inhibitors plus anti-angiogenesis in patients with resected high-risk hepatitis B virus-associated hepatocellular carcinoma. World J Gastrointest Oncol 2025; 17:101371. [DOI: 10.4251/wjgo.v17.i4.101371] [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: 09/12/2024] [Revised: 01/25/2025] [Accepted: 02/13/2025] [Indexed: 03/25/2025] Open
Abstract
BACKGROUND Currently, there is a lack of effective adjuvant therapies for patients at high-risk of recurrent hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) after radical resection. Given the efficacy of anti-programmed death 1/anti-programmed death ligand 1 plus anti-vascular endothelial growth factor receptor agents in advanced HCC, we conducted this study to investigate the efficacy of this combination regimen in the postoperative adjuvant treatment of patients with HBV-HCC.
AIM To evaluate the value of postoperative combined therapy (PCT) with anti-programmed death 1/anti-programmed death ligand 1 and anti-vascular endothelial growth factor receptor agents in patients with HBV-HCC.
METHODS Patients with HBV-HCC who underwent radical resection surgery at Anhui Provincial Hospital Affiliated to Anhui Medical University between July 2020 and April 2023 were included. Recurrence-free survival (RFS) and overall survival were assessed using propensity score matching and inverse probability of treatment weighting. Cox regression analysis was used to identify factors affecting recurrence, and subgroup analysis was conducted to investigate the impact of medications on different populations. Treatment-related adverse events and liver function measurements were evaluated.
RESULTS A total of 150 patients were recruited, of whom 30 underwent PCT and 120 did not. After adjusting for confounders, patients who underwent PCT had better RFS at 6 and 12 months than those who did not (P > 0.05). Similar results were observed in the Kaplan-Meier curves after propensity score matching or inverse probability of treatment weighting, although the difference was not statistically significant (P > 0.05). A maximum diameter of > 5 cm, vascular invasion, satellite nodules, and high gamma-glutamyl transferase levels were independent risk factors for recurrence (P < 0.05). No significant interaction effects were observed in subgroup analyses. The most prevalent adverse event was hypertension (66.7%). PCT was associated with an increased risk of hepatic impairment which may predict RFS rates (P = 0.041).
CONCLUSION The recurrence rate was not significantly reduced in patients who underwent PCT. Hepatic impairment during treatment may indicate recurrence, and close monitoring of liver function and HBV infection is recommended.
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Affiliation(s)
- Jian-Lin Lu
- Department of Hepatic Surgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, Anhui Province, China
| | - Yuan Cheng
- Department of Hepatic Surgery, Anhui Provincial Hospital, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Science and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
| | - Zi-Ling Xu
- Department of Hepatic Surgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, Anhui Province, China
| | - Gui-Xiang Qian
- Department of Hepatic Surgery, Anhui Provincial Hospital, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Science and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
| | - Ming-Tong Wei
- Department of Hepatic Surgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, Anhui Province, China
| | - Wei-Dong Jia
- Department of Hepatic Surgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, Anhui Province, China
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Vutien P, Nguyen MH. HBV Reactivation in Immunosuppressed Patients: Screening, Prevention, and Management Including Solid Organ Transplant Recipients. Viruses 2025; 17:388. [PMID: 40143316 PMCID: PMC11945625 DOI: 10.3390/v17030388] [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: 01/08/2025] [Revised: 03/05/2025] [Accepted: 03/07/2025] [Indexed: 03/28/2025] Open
Abstract
Hepatitis B virus (HBV) infection remains a global health challenge, affecting over 254 million individuals chronically and contributing significantly to cirrhosis, liver failure, and hepatocellular carcinoma. Despite advancements in antiviral therapy, HBV reactivation remains a critical concern, particularly in immunosuppressed individuals, including non-transplant patients undergoing immunosuppressive therapy and solid organ transplant recipients. This review provides screening and management strategies for HBV reactivation in these populations.
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Affiliation(s)
- Philip Vutien
- Division of Gastroenterology and Hepatology, University of Washington Medical Center, 1959 NE Pacific Street, Box 356175, Seattle, WA 98195, USA
| | - Mindie H. Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA 94305, USA;
- Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, CA 94305, USA
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Wu JF, Tai CS, Chang KC, Chen YJ, Hsu CT, Chen HL, Ni YH, Chang MH. Predictors of Functional Cure of Chronic Hepatitis B Virus Infection: A Long-Term Follow-Up Study. Clin Gastroenterol Hepatol 2025; 23:583-590.e3. [PMID: 39209206 DOI: 10.1016/j.cgh.2024.07.036] [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: 05/22/2024] [Revised: 07/24/2024] [Accepted: 07/25/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND & AIMS A functional cure is an essential endpoint in the management of patients with chronic hepatitis B virus (HBV) infection. We evaluated the cumulative probability and predictors of functional cure in patients with chronic HBV infection after hepatitis B e antigen (HBeAg) seroconversion. METHODS We retrospectively analyzed 413 (249 males and 164 females) initially HBeAg-positive chronic HBV-infected patients who were followed up for a mean of 26.36 ± 0.53 years. All underwent HBeAg seroconversion during follow-up. A functional cure was defined as durable HBsAg and HBV DNA loss without antiviral treatment for more than 24 weeks. RESULTS After 10,888 person-years of follow-up, the cumulative probability of functional cure was 14.53% (n = 60). There were 24 (40%) subjects with functional cure after antiviral therapy. The annual functional cure rate was 0.55% per person-year, and increased to 0.96% per person-year after HBeAg seroconversion. In subjects with functional cure, the HBsAg and HBV DNA titers after HBeAg seroconversion were positively correlated with the time to functional cure (P < .001 and < .001, respectively). Multivariate Cox proportional hazards analysis of the cohort revealed that HBeAg seroconversion at <18 years of age, high-genetic-barrier nucleos(t)ide analogue(s) therapy before HBeAg seroconversion, and a serum HBsAg titer <1000 IU/mL at 18 months after HBeAg seroconversion were significant predictors of functional cure (P < .001, .001, and .001, respectively). CONCLUSIONS In a cohort of chronic HBV-infected patients with long-term follow-up, HBeAg seroconversion in childhood, high-genetic-barrier nucleos(t)ide analogue(s) therapy, and low HBsAg titers after HBeAg seroconversion were significant predictors of functional cure.
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Affiliation(s)
- Jia-Feng Wu
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Department of Pediatrics, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chi-San Tai
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Kai-Chi Chang
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Yuh-Jue Chen
- Department of Pediatrics, National Taiwan University Hospital Yunlin Branch, Yunlin County, Taiwan
| | - Chien-Ting Hsu
- Department of Pediatrics, National Taiwan University BioMedical Park Hospital, Hsinchu County, Taiwan
| | - Huey-Ling Chen
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Education, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan; Graduate Institute of Medical Education and Bioethics, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Yen-Hsuan Ni
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Department of Pediatrics, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Mei-Hwei Chang
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
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4
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Yu HC, Chen CL, Lin KH, Hsu CY, Lee PT. Novel Hepatitis B Virus Reactivation Monitoring Strategies for Kidney Transplant Patients. Kidney Int Rep 2025; 10:601-604. [PMID: 39990886 PMCID: PMC11843105 DOI: 10.1016/j.ekir.2024.10.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 10/21/2024] [Accepted: 10/28/2024] [Indexed: 02/25/2025] Open
Affiliation(s)
- Hsien-Chung Yu
- Health Management Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Department of Nursing, Meiho Institute of Technology, Ping-Tung, Taiwan
| | - Chien-Liang Chen
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Kung-Hung Lin
- Health Management Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Chih-Yang Hsu
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Po-Tsang Lee
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
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Sheng B, Wang D, Wang J. Hepatitis B Virus Reactivation in Patients With HBV-Related Advanced Hepatocellular Carcinoma Undergoing Lenvatinib and Camrelizumab Treatment. Cancer Control 2025; 32:10732748241309046. [PMID: 39754312 DOI: 10.1177/10732748241309046] [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: 01/06/2025] Open
Abstract
OBJECTIVE This study aimed to evaluate hepatitis B virus (HBV) reactivation and its effect on tumor response and survival outcomes in patients with HBV-related advanced hepatocellular carcinoma (HCC) undergoing lenvatinib plus camrelizumab treatment. METHODS 216 patients with HBV-related advanced HCC receiving lenvatinib and camrelizumab were enrolled. Overall survival (OS), progression-free survival, and tumor response were evaluated. Univariate and multivariate analyses were performed to determine risk factors for HBV reactivation. RESULTS HBV reactivation occurred in 24 patients (11.1%). It was associated with poor survival and tumor response in these patients. Undetectable DNA levels, the absence of antiviral therapy, and high ALT levels were identified as vital risk factors for HBV reactivation. After receiving or adjusting the antiviral strategy, tumor response improved in patients with HBV reactivation. CONCLUSIONS HBV reactivation could occur in patients with HBV-related HCC, treated with lenvatinib and camrelizumab, worsening tumor response and patient survival. Regular monitoring of the indicators of HBV infection and effective antiviral treatments are recommended for these patients to prevent severe complications.
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Affiliation(s)
- Bi Sheng
- Department of Pharmacy, Wuhan Third Hospital, Wuhan, China
| | - Dong Wang
- Department of Oncology, Wuhan Union Hospital, Wuhan, China
| | - Jingjing Wang
- Department of Pharmacy, Wuhan Third Hospital, Wuhan, China
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Alhalabi MM, Almokdad R. The incidence of hepatitis B reactivation in patients receiving ustekinumab: a systematic review and proportional meta-analysis. Eur J Gastroenterol Hepatol 2025; 37:1-9. [PMID: 39621878 DOI: 10.1097/meg.0000000000002863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2024]
Abstract
BACKGROUND This meta-analysis will evaluate the risk of hepatitis B reactivation in patients treated with ustekinumab for inflammatory bowel disease and psoriasis. We aim to determine the true incidence of this adverse event, reconcile discrepancies in reported reactivation rates, and elucidate the associated risk. METHODS We conducted a rigorous systematic review adhering to established guidelines. Major databases like MEDLINE, Google Scholar, CENTRAL, and ClinicalTrials.gov were searched. Studies involving patients with documented hepatitis B infection undergoing ustekinumab therapy were included. Patients receiving concurrent antiviral medications were excluded. To account for potential underreporting, studies without reactivation events or with sample sizes ≥3 were also considered by using generalized linear mixed models and Clopper-Pearson confidence intervals. This review was prospectively registered in PROSPERO (CRD42023418130). RESULTS We analyzed data from nine studies involving 104 hepatitis B virus (HBV)-infected patients. The pooled HBV reactivation (HBVr) incidence among hepatitis B surface antigen-positive patients was 10% [95% confidence interval (CI): 0-31%], with low heterogeneity (I2 = 7.13%, τ2 = 0.4) and a nonsignificant Q-statistic (Q = 5.38, P = 0.37). For the occult HBV-infected patients, the pooled HBVr incidence was 3% (95% CI: 0-11%), with no heterogeneity (I2 = 0%, τ2 = 0.0) and a nonsignificant Q-statistic (Q = 2.7, P = 0.61). The reactivation rates showed high consistency across studies, with no significant difference between the two groups. CONCLUSIONS While our data suggest lower HBVr risk with ustekinumab, confirmation is needed due to limited sample size and retrospective design.
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Kuo MH, Ko PH, Wang ST, Tseng CW. Incidence of HBV Reactivation in Psoriasis Patients Undergoing Cytokine Inhibitor Therapy: A Single-Center Study and Systematic Review with a Meta-Analysis. Viruses 2024; 17:42. [PMID: 39861831 PMCID: PMC11769189 DOI: 10.3390/v17010042] [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: 11/26/2024] [Revised: 12/20/2024] [Accepted: 12/27/2024] [Indexed: 01/27/2025] Open
Abstract
BACKGROUND Psoriasis patients who are seropositive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) face an elevated risk of hepatitis B virus reactivation (HBVr) when treated with cytokine inhibitors. This study aims to elucidate the risk in this population. METHODS A retrospective chart review was conducted to assess the risk of HBVr in 73 psoriasis patients treated with cytokine inhibitors from 2013 to 2023. Additionally, a systematic review and meta-analysis were performed, pooling data from 10 studies (including our cohort) and adhering to PRISMA guidelines. Statistical heterogeneity was assessed using the I2 statistic, and pooled proportions were calculated using a random effects model. RESULTS No HBVr cases were observed among the 11 HBsAg+ patients in the cohort. However, two of the sixty-two (3.2%) HBsAg-/HBcAb+ patients experienced reactivation during therapy, with outcomes ranging from spontaneous recovery in one case to death from hepatic failure despite antiviral treatment in the other. The meta-analysis, pooling data from 10 studies, revealed a reactivation rate of 21.2% (95% CI: 9.4-41.0%) in HBsAg+ patients without prophylaxis and 4.4% (95% CI: 2.2-8.7%) in HBsAg-/HBcAb+ patients. CONCLUSION Antiviral prophylaxis is essential for HBsAg+ patients receiving cytokine inhibitors, given the high risk of reactivation. Despite the lower risk for HBsAg-/HBcAb+ patients, the potential severity of outcomes demands careful monitoring and timely action.
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Affiliation(s)
- Meng Hsuan Kuo
- Department of Pharmacy, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi 622, Taiwan;
| | - Ping-Hung Ko
- School of Medicine, Tzuchi University, Hualien 970, Taiwan; (P.-H.K.); (S.-T.W.)
- Division of Gastroenterology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi 622, Taiwan
| | - Sz-Tsan Wang
- School of Medicine, Tzuchi University, Hualien 970, Taiwan; (P.-H.K.); (S.-T.W.)
- Division of Rheumatology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi 622, Taiwan
| | - Chih-Wei Tseng
- School of Medicine, Tzuchi University, Hualien 970, Taiwan; (P.-H.K.); (S.-T.W.)
