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Wang Z, Lu J, Liu X, Liu J, Li J. Identification of key exosomes-related genes in hepatitis B virus-related hepatocellular carcinoma. Technol Health Care 2025; 33:1343-1357. [PMID: 40331539 DOI: 10.1177/09287329241296353] [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] [Indexed: 05/08/2025]
Abstract
One of the primary risk factors for hepatocellular carcinoma (HCC) is the hepatitis B virus (HBV). Exosomes have a significant impact on the dissemination of HBV-infected HCC. This study aimed to screen HBV exosome-related hub genes in HCC for a better understanding of the HCC pathogenic mechanism. First, multiple HBV-induced HCC datasets were collected from the Gene Expression Omnibus (GEO) database, and the exosome-related gene set was obtained from relevant literature. Nine HBV-related HCC exosome hub genes (HP, C9, APOA1, PON1, TTR, LPA, FCN2, FCN3, and MBL2) were selected through differential analysis and network analysis. An analysis of the receiver operation characteristic (ROC) revealed that these genes had good diagnostic value. These hub genes were primarily enriched in biological processes such as the citrate cycle tca cycle, phenylalanine metabolism, and fatty acid metabolism, according to gene set enrichment analysis (GSEA). Furthermore, this study predicted the miRNA (hsa-miR-590-5p) targeting LPA, as well as 12 lncRNAs (AL121655, SAP30-DT, LINC00472, etc.) targeting hsa-miR-590-5p. Finally, nelarabine, methylprednisolone, and methylprednisolone were predicted to be possible medications that target the hub gene based on the CellMiner database. To sum up, this work was crucial for discovering new biomarkers and comprehending the function of exosome-related genes in the growth of HBV-infected HCC.
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Affiliation(s)
- Zhuoyi Wang
- Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Shulan International Medical College of Zhejiang Shuren University, Hangzhou, China
| | - Jianfang Lu
- Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Shulan International Medical College of Zhejiang Shuren University, Hangzhou, China
| | - Xiangyan Liu
- Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Shulan International Medical College of Zhejiang Shuren University, Hangzhou, China
| | - Jingfeng Liu
- Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Shulan International Medical College of Zhejiang Shuren University, Hangzhou, China
| | - Jianhui Li
- Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Shulan International Medical College of Zhejiang Shuren University, Hangzhou, China
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Habash N, Absah I. Hepatitis B Risk in Vaccinated Patients with Celiac Disease - Do Titers Matter? Dig Dis Sci 2025:10.1007/s10620-025-08998-w. [PMID: 40111704 DOI: 10.1007/s10620-025-08998-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2025] [Accepted: 03/14/2025] [Indexed: 03/22/2025]
Affiliation(s)
- Nawras Habash
- Division of Pediatric Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
| | - Imad Absah
- Division of Pediatric Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
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3
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Pan H, Yu Y, Li X, Wang M, Wen C, Dai Q, Huang L. Vaccination and rheumatoid arthritis: an updated systematic review and meta-analysis of data from 25,949,597 participants. BMC Public Health 2025; 25:933. [PMID: 40065303 PMCID: PMC11892200 DOI: 10.1186/s12889-025-22093-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Accepted: 02/25/2025] [Indexed: 03/14/2025] Open
Abstract
OBJECTIVES This systematic review and meta-analysis aimed to investigate the association between vaccinations and the risk of rheumatoid arthritis (RA), specifically addressing concerns about a potential increased risk among vaccinated individuals. METHODS A systematic search for cohort studies and case-control studies examining the association between vaccinations and RA was conducted using Medical Subject Headings and relevant keywords across PubMed, EMBASE, and Cochrane Library databases from inception to September 2024. The risk of bias of included studies was assessed using the Newcastle-Ottawa Scale. