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Nuermaimaiti A, Chang L, Yan Y, Sun H, Xiao Y, Song S, Feng K, Lu Z, Ji H, Wang L. The role of sex hormones and receptors in HBV infection and development of HBV-related HCC. J Med Virol 2023; 95:e29298. [PMID: 38087447 DOI: 10.1002/jmv.29298] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 10/02/2023] [Accepted: 11/18/2023] [Indexed: 12/18/2023]
Abstract
Gender disparity in hepatitis B virus (HBV)-related diseases has been extensively documented. Epidemiological studies consistently reported that males have a higher prevalence of HBV infection and incidence of hepatocellular carcinoma (HCC). Further investigations have revealed that sex hormone-related signal transductions play a significant role in gender disparity. Sex hormone axes showed significantly different responses to virus entry and replication. The sex hormones axes change the HBV-specific immune responses and antitumor immunity. Additionally, Sex hormone axes showed different effects on the development of HBV-related disease. But the role of sex hormones remains controversial, and researchers have not reached a consensus on the role of sex hormones and the use of hormone therapies in HCC treatment. In this review, we aim to summarize the experimental findings on sex hormones and provide a comprehensive understanding of their roles in the development of HCC and their implications for hormone-related HCC treatment.
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Affiliation(s)
- Abudulimutailipu Nuermaimaiti
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
- Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
- National Center for Clinical Laboratories, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Le Chang
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
- Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
| | - Ying Yan
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
- Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
| | - Huizhen Sun
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
- Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
- National Center for Clinical Laboratories, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Yingzi Xiao
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
- Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
- National Center for Clinical Laboratories, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Shi Song
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
- Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
- National Center for Clinical Laboratories, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Kaihao Feng
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
- Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
- National Center for Clinical Laboratories, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Zhuoqun Lu
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
- Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
| | - Huimin Ji
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
- Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
| | - Lunan Wang
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
- Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
- National Center for Clinical Laboratories, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
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Kan K, Wong DKH, Hui RWH, Seto WK, Yuen MF, Mak LY. Anti-HBc: a significant host predictor of spontaneous HBsAg seroclearance in chronic hepatitis B patients - a retrospective longitudinal study. BMC Gastroenterol 2023; 23:348. [PMID: 37803352 PMCID: PMC10557289 DOI: 10.1186/s12876-023-02983-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Accepted: 09/28/2023] [Indexed: 10/08/2023] Open
Abstract
BACKGROUND AND AIM In chronic hepatitis B infection (CHB), seroclearance of hepatitis B surface antigen (HBsAg) is associated with favourable clinical outcomes compared to those with persistent HBsAg seropositivity, and thus considered as a desired treatment endpoint. This current study explores the possibility of serum antibody to hepatitis B core antigen (anti-HBc) as a potential predictive factor of HBsAg seroclearance. METHODS This is a retrospective study that analyzed the plasma samples of CHB patients using the LUMIPULSE® G1200 analyzer. The longitudinal anti-HBc level between patients who subsequently achieved HBsAg seroclearance (S-losers) and those with persistent HBsAg-positivity (controls) were compared at multiple time points before the event. RESULTS A total of 240 subjects (120 S-losers and 120 controls; age- and gender-matched) were included (mean age 56.42 ± 10.81, 65% male). Compared to controls, S-losers had significantly lower plasma anti-HBc levels prior to HBsAg seroclearance, with a significant trend of declining plasma anti-HBc 8-5 years prior to HBsAg seroclearance (p < 0.01), while such trend was not observed in controls. ROC curve analysis revealed that plasma anti-HBc at multiple time points before HBsAg seroclearance return AUC greater than 0.7. Plasma anti-HBc level at the cut-off value of 82.50 COI was 68.3% sensitive and 90% specific for HBsAg seroclearance within 1 year. Combining with quantitative HBsAg < 100 IU/mL, anti-HBc < 82.5 COI identified 88.2% patients who would develop HBsAg seroclearance within 1 year. CONCLUSION Plasma anti-HBc level began to decline 10 years prior to HBsAg seroclearance and can serve as a potential predictor for subsequent HBsAg seroclearance.
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Affiliation(s)
- Karin Kan
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China
- State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China
| | - Danny Ka-Ho Wong
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China
- State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China
| | - Rex Wan-Hin Hui
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China
| | - Wai Kay Seto
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China
- State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China
| | - Man-Fung Yuen
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China.
- State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China.
| | - Lung-Yi Mak
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China.