- Division of Gastroenterology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi 622, Taiwan
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Nowicka AA, Szymanek-Pasternak A, Janocha-Litwin J, Simon K. A Sleeping Giant: Late HBV Reactivation After Rituximab-Based Chemotherapy Despite Correct Prophylaxis. Int Med Case Rep J 2024; 17:1063-1067. [PMID: 39723430 PMCID: PMC11669280 DOI: 10.2147/imcrj.s495506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Accepted: 12/04/2024] [Indexed: 12/28/2024] Open
Abstract
Hepatitis B virus (HBV) reactivation is a recognized complication of long-term immunosuppressive or cytotoxic therapy, typically occurring during immunosuppression or within a few months after treatment. To mitigate this risk, hepatological societies recommend the use of nucleos(t)ide analogues (NA) for HBV reactivation prophylaxis, along with post-treatment monitoring; though, these recommendations are not universally consistent across different guidelines. We present a case of late HBV reactivation in a 76-year-old male with occult HBV infection who received rituximab-based therapy for chronic lymphocytic leukemia. In accordance with HBV reactivation guidelines, the patient was prescribed entecavir 0.5 mg daily during chemotherapy and for 18 months following the completion of hematological treatment. Despite adherence to these recommendations, the patient developed HBV reactivation 2 years and 5 months after the cessation of rituximab-based therapy, which progressed to acute HBV hepatitis. Our case emphasizes the need for extended follow-up in patients undergoing rituximab-based immunosuppression. It highlights the critical importance of vigilance for HBV reactivation and the potential consequences of delayed treatment. This case supports evidence on the unpredictability of HBV reactivation timelines and underscores the need for standardized monitoring protocols.
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Affiliation(s)
- Anna A Nowicka
- Clinical Department of Infectious Diseases and Hepatology, Wroclaw Medical University, Wroclaw, Poland
- First Department of Infectious Diseases, J. Gromkowski Specialistic Regional Hospital, Wroclaw, Poland
- Infermedica Sp. z o. o., Wrocław, Poland
| | - Anna Szymanek-Pasternak
- Clinical Department of Infectious Diseases and Hepatology, Wroclaw Medical University, Wroclaw, Poland
- First Department of Infectious Diseases, J. Gromkowski Specialistic Regional Hospital, Wroclaw, Poland
| | - Justyna Janocha-Litwin
- Clinical Department of Infectious Diseases and Hepatology, Wroclaw Medical University, Wroclaw, Poland
- First Department of Infectious Diseases, J. Gromkowski Specialistic Regional Hospital, Wroclaw, Poland
- Novum Clinic, sp. z o. o., Wrocław, Poland
| | - Krzysztof Simon
- Clinical Department of Infectious Diseases and Hepatology, Wroclaw Medical University, Wroclaw, Poland
- First Department of Infectious Diseases, J. Gromkowski Specialistic Regional Hospital, Wroclaw, Poland
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Lin F, Hao S, Xiao X, Li X. Association between Hepatitis B virus infection and COVID-19: outcomes from clinical analysis and online survey from Beijing, China. BMC Infect Dis 2024; 24:1438. [PMID: 39696010 DOI: 10.1186/s12879-024-10333-z] [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: 09/20/2024] [Accepted: 12/09/2024] [Indexed: 12/20/2024] Open
Abstract
OBJECTIVE We aim to investigate whether Coronavirus disease 2019 (COVID-19) worsens chronic hepatitis B virus(HBV)infection and explore the incidence of long COVID symptoms in patients with chronic hepatitis B virus infection. METHODS Patients with chronic HBV infection and COVID-19 patients attending the hepatitis clinic or fever clinic were included in the study. Clinical manifestations of COVID-19 and information about long COVID were collected for all patients. For patients with chronic hepatitis B virus infection, laboratory test results such as HBV-DNA, liver function, and kidney function were collected three months before and after COVID-19. RESULTS A total of 940 patients with COVID-19 were included in this study. These patients were divided into two groups: the hepatitis B virus infection group with 189 patients and the non-hepatitis B group with 751 patients. Further matching analysis was conducted, selecting 156 patients from each group. Within the hepatitis B group, patients were further divided into two subgroups based on whether they received antiviral therapy: 90 patients in the antiviral therapy group and 99 patients in the non-antiviral therapy group. Neither group experienced a significant increase in HBV-DNA after COVID-19. There were significant differences between the two groups regarding BMI and symptoms of sore throat, loss of smell, and nasal congestion during COVID-19. The incidence of long COVID symptoms was higher in the hepatitis B group compared to the non-hepatitis B group (64.1% vs. 48.7%, p < 0.001), with the top five symptoms being cough, fatigue, palpitations, insomnia, and memory impairment. CONCLUSION Patients with chronic HBV infection did not show a significant rise in HBV DNA after COVID-19 in this study. They had a lower incidence of COVID-19 symptoms but experienced a higher incidence of long COVID symptoms.
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Affiliation(s)
- Fei Lin
- Department of Infectious Diseases, Peking University Third Hospital, Beijing, China
| | - Sihan Hao
- The David C. Frederick Honors College, University of Pittsburgh, Pittsburgh, PA, USA
| | - Xiumei Xiao
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
| | - Xiaoguang Li
- Department of Infectious Diseases, Peking University Third Hospital, Beijing, China.
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10
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Zhang G, Yan H, Zhang H, Zhu L, Fu J. Drug-induced hepatitis B virus reactivation: insights from FAERS database analysis. Expert Opin Drug Saf 2024:1-6. [PMID: 39630586 DOI: 10.1080/14740338.2024.2438752] [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: 07/12/2024] [Revised: 09/27/2024] [Accepted: 09/30/2024] [Indexed: 12/07/2024]
Abstract
BACKGROUND Reactivation of the hepatitis B virus (HBV) induced by drugs is a commonly overlooked but clinically significant complication, posing risks of treatment interruptions, hepatitis exacerbation, liver failure, and even mortality. METHODS Disproportionality analyses were conducted on the Food and Drug Administration Adverse Event Reporting System (FAERS) database data spanning from January 2017 to December 2023 to detect drugs posing a risk of HBV reactivation (HBV-R). HBV-R cases were identified using the Medical Dictionary for Regulatory Activities (MedDRA), and drug generic names were ascertained from the DrugBank database. RESULTS A total of 2596 adverse event reports (AERs) were found to be related to drug-induced HBV-R.According to the disproportionality analysis, the top five drugs with the highest ROR and PRR were daklinza, vocabria, doxorubicin, sovaldi, and ribavirin. The top 40 drugs causing drug-induced HBV-R can be roughly divided into three categories: anti-tumor drugs, immunosuppressive drugs, and antiviral drugs. Among them, 23 drugs do not explicitly mention the risk of HBV-R in their drug instructions. CONCLUSIONS It was observed that some pharmaceuticals do not adequately address the risk of HBV-R in their drug documentation. These findings could assist healthcare providers in promptly recognizing drug-induced HBV-R.
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Affiliation(s)
- Genshan Zhang
- Department of Gastrointestinal Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hanpeng Yan
- Department of Gastrointestinal Surgery, Wuhan Hospital of Traditional Chinese and Western Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Haokun Zhang
- School of Public Health and Health Management, Gannan Medical University, Ganzhou, PR China
| | - Lin Zhu
- Department of Transfusion Medicine, Wuhan Hospital of Traditional Chinese and Western Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jie Fu
- Department of Nursing, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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11
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Mak LY, Liu K, Chirapongsathorn S, Yew KC, Tamaki N, Rajaram RB, Panlilio MT, Lui R, Lee HW, Lai JCT, Kulkarni AV, Premkumar M, Lesmana CRA, Hsu YC, Huang DQ. Liver diseases and hepatocellular carcinoma in the Asia-Pacific region: burden, trends, challenges and future directions. Nat Rev Gastroenterol Hepatol 2024; 21:834-851. [PMID: 39147893 DOI: 10.1038/s41575-024-00967-4] [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] [Accepted: 07/10/2024] [Indexed: 08/17/2024]
Abstract
Globally, nearly half of deaths from cirrhosis and chronic liver diseases (CLD) and three-quarters of deaths from hepatocellular carcinoma (HCC) occur in the Asia-Pacific region. Chronic hepatitis B is responsible for the vast majority of liver-related deaths in the region. Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common form of CLD, affecting an estimated 30% of the adult population. Compared with people of European descent, people from the Asia-Pacific region carry more genetic variants associated with MASLD and its progression. Alcohol is a fast-growing cause of CLD and HCC in Asia as a result of the rising per-capita consumption of alcohol. Drug-induced liver injury is under-recognized and probably has a high prevalence in this region. The epidemiological and outcome data of acute-on-chronic liver failure are heterogeneous, and non-unified definitions across regions contribute to this heterogeneity. CLDs are severely underdiagnosed, and effective treatments and vaccinations are underutilized. In this Review, we highlight trends in the burden of CLD and HCC in the Asia-Pacific region and discuss the rapidly changing aetiologies of liver disease. We examine the multiple gaps in the care cascade and propose mitigating strategies and future directions.
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Affiliation(s)
- Lung-Yi Mak
- The University of Hong Kong, Hong Kong, China
| | - Ken Liu
- The University of Sydney, Sydney, Australia
| | | | | | | | | | | | - Rashid Lui
- The Chinese University of Hong Kong, Hong Kong, China
| | - Hye Won Lee
- Yonsei University College of Medicine, Seoul, Korea
| | | | - Anand V Kulkarni
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Madhumita Premkumar
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | | | - Yao Chun Hsu
- Department of Medical Research, E-Da Hospital, Kaohsiung, Taiwan; School of Medicine and Graduate Institute of Medicine, I-Shou University, Kaohsiung, Taiwan
- School of Medicine and Graduate Institute of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Daniel Q Huang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
- Division of Gastroenterology and Hepatology, National University Hospital, Singapore, Singapore.
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12
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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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Hou KC, Su TH, Kao CN, Cheng HR, Tseng TC, Liu CJ, Hsieh SC, Kao JH. Rituximab carries high risks of hepatitis B virus reactivation in hematologic and rheumatic patients with chronic or resolved hepatitis B. J Gastroenterol Hepatol 2024; 39:2447-2455. [PMID: 39180413 DOI: 10.1111/jgh.16725] [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: 01/15/2024] [Revised: 06/04/2024] [Accepted: 08/09/2024] [Indexed: 08/26/2024]
Abstract
BACKGROUND AND AIM Rituximab therapy is associated with a high risk of hepatitis B virus (HBV) reactivation. We aimed to assess whether the risk of reactivation differed among various underlying diseases and between hepatitis B surface antigen (HBsAg) carriers and patients with resolved HBV infection. METHODS We retrospectively analyzed patients with chronic or resolved HBV infection who received rituximab without prophylactic anti-HBV therapy at a tertiary medical center. The risks of HBV reactivation, hepatitis, and hepatic decompensation were compared between the patients with hematologic and rheumatic diseases. RESULTS There were 78 patients with hematologic diseases and 39 patients with rheumatic diseases included. Among them, 43 (59%) HBsAg-positive patients and 24 (55%) patients with resolved HBV infection experienced HBV reactivation at a median of 14.6 months after rituximab therapy. After rituximab treatment, the 1-year HBV reactivation rate among patients with hematologic and rheumatic diseases was 29% and 45% in HBsAg-positive patients, respectively, while the rates were 38% and 17% in patients with resolved HBV infection. The reactivation risk continued to increase even 2 years after rituximab therapy and was comparable between hematologic and rheumatic patients. A higher baseline HBV DNA level (≥20 IU/mL vs <20 IU/mL) was an independent predictor for HBV reactivation (adjusted hazard ratio [aHR]: 10.9, 95% confidence interval [CI]: 1.1-107) and HBV-associated hepatitis (aHR: 14.8, 95% CI: 1.4-158). CONCLUSIONS Rituximab therapy is associated with a 50-64% risk of HBV reactivation regardless of underlying diseases and HBsAg status. HBV DNA levels should be assessed before initiating rituximab.
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Affiliation(s)
- Kuan-Chu Hou
- School of Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chien-Neng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan
| | - Huei-Ru Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Tai-Chung Tseng
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Song-Chou Hsieh
- Division of Rheumatology, Immunology and Allergy, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
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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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15
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Wang J, Jiang H, Zhang G, Dai X, Gao H, Li L. Real-World Pharmacovigilance Study Identifies Drugs Linked to Hepatitis B Virus Reactivation. J Med Virol 2024; 96:e70055. [PMID: 39558790 DOI: 10.1002/jmv.70055] [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: 09/03/2024] [Revised: 10/19/2024] [Accepted: 10/29/2024] [Indexed: 11/20/2024]
Abstract
Hepatitis B virus reactivation (HBVr) can be a serious clinical complication that has not been fully characterized in terms of the drugs associated with this adverse effect. Leveraging the expansive data available in the FDA Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report (JADER) databases, we conducted a retrospective analysis to identify drugs significantly linked to HBVr using three disproportionality analyses. Our study identified 44 drugs associated with HBVr, of which 35 did not have warnings in their product labels. The majority of these drugs were antineoplastic and immunomodulating agents, with a tendency for early occurrence of HBVr, particularly among antineoplastic agents and systemic corticosteroids. Additionally, entecavir, tenofovir disoproxil and tenofovir alafenamide demonstrated better safety profiles in preventing HBVr. These findings enhance our understanding of the demographic characteristics of patients at risk for HBVr, the drugs that pose a high risk for HBVr, the timing of such events, and the appropriate preventive medications. This knowledge contributes to the development of better prevention and treatment strategies, ultimately optimizing patient outcomes.