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was employed to evaluate the overall certainty of evidence. Statistical analyses, i.e., pooling of relative risk (RR) and corresponding 95% confidence intervals (CI), were performed using a random-effects model on STATA software (version 14.0). Due to the I² value exceeding 50%, we did not perform an asymmetry test to assess publication bias. RESULTS This meta-analysis included 16 observational studies conducted between 2008 and 2024 and involving a total of 25,949,597 participants. The follow-up duration ranged from 0.03 to 9 years, while the data collection period varied from 2.75 to 9.5 years. The analysis found no significant association between vaccination exposure and RA [RR = 1.03, 95% CI (0.95-1.11), I²=93.4%, P = 0.456, low level of evidence]. Sensitivity analyses confirmed the robustness of this result. Subgroup analyses revealed no significant risk of RA associated with HPV vaccination [RR = 1.27 95% CI (0.78-2.08), I²=81.4%, P = 0.339], influenza vaccination [RR = 1.10, 95% CI (0.98-1.23), I²=52.4%, P = 0.112], Anthrax vaccination [RR = 2.21, 95% CI (0.75-6.52)], Herpes Zoster vaccination [RR = 2.70, 95% CI (1.70-4.29)], or COVID-19 vaccination [RR = 0.94, 95% CI (0.82-1.07), I²=97.4%, P = 0.340]. However, the subgroup with a follow-up duration varying between 0.5 and 1.8 years showed that (HPV & COVID-19) vaccination had a significant protective effect on RA [RR = 0.92, 95% CI (0.87-0.98), I²=95.3%, P = 0.005]. CONCLUSION The evidence for the association between vaccination and RA risk is insufficient, and vaccination may serve as a protective factor for RA over a less than one year follow-up duration.
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Affiliation(s)
- Hejing Pan
- School of Basic Medical Sciences of Zhejiang, Chinese Medical University, Binwen Road, Binjiang District, Hangzhou, China
| | - Yin Yu
- School of Basic Medical Sciences of Zhejiang, Chinese Medical University, Binwen Road, Binjiang District, Hangzhou, China
| | - Xuanlin Li
- School of Basic Medical Sciences of Zhejiang, Chinese Medical University, Binwen Road, Binjiang District, Hangzhou, China
| | - Meijiao Wang
- School of Basic Medical Sciences of Zhejiang, Chinese Medical University, Binwen Road, Binjiang District, Hangzhou, China
| | - Chengping Wen
- School of Basic Medical Sciences of Zhejiang, Chinese Medical University, Binwen Road, Binjiang District, Hangzhou, China
| | - Qiaoding Dai
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
- Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, China.
| | - Lin Huang
- School of Basic Medical Sciences of Zhejiang, Chinese Medical University, Binwen Road, Binjiang District, Hangzhou, China.
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Zhang Z, Wu Y, Xu J, Meng Z, Chen Q, Yin S. Quantitative Analysis of Hepatitis D Virus Using gRNA-Sensitive Semiconducting Polymer Dots. Anal Chem 2025; 97:1575-1583. [PMID: 39807540 DOI: 10.1021/acs.analchem.4c04147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2025]
Abstract
Hepatitis D virus (HDV) significantly influences the progression of liver diseases. Through clinical observations and database analyses, it has been established that patients coinfected with HDV and hepatitis B virus (HBV) experience accelerated progression toward cirrhosis, hepatocellular carcinoma (HCC), and liver failure compared to those infected solely with HBV. A higher viral load correlates with increased replicative activity, enhanced infectivity, and more severe disease manifestations. In this study, we use HDV gRNA-sensitive semiconducting polymer dots (Pdots) as the nanoprobes for the quantitative analysis of HDV copy number variations. The surface of the Pdots is engineered with a clamp design that includes a pair of reporter sequences, protection sequences, and capture sequences tailored to the conserved sequence length of the HDV genome. The capture sequence, comprising leading and trailing chains, specifically binds to the gRNA of the target virus. The protection sequence shields the Pdots from external interference, while the reporter sequence detects the presence of target gRNA through the degradation of fluorescent dye Cy5.5dt. We demonstrate the effectiveness of this assay in a stably transfected cell line derived from HepG2-HDV cells and its translational application in clinical samples from patients. Additionally, this nanobiosensor can accurately detect gRNA at femtomolar (fM) levels, a sensitivity unachievable by previously reported methods. This novel virus quantification system offers significant potential for clinical and virological applications, enhancing screening, early diagnosis, and personalized treatment strategies.