- State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China.
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Duan H, Wang X, Qi W, Shi J, Han L, Wang G, Xu Y, Liu J, Wang J. Two genetic variants in the SRD5A2 gene are found to be associated with sex differences in the disease characteristics of patients with chronic hepatitis B virus infection. Biol Sex Differ 2023; 14:68. [PMID: 37784175 PMCID: PMC10546680 DOI: 10.1186/s13293-023-00553-4] [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: 07/27/2023] [Accepted: 09/24/2023] [Indexed: 10/04/2023] Open
Abstract
BACKGROUND To examine the expression characteristics of single nucleotide polymorphisms (SNPs) in the SRD5A2 gene and investigate their potential association with differences in the clinical characteristics between sexes in patients with chronic hepatitis B virus (HBV) infection. METHODS A total of 30 loci in six genes primarily involved in the metabolism and signaling of sex hormones/sex hormone receptors, namely AKR1C2, AKR1C3, HSD17B6, SRD5A1, SRD5A2, and ESR1, were genotyped in 1007 patients from eight counties (cities) in Northeastern China with chronic HBV infection and 1040 healthy controls, and their association with viral replication characteristics and the differences in disease severity between sexes was assessed. Western blotting was conducted to determine the hepatic SRD5A2 protein level and its relationship with the inflammatory activity and fibrosis degree in male and female patients. RESULTS Two SNP loci in the SRD5A2 gene (rs12470143 and rs7594951) exhibited significant differences in genotype and allele frequencies between sexes, with the proportion of T alleles significantly higher in males than in females. It was found that the incidence and severity of HBV-related liver fibrosis were significantly higher in patients with the T/T genotype in SRD5A2 rs12470143 and rs7594951 than those with the non-T/T genotype. Additionally, serum HBV DNA levels were significantly elevated in T/T patients compared to non-T/T patients. Female patients exhibited significantly lower serum DNA levels compared to male patients. Western blot analysis indicated that greater hepatic SRD5A2 protein levels were associated with higher METAVIR inflammation and fibrosis scores. Furthermore, multivariate analysis showed that the two genetic variants in the SRD5A2 gene (rs12470143 C > T, r7594951 C > T), together with the male sex, age > 50 years old, HBeAg positive status, elevated serum HBsAg load, high serum HBV DNA load, and HBV genotype C, were independent risk factors for HBV-related liver fibrosis. CONCLUSIONS This study demonstrated that two genetic variants in the SRD5A2 gene (rs12470143 C > T, r7594951 C > T) are associated with sex differences in the clinical characteristics of patients with chronic HBV infection.
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Affiliation(s)
- Honglei Duan
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, No. 126 Xiantai St., Changchun, 130033, Jilin, China
| | - Xu Wang
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, No. 126 Xiantai St., Changchun, 130033, Jilin, China
| | - Wenqian Qi
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, No. 126 Xiantai St., Changchun, 130033, Jilin, China
| | - Jingyi Shi
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, No. 126 Xiantai St., Changchun, 130033, Jilin, China
| | - Liang Han
- Department of Pathology, China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin, China
| | - Guohua Wang
- Department of Gastroenterology and Nephrology, Songyuan Jilin Oilfield Hospital, Songyuan, 138000, Jilin, China
| | - Yanhui Xu
- Department of Gastroenterology and Hepatology, People's Hospital of Zhengzhou University and Henan Provincial People's Hospital, Zhengzhou, 450003, Henan, China
| | - Jia Liu
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, No. 126 Xiantai St., Changchun, 130033, Jilin, China
| | - Jiangbin Wang
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, No. 126 Xiantai St., Changchun, 130033, Jilin, China.