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Affiliation(s)
- Jie Wang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - He Jiang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Guoqi Zhang
- Department of Critical Care Medicine, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, Zhejiang Province, China
| | - Xiahong Dai
- Department of Infectious Diseases, ShuLan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, Zhejiang Province, China
| | - Hainv Gao
- Department of Infectious Diseases, ShuLan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, Zhejiang Province, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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16
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Price CF, Wood JP, Ismail I, Smith S, Hanson J. The Incidence, Aetiology and Clinical Course of Serious Infections Complicating Biological and Targeted Synthetic Disease-Modifying Antirheumatic Drug Therapy in Patients with Rheumatoid Arthritis in Tropical Australia. Pathogens 2024; 13:943. [PMID: 39599496 PMCID: PMC11597851 DOI: 10.3390/pathogens13110943] [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: 09/27/2024] [Revised: 10/24/2024] [Accepted: 10/28/2024] [Indexed: 11/29/2024] Open
Abstract
Introduction: Patients receiving biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) for rheumatological conditions are at an increased risk of serious, potentially life-threatening, infection. However, the incidence, aetiology, and clinical course of serious infection in patients receiving b/tsDMARDs in tropical settings are incompletely defined. Methods: We retrospectively reviewed all patients with rheumatoid arthritis receiving b/tsDMARDs between October 2012 and October 2021, at Cairns Hospital in tropical Australia. The incidence, aetiology, and clinical course of serious infections (those requiring admission to hospital or parenteral antibiotics) were determined. Results: 310 patients had 1468 patient years of b/tsDMARD therapy during the study period; 74/310 (24%) had 147 serious infections translating to an overall risk of 10.0 episodes of serious infection per 100 patient years. The respiratory tract (50/147, 34%) and skin (37/147, 25%) were the most frequently affected sites. A pathogen was identified in 59/147 (40%) episodes and was most commonly Staphylococcus aureus (24/147, 16%). Only 2/147 (1%) were confirmed "tropical infections": 1 case of Burkholderia pseudomallei and 1 case of mixed B. pseudomallei and community-acquired Acinetobacter baumannii infection. Overall, 13/147 (9%) episodes of serious infection required Intensive Care Unit admission (0.9 per 100-patient years of b/tsDMARD therapy) and 4/147 (3%) died from their infection (0.3 per 100-patient years of b/tsDMARD therapy). The burden of comorbidity and co-administration of prednisone were the strongest predictors of death or a requirement for ICU admission. Conclusions: The risk of serious infection in patients taking b/tsDMARDs in tropical Australia is higher than in temperate settings, but this is not explained by an increased incidence of traditional tropical pathogens.
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Affiliation(s)
- Cody F. Price
- Department of Medicine, Cairns Hospital, Cairns, QLD 4870, Australia; (C.F.P.); (J.P.W.); (I.I.); (S.S.)
| | - John P. Wood
- Department of Medicine, Cairns Hospital, Cairns, QLD 4870, Australia; (C.F.P.); (J.P.W.); (I.I.); (S.S.)
- College of Medicine and Dentistry, James Cook University, Cairns, QLD 4878, Australia
| | - Ibrahim Ismail
- Department of Medicine, Cairns Hospital, Cairns, QLD 4870, Australia; (C.F.P.); (J.P.W.); (I.I.); (S.S.)
| | - Simon Smith
- Department of Medicine, Cairns Hospital, Cairns, QLD 4870, Australia; (C.F.P.); (J.P.W.); (I.I.); (S.S.)
| | - Josh Hanson
- Department of Medicine, Cairns Hospital, Cairns, QLD 4870, Australia; (C.F.P.); (J.P.W.); (I.I.); (S.S.)
- The Kirby Institute, University of New South Wales, Kensington, NSW 2052, Australia
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Mihai N, Olariu MC, Ganea OA, Adamescu AI, Molagic V, Aramă ȘS, Tilișcan C, Aramă V. Risk of Hepatitis B Virus Reactivation in COVID-19 Patients Receiving Immunosuppressive Treatment: A Prospective Study. J Clin Med 2024; 13:6032. [PMID: 39457983 PMCID: PMC11508539 DOI: 10.3390/jcm13206032] [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: 09/13/2024] [Revised: 10/04/2024] [Accepted: 10/08/2024] [Indexed: 10/28/2024] Open
Abstract
Objectives: This study aimed to evaluate the risk of hepatitis B virus reactivation (HBVr) in COVID-19 patients receiving immunosuppressive treatment, which has been insufficiently studied to date. Secondarily, we aimed to evaluate the seroprevalence of HBV infection in COVID-19 patients. Methods: We performed HBV screening on all Romanian adults hospitalized in four COVID-19 wards between October 2021 and September 2022. We enrolled patients with positive hepatitis B core antibody (anti-HBc) without protective hepatitis B surface antibody (anti-HBs), HBV treatment, or baseline immunosuppressive conditions, and we conducted a virological follow-up on these patients at 3 months. Results: We identified 333/835 (39.9%) anti-HBc-positive patients. Follow-up was performed for 13 patients with positive hepatitis B surface antigen (HBsAg) and 19 HBsAg-negative/anti-HBc-positive patients. Among those who received immunosuppressants, 4/23 (17.4%) patients experienced HBVr: 1 out of 8 (12.5%) HBsAg-positive patients (with 1.99 log increase in HBV DNA level) and 3 out of 15 (20%) HBsAg-negative/anti-HBc-positive patients (with a de novo detectable HBV DNA level). Conclusions: Administration of COVID-19 immunosuppressants may result in a significant risk of HBVr in co-infected patients. We recommend performing an HBV triple screen panel (HBsAg, anti-HBs, anti-HBc) for all COVID-19 patients receiving immunosuppressive treatment. HBV prophylaxis may be indicated in certain patients. Larger studies are needed in order to establish appropriate and cost-effective management for these patients.
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Affiliation(s)
- Nicoleta Mihai
- Faculty of Medicine, University of Medicine and Pharmacy ‘Carol Davila’, No 37, Dionisie Lupu, 020021 Bucharest, Romania; (N.M.); (O.-A.G.); (V.M.); (V.A.)
- National Institute of Infectious Diseases ‘Matei Bals’, 1 Dr. Calistrat Grozovici, 021105 Bucharest, Romania; (A.-I.A.); (Ș.S.A.); (C.T.)
| | - Mihaela Cristina Olariu
- Faculty of Medicine, University of Medicine and Pharmacy ‘Carol Davila’, No 37, Dionisie Lupu, 020021 Bucharest, Romania; (N.M.); (O.-A.G.); (V.M.); (V.A.)
- National Institute of Infectious Diseases ‘Matei Bals’, 1 Dr. Calistrat Grozovici, 021105 Bucharest, Romania; (A.-I.A.); (Ș.S.A.); (C.T.)
| | - Oana-Alexandra Ganea
- Faculty of Medicine, University of Medicine and Pharmacy ‘Carol Davila’, No 37, Dionisie Lupu, 020021 Bucharest, Romania; (N.M.); (O.-A.G.); (V.M.); (V.A.)
- National Institute of Infectious Diseases ‘Matei Bals’, 1 Dr. Calistrat Grozovici, 021105 Bucharest, Romania; (A.-I.A.); (Ș.S.A.); (C.T.)
| | - Aida-Isabela Adamescu
- National Institute of Infectious Diseases ‘Matei Bals’, 1 Dr. Calistrat Grozovici, 021105 Bucharest, Romania; (A.-I.A.); (Ș.S.A.); (C.T.)
- Faculty of Dental Medicine, University of Medicine and Pharmacy ‘Carol Davila’, No 37, Dionisie Lupu, 020021 Bucharest, Romania
| | - Violeta Molagic
- Faculty of Medicine, University of Medicine and Pharmacy ‘Carol Davila’, No 37, Dionisie Lupu, 020021 Bucharest, Romania; (N.M.); (O.-A.G.); (V.M.); (V.A.)
- National Institute of Infectious Diseases ‘Matei Bals’, 1 Dr. Calistrat Grozovici, 021105 Bucharest, Romania; (A.-I.A.); (Ș.S.A.); (C.T.)
| | - Ștefan Sorin Aramă
- National Institute of Infectious Diseases ‘Matei Bals’, 1 Dr. Calistrat Grozovici, 021105 Bucharest, Romania; (A.-I.A.); (Ș.S.A.); (C.T.)
- Faculty of Dental Medicine, University of Medicine and Pharmacy ‘Carol Davila’, No 37, Dionisie Lupu, 020021 Bucharest, Romania
| | - Cătălin Tilișcan
- National Institute of Infectious Diseases ‘Matei Bals’, 1 Dr. Calistrat Grozovici, 021105 Bucharest, Romania; (A.-I.A.); (Ș.S.A.); (C.T.)
- Faculty of Dental Medicine, University of Medicine and Pharmacy ‘Carol Davila’, No 37, Dionisie Lupu, 020021 Bucharest, Romania
| | - Victoria Aramă
- Faculty of Medicine, University of Medicine and Pharmacy ‘Carol Davila’, No 37, Dionisie Lupu, 020021 Bucharest, Romania; (N.M.); (O.-A.G.); (V.M.); (V.A.)
- National Institute of Infectious Diseases ‘Matei Bals’, 1 Dr. Calistrat Grozovici, 021105 Bucharest, Romania; (A.-I.A.); (Ș.S.A.); (C.T.)
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18
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Xiong D, Cai W, Zhao W. Risk factors of HBV reactivation in leukemia patients with resolved HBV infection after allogeneic hematopoietic stem cell transplantation. Clin Res Hepatol Gastroenterol 2024; 48:102447. [PMID: 39181184 DOI: 10.1016/j.clinre.2024.102447] [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: 01/29/2024] [Revised: 08/12/2024] [Accepted: 08/14/2024] [Indexed: 08/27/2024]
Abstract
BACKGROUND The hepatitis B surface antigen (HBsAg)-negative and antibody to hepatitis B core antigen (anti-HBc)-positive patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk of HBV reactivation (HBVr). METHODS To analyze the risk factors for HBVr, a total of 1,042 leukemia patients(≥18years of age), who underwent allo-HSCT from January 2016 to April 2022 in The First Affiliated Hospital of Soochow University, were enrolled in the study. Finally, 193 leukemia patients with resolved HBV infection were included into the study. RESULTS HBVr occurred in 22 patients (11.39 %), and the median time to HBVr was 24 months (with a range of 11-51months). Hepatitis flares developed in 22.73 % of patients with HBVr, and hepatic failure occurred in 1 patient. During the follow-up period, only 1(1.3 %) patient experienced HBVr among 79 patients with antiviral prophylaxis. While 21(18.42 %) patients experienced HBVr among 114 patients without antiviral prophylaxis. The cumulative incidence of HBV reactivation at 3 years was 44.4. % for anti-HBs-negative donors/recipients with a low anti-HBs titer (<100IU/L) and 7.1 % for anti-HBs-positive donors/recipients with a high anti-HBs titer (≥100IU/L) respectively. In addition, univariate and multivariate Cox regression analyses confirmed the use of rituximab as a risk factor for HBV reactivation. CONCLUSION The univariate and multivariate analyses confirmed that the anti-HBs titer in both recipients and donors are protective indicators to prevent incidence of HBVr. In addition, antiviral prophylaxis can significantly reduce the incidence of HBVr.
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Affiliation(s)
- Danping Xiong
- Department of Infection Diseases, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Wen Cai
- Department of Infection Diseases, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Weifeng Zhao
- Department of Infection Diseases, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
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Wang CW, Huang CF, Yeh ML, Liang PC, Jang TY, Wei YJ, Hsu PY, Hsieh MY, Lin YH, Huang JF, Dai CY, Chuang WL, Yu ML. Assessment of hepatitis B virus relapse in cancer patients receiving chemotherapy with prophylactic nucleos(t)ide analogues: Implications for overall mortality. Liver Int 2024; 44:2592-2604. [PMID: 38984849 DOI: 10.1111/liv.16030] [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: 02/16/2024] [Revised: 05/24/2024] [Accepted: 06/26/2024] [Indexed: 07/11/2024]
Abstract
BACKGROUND AND AIMS We aimed to explore the risk factors associated with virological and clinical relapse, as well as their impact on overall mortality, in hepatitis B virus (HBV)-infected patients receiving nucleos(t)ide analogues (NUCs) therapy prior to chemotherapy initiation. METHODS From 2010 to 2020, we conducted a prospective cohort study involving patients with HBV infection undergoing cytotoxic chemotherapy. We utilized the Kaplan-Meier method and Cox proportional hazard regression models to assess risk factors. RESULTS We observed that TDF or TAF (HR: 2.16, 95% CI 1.06-4.41; p = .034), anthracycline (HR: 1.73, 95% CI 1.10-2.73; p = .018), baseline HBV DNA (HR: 1.55, 95% CI 1.33-1.81; p < .001) and end-of-treatment HBsAg titre >100 IU/mL (HR: 7.81, 95% CI 1.94-31.51; p = .004) were associated with increased risk of virological relapse. Additionally, TDF or TAF (HR: 4.91, 95% CI 1.45-16.64; p = .011), baseline HBV DNA (HR: 1.48, 95% CI 1.10-1.99; p = .009) and end-of-treatment HBsAg titre >100 IU/mL (HR: 6.09, 95% CI .95-38.87; p = .056) were associated with increased risk of clinical relapse. Furthermore, we found that virological relapse (HR: 3.32, 95% CI 1.33-8.32; p = .010) and clinical relapse (HR: 3.59, 95% CI 1.47-8.80; p = .005) significantly correlated with all-cause mortality in HBV patients receiving cytotoxic chemotherapy with prophylactic NUCs therapy. CONCLUSIONS The risk of virological and clinical relapse was linked to baseline HBV DNA, end-of-treatment HBsAg levels and TDF or TAF for prophylaxis; additionally, experiencing relapse heightens the risk of all-cause mortality. Further research is warranted to explore potential strategies for preventing virological and clinical relapse in high-risk patients.