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Affiliation(s)
- Ze Zhang
- Department of Hepatobiliary and Pancreatic Surgery II, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin 130012, P. R. China
- State Key Laboratory of Integrated Optoelectronics, College of Electronics Science and Engineering, Jilin University, No. 2699 Qianjin Street, Changchun, Jilin 130012, P. R. China
| | - Yuyang Wu
- State Key Laboratory of Integrated Optoelectronics, College of Electronics Science and Engineering, Jilin University, No. 2699 Qianjin Street, Changchun, Jilin 130012, P. R. China
| | - Jinglun Xu
- Department of Hepatobiliary-Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130000, P. R. China
| | - Zihui Meng
- Department of Hepatobiliary-Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130000, P. R. China
| | - Qingmin Chen
- Department of Hepatobiliary and Pancreatic Surgery II, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin 130012, P. R. China
| | - Shengyan Yin
- State Key Laboratory of Integrated Optoelectronics, College of Electronics Science and Engineering, Jilin University, No. 2699 Qianjin Street, Changchun, Jilin 130012, P. R. China
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Jiang J, Xie Z, Wang Q, Wang B, Huang R, Xu W, Shang C, Chen Y. Epidemiological trends in gastrointestinal cancers and risk factors across U.S. states from 2000 to 2021: a systematic analysis for the global burden of disease study 2021. BMC Public Health 2025; 25:43. [PMID: 39762826 PMCID: PMC11702109 DOI: 10.1186/s12889-024-21192-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Accepted: 12/23/2024] [Indexed: 01/11/2025] Open
Abstract
INTRODUCTION Gastrointestinal (GI) cancers account for over a quarter of all cancer-related deaths in the United States; however, the latest trends in their prevalence remain unclear. METHODS Data on GI cancers were obtained from the Global Burden of Disease Study 2021. Age-standardized incidence rates (ASIR) and age-standardized mortality rates (ASMR) were estimated across various states, sexes, ages, and risk factors, and annual percentage changes were calculated. RESULTS From 2000 to 2021, liver cancer exhibited the greatest increase in both the ASIR and the ASMR, followed by pancreatic cancer. In contrast, stomach cancer showed the greatest decline, followed by colorectal cancer, esophageal cancer, and biliary tract cancer. Most GI cancers predominantly affect men and tend toward a younger age of onset. Geographic disparities exist in the burden of GI cancers and their risk factors. For esophageal, stomach, and colorectal cancers, mortality rates linked to diet and smoking decreased, whereas alcohol-related mortality increased in several states, especially West Virginia. Hepatitis C remains the leading cause of liver cancer, with intravenous drug use as the primary risk factor. Non-alcoholic steatohepatitis (NASH) is the fastest-growing cause of liver cancer, followed by excessive alcohol use. Mortality rates for pancreatic cancer due to high body-mass index and high fasting plasma glucose have increased across states and age groups. DISCUSSION The epidemiological trends of GI cancers in the U.S. have shifted substantially. States need to implement targeted policies that address specific populations and risk factors for each cancer type.
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Affiliation(s)
- Jiahao Jiang
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, Guangdong Province, China
| | - Zhiqin Xie
- Center of Hepatobiliary and Pancreatic Surgery, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou City, 412007, Hunan Province, China
| | - Qingbin Wang
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, Guangdong Province, China
| | - Bingkun Wang
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, Guangdong Province, China
| | - Rong Huang
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, Guangdong Province, China
| | - Weikai Xu
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, Guangdong Province, China
| | - Changzhen Shang
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, Guangdong Province, China.
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, Guangdong Province, China.
| | - Yajin Chen
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, Guangdong Province, China.
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, Guangdong Province, China.