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Cam Huong NT, Van Luu N, Nam NH, Ghula S, Atieh Qarawi AT, Mai Truc PT, Trung An DN, Huy NT, Le Hoa PT. Prevalence of hepatitis B virus infection in health check-up participants: a cross-sectional study at University Medical Center, Ho Chi Minh City, Vietnam. Hosp Pract (1995) 2023. [PMID: 37262352 DOI: 10.1080/21548331.2023.2221132] [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: 11/01/2022] [Accepted: 05/31/2023] [Indexed: 06/03/2023]
Abstract
OBJECTIVES Vietnam is one of the countries in highly endemic areas of hepatitis B virus (HBV) infection in the world. Our study aims to determine the prevalence of HBV infection among different age groups of workers who had been included for annual general health checkups. METHODS This cross-sectional study was conducted at the Health Screening Department, University Medical Center at Ho Chi Minh City, Vietnam, using anonymous data from employees who had health checkups from June 2017 to June 2018. RESULTS A total of 5727 subjects were included, with an overall HBV prevalence of 9.0%. The prevalence of HBV infection was significantly higher in men and lowest in the age groups of 18-30. In multivariable analysis, the variables that were independently associated with HBV infection were male gender (Odd ratio (OR), 2.03; 95% confidence interval (CI), 1.58-2.60; p < 0.001), older than 30 years old (age group of 31-40: OR 1.7; 95% CI, 1.33-2.18; p < 0.001; of 41-50, OR 1.82; 95% CI, 1.37-2.43; p < 0.001); high total cholesterol (OR, 0.77; 95% CI, 0.64-0.94; p = 0.011), high triglyceride (OR, 0.53; 95% CI, 0.42-0.65; p < 0.001), and having significant fibrosis (OR, 2.7; 95% CI 1.85-3,95; p < 0.001). CONCLUSIONS The prevalence of HBV infection among employees on health assessments is still high (9%), even in the age group under 30 (7%). Male, age group older than 30, and significant liver fibrosis were the factors related to HBV infection. High cholesterol and level triglyceride were protective factors against HBV infection.
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Affiliation(s)
- Nguyen Thi Cam Huong
- Infectious Diseases Department, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
- Outpatient Department, University Medical Center, Ho Chi Minh City, Vietnam
| | - Nguyen Van Luu
- Infectious Diseases Department, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Nguyen Hai Nam
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
- Online Research Club , Nagasaki, Japan, Http://Www.Onlineresearchclub.org
| | - Suhaib Ghula
- Online Research Club , Nagasaki, Japan, Http://Www.Onlineresearchclub.org
- Medical School, University of Buckingham, Buckingham, UK
| | - Ahmad Taysir Atieh Qarawi
- Online Research Club , Nagasaki, Japan, Http://Www.Onlineresearchclub.org
- Lower Westchester Medical Associate, New York, P.C. Mount Vernon, USA
| | - Pham Thi Mai Truc
- Online Research Club , Nagasaki, Japan, Http://Www.Onlineresearchclub.org
- Imaging Diagnostic Department, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Dang Nguyen Trung An
- Imaging Diagnostic Department, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
- Health Screening Department, University Medical Center, Ho Chi Minh City, Vietnam
| | - Nguyen Tien Huy
- Online Research Club , Nagasaki, Japan, Http://Www.Onlineresearchclub.org
- School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan
| | - Pham Thi Le Hoa
- Infectious Diseases Department, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
- Outpatient Department, University Medical Center, Ho Chi Minh City, Vietnam
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Zhang L, Wu J, Wu Q, Zhang X, Lin S, Ran W, Zhu L, Tang C, Wang X. Sex steroid axes in determining male predominance in hepatocellular carcinoma. Cancer Lett 2023; 555:216037. [PMID: 36563929 DOI: 10.1016/j.canlet.2022.216037] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 11/23/2022] [Accepted: 12/05/2022] [Indexed: 12/24/2022]
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death. The mechanisms for male propensity in HCC incidence, prognosis and treatment responses are complicated and remain inconclusive. Sex-biased molecular signatures in carcinogenesis, viral infections and immune responses have been studied predominantly within the context of sex hormones effects. This review integrates current knowledge on the mechanisms through which the hormones regulate HCC development in sexually dimorphic fashion. Firstly, the androgen/androgen receptor (AR) accelerate cell proliferation and virus infection, especially during the initial stage of HCC, while estrogen/estrogen receptor (ER) function in an opposite way to induce cell apoptosis and immune responses. Interestingly, the controversial effects of AR in late stage of HCC metastasis are summarized and the reasons are attributed to inconsistent cancer grading or experimental models between the studies. In addition, the new insights into these intricate cellular and molecular mechanisms underlying sexual dimorphism are fully discussed. A detailed understanding of sex hormones-associated regulation to male predominance in HCC may help to develop personalized therapeutic strategies in high-risk populations.