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Affiliation(s)
- Chih-Wen Wang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Po-Cheng Liang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Tyng-Yuan Jang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yu-Ju Wei
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Po-Yao Hsu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Yen Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Hung Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan
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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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21
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Oon HH, Tan C, Aw DCW, Chong WS, Koh HY, Leung YY, Lim KS, Pan JY, Tan EST, Tan KW, Tham SN, Theng C, Wong SN. 2023 guidelines on the management of psoriasis by the Dermatological Society of Singapore. ANNALS OF THE ACADEMY OF MEDICINE, SINGAPORE 2024; 53:562-577. [PMID: 39373375 DOI: 10.47102/annals-acadmedsg.2023367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/08/2024]
Abstract
Introduction Psoriasis is a multisystem, chronic, inflammatory dermatological disease. In routine clinical practice, the management of psoriasis varies significantly. The current study aimed to develop a set of practice guidelines relevant to dermatology practice in Singapore. Method The Psoriasis Therapeutic Guidelines Workgroup, comprising members of the Dermato-logical Society of Singapore with a subspecialisation in psoriasis, was convened to develop the guidelines. Clinical questions on selected topics were generated and refined by the workgroup. A literature search using PubMed was performed on their assigned topics from June 2013 to December 2023. The articles were included and graded based on the level of evidence. Results The guidelines address topics ranging from clinical assessment to practical considerations in the management of mild, moderate and severe psoriasis, including delivery of care, referrals to specialists and adherence to treatment. The recommended therapies include phototherapy, methotrexate, acitretin, cyclosporine; apremilast; topical corticoste-roids, calcipotriol, topical calcineurin inhibitors; and biologics (i.e. adalimumab, infliximab, secukinumab, ixekizumab, ustekinumab, etanercept) either in combina-tion or as monotherapy. Common therapeutic concerns relating to biologic use were addressed. Recommendations on generalised pustular psoriasis, palmoplantar pustular psoriasis and psoriatic arthritis were also made. Patients on systemic therapy would receive appropriate vaccine counselling. Therapeutic implica-tions in special populations, such as pregnant/ lactating women, children, the elderly, those undergo-ing surgery and those suffering from specific infections and cancer were addressed. Conclusion These guidelines were developed for dermatologists, family physicians, rheumatologists and other specialists to support their selection of appropriate management options.
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Affiliation(s)
| | - Chris Tan
- Division of Dermatology, National University Hospital, Singapore
| | | | | | - Hong Yi Koh
- TSN Dermatology Skin Specialist Clinic, Singapore
| | - Ying-Ying Leung
- Department of Rheumatology and Immunology, Singapore General Hospital, Singapore
- Duke-NUS Medical School, Singapore
| | | | | | | | - Ki Wei Tan
- Department of Dermatology, Changi General Hospital, Singapore
| | | | - Colin Theng
- The Skin Specialists & Laser Clinic, Singapore
| | - Su-Ni Wong
- Dr SN Wong Skin, Hair, Nails & Laser Specialist Clinic, Singapore
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22
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Shenavandeh S, Taghavi SA, Nekooeian A, Moini M. Pharmacological considerations in pharmacotherapy of rheumatology patients with liver disease: a brief narrative review. Reumatologia 2024; 62:282-293. [PMID: 39381733 PMCID: PMC11457314 DOI: 10.5114/reum/191791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Accepted: 07/30/2024] [Indexed: 10/10/2024] Open
Abstract
The presence of chronic liver diseases such as metabolic dysfunction-associated steatosis liver disease, viral hepatitis, and cirrhosis may affect the treatment plan in patients with rheumatologic disorders, with concern about the adverse effects of the rheumatic medications on the course of liver disease. Advanced liver disease can change the elimination and activation of many drugs. In addition, there are concerns about the risk of viral reactivation after using biologics and immunosuppressants in patients with chronic viral hepatitis. This narrative review will assess the considerations that should be made before starting the most frequently used drugs in all common rheumatic diseases and patients with chronic liver diseases including chronic viral hepatitis.
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Affiliation(s)
- Saeedeh Shenavandeh
- Division of Rheumatology, Department of Internal Medicine, Shiraz University of Medical Science, Iran
| | | | | | - Maryam Moini
- Division of Gastroenterology, University of Ottawa, Canada
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23
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Zong Y, Kamoi K, Miyagaki M, Zhang J, Yang M, Zou Y, Ohno-Matsui K. Applications of Biological Therapy for Latent Infections: Benefits and Risks. Int J Mol Sci 2024; 25:9184. [PMID: 39273134 PMCID: PMC11394918 DOI: 10.3390/ijms25179184] [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: 07/18/2024] [Revised: 08/20/2024] [Accepted: 08/22/2024] [Indexed: 09/15/2024] Open
Abstract
Biological therapies have revolutionized medical treatment by targeting the key mediators or receptors involved in inflammatory responses, thereby effectively suppressing inflammation and achieving beneficial outcomes. They are more advanced than conventional therapies using corticosteroids and immunosuppressants, offering effective solutions for autoimmune diseases, cancer, transplant rejection, and various infectious diseases, including coronavirus disease 2019. Although they exert low immunosuppressive effects, biological therapies can reactivate specific biological targets associated with infections. This review summarizes the currently available biological therapies and discusses their immunosuppressive mechanisms and clinical applications, highlighting the variations in the types and frequencies of infection recurrence induced by different biological agents. Additionally, this review describes the risk factors associated with various biological agents, thus aiding clinicians in selecting the most appropriate biological therapy.
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Affiliation(s)
- Yuan Zong
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
| | - Koju Kamoi
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
| | - Miki Miyagaki
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
| | - Jing Zhang
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
| | - Mingming Yang
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
| | - Yaru Zou
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
| | - Kyoko Ohno-Matsui
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
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24
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Gish R, Agarwal K, Mahajan A, Desai S, Kharawala S, Elston R, Das J, Kendrick S, Gielen V. Nucleos(t)ide Analog Treatment Discontinuation in Chronic Hepatitis B Virus Infection: A Systematic Literature Review. GASTRO HEP ADVANCES 2024; 4:100536. [PMID: 39790247 PMCID: PMC11714690 DOI: 10.1016/j.gastha.2024.08.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Accepted: 08/16/2024] [Indexed: 01/03/2025]
Abstract
Background and Aims The aim of this systematic literature review (SLR) was to examine outcomes and associated predictors following nucleos(t)ide analog (NA) treatment cessation in adult patients with chronic hepatitis B virus infection. Methods The SLR was conducted according to PRISMA methodology. All included studies were quality assessed using appropriate scales or checklists. Results The SLR identified 145 studies. Cumulative rates of clinical relapse (40 studies), virological relapse (53 studies), biochemical relapse (10 studies) and retreatment events (14 studies) post NA cessation varied widely across studies (clinical relapse: 40%-65%, virological relapse: 75%-94%, biochemical relapse: 63%-73%, retreatment rates: 30%-78% at 24 and 144 weeks, respectively). Significant predictors with adequate evidence of clinical relapse included older age, male gender, and higher hepatitis B surface antigen (HBsAg) and hepatitis B virus DNA at baseline and end of treatment. HBsAg loss was reported in 25 studies, with overall median HBsAg loss rates ranging from 2% at 24 weeks (5 studies) to 11% at 192 weeks (2 studies) post NA cessation. There was adequate evidence for lower HBsAg level at baseline and end of treatment as a significant and consistent predictor of HBsAg loss. Conclusion There is considerable heterogeneity among studies of NA cessation. Data are currently incomplete to provide strong recommendations for NA cessation or to identify patients who may benefit most from this approach in clinical practice. Further studies are required to provide clearer guidelines, and tools to assess and monitor patients who may benefit from NA treatment cessation.
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Affiliation(s)
- Robert Gish
- Hepatitis B Foundation, Doylestown, Pennsylvania
| | - Kosh Agarwal
- Institute of Liver Studies, King’s College Hospital, London, UK
| | | | | | | | - Rob Elston
- Clinical Research, GSK, Stevenage, Hertfordshire, UK
| | - Joyeta Das
- Hepatology Global Medical Affairs, GSK, London, UK
| | | | - Vera Gielen
- Value Evidence and Outcomes, GSK, London, UK
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25
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Erdogan T, Cansu C, Kocer B, Akkaya S, Kokmen H. Real-world effectiveness, safety and immunogenicity of ocrelizumab in turkish multiple sclerosis patients: a single-center experience for 4-year follow-up. Acta Neurol Belg 2024; 124:1385-1391. [PMID: 38769274 DOI: 10.1007/s13760-024-02572-3] [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: 02/09/2024] [Accepted: 05/06/2024] [Indexed: 05/22/2024]
Abstract
OBJECTIVE The aim of this study was to evaluate postmarketing ocrelizumab safety and effectiveness in a real-world population with multiple sclerosis (MS) and matching these parameters among MS disease types. METHODS This was a retrospective, single-center study with MS patients treated with ocrelizumab. Demographic, clinical characteristics and immunological data were analyzed, including annualized relapse rate (ARR), relapse-free rate, Expanded Disability Status Scale (EDSS), complete blood count parameters, immunoglobulin (Ig) levels, liver function tests (LFT), hepatitis markers and adverse events in the 4-year follow-up. A total of 96 patients, 22 with relapsing-remitting MS (RRMS), 54 with secondary progressive MS (SPMS), and 20 with primary progressive MS (PPMS) who were treated with at least two doses of ocrelizumab between January 2018 and September 2023 were included in the study. RESULTS Sixty-five (68%) were women and 31 (32%) were men. The mean age was 48.4 ± 11.1 years (20-70 years). Ninety-three patients were evaluated in the first year, 65 in the second year, 39 in the third year and 24 in the fourth year of treatment. 96% of patients were relapse-free rate in the first year, 91% in the second year, 85% in the third year and 75% in the fourth year. Eighty-six percent of patients were progression free in the 1st year of treatment, 71% in the 2nd year, in 64% in the 3rd year, and in 62% in the 4th year. During the follow-up of the cases, EDSS remained stable in 77% of RRMS patients, improved in 14%, and worsened in 9%; while EDSS remained stable in 65% of SPMS patients with attacks, it improved in 9% and worsened in 26%; while EDSS remained stable in 60% of PPMS patients, worsening was observed in 40%. There is a significant decrease in IgM and IgG values during the follow-up of ocrelizumab therapy (p < 0.001, p = 0.014). There is no significant difference in IgA, lymphocyte and neutrophil values (p = 0.713, p = 0.086, p = 0.999). No significant relationship was found between low serum IgM levels and the risk of developing infection (p > 0.05). Liver function tests was found to be within normal limits in 94% of the patients over a 4-year period. No hepatitis B, C or A infection, hepatitis B reactivation, tuberculosis, HIV infection, malignancy or drug related death occurred during 4-years follow-up. The most common side effect during ocrelizumab treatment is urinary tract infection (29%); others were upper respiratory tract infections (13%), numbness/tingling of the face, trunk, or extremities (8%), insomnia (6%), headache (5%), and soft tissue infections (cellulitis and dental abscess, 2%). CONCLUSIONS Our results show that ocrelizumab reduces the frequency of attacks and prevent the disease progression in RRMS patients, and reducing the disease progression by primarily stabilizing EDSS scores in SPMS with attacks and PPMS. It is thought that the relatively high rates of urinary tract infection detected in this study may be related with advanced stage of the disease. The absence of hepatitis B reactivation, chronic infection or malignancy in the 4-year follow-up of our cases supports the long-term safety of ocrelizumab treatment. Ocrelizumab may be preferred as an effective and reliable treatment of different types of MS due to non-serious side effects.
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Affiliation(s)
- Tugba Erdogan
- Department of Neurology, Gazi University School of Medicine, Emniyet Mahallesi, Mevlana Bulvari No: 29, 06560, Ankara, Turkey.
| | - Cagri Cansu
- Department of Neurology, Gazi University School of Medicine, Emniyet Mahallesi, Mevlana Bulvari No: 29, 06560, Ankara, Turkey
| | - Belgin Kocer
- Department of Neurology, Gazi University School of Medicine, Emniyet Mahallesi, Mevlana Bulvari No: 29, 06560, Ankara, Turkey
| | - Sedanur Akkaya
- Department of Neurology, Gazi University School of Medicine, Emniyet Mahallesi, Mevlana Bulvari No: 29, 06560, Ankara, Turkey
| | - Helin Kokmen
- Department of Neurology, Gazi University School of Medicine, Emniyet Mahallesi, Mevlana Bulvari No: 29, 06560, Ankara, Turkey
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26
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Lee Y, Seong J, Ahn S, Han M, Lee JA, Kim JH, Ahn JY, Ku NS, Choi JY, Yeom JS, Kim BK, Jeong SJ. Hepatitis B Reactivation and Vaccination Effectiveness after Solid Organ Transplantation: A Matched Case-Control Study. Vaccines (Basel) 2024; 12:804. [PMID: 39066442 PMCID: PMC11281428 DOI: 10.3390/vaccines12070804] [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: 06/21/2024] [Revised: 07/13/2024] [Accepted: 07/18/2024] [Indexed: 07/28/2024] Open
Abstract
Solid organ transplant (SOT) recipients are at significant risk of hepatitis B (HB) virus (HBV) reactivation (HBVr). Despite the clinical significance of HBVr after solid organ transplantation, data on the risk factors for HBVr and vaccine effectiveness in SOT recipients with resolved HBV infection are limited. This study evaluated the risk factors for HBVr and the seroconversion rates after HBV vaccination in SOT recipients. Patients who had undergone solid organ transplantation and those with a resolved HBV infection were identified. We matched patients who experienced post-transplantation HBVr with those who did not. We also explored the characteristics and seroconversion rates of HBV-vaccinated patients following transplantation. In total, 1299 SOT recipients were identified as having a resolved HBV infection at the time of transplantation. Thirty-nine patients experienced HBVr. Pre-transplant HB surface antibodies (anti-HBs) positivity and allograft rejection within 3 months after transplantation were independently associated with HBVr. Among the 17 HBV-vaccinated patients, 14 (82.4%) received three or fewer vaccine doses, and 13 (76.5%) had seroconversion with positive anti-HBs results. Pre-transplant anti-HBs(-) status and allograft rejection were risk factors for HBVr in SOT recipients with a resolved HBV infection, and HBV vaccination after transplantation resulted in a high rate of anti-HBs seroconversion. HBV vaccination after transplantation should be considered to reduce the HBVr risk.