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Hornung LB, Hamm SR, Hald A, Harboe ZB, Lundbo LF, Wareham NE, Heftdal LD, Ekenberg C, Bjerrum S, Holler JG, Mathiesen IHM, Krohn PS, Bjerring PN, Gustafsson F, Perch M, Rasmussen A, Nielsen SD. Post-Transplantation Seroprotection Rates in Liver, Lung, and Heart Transplant Recipients Vaccinated Pre-Transplantation against Hepatitis B Virus and Invasive Pneumococcal Disease. Vaccines (Basel) 2024; 12:1092. [PMID: 39460259 PMCID: PMC11511315 DOI: 10.3390/vaccines12101092] [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: 07/17/2024] [Revised: 08/24/2024] [Accepted: 09/19/2024] [Indexed: 10/28/2024] Open
Abstract
Vaccination before solid organ transplantation is recommended since post-transplantation immunosuppression is known to impair vaccine responses. However, little is known about post-transplantation seroprotection rates in organ transplant recipients vaccinated pre-transplantation. We aimed to investigate the proportion of transplant recipients vaccinated against hepatitis B virus (HBV) and invasive pneumococcal disease (IPD) pre-transplantation at the time of listing for transplantation with post-transplantation seroprotection. We included 136 solid organ transplant (SOT) recipients vaccinated at the time of listing for transplantation. We investigated post-transplantation antibody concentrations against HBV and IPD. Established antibody thresholds were used to define seroprotection. The proportions of SOT recipients with post-transplantation seroprotection were 27.9% (n = 38) and 42.6% (n = 58) against HBV and IPD, respectively. Compared to completing HBV vaccination pre-transplantation, completing post-transplantation vaccination (adjusted odds ratio (aOR): 7.8, 95% CI: 2.5-24.5, p < 0.001) and incomplete vaccination (aOR: 6.3, 95% CI: 1.2-32.6, p = 0.028) were associated with non-response against HBV, after adjustment for confounders. Importantly, patients with seroprotection at the time of listing had lower odds of non-response against HBV (aOR: 0.04, 95% CI: 0.0-0.1, p < 0.001) and IPD (aOR: 0.3, 95% CI: 0.1-0.7, p = 0.007) compared to those without seroprotection. SOT recipients vaccinated pre-transplantation had low post-transplantation seroprotection rates against HBV and IPD. However, SOT recipients with seroprotection at the time of listing had lower odds of non-response, suggesting early vaccination should be a priority.
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Affiliation(s)
- Lise Bank Hornung
- Viro-Immunology Research Unit, Department of Infectious Diseases, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark (S.R.H.)
| | - Sebastian Rask Hamm
- Viro-Immunology Research Unit, Department of Infectious Diseases, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark (S.R.H.)
| | - Annemette Hald
- Viro-Immunology Research Unit, Department of Infectious Diseases, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark (S.R.H.)
| | - Zitta Barrella Harboe
- Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital—North Zealand, 3400 Hillerød, Denmark
- Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark
| | - Lene Fogt Lundbo
- Department of Infectious Diseases, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark
| | - Neval Ete Wareham
- Department of Infectious Diseases, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark
| | - Line Dam Heftdal
- Viro-Immunology Research Unit, Department of Infectious Diseases, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark (S.R.H.)
| | - Christina Ekenberg
- Department of Infectious Diseases, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark
| | - Stephanie Bjerrum
- Department of Infectious Diseases, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark
| | - Jon Gitz Holler
- Department of Infectious Diseases, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark
| | - Inger Hee Mabuza Mathiesen
- Department of Infectious Diseases, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark
| | - Paul Suno Krohn
- Department of Surgical Gastroenterology and Transplantation, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark
| | - Peter Nissen Bjerring
- Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark
- Department of Intestinal Failure and Liver Diseases, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark
| | - Finn Gustafsson
- Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark
- Department of Cardiology, Heart and Lung Transplant Unit, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark
| | - Michael Perch
- Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark
- Department of Cardiology, Heart and Lung Transplant Unit, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark
| | - Allan Rasmussen
- Department of Surgical Gastroenterology and Transplantation, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark
| | - Susanne Dam Nielsen
- Viro-Immunology Research Unit, Department of Infectious Diseases, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark (S.R.H.)
- Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark
- Department of Surgical Gastroenterology and Transplantation, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark
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Akbar SMF, Al Mahtab M, Yoshida O, Aguilar J, Gerardo GN, Hiasa Y. Development of Therapy Based on the Exploration of Biological Events Underlying the Pathogenetic Mechanisms of Chronic Hepatitis B Infection. Biomedicines 2023; 11:1944. [PMID: 37509583 PMCID: PMC10376977 DOI: 10.3390/biomedicines11071944] [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: 06/21/2023] [Revised: 07/06/2023] [Accepted: 07/07/2023] [Indexed: 07/30/2023] Open
Abstract
According to the World Health Organization (WHO), an estimated 296 million people are chronically infected with hepatitis B virus (HBV). Approximately 15-25% of these people develop complications such as advanced chronic liver diseases (ACLDs). Mortality due to HBV-related complications accounted for an estimated 882,000 deaths in 2019. Potent preventive vaccines have already restricted new HBV infections, and several drugs are available to treat chronic HBV infections. However, the positive impacts of these drugs have been recorded in only a few patients with chronic HBV infection. These drugs do not show long-term efficacy and cannot halt the progression to complications. Thus, more effective and evidence-based therapeutic strategies need to be urgently developed for patients with chronic HBV infection. CHB is a pathological entity induced by HBV that progresses due to impaired host immunity. This indicates the inherent limitations of antiviral-drug-based monotherapy for treating patients with chronic HBV infection. Additionally, commercially available antiviral drugs are not available to patients in developing and resource-constrained countries, posing a challenge to achieving the following WHO goal: "Elimination of Hepatitis by 2030". As such, this review aimed to provide insights regarding evidence-based and effective management strategies for chronic HBV infection.
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Affiliation(s)
- Sheikh Mohammad Fazle Akbar
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon 791-0295, Japan
- Miyakawa Memorial Research Foundation, Tokyo 107-0062, Japan
| | - Mamun Al Mahtab
- Interventional Hepatology Division, Bangabandhu Sheikh Mujib Medical University, Dhaka 1000, Bangladesh
| | - Osamu Yoshida
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon 791-0295, Japan
| | - Julio Aguilar
- Center for Genetic Engineering and Biotechnology, Havana 10400, Cuba
| | | | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon 791-0295, Japan
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Abstract
Chronic hepatitis B remains a major public health concern and a leading cause of morbidity and mortality worldwide, specifically through its causative role in chronic liver disease and hepatocellular carcinoma. Worldwide, it affects up to 292 million people. In this paper, we review the historic discovery of the hepatitis B virus and chronicle the significant advances in our understanding of the virus and its interactions with the human host to cause disease. We also overview advancements in therapies for hepatitis B virus and the current absence of curative therapies and highlight on-going therapeutic efforts in search of curative therapies to control transmission and eradicate hepatitis B virus.