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Affiliation(s)
- Yongseop Lee
- Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; (Y.L.); (J.S.); (S.A.); (M.H.); (J.A.L.); (J.H.K.); (J.Y.A.); (N.S.K.); (J.Y.C.); (J.-S.Y.)
| | - Jaeeun Seong
- Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; (Y.L.); (J.S.); (S.A.); (M.H.); (J.A.L.); (J.H.K.); (J.Y.A.); (N.S.K.); (J.Y.C.); (J.-S.Y.)
| | - Sangmin Ahn
- Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; (Y.L.); (J.S.); (S.A.); (M.H.); (J.A.L.); (J.H.K.); (J.Y.A.); (N.S.K.); (J.Y.C.); (J.-S.Y.)
| | - Min Han
- Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; (Y.L.); (J.S.); (S.A.); (M.H.); (J.A.L.); (J.H.K.); (J.Y.A.); (N.S.K.); (J.Y.C.); (J.-S.Y.)
| | - Jung Ah Lee
- Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; (Y.L.); (J.S.); (S.A.); (M.H.); (J.A.L.); (J.H.K.); (J.Y.A.); (N.S.K.); (J.Y.C.); (J.-S.Y.)
| | - Jung Ho Kim
- Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; (Y.L.); (J.S.); (S.A.); (M.H.); (J.A.L.); (J.H.K.); (J.Y.A.); (N.S.K.); (J.Y.C.); (J.-S.Y.)
| | - Jin Young Ahn
- Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; (Y.L.); (J.S.); (S.A.); (M.H.); (J.A.L.); (J.H.K.); (J.Y.A.); (N.S.K.); (J.Y.C.); (J.-S.Y.)
| | - Nam Su Ku
- Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; (Y.L.); (J.S.); (S.A.); (M.H.); (J.A.L.); (J.H.K.); (J.Y.A.); (N.S.K.); (J.Y.C.); (J.-S.Y.)
| | - Jun Yong Choi
- Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; (Y.L.); (J.S.); (S.A.); (M.H.); (J.A.L.); (J.H.K.); (J.Y.A.); (N.S.K.); (J.Y.C.); (J.-S.Y.)
| | - Joon-Sup Yeom
- Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; (Y.L.); (J.S.); (S.A.); (M.H.); (J.A.L.); (J.H.K.); (J.Y.A.); (N.S.K.); (J.Y.C.); (J.-S.Y.)
| | - Beom Kyung Kim
- Institute of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea;
| | - Su Jin Jeong
- Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; (Y.L.); (J.S.); (S.A.); (M.H.); (J.A.L.); (J.H.K.); (J.Y.A.); (N.S.K.); (J.Y.C.); (J.-S.Y.)
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Çelik M, Baba C, Irmak Ç, Özakbaş S, Avkan-Oğuz V. Risk of hepatitis B virus reactivation in people with multiple sclerosis treated with ocrelizumab: an observational study from Turkey. J Neurol 2024; 271:4131-4137. [PMID: 38578494 PMCID: PMC11233278 DOI: 10.1007/s00415-024-12333-0] [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: 01/10/2024] [Revised: 03/04/2024] [Accepted: 03/13/2024] [Indexed: 04/06/2024]
Abstract
BACKGROUND The risk of hepatitis B virus (HBV) reactivation remains unclear in people with multiple sclerosis (MS) receiving ocrelizumab. We aimed to assess HBV seroprevalence and reactivation risk in MS patients on ocrelizumab and to evaluate the effectiveness of antiviral prophylaxis against HBV reactivation. METHODS In this single-center, cross-sectional study, 400 people with MS receiving ocrelizumab were screened for HBV at baseline and antiviral prophylaxis was implemented based on serological results. Patients were monitored for HBV reactivation, and outcomes were analyzed. RESULTS Among 56 (14%) patients who had serology compatible with occult or resolved HBV infection, 49 (85.7%) received antiviral prophylaxis regularly and had no HBV reactivation during the follow-up. Reactivation of HBV occurred in 2 out of 7 (28.6%) patients who did not receive antiviral prophylaxis and in one patient who did not adhere to the prophylaxis regimen. All patients with reactivation had anti-HBs levels below 100 mIU/mL and the median titer was significantly lower than the patients with no HBV reactivation (p = 0.034). CONCLUSION This study highlights a 14% anti-HBc positivity, indicating a potential risk for HBV reactivation in people with MS receiving ocrelizumab. This suggests the importance of vigilant monitoring and the implementation of prophylactic measures. Our recommendation emphasizes antiviral prophylaxis, particularly for patients with low anti-HBs, and a pre-emptive strategy for others.
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Affiliation(s)
- Muammer Çelik
- Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology, Dokuz Eylul University, 35330, Izmir, Turkey.
| | - Cavid Baba
- Dokuz Eylul University, Graduate School of Health Sciences and Urla State Hospital, Izmir, Turkey
| | - Çağlar Irmak
- Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology, Dokuz Eylul University, 35330, Izmir, Turkey
| | - Serkan Özakbaş
- Faculty of Medicine, Department of Neurology, Izmir University of Economics, Izmir, Turkey
| | - Vildan Avkan-Oğuz
- Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology, Dokuz Eylul University, 35330, Izmir, Turkey
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Chiu CY, Brumble LM, Vikram HR, Watt KD, Beam E. Hepatitis B Virus Reactivation in Non-Liver Solid Organ Transplantation: Incidence and Risk Analysis. Clin Transplant 2024; 38:e15389. [PMID: 38952185 DOI: 10.1111/ctr.15389] [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: 03/06/2024] [Revised: 06/05/2024] [Accepted: 06/08/2024] [Indexed: 07/03/2024]
Abstract
INTRODUCTION Hepatitis B virus reactivation (HBVr) can occur in solid organ transplant (SOT) recipients with previously inactive hepatitis B virus (HBV) infection. Previous studies have reported that HBVr is generally less than 10% in nonliver SOT recipients with past HBV infection. METHODS We conducted a retrospective study from January 2018 to August 2023 at Mayo Clinic sites in Arizona, Florida, and Minnesota. We examined the antiviral prophylaxis strategy used and the characteristics of HBVr in hepatitis B core antibody-positive (HBcAb +) nonliver SOT adult recipients. Past HBV infection was defined as HBcAb + / hepatitis B surface antigen (HBsAg) -. Chronic HBV infection was defined as HBcAb + / HBsAg +. RESULTS A total of 180 nonliver SOT recipients were identified during the study period. Indefinite antiviral prophylaxis was utilized in 77 recipients, and none developed HBVr after transplantation. In 103 recipients without antiviral prophylaxis, the incidence of HBVr was 12% (12/97) and 33% (2/6) in those with past HBV infection and chronic HBV infection. The incidence of HBVr in patients with past HBV infection is 16% (8/50), 15% (3/20), and 5% (1/22) in kidney, heart, and lungs, respectively. HBVr was more frequent in those who received alemtuzumab. Among 14 recipients with HBVr, none had HBV-associated liver failure or death. CONCLUSIONS Our study observed a higher rate of HBVr (12%) in nonliver SOT recipients with past HBV infection compared to the previous studies. Further studies are needed to identify predictors of HBVr in nonliver SOT recipients and optimize antiviral prophylaxis guidance.
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Affiliation(s)
- Chia-Yu Chiu
- Division of Public Health, Infectious Diseases, and Occupational Medicine, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Lisa M Brumble
- Division of Infectious Diseases, Mayo Clinic, Jacksonville, Florida, USA
| | | | - Kymberly D Watt
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA
| | - Elena Beam
- Division of Public Health, Infectious Diseases, and Occupational Medicine, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA
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Savaliya BP, Shekouhi R, Mubarak F, Manaise HK, Jimenez PB, Kowkabany G, Popp RA, Popp K, Gabriel E. Risk of hepatitis B virus reactivation in cancer patients undergoing treatment with tyrosine kinase-inhibitors. World J Gastroenterol 2024; 30:3052-3058. [PMID: 38983963 PMCID: PMC11230056 DOI: 10.3748/wjg.v30.i24.3052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 05/10/2024] [Accepted: 05/30/2024] [Indexed: 06/25/2024] Open
Abstract
This editorial commented on an article in the World Journal of Gastroenterology titled "Risks of Reactivation of Hepatitis B Virus in Oncological Patients Using Tyrosine Kinase-Inhibitors: Case Report and Literature Analysis" by Colapietro et al. In this editorial, we focused on providing a more comprehensive exploration of hepatitis B virus reactivation (HBVr) associated with the usage of tyrosine kinase inhibitors (TKIs). It includes insights into the mechanisms underlying HBV reactivation, the temporal relationship between TKIs and HBV reactivation, and preventive measures. The aim is to understand the need for nucleos(t)ide analogs (NAT) and serial blood tests for early recognition of reactivation and acute liver injury, along with management strategies. TKIs are considered to be an intermediate (1%-10%) of HBVr. Current guidelines stipulate that patients receiving therapy with high or moderate risks of reactivation or recent cancer diagnosis must have at least tested hepatitis B surface antigen, anti-hepatitis B core antigen (HBc), and anti-hepatitis B surface antibody. Anti-HBc screening in highly endemic areas means people with negative tests should be vaccinated against HBV. Nucleoside or nucleotide analogs (NAs) like entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) form the basis of HBV reactivation prophylaxis and treatment during immunosuppression. Conversely, lamivudine, telbivudine, and adefovir are generally discouraged due to their reduced antiviral efficacy and higher risk of fostering drug-resistant viral strains. However, these less effective NAs may still be utilized in cases where ETV, TDF, and TAF are not feasible treatment options.
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Affiliation(s)
- Bansi P Savaliya
- Department of Surgery, Medical Academy Named after SI Georgievsky of Vernadsky Crimean Federal University, Simferopol 295015, Crimea, Russia
| | - Ramin Shekouhi
- Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Florida, Gainesville, FL 32608, United States
| | - Fatima Mubarak
- Department of Surgery, Aga Khan University, Karachi 74800, Sindh, Pakistan
| | - Harsheen K Manaise
- Department of Surgery, Government Medical College and Hospital, Chandigarh 160030, Punjab, India
| | - Paola Berrios Jimenez
- Department of Surgery, University of Puerto Rico School of Medicine, San Juan 00921, Puerto Rico
| | - Gabrielle Kowkabany
- Department of Chemical and Biological Engineering, University of Alabama, Tuscaloosa, AL 35487, United States
| | - Reed A Popp
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610, United States
| | - Kyle Popp
- Department of Surgery, Florida State University, Tallahassee, FL 32306, United States
| | - Emmanuel Gabriel
- Department of Surgery, Mayo Clinic, Jacksonville, FL 32224, United States
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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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Mikulska M, Oltolini C, Zappulo E, Bartoletti M, Frustaci AM, Visentin A, Vitale C, Mauro FR. Prevention and management of infectious complications in patients with chronic lymphocytic leukemia (CLL) treated with BTK and BCL-2 inhibitors, focus on current guidelines. Blood Rev 2024; 65:101180. [PMID: 38331696 DOI: 10.1016/j.blre.2024.101180] [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: 12/08/2023] [Revised: 01/27/2024] [Accepted: 01/31/2024] [Indexed: 02/10/2024]
Abstract
CLL is associated with an increased risk of infectious complications. Treatment with BTK or BCL-2 inhibitors does not seem to increase significantly the risk of opportunistic infections, but the role of combination therapies including BTK and/or BCL-2 inhibitors remains to be established. Various infectious complications can be successfully prevented with appropriate risk management strategies. In this paper we reviewed the international guidelines on prevention and management of infectious complications in patients with CLL treated with BTK or BCL-2 inhibitors. Universal pharmacological anti-herpes, antibacterial or antifungal prophylaxis is not warranted. Reactivation of HBV should be prevented in HBsAg-positive subjects. For HBsAg-negative/HBcAb-positive patients recommendations differ, but in case of combination treatment should follow those for other, particularly anti-CD20, agent. Immunization should be provided preferably before the onset of treatment. Immunoglobulin therapy has favourable impact on morbidity but not mortality in patients with hypogammaglobulinemia and severe or recurrent infections. Lack of high-quality data and heterogeneity of patients or protocols included in the studies might explain differences among the main guidelines. Better data collection is warranted.
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Affiliation(s)
- Malgorzata Mikulska
- Infectious Diseases Unit, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
| | | | - Emanuela Zappulo
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Michele Bartoletti
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele Milan, Italy; Infectious Disease Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy
| | | | - Andrea Visentin
- Hematology and Clinical Immunology Unit, Department of Medicine, University of Padua, Italy
| | - Candida Vitale
- Division of Hematology, A.O.U. Città della Salute e della Scienza di Torino, Italy; Department of Molecular Biotechnology and Health Sciences, University of Turin, Italy
| | - Francesca R Mauro
- Hematology, Department of Translational and Precision Medicine, Sapienza University, Rome, Italy
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Qin Y, Zhou W, Zhou X, Li H. Case report: Recombinant human type II tumour necrosis factor receptor-antibody fusion protein induced occult hepatitis B virus reactivation leading to liver failure. J Int Med Res 2024; 52:3000605241252580. [PMID: 38760056 PMCID: PMC11107333 DOI: 10.1177/03000605241252580] [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: 10/18/2023] [Accepted: 04/15/2024] [Indexed: 05/19/2024] Open
Abstract
Recombinant human type II tumour necrosis factor receptor-antibody fusion protein (rh TNFR:Fc) is an immunosuppressant approved for treating rheumatoid arthritis (RA). This case report describes a case of hepatitis B reactivation in a patient with drug-induced acute-on-chronic liver failure. A 58-year-old woman with a history of RA was treated with rh TNFR:Fc; and then subsequently received 25 mg rh TNFR:Fc, twice a week, as maintenance therapy. No anti-hepatitis B virus (HBV) preventive treatment was administered. Six months later, she was hospitalized with acute jaundice. HBV reactivation was observed, leading to acute-on-chronic liver failure. After active treatment, the patient's condition improved and she recovered well. Following careful diagnosis and treatment protocols are essential when treating RA with rh TNFR:Fc, especially in anti-hepatitis B core antigen antibody-positive patients, even when the HBV surface antigen and the HBV DNA are negative. In the case of HBV reactivation, liver function parameters, HBV surface antigen and HBV DNA should be closely monitored during treatment, and antiviral drugs should be used prophylactically when necessary, as fatal hepatitis B reactivation may occur in rare cases. A comprehensive evaluation and medication should be administered in a timely manner after evaluating the patient's physical condition and closely monitoring the patient.