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Affiliation(s)
- Rukaiya Bashir Hamidu
- Department of Medicine, Division of Gastroenterology and Hepatology, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Richard R. Hann
- Liver Disease prevention Center, Division of Gastroenterology and Hepatology, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Hie-Won Hann
- Department of Medicine, Division of Gastroenterology and Hepatology, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
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Huang SW, Li XT, Chen C, Ning Q, Huang JQ. Effect of Anti-HBs on Mortality Among Resolved HBV Infection: a Population-Based Prospective Cohort Study. Infect Dis Ther 2023; 12:871-890. [PMID: 36754951 PMCID: PMC10017907 DOI: 10.1007/s40121-023-00766-5] [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: 11/24/2022] [Accepted: 01/25/2023] [Indexed: 02/10/2023] Open
Abstract
INTRODUCTION Surveillance programs after hepatitis B surface antigen (HBsAg) loss are not yet well established, and the role of hepatitis B surface antibodies (anti-HBs) remains controversial. We aimed to evaluate the risk factors for increased mortality and the association between anti-HBs and all-cause and cause-specific mortality in a representative US (United States) population of patients with resolved HBV (Hepatitis B virus) infections. METHODS Data were taken from the US National Health and Nutrition Examination Survey (NHANES) 1999-2018. A total of 3455 US adults with resolved HBV infection [defined as hepatitis B surface antigen (HBsAg) negative/anti-hepatitis B core antigen (anti-HBc) positive] were enrolled in this study. The primary outcome measures were all-cause and cause-specific mortality from baseline until 31 December 2019. RESULTS During a mean follow-up of 10.3 years, 741 deaths occurred. Age, race, marital status, smoking status, physical activity level, and presence of cirrhosis, diabetes, cardiovascular diseases, chronic obstructive pulmonary diseases, cancer, and anti-HBs were significant factors for increased mortality, and a nomogram tool was developed and validated for the risk stratification of mortality. Compared with participants who were anti-HBs positive, those who were anti-HBs negative had a 23% (hazard ratio 1.23, 95% CI 1.02-1.46) higher risk of all-cause mortality in NHANES 1999-2018. For cause-specific mortality, the fully adjusted hazard ratios of participants who were anti-HBs negative were 0.71 (95% CI 0.48-1.06) for heart disease, 1.44 (95% CI 1.01-2.05) for cancer, and 1.44 (95% CI 1.13-1.83) for other conditions, compared to those of participants who were anti-HBs positive. CONCLUSIONS Among US adults with resolved HBV infections, anti-HBs-negative status was associated with an increased risk of death from all causes and cancer, implying that the role of anti-HBs in resolved HBV infection should not be ignored. On the public health level, more rigorous surveillance was needed for populations of individuals who were isolated anti-HBc positive.
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Affiliation(s)
- Shuai-Wen Huang
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
| | - Xi-Tang Li
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China.,National Medical Center for Major Public Health Events, Wuhan, China
| | - Chen Chen
- Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA
| | - Qin Ning
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China.,National Medical Center for Major Public Health Events, Wuhan, China
| | - Jia-Quan Huang
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China. .,National Medical Center for Major Public Health Events, Wuhan, China.
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10
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Li C, Hall TG, Hall JJ, He WQ. Effectiveness of quadrivalent HPV vaccination in reducing vaccine-type and nonvaccine-type high risk HPV infection. Epidemiol Infect 2023; 151:e37. [PMID: 36789960 PMCID: PMC10028998 DOI: 10.1017/s0950268823000213] [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] [Indexed: 02/16/2023] Open
Abstract
This study aimed to assess human papillomavirus (HPV) vaccine effectiveness (VE) against both vaccine-type and nonvaccine-type high-risk HPV (hrHPV) infection, and duration of protection in United States. The study population was female participants aged 18-35 years with an HPV vaccination history and genital testing for HPV from the National Health and Nutrition Examination Survey, 2007-2016. Participants vaccinated before sexual debut were assessed against 13 nonvaccine-type hrHPV infection including 31/33/35/39/45/51/52/56/58/59/68/73/82. Multivariable logistic regression was used to estimate VE overall, by age at diagnosis, time since vaccination and lifetime sexual partners. A total of 3866 women were included in the analysis, with 23.3% (95% CI 21.3%-25.4%) having been vaccinated (≥1 dose). VE against vaccine-type HPV18/16/11/6 infection was 58% overall, which was mainly driven by those aged 18-22 years (VE = 64%) and 23-27 years (65%). Among participants aged 18-22 years vaccinated before sexual debut, the VE was 47% (23%-64%) against 13 nonvaccine-type hrHPV and 61% (95% CI 36%-77%) against 5 selected nonvaccine-type hrHPV35/39/52/58/59. Both direct effectiveness and cross-protection maintained effective for 5-10 years post vaccination. We also found the prevalence of ever diagnosed cervical cancer among vaccinated was significantly lower (0.46%, 4/874) than that among unvaccinated participants (1.27%, 38/2992). These findings highlight the potential of significant reduction of cervical cancer following the universal HPV vaccination programme.
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Affiliation(s)
- Chenxi Li
- Melbourne School of Population & Global Health, The University of Melbourne, Melbourne, 3053, Australia
| | - Thomas G Hall
- Children's Hospital at Westmead, Westmead, 2145, Australia
| | - John J Hall
- School of Population Health, UNSW Sydney, Sydney, 2052, Australia
| | - Wen-Qiang He
- Childrens Hospital at Westmead Clinical School, The University of Sydney, Sydney, 2145, Australia
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Insights on 21 Years of HBV Surveillance in Blood Donors in France. Viruses 2022; 14:v14112507. [PMID: 36423116 PMCID: PMC9693332 DOI: 10.3390/v14112507] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 11/07/2022] [Accepted: 11/09/2022] [Indexed: 11/16/2022] Open
Abstract
Hepatitis B virus (HBV) infection is the most frequent viral infection found in blood donors (BDs) in France. We analyzed the epidemiological and sero-molecular data on HBV infection gathered over the past two decades by the French haemovigilance surveillance network, blood screening laboratories, and the national reference center for transfusion infectious risks (NRC). Between 2000 and 2020, 6149 of the 58,160,984 donations (1.06/10,000) tested HBV positive, 98% of them from first-time blood donors (FTBDs). In addition, 2212 (0.0071%) of the 30,977,753 donations screened for HBV DNA tested DNA positive, of which 25 (1.1%) were positive only for this marker. HBV prevalence decreased by 2.8-fold and the residual risk for transfusion-transmitted HBV infection decreased 13-fold and was divided by 13. The major risk factor for HBV infection was the origin of donors (endemic country, 66.5%), followed by parenteral exposure (10.7%). In the whole HBV-positive BD population, genotype D was predominant (41.8%), followed by genotypes A (26.2%) and E (20.4%), reflecting the geographical origin of donors. The low and decreasing prevalence and incidence of HBV infection in French BDs, coupled with a screening strategy using three HBV markers (HBsAg, anti-HBc and DNA), ensures a high level of blood safety, further reinforced by the implementation of pathogen-reduction measures.
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12
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Li C, He W. Comparison of primary liver cancer mortality estimates from World Health Organization, global burden disease and global cancer observatory. Liver Int 2022; 42:2299-2316. [PMID: 35779247 PMCID: PMC9543750 DOI: 10.1111/liv.15357] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 06/18/2022] [Accepted: 06/26/2022] [Indexed: 12/14/2022]
Abstract
AIMS This study aims to compare estimates of primary liver cancer mortality from World Health Organization (WHO), Global Burden Disease (GBD) and Global Cancer Observatory (GCO). METHODS Liver cancer mortality was extracted from WHO, GBD and GCO for 92 countries for the most recent year. Age-standardized rate (ASR) was computed and used for current comparisons across the three data sources. Temporal trend for 75 countries was analysed and compared between WHO and GBD from 1990 to 2019 using joinpoint regression. Average annual percentage change for the most recent 10 years was used as indicator for change. RESULTS The estimates of ASR were quite consistent across the three data sources, but most similar estimates were found between WHO and GCO in both region and country levels. The differences in ASR were negatively correlated with completeness of cause-of-death registration, human development index and proportion of liver cancer because of alcohol consumption. Consistent trends of ASR were found from 35 countries between WHO and GBD in the most recent 10 years. However, opposite trends were found from 10 countries with five from Southern America, four from Europe and one from Asia. Of the 18 countries for projection, opposite trends between WHO and GBD were found from seven countries. CONCLUSION While the ASR of primary liver cancer mortality was comparable across the three data sources, most similar estimates were found between WHO and GCO. The opposite trends found from 10 countries between WHO and GBD raised concerns of true patterns in these countries.