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Affiliation(s)
- Yujie Qin
- Department of Infectious Diseases, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, China
| | - Wenxiu Zhou
- Department of Infectious Diseases, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, China
| | - Xingnian Zhou
- Department of Infectious Diseases, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, China
| | - Hong Li
- Department of Infectious Diseases, Guizhou Provincial People’s Hospital, Guiyang, Guizhou Province, China
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Li H, Lu D, Chen J, Zhang J, Zhuo J, Lin Z, Cao C, Shen W, He C, Chen H, Hu Z, Sun Y, Wei X, Zhuang L, Zheng S, Xu X. Post-transplant hepatitis B virus reactivation impacts the prognosis of patients with hepatitis B-related hepatocellular carcinoma: a dual-centre retrospective cohort study in China. Int J Surg 2024; 110:2263-2274. [PMID: 38348848 PMCID: PMC11019990 DOI: 10.1097/js9.0000000000001141] [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: 11/20/2023] [Accepted: 01/25/2024] [Indexed: 04/18/2024]
Abstract
BACKGROUND Highly active hepatitis B virus (HBV) is known to be associated with poor outcomes in patients with hepatocellular carcinoma (HCC). This study aims to investigate the relationship between HBV status and HCC recurrence after liver transplantation. METHODS The study retrospectively analyzed HCC patients undergoing liver transplantation in two centres between January 2015 and December 2020. The authors reviewed post-transplant HBV status and its association with outcomes. RESULTS The prognosis of recipients with hepatitis B surface antigen (HBsAg) reappearance ( n =58) was poorer than those with HBsAg persistent negative ( n =351) and positive ( n =53). In HBsAg persistent positive group, recipients with HBV DNA reappearance or greater than 10-fold increase above baseline had worse outcomes than those without ( P <0.01). HBV reactivation was defined as (a) HBsAg reappearance or (b) HBV DNA reappearance or greater than 10-fold increase above baseline. After propensity score matching, the 5-year overall survival rate and recurrence-free survival rate after liver transplantation in recipients with HBV reactivation were significantly lower than those without (32.0% vs. 62.3%; P <0.01, and 16.4% vs. 63.1%; P <0.01, respectively). Moreover, HBV reactivation was significantly related to post-transplant HCC recurrence, especially lung metastasis. Cox regression analysis revealed that beyond Milan criteria, microvascular invasion and HBsAg-positive graft were independent risk factors for post-transplant HBV reactivation, and a novel nomogram was established accordingly with a good predictive efficacy (area under the time-dependent receiver operating characteristic curve=0.78, C-index =0.73). CONCLUSIONS Recipients with HBV reactivation had worse outcomes and higher tumour recurrence rates than those without. The nomogram could be used to evaluate the risk of post-transplant HBV reactivation effectively.
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Affiliation(s)
- Huigang Li
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou
| | - Di Lu
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou
| | - Jinyan Chen
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou
| | | | - Jianyong Zhuo
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou
| | - Zuyuan Lin
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou
| | - Chenghao Cao
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou
| | - Wei Shen
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou
| | - Chiyu He
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou
| | - Hao Chen
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou
| | - Zhihang Hu
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou
| | - Yiyang Sun
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou
- The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou
| | - Xuyong Wei
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou
| | - Li Zhuang
- The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou
| | - Shusen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou
- National Center for Healthcare Quality Management in Liver Transplant, Hangzhou China
| | - Xiao Xu
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou
- National Center for Healthcare Quality Management in Liver Transplant, Hangzhou China
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Gao MZ, Xu LL, Li Y, Wang X, Chen P, Shi SF, Liu LJ, Lv JC, Hong FY, Zhang H, Zhou XJ. Hepatitis B Virus Status and Clinical Outcomes in IgA Nephropathy. Kidney Int Rep 2024; 9:1057-1066. [PMID: 38765575 PMCID: PMC11101714 DOI: 10.1016/j.ekir.2024.01.009] [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: 11/28/2023] [Revised: 12/26/2023] [Accepted: 01/02/2024] [Indexed: 05/22/2024] Open
Abstract
Introduction Immunoglobulin A nephropathy (IgAN) has been reported to coexist with hepatitis B virus (HBV) infection. Despite the clinical significance of this association, there is a lack of comprehensive research investigating the impact of various common conditions following HBV infection and the potential influence of anti-HBV therapy on the progression of IgAN. Methods We investigated 3 distinct states of HBV infection, including chronic HBV infection, resolved HBV infection, and the deposition of hepatitis B antigens in renal tissue, in a follow-up database of 1961 patients with IgAN. IgAN progression was defined as a loss of estimated glomerular filtration rate (eGFR) >40%. Multivariable cause-specific hazards models to analyze the relationship between HBV states and IgAN progression. Results Chronic HBV infection was identified as an independent risk factor for IgAN progression, supported by both prematching analysis (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.06-2.44; P = 0.024) and propensity-score matching analysis (HR, 1.74; 95% CI 1.28-2.37; P < 0.001). Conversely, resolved HBV infection showed no significant association with IgAN progression (HR, 1.01; 95% CI 0.67-1.52; P = 0.969). Moreover, the presence of HBV deposition in the kidneys and the utilization of anti-HBV therapy did not appear to be significant risk factors for renal outcomes (P > 0.05). Conclusion Chronic HBV infection is an independent risk factor for IgAN progression, whereas resolved HBV infection is not. In patients with IgAN, management of concurrent chronic HBV infection should be enhanced. The presence of HBV deposition in the kidneys and the use of anti-HBV medications do not impact the kidney disease progression in patients with IgAN with concurrent HBV infection.
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Affiliation(s)
- Mei-zhu Gao
- Renal Division, Peking University First Hospital; Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education; Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
- Department of Nephrology, Fujian Provincial Hospital, Shengli Clinical College of Fujian Medical University, Fuzhou, China
| | - Lin-lin Xu
- Renal Division, Peking University First Hospital; Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education; Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
| | - Yang Li
- Renal Division, Peking University First Hospital; Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education; Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
| | - Xin Wang
- Renal Division, Peking University First Hospital; Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education; Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
| | - Pei Chen
- Renal Division, Peking University First Hospital; Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education; Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
| | - Su-fang Shi
- Renal Division, Peking University First Hospital; Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education; Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
| | - Li-jun Liu
- Renal Division, Peking University First Hospital; Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education; Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
| | - Ji-cheng Lv
- Renal Division, Peking University First Hospital; Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education; Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
| | - Fu-Yuan Hong
- Department of Nephrology, Fujian Provincial Hospital, Shengli Clinical College of Fujian Medical University, Fuzhou, China
| | - Hong Zhang
- Renal Division, Peking University First Hospital; Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education; Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
| | - Xu-jie Zhou
- Renal Division, Peking University First Hospital; Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education; Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
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Mao Y, Ma S, Liu C, Liu X, Su M, Li D, Li Y, Chen G, Chen J, Chen J, Zhao J, Guo X, Tang J, Zhuge Y, Xie Q, Xie W, Lai R, Cai D, Cai Q, Zhi Y, Li X. Chinese guideline for the diagnosis and treatment of drug-induced liver injury: an update. Hepatol Int 2024; 18:384-419. [PMID: 38402364 DOI: 10.1007/s12072-023-10633-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Accepted: 12/18/2023] [Indexed: 02/26/2024]
Abstract
Drug-induced liver injury (DILI) is an important adverse drug reaction that can lead to acute liver failure or even death in severe cases. Currently, the diagnosis of DILI still follows the strategy of exclusion. Therefore, a detailed history taking and a thorough and careful exclusion of other potential causes of liver injury is the key to correct diagnosis. This guideline was developed based on evidence-based medicine provided by the latest research advances and aims to provide professional guidance to clinicians on how to identify suspected DILI timely and standardize the diagnosis and management in clinical practice. Based on the clinical settings in China, the guideline also specifically focused on DILI in chronic liver disease, drug-induced viral hepatitis reactivation, common causing agents of DILI (herbal and dietary supplements, anti-tuberculosis drugs, and antineoplastic drugs), and signal of DILI in clinical trials and its assessment.
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Affiliation(s)
- Yimin Mao
- Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, NHC Key Laboratory of Digestive Diseases, Shanghai Research Center of Fatty Liver Disease, Shanghai, 200001, China.
| | - Shiwu Ma
- Department of Infectious Diseases, The 920th Hospital of Chinese PLA Joint Logistics Support Force, Kunming, 650032, Yunnan, China
| | - Chenghai Liu
- Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Xiaoyan Liu
- Department of Pharmacy, Huangpu Branch of the 9th People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200011, China
| | - Minghua Su
- Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Dongliang Li
- Department of Hepatobiliary Medicine, The 900th Hospital of Chinese PLA Joint Logistics Support Force, Fuzhou, 350025, Fujian, China
| | - Yiling Li
- Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning, China
| | - Gongying Chen
- Department of Liver Diseases, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, 310015, Zhejiang, China
| | - Jun Chen
- Department of Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen, 518112, Guangdong, China
| | - Jinjun Chen
- Hepatology Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Jingmin Zhao
- Department of Pathology and Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Xiaoyan Guo
- Department of Gastroenterology, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China
| | - Jieting Tang
- Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, NHC Key Laboratory of Digestive Diseases, Shanghai Research Center of Fatty Liver Disease, Shanghai, 200001, China
| | - Yuzheng Zhuge
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, Jiangsu, China
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
| | - Wen Xie
- Center of Liver Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, 100088, China
| | - Rongtao Lai
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
| | - Dachuan Cai
- Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China
| | - Qingxian Cai
- Department of Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen, 518112, Guangdong, China
| | - Yang Zhi
- Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, NHC Key Laboratory of Digestive Diseases, Shanghai Research Center of Fatty Liver Disease, Shanghai, 200001, China
| | - Xiaoyun Li
- Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, NHC Key Laboratory of Digestive Diseases, Shanghai Research Center of Fatty Liver Disease, Shanghai, 200001, China
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Cohen EB, Regev A, Garg A, Di Bisceglie AM, Lewis JH, Vierling JM, Hey-Hadavi J, Steplewski K, Fettiplace A, Chen CL, Pehlivanov N, Kendrick S, I Avigan M. Consensus Guidelines: Best Practices for the Prevention, Detection and Management of Hepatitis B Virus Reactivation in Clinical Trials with Immunosuppressive/Immunomodulatory Therapy. Drug Saf 2024; 47:321-332. [PMID: 38353882 PMCID: PMC10954982 DOI: 10.1007/s40264-024-01399-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/18/2024] [Indexed: 03/21/2024]
Abstract
Hepatitis B virus reactivation (HBVr) during and after immunosuppressive/immunomodulatory (IS/IM) therapy is associated with significant morbidity and mortality, including hepatic decompensation and acute liver failure. The risk of HBVr with IS/IM has been heterogeneous and often unpredictable. As a result, patients with active or previous HBV infection are often excluded from clinical drug trials of such agents. Thorough screening for HBV infection, antiviral prophylaxis, and careful monitoring for HBVr have proven to be effective in reducing the rate of HBVr and improving its outcome in the context of IS/IM. Therefore, safe enrollment and management of certain HBV-marker-positive patients in clinical trials is possible. There is a great, unmet need for consistent, evidence-based recommendations for best practices pertaining to enrollment, monitoring, and management of HBVr in clinical trial participants receiving IS/IM. The aim of these consensus guidelines is to provide a step-by-step blueprint to safely enroll, monitor and manage the patient with inactive chronic or resolved HBV in IS/IM clinical trials from the time of screening through to the end of post-treatment follow up.
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Affiliation(s)
- Eric B Cohen
- AbbVie Inc., Pharmacovigilance and Patient Safety, North Chicago, IL, USA.
| | - Arie Regev
- Eli Lilly and Company, Global Patient Safety, Indianapolis, IN, USA
| | - Anju Garg
- Sanofi, Patient Safety & Pharmacovigilance, Bridgewater, NJ, USA
| | | | - James H Lewis
- Division of Gastroenterology, Georgetown University, Washington, DC, USA
| | - John M Vierling
- Section of Gastroenterology and Hepatology and Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX, USA
| | | | - Klaudia Steplewski
- GlaxoSmithKline LLC, Clinical Safety and Pharmacovigilance, Collegeville, PA, USA
| | | | - Chunlin L Chen
- Bayer HealthCare Pharmaceuticals, LLC. Pharmacovigilance, Berlin, Germany
| | - Nonko Pehlivanov
- Merck & Co., INC, Clinical Safety Risk Management, Rahway, NJ, USA
| | - Stuart Kendrick
- GlaxoSmithKline LLC, Medical Affairs-Hepatology, Stevenage, UK
| | - Mark I Avigan
- Food and Drug Administration, Center for Drug Evaluation and Research, Silver Spring, MD, USA
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Wang R, Tan G, Lei D, Li Y, Gong J, Tang Y, Pang H, Luo H, Qin B. Risk of HBV reactivation in HCC patients undergoing combination therapy of PD-1 inhibitors and angiogenesis inhibitors in the antiviral era. J Cancer Res Clin Oncol 2024; 150:158. [PMID: 38530426 PMCID: PMC10965597 DOI: 10.1007/s00432-024-05677-7] [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: 01/22/2024] [Accepted: 03/01/2024] [Indexed: 03/28/2024]
Abstract
BACKGROUND Although routine antiviral therapy has been implemented in HCC patients, the risk of HBV reactivation (HBVr) remains with the use of programmed cell death-1(PD-1) blockade-based combination immunotherapy and the relevant risk factors are also unclear. Therefore, we aimed to identify the incidence and risk factors of HBVr in HCC patients undergoing combination therapy of PD-1 inhibitors and angiogenesis inhibitors and concurrent first-line antivirals. METHODS We included a total of 218 HBV-related HCC patients with first-line antivirals who received PD-1 inhibitors alone or together with angiogenesis inhibitors. According to the anti-tumor therapy modalities, patients were divided into PD-1 inhibitors monotherapy group (anti-PD-1 group) and combination therapy group (anti-PD-1 plus angiogenesis inhibitors group). The primary study endpoint was the incidence of HBVr. RESULTS HBVr occurred in 16 (7.3%) of the 218 patients, 2 cases were found in the anti-PD-1 group and the remaining 14 cases were in the combination group. The Cox proportional hazard model identified 2 independent risk factors for HBVr: combination therapy (hazard ratio [HR], 4.608, 95%CI 1.010-21.016, P = 0.048) and hepatitis B e antigen (HBeAg) positive (HR, 3.695, 95%CI 1.246-10.957, P = 0.018). Based on the above results, we developed a simple risk-scoring system and found that the high-risk group (score = 2) developed HBVr more frequently than the low-risk group (score = 0) (Odds ratio [OR], 17.000, 95%CI 1.946-148.526, P = 0.01). The area under the ROC curve (AUC-ROC) was 7.06 (95%CI 0.581-0.831, P = 0.006). CONCLUSION HBeAg-positive patients receiving combination therapy have a 17-fold higher risk of HBVr than HBeAg-negative patients with PD-1 inhibitors monotherapy.