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Affiliation(s)
- Chenxi Li
- Melbourne School of Population & Global HealthThe University of MelbourneMelbourneAustralia
| | - Wen‐Qiang He
- School of Population HealthUNSW SydneySydneyAustralia,Childrens Hospital at Westmead Clinical SchoolThe University of SydneySydneyAustralia
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Zunica ERM, Heintz EC, Axelrod CL, Kirwan JP. Obesity Management in the Primary Prevention of Hepatocellular Carcinoma. Cancers (Basel) 2022; 14:cancers14164051. [PMID: 36011044 PMCID: PMC9406638 DOI: 10.3390/cancers14164051] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 08/16/2022] [Accepted: 08/20/2022] [Indexed: 11/16/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most frequent primary hepatic malignancy and a leading cause of cancer-related death globally. HCC is associated with an indolent clinical presentation, resulting in frequent advanced stage diagnoses where surgical resection or transplant therapies are not an option and medical therapies are largely ineffective at improving survival. As such, there is a critical need to identify and enhance primary prevention strategies to mitigate HCC-related morbidity and mortality. Obesity is an independent risk factor for the onset and progression of HCC. Furthermore, obesity is a leading cause of nonalcoholic steatohepatitis (NASH), the fasting growing etiological factor of HCC. Herein, we review evolving clinical and mechanistic associations between obesity and hepatocarcinogenesis with an emphasis on the therapeutic efficacy of prevailing lifestyle/behavioral, medical, and surgical treatment strategies for weight reduction and NASH reversal.
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Affiliation(s)
| | | | | | - John P. Kirwan
- Correspondence: (C.L.A.); (J.P.K.); Tel.: +1-225-763-2513 (J.P.K.)
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Di Lello FA, Martínez AP, Flichman DM. Insights into induction of the immune response by the hepatitis B vaccine. World J Gastroenterol 2022; 28:4249-4262. [PMID: 36159002 PMCID: PMC9453777 DOI: 10.3748/wjg.v28.i31.4249] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 05/21/2022] [Accepted: 07/25/2022] [Indexed: 02/06/2023] Open
Abstract
After more than four decades of hepatitis B virus (HBV) vaccine implementation, its safety and efficacy in preventing HBV infection have been proven and several milestones have been achieved. Most countries have included HBV immunization schedules in their health policies and progress has been made regarding universalization of the first HBV vaccine dose at birth. All of these actions have significantly contributed to reducing both the incidence of HBV infection and its related complications. However, there are still many drawbacks to overcome. The main concerns are the deficient coverage rate of the dose at birth and the large adult population that has not been reached timely by universal immunization. Additionally, the current most widely used second-generation vaccines do not induce protective immunity in 5% to 10% of the population, particularly in people over 40-years-old, obese (body mass index > 25 kg/m2), heavy smokers, and patients undergoing dialysis or infection with human immunodeficiency virus. Recently developed and approved novel vaccine formulations using more potent adjuvants or multiple antigens have shown better performance, particularly in difficult settings. These advances re-launch the expectations of achieving the World Health Organization’s objective of completing hepatitis control by 2030.
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Affiliation(s)
- Federico Alejandro Di Lello
- Microbiology, Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones en Bacteriología y Virología Molecular, Buenos Aires C1113AAD, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires C1425FQB, Argentina
| | - Alfredo Pedro Martínez
- Virology Section, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno “CEMIC”, Buenos Aires C1431FWO, Argentina
| | - Diego Martín Flichman
- Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires C1425FQB, Argentina
- Microbiology, Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas en Retrovirus y Síndrome de Inmunodeficiencia Adquirida, Buenos Aires C1121ABG, Argentina
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Coffin CS. The remarkable success of the vaccine for a killer virus: Hepatitis B. Hepatology 2022; 75:1365-1367. [PMID: 35403231 DOI: 10.1002/hep.32346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 01/11/2022] [Indexed: 12/08/2022]
Affiliation(s)
- Carla S Coffin
- Cumming School of MedicineUniversity of CalgaryCalgaryAlbertaCanada
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