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Affiliation(s)
- Rui Wang
- Department of Infectious Diseases, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Guili Tan
- Department of Infectious Diseases, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Dingjia Lei
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Chengdu Medical College (China National Nuclear Corporation 416 Hospital), Chengdu, China
| | - Yadi Li
- Department of Infectious Diseases, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - JiaoJiao Gong
- Department of Infectious Diseases, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Yao Tang
- Department of Infectious Diseases, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Hao Pang
- Department of Infectious Diseases, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Huating Luo
- Department of Geriatrics, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
| | - Bo Qin
- Department of Infectious Diseases, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
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Zeng Y, Huang J, Pang J, Pan S, Wu Y, Jie Y, Li X, Chong Y. The occurrence of immune-related adverse events is an independent risk factor both for serum HBsAg increase and HBV reactivation in HBsAg-positive cancer patients receiving PD-1 inhibitor combinational therapy. Front Immunol 2024; 15:1330644. [PMID: 38558804 PMCID: PMC10979302 DOI: 10.3389/fimmu.2024.1330644] [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: 10/31/2023] [Accepted: 02/20/2024] [Indexed: 04/04/2024] Open
Abstract
Background Previous studies have suggested the potential of PD-1/PD-L1 inhibitors in the treatment of chronic HBV infection. However, since phase III clinical trials have not yet been announced, additional clinical insights may be obtained by observing changes in serum hepatitis B surface antigen (HBsAg) and HBV-DNA levels in cancer patients undergoing PD-1 inhibitor therapy. Objective To explore the effects of PD-1 inhibitor combinational therapy on serum HBsAg and HBV-DNA levels, investigate the incidence of HBsAg loss, HBV reactivation (HBVr), and immune-related adverse events (irAEs), and identify the risk factors associated with significant HBsAg fluctuations and HBVr. Methods A retrospective study including 1195 HBsAg-positive cancer patients who received PD-1 inhibitors between July 2019 and June 2023 was conducted, and 180 patients were enrolled in this study. Serum HBsAg levels before and after PD-1 inhibitor administration were compared across different subgroups. The Pearson χ2 or Fisher exact test was performed to investigate the relationships between categorical variables. Univariable and multivariable analysis were performed to identify the risk factors associated with significant HBsAg fluctuations and HBVr. Results With the concurrent use of antiviral agents, serum HBsAg levels decreased (Z=-3.966, P < 0.0001) in 129 patients and increased (t=-2.047, P=0.043) in 51 patients. Additionally, 7 patients (3.89%) achieved serum HBsAg loss. Virus replication was suppressed in most of the enrolled patients. When divided patients into different subgroups, significant HBsAg decreases after PD-1 inhibitor administration were discovered in lower baseline HBsAg group (Z=-2.277, P=0.023), HBeAg-seronegative group (Z=-2.200, P=0.028), non-irAEs occurrence group (Z=-2.007, P=0.045) and liver cancer group (Z=-1.987, P=0.047). Of note, 11 patients and 36 patients experienced HBVr (6.11%) and irAEs (20%), respectively, which could lead to discontinuation or delayed use of PD-1 inhibitors. After multivariable analysis, HBeAg-seropositive (OR, 7.236 [95% CI, 1.757-29.793], P=0.01) and the occurrence of irAEs (OR, 4.077 [95% CI, 1.252-13.273], P=0.02) were identified as the independent risk factors for significant HBsAg increase, the occurrence of irAEs (OR, 5.560 [95% CI, 1.252-13.273], P=0.01) was identified as the only independent risk factor for HBVr. Conclusion PD-1 inhibitors combined with nucleos(t)ide analogues (NAs) may exert therapeutic potential for chronic HBV infection in cancer patients. However, attention also should be paid to the risk of significant elevation in HBsAg levels, HBVr, and irAEs associated with PD-1 inhibitor combinational therapy.
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Affiliation(s)
- Yingfu Zeng
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jiwei Huang
- Department of Pharmacy, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jiahui Pang
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Shufang Pan
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yuankai Wu
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yusheng Jie
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xinhua Li
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yutian Chong
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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Yang Z, Guan R, Fu Y, Hu D, Zhou Z, Chen M, Zhang Y. Risk of hepatitis B virus reactivation and its effect on survival in advanced hepatocellular carcinoma patients treated with hepatic arterial infusion chemotherapy and lenvatinib plus programmed death receptor-1 inhibitors. Front Cell Infect Microbiol 2024; 14:1336619. [PMID: 38415009 PMCID: PMC10896825 DOI: 10.3389/fcimb.2024.1336619] [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: 11/11/2023] [Accepted: 02/01/2024] [Indexed: 02/29/2024] Open
Abstract
Background Hepatitis B virus (HBV) reactivation is a common complication in hepatocellular carcinoma (HCC) patients treated with chemotherapy or immunotherapy. This study aimed to evaluate the risk of HBV reactivation and its effect on survival in HCC patients treated with HAIC and lenvatinib plus PD1s. Methods We retrospectively collected the data of 213 HBV-related HCC patients who underwent HAIC and lenvatinib plus PD1s treatment between June 2019 to June 2022 at Sun Yat-sen University, China. The primary outcome was the risk of HBV reactivation. The secondary outcomes were overall survival (OS), progression-free survival (PFS), and treatment-related adverse events. Results Sixteen patients (7.5%) occurred HBV reactivation in our study. The incidence of HBV reactivation was 5% in patients with antiviral prophylaxis and 21.9% in patients without antiviral prophylaxis, respectively. The logistic regression model indicated that for HBV reactivation, lack of antiviral prophylaxis (P=0.003) and tumor diameter (P=0.036) were independent risk factors. The OS and PFS were significantly shorter in the HBV reactivation group than the non-reactivation group (P=0.0023 and P=0.00073, respectively). The number of AEs was more in HBV reactivation group than the non-reactivation group, especially hepatic AEs. Conclusion HBV reactivation may occur in HCC patients treated with HAIC and lenvatinib plus PD1s. Patients with HBV reactivation had shorter survival time compared with non-reactivation. Therefore, HBV-related HCC patients should undergo antiviral therapy and HBV-DNA monitoring before and during the combination treatment.
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Affiliation(s)
- Zhenyun Yang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
- Guangdong Provnvial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
| | - Renguo Guan
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
- Guangdong Provnvial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
| | - Yizhen Fu
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
- Guangdong Provnvial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
| | - Dandan Hu
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
- Guangdong Provnvial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
| | - Zhongguo Zhou
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
- Guangdong Provnvial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
| | - Minshan Chen
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
- Guangdong Provnvial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
| | - Yaojun Zhang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
- Guangdong Provnvial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
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Tonnini M, Solera Horna C, Ielasi L. Prevention of hepatitis B reactivation in patients with hematologic malignancies treated with novel systemic therapies: Who and Why? World J Gastroenterol 2024; 30:509-511. [PMID: 38414584 PMCID: PMC10895601 DOI: 10.3748/wjg.v30.i5.509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Revised: 12/15/2023] [Accepted: 01/11/2024] [Indexed: 01/31/2024] Open
Abstract
The risk of reactivation in patients with chronic or past/resolved hepatitis B virus (HBV) infection receiving chemotherapy or immunosuppressive drugs is a well-known possibility. The indication of antiviral prophylaxis with nucleo(t)side analogue is given according to the risk of HBV reactivation of the prescribed therapy. Though the advent of new drugs is occurring in all the field of medicine, in the setting of hematologic malignancies the last few years have been characterized by several drug classes and innovative cellular treatment. As novel therapies, there are few data about the rate of HBV reactivation and the decision of starting or not an antiviral prophylaxis could be challenging. Moreover, patients are often treated with a combination of different drugs, so evaluating the actual role of these new therapies in increasing the risk of HBV reactivation is difficult. First results are now available, but further studies are still needed. Patients with chronic HBV infection [hepatitis B surface antigen (HBsAg) positive] are reasonably all treated. Past/resolved HBV patients (HBsAg negative) are the actual area of uncertainty where it could be difficult choosing between prophylaxis and pre-emptive strategy.
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Affiliation(s)
- Matteo Tonnini
- Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Clara Solera Horna
- Infectious Disease Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia 42123, Italy
| | - Luca Ielasi
- Department of Internal Medicine, Ospedale degli Infermi di Faenza, Faenza 48018, Italy
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Kuo MH, Tseng CW, Ko PH, Wang ST, Lu MC, Tung CH, Tseng KC, Huang KY, Lee CH, Lai NS. HBV reactivation in HBsAg-/HBcAb+ rheumatoid arthritis patients receiving biologic/targeted synthetic DMARDs. Liver Int 2024; 44:497-507. [PMID: 38010984 DOI: 10.1111/liv.15793] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Revised: 10/05/2023] [Accepted: 11/07/2023] [Indexed: 11/29/2023]
Abstract
BACKGROUND Rheumatoid arthritis (RA) patients seropositive for hepatitis B core antibody (HBcAb) and negative for hepatitis B surface antigen (HBsAg) are at risk of hepatitis B virus (HBV) reactivation when treated with biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs). The study aims to investigate the risk in this population. METHODS From January 2004 through December 2020, 1068 RA patients undergoing b/tsDMARDs therapy and 416 patients with HBsAg-/HBcAb+ were enrolled. Factors associated with HBV reactivation were analysed. RESULTS During 2845 person-years of follow-up, 27 of 416 (6.5%,9.5 per 1000 person-years) patients developed HBV reactivation, with a cumulative rate of HBV reactivation of 3.5% at 5 years, 6.1% at 10 years and 24.2% at 17 years. The median interval from beginning b/tsDMARDs to HBV reactivation was 85 months (range: 9-186 months). The risk of HBV reactivation varied by type of b/tsDMARD, with rituximab having the highest risk (incidence rate: 48.3 per 1000 person-years), followed by abatacept (incidence rate: 24.0 per 1000 person-years). In multivariate analysis, rituximab (adjusted hazard ratio [aHR]: 15.77, 95% confidence interval [CI]: 4.12-60.32, p = .001), abatacept (aHR: 9.30, 1.83-47.19, p = .007), adalimumab (aHR: 3.86, 1.05-14.26, p = .04) and negative baseline HBV surface antibody (anti-HBs, <10 mIU/mL) (aHR: 3.89, 1.70-8.92, p < .001) were independent risk factors for HBV reactivation. CONCLUSION HBsAg-/HBcAb+ RA patients are susceptible to HBV reactivation during b/tsDMARD therapy. Those with negative baseline anti-HBs and those on certain b/tsDMARDs, such as rituximab, abatacept and adalimumab, have high reactivation risks. Risk stratification and management should be based on the patient's baseline anti-HBs titre and type of therapy.
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Affiliation(s)
- Meng Hsuan Kuo
- Department of Pharmacy, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan
| | - Chih-Wei Tseng
- School of Medicine, Tzuchi University, Hualien, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan
| | - Ping-Hung Ko
- School of Medicine, Tzuchi University, Hualien, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan
| | - Sz-Tsan Wang
- School of Medicine, Tzuchi University, Hualien, Taiwan
- Division of Rheumatology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan
| | - Ming-Chi Lu
- School of Medicine, Tzuchi University, Hualien, Taiwan
- Division of Rheumatology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan
| | - Chien-Hsueh Tung
- School of Medicine, Tzuchi University, Hualien, Taiwan
- Division of Rheumatology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan
| | - Kuo-Chih Tseng
- School of Medicine, Tzuchi University, Hualien, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan
| | - Kuang-Yung Huang
- School of Medicine, Tzuchi University, Hualien, Taiwan
- Division of Rheumatology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan
| | - Chi-Hui Lee
- Department of Pharmacy, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan
| | - Ning-Sheng Lai
- School of Medicine, Tzuchi University, Hualien, Taiwan
- Division of Rheumatology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan
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Anvari S, Tsoi K. Hepatitis B Virus Reactivation with Immunosuppression: A Hidden Threat? J Clin Med 2024; 13:393. [PMID: 38256527 PMCID: PMC10816226 DOI: 10.3390/jcm13020393] [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: 11/30/2023] [Revised: 12/23/2023] [Accepted: 01/09/2024] [Indexed: 01/24/2024] Open
Abstract
Hepatitis B virus (HBV) reactivation in the setting of immunosuppressive therapy is an increasingly recognized and preventable cause of elevated liver enzymes and clinical hepatitis in treated patients. However, not all immunosuppressive therapies confer the same risk. The purpose of this article was to review the literature on risks of HBV reactivation associated with immunosuppressive agents and propose a management algorithm. We searched Google Scholar, PubMed, and MEDLINE for studies related to hepatitis B reactivation and various immunosuppressive agents. The risk of HBV reactivation was found to differ by agent and depending on whether a patient had chronic HBV (HBsAg+) or past HBV (HBsAg-, anti-HBc+). The highest risk of reactivation (>10%) was associated with anti-CD20 agents and hematopoietic stem cell transplants. Multiple societies recommend HBV-specific anti-viral prophylaxis for patients with positive HBsAg prior to the initiation of immunosuppressive therapy, while the guidance for HBsAg- patients is more variable. Clinicians should check HBV status prior to beginning an immune-suppressive therapy. Patients with positive HBsAg should be initiated on antiviral prophylaxis in the majority of cases, whereas HBsAg- individuals should be evaluated on a case-by-case basis. Further research is required to determine the optimum duration of therapy.
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Affiliation(s)
- Sama Anvari
- Division of Gastroenterology, Department of Internal Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada;
- Division of Gastroenterology, St. Joseph’s Healthcare Hamilton, Hamilton, ON L8N 4A6, Canada
| | - Keith Tsoi
- Division of Gastroenterology, Department of Internal Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada;
- Division of Gastroenterology, St. Joseph’s Healthcare Hamilton, Hamilton, ON L8N 4A6, Canada
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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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Chen J, Lau G. HBV "Viral Elimination" in the Asia-Pacific region: Current status and challenges. Clin Liver Dis (Hoboken) 2024; 23:e0132. [PMID: 38455235 PMCID: PMC10919499 DOI: 10.1097/cld.0000000000000132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Accepted: 01/04/2024] [Indexed: 03/09/2024] Open
Affiliation(s)
- Jing Chen
- JC School of Public Health and Primary Care, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China
- Humanity and Health Clinical Trial Center, Humanity and Health Medical Group, Hong Kong SAR, China
| | - George Lau
- Humanity and Health Clinical Trial Center, Humanity and Health Medical Group, Hong Kong SAR, China
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Liu Y, Nuersulitan R, Zhang C, Huo N, Li J, Song Y, Zhu J, Liu W, Zhao H. Steady Decline of HBV DNA Load under NAs in Lymphoma Patients and a Higher Level of qAnti-HBc Predict HBV Reactivation. J Clin Med 2023; 13:23. [PMID: 38202030 PMCID: PMC10779810 DOI: 10.3390/jcm13010023] [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: 08/24/2023] [Revised: 11/06/2023] [Accepted: 12/08/2023] [Indexed: 01/12/2024] Open
Abstract
Background: Patients with lymphoma and chronic hepatitis B virus infection need to be treated with both chemotherapy and nucleotide analogue (NA) therapy. However, dynamic changes in HBV DNA loads with increasing chemotherapy cycles are lacking. It is unknown whether HBV replication markers, namely, the quantitative hepatitis B core antibody (qAnti-HBc), HBV RNA, and the hepatitis B virus core-related antigen (HBcrAg), are also markers for predicting HBV reactivation (HBVr). Methods: From 29 June 2010 to 6 December 2021, the data of patients with single-site diffuse large B-cell lymphoma and HBV infection (HBsAg+ and HBsAg-/anti-HBc+) were collected from a hospital medical record system, retrospectively. Serum HBV DNA loads (using real-time fluorescent quantitative PCR tests), qAnti-HBc levels (using a newly developed chemiluminescent particle immunoassay), HBV RNA levels (using the simultaneous amplification testing method based on real-time fluorescence detection), and HBcrAg levels (using a Lumipulse G HBcrAg assay) were tested, and factors related to HBVr were analyzed. Results: Under NAs, the HBV DNA loads of 69 HBsAg+ lymphoma patients declined from 3.15 (2.13-4.73) lg IU/mL to 1.00 (1.00-1.75) lg IU/mL, and further declined to 1.00 (1.00-1.04) lg IU/mL at the end of a 24-month follow-up. The qAnti-HBc levels decreased gradually during chemotherapy in HBsAg+ lymphoma patients (F = 7.090, p = 0.009). The HBV RNA and HBcrAg levels remained stable. A multivariate analysis revealed that higher qAnti-HBc levels (1.97 ± 1.20 vs. 1.12 ± 0.84 lg IU/mL, OR = 6.369, [95% CI: 1.523-26.641], p = 0.011) and higher HBV RNA levels (1.00 ± 1.13 vs. 0.37 ± 0.80 lg copies/mL, OR = 3.299, [95% CI: 1.229-8.854], p = 0.018) were related to HBVr in HBsAg-/anti-HBc+ lymphoma patients. Conclusions: HBV DNA loads declined under NAs during chemotherapy in lymphoma patients. In HBsAg-/anti-HBc+ lymphoma patients, a higher level of baseline serum qAnti-HBc and HBV RNA levels can predict the likelihood of HBVr during chemotherapy.
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Affiliation(s)
- Yiqi Liu
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, No. 8 XishiKu Street, Xicheng District, Beijing 100034, China; (Y.L.); (C.Z.); (N.H.); (J.L.)
| | - Reyizha Nuersulitan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology, Peking University Cancer Hospital & Institute, Beijing 100143, China;
| | - Chi Zhang
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, No. 8 XishiKu Street, Xicheng District, Beijing 100034, China; (Y.L.); (C.Z.); (N.H.); (J.L.)
| | - Na Huo
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, No. 8 XishiKu Street, Xicheng District, Beijing 100034, China; (Y.L.); (C.Z.); (N.H.); (J.L.)
| | - Jun Li
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, No. 8 XishiKu Street, Xicheng District, Beijing 100034, China; (Y.L.); (C.Z.); (N.H.); (J.L.)
| | - Yuqin Song
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing 100143, China; (Y.S.); (J.Z.)
| | - Jun Zhu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing 100143, China; (Y.S.); (J.Z.)
| | - Weiping Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing 100143, China; (Y.S.); (J.Z.)
| | - Hong Zhao
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, No. 8 XishiKu Street, Xicheng District, Beijing 100034, China; (Y.L.); (C.Z.); (N.H.); (J.L.)
- Department of Infectious Diseases, Peking University International Hospital, Beijing 102206, China
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46
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You H, Wang F, Li T, Xu X, Sun Y, Nan Y, Wang G, Hou J, Duan Z, Wei L, Jia J, Zhuang H. Guidelines for the Prevention and Treatment of Chronic Hepatitis B (version 2022). J Clin Transl Hepatol 2023; 11:1425-1442. [PMID: 37719965 PMCID: PMC10500285 DOI: 10.14218/jcth.2023.00320] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 08/02/2023] [Accepted: 08/03/2023] [Indexed: 09/19/2023] Open
Abstract
To facilitate the achieving of the goal of "eliminating viral hepatitis as a major public health threat by 2030" set by the World Health Organization, the Chinese Society of Hepatology together with the Chinese Society of Infectious Diseases (both are branches of the Chinese Medical Association) organized a panel of experts and updated the guidelines for prevention and treatment of chronic hepatitis B in China (version 2022). With the support of available evidence, this revision of the guidelines focuses on active prevention, large scale testing, and expansion of therapeutic indication of chronic hepatitis B with the aim of reducing the hepatitis B related disease burden.
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Affiliation(s)
- Hong You
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Fusheng Wang
- The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Taisheng Li
- Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Xiaoyuan Xu
- Peking University First Hospital, Beijing, China
| | - Yameng Sun
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yuemin Nan
- Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | | | - Jinlin Hou
- Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Zhongping Duan
- Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Lai Wei
- Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Jidong Jia
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Hui Zhuang
- Peking University Health Science Center, Beijing, China
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Shoraka S, Mohebbi SR, Hosseini SM, Ghaemi A, Zali MR. SARS-CoV-2 and chronic hepatitis B: Focusing on the possible consequences of co-infection. JOURNAL OF CLINICAL VIROLOGY PLUS 2023; 3:100167. [DOI: 10.1016/j.jcvp.2023.100167] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
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Manne V, Kowdley KV. Hepatitis B down under: consensus recommendations from the Gastroenterological Society of Australia. Hepatobiliary Surg Nutr 2023; 12:768-771. [PMID: 37886190 PMCID: PMC10598304 DOI: 10.21037/hbsn-23-348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Accepted: 08/17/2023] [Indexed: 10/28/2023]
Affiliation(s)
- Vignan Manne
- Division of Gastroenterology and Hepatology, University of Nevada, Las Vegas Kirk Kerkorian School of Medicine, Las Vegas, NV, USA
| | - Kris V. Kowdley
- Liver Institute Northwest Washington State University, Seattle, WA, USA
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49
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Han P, Wang Z, Wang Z. Risk of Hepatitis B Virus Reactivation in Patients with Resolved Infection on Therapy with Corticosteroids and Conventional Synthesis Immunosuppressants for Kidney Disease: A Single-Center Analysis of 258 Patients. THE TURKISH JOURNAL OF GASTROENTEROLOGY : THE OFFICIAL JOURNAL OF TURKISH SOCIETY OF GASTROENTEROLOGY 2023; 34:1035-1040. [PMID: 37681265 PMCID: PMC10645278 DOI: 10.5152/tjg.2023.22511] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Accepted: 11/26/2022] [Indexed: 09/09/2023]
Abstract
BACKGROUND/AIMS The risk of hepatitis B virus reactivation in patients with a previously resolved hepatitis B virus infection on therapy with corticosteroids and conventional synthesis immunosuppressants for kidney disease has not been well described. MATERIALS AND METHODS We performed a retrospective study on the risk of hepatitis B virus reactivation in patients with a previously resolved hepatitis B virus infection on therapy with corticosteroids and conventional synthesis immunosuppressants for kidney disease between January 2012 and December 2021 in the Department of Nephrology at Ruijin Hospital. RESULTS A total of 258 patients with a previously resolved hepatitis B virus infection [all treated with high-dose corticosteroids, of whom 192 were receiving corticosteroids combined with conventional synthesis immunosuppressant therapy, including cyclophosphamide (155), cyclosporine A (14), mycophenolate mofetil (14), and tacrolimus (9)] were enrolled. During a mean follow-up time of 21.66 months (range 9-70 months), hepatitis B virus reactivation was not observed in these patients. CONCLUSIONS Among patients with a previously resolved hepatitis B virus infection on therapy with corticosteroids and conventional synthesis immunosuppressants for kidney disease, hepatitis B virus reactivation was not common and severe, suggesting that universal prophylaxis may not be justified or cost-effective in this clinical setting.
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Affiliation(s)
- Pingyang Han
- Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University Faculty of Medicine, Shanghai, China
- Department of Nephrology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang Province, China
| | - Ziqiu Wang
- Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University Faculty of Medicine, Shanghai, China
- Department of Clinical Medicine, Shanghai Jiao Tong University Faculty of Medicine, Shanghai, China
| | - Zhaohui Wang
- Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University Faculty of Medicine, Shanghai, China
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50
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Zhang W, Jin P, Liu J, Wu Y, Wang R, Zhang Y, Shen Y, Zhang M, Bai X, Fung J, Liang T. Dynamic evaluation based on acute-on-chronic liver failure predicts survival of patients after liver transplantation: a cohort study. Int J Surg 2023; 109:3117-3125. [PMID: 37498133 PMCID: PMC10583902 DOI: 10.1097/js9.0000000000000596] [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: 03/08/2023] [Accepted: 06/26/2023] [Indexed: 07/28/2023]
Abstract
BACKGROUND AND AIMS Dynamic evaluation of critically ill patients is the key to predicting their outcomes. Most scores based on the Model for End-stage Liver Disease (MELD) and acute-on-chronic liver failure (ACLF) utilize point-in-time assessment. This study mainly aimed to investigate the impact of dynamic clinical course change on post-liver transplantation (LT) survival. METHODS This study included 637 adults (overall cohort) with benign end-stage liver diseases. The authors compared the MELD scores and our ACLF-based dynamic evaluation scores. Patients enrolled or transplanted with ACLF-3 were defined as the ACLF-3 cohort ( n =158). The primary outcome was 1-year mortality. ΔMELD and ΔCLIF-OF (Chronic Liver Failure-Organ Failure) represented the respective dynamic changes in liver transplant function. Discrimination was assessed using the area under the curve. A Cox regression analysis identified independent risk factors for specific organ failure and 1-year mortality. RESULTS Patients were grouped into three groups: the deterioration group (D), the stable group (S), and the improvement group (I). The deterioration group (ΔCLIF-OF ≥2) was more likely to receive national liver allocation ( P =0.012) but experienced longer cold ischemia time ( P =0.006) than other groups. The area under the curves for ΔCLIF-OF were 0.752 for the entire cohort and 0.767 for ACLF-3 cohorts, both superior to ΔMELD ( P <0.001 for both). Compared to the improvement group, the 1-year mortality hazard ratios (HR) of the deterioration group were 12.57 (6.72-23.48) for the overall cohort and 7.00 (3.73-13.09) for the ACLF-3 cohort. Extrahepatic organs subscore change (HR=1.783 (1.266-2.512) for neurologic; 1.653 (1.205-2.269) for circulation; 1.906 (1.324-2.743) for respiration; 1.473 (1.097-1.976) for renal) were key to transplantation outcomes in the ACLF-3 cohort. CLIF-OF at LT (HR=1.193), ΔCLIF-OF (HR=1.354), and cold ischemia time (HR=1.077) were independent risk factors of mortality for the overall cohort, while ΔCLIF-OF (HR=1.384) was the only independent risk factor for the ACLF-3 cohort. Non-ACLF-3 patients showed a higher survival rate than patients with ACLF-3 in all groups ( P =0.002 for I, P =0.005 for S, and P =0.001 for D). CONCLUSION This was the first ACLF-based dynamic evaluation study. ΔCLIF-OF was a more powerful predictor of post-LT mortality than ΔMELD. Extrahepatic organ failures were core risk factors for ACLF-3 patients. CLIF-OF at LT, ΔCLIF-OF, and cold ischemia time were independent risk factors for post-LT mortality. Patients with a worse baseline condition and a deteriorating clinical course had the worst prognosis. Dynamic evaluation was important in risk stratification and recipient selection.
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Affiliation(s)
- Wei Zhang
- Department of Hepatobiliary and Pancreatic Surgery
- Liver Transplant Center
| | - Pingbo Jin
- Department of Hepatobiliary and Pancreatic Surgery
- Liver Transplant Center
| | - Junfang Liu
- Department of Hepatobiliary and Pancreatic Surgery
- Liver Transplant Center
| | - Yue Wu
- Department of Hepatobiliary and Pancreatic Surgery
- Liver Transplant Center
| | | | - Yuntao Zhang
- Department of Hepatobiliary and Pancreatic Surgery
- Liver Transplant Center
| | - Yan Shen
- Department of Hepatobiliary and Pancreatic Surgery
- Liver Transplant Center
| | - Min Zhang
- Department of Hepatobiliary and Pancreatic Surgery
- Liver Transplant Center
| | - Xueli Bai
- Department of Hepatobiliary and Pancreatic Surgery
- Liver Transplant Center
| | - John Fung
- Transplantation Institute, Department of Surgery, University of Chicago, Chicago, Illinois, USA
| | - Tingbo Liang
- Department of Hepatobiliary and Pancreatic Surgery
- Liver Transplant Center
- Key Lab of Combined Multi-organ Transplantation of the Ministry of Health
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China
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