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Affiliation(s)
- Lei Zhang
- Key Laboratory of Gastrointestinal Cancer (Ministry of Education), School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - JinFeng Wu
- Key Laboratory of Gastrointestinal Cancer (Ministry of Education), School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - QiuMei Wu
- Key Laboratory of Gastrointestinal Cancer (Ministry of Education), School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - XiangJuan Zhang
- Key Laboratory of Gastrointestinal Cancer (Ministry of Education), School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - ShuaiCai Lin
- Key Laboratory of Gastrointestinal Cancer (Ministry of Education), School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - WanLi Ran
- Key Laboratory of Gastrointestinal Cancer (Ministry of Education), School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Li Zhu
- Key Laboratory of Gastrointestinal Cancer (Ministry of Education), School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - ChengYan Tang
- Key Laboratory of Gastrointestinal Cancer (Ministry of Education), School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Xing Wang
- Key Laboratory of Gastrointestinal Cancer (Ministry of Education), School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China.
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Ward JW, Wanlapakorn N, Poovorawan Y, Shouval D. Hepatitis B Vaccines. PLOTKIN'S VACCINES 2023:389-432.e21. [DOI: 10.1016/b978-0-323-79058-1.00027-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Nieminen T, Salo H, Nurhonen M, Leino T. Health care costs related to hepatitis B in Finland are mostly due to chronic infections: a register-based study. Infect Dis (Lond) 2022; 54:722-730. [PMID: 35857779 DOI: 10.1080/23744235.2022.2082519] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND Finland is among the countries with low hepatitis B endemicity. We evaluate the hepatitis B-related disease and economic burden needed for evidence-based immunisation policy decision-making. METHODS Hepatitis B-related cases in 2004-2012 were retrieved from population-based nationwide registers. We evaluated the incidence, health care resource use, health care costs, and life years lost due to hepatitis B-related outcomes. An episode of care was constructed from each individual's hepatitis B-related events retrieved from individually linkable registers. RESULTS The mean health care costs per an acute hepatitis B case were €450 (SD 240), €2030 (SD 350), and €5400 (SD 3370) in those aged 0-14, 15-64, and ≥65 years, respectively. For chronic infection, the mean cost per case among Finnish-born individuals was €990 and among foreign-born €1360. The costs per case of liver cirrhosis were €15,350 and liver cancer €19,080. In addition, the annual antiviral medication costs per case receiving antiviral medication were €4710 to €5530. Annually <10% of the chronic and approximately 20% of liver cirrhosis cases received antiviral medication. We identified annually 21 acute, 264 chronic, three liver cirrhosis, and four liver cancer cases and 63.7 life years lost due to hepatitis B per 5.3 million inhabitants. The total annual health care costs were €1.2 million of which 60% were antiviral medication costs and 86% accounted for chronic hepatitis B. CONCLUSIONS When planning prevention of hepatitis B infection, it is pivotal to notice that the overall disease and economic burden due to hepatitis B is mostly due to chronic infection.
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Affiliation(s)
- Tanja Nieminen
- Department of Health Security, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Heini Salo
- Department of Health Security, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Markku Nurhonen
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Tuija Leino
- Department of Health Security, Finnish Institute for Health and Welfare, Helsinki, Finland
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Hepatitis B Virus Chronic Infection in Blood Donors from Asian and African High or Medium Prevalence Areas: Comparison According to Sex. Viruses 2022; 14:v14040673. [PMID: 35458403 PMCID: PMC9029447 DOI: 10.3390/v14040673] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Revised: 03/16/2022] [Accepted: 03/21/2022] [Indexed: 02/07/2023] Open
Abstract
Immune control of various infectious diseases, particularly viral, was shown to be more efficient for females than males. Response to viral vaccines (HAV, HBV) was higher in females. Data on hepatitis B virus (HBV) markers accumulated over 15 years in blood donors was stratified according to sex, including HBsAg, HBV viral load and levels of anti-HBs in areas where genotypes B and C (China), genotype D (Iran, Lebanon, Tunisia) and genotype E (Ghana, Burkina Faso, Gabon) were prevalent. HBsAg was screened by either ELISA or rapid tests, anti-HBc and anti-HBs by ELISA, HBV DNA load by a standardized method across sites. In Ghanaian children less than 5 years, HBV DNA load was significantly lower in females than in males (p = 0.035). In China, Ghana, Burkina Faso and Gabon blood donors, median HBsAg prevalence was ~5% and 3% in China, ~8.5% and 4.5% in Gabon, ~16% and 11% in Burkina Faso and ~11% and 7% in Ghana for male and female donors, respectively (p < 0.001). In HBsAg+ Ghanaian blood donors, distribution and median viral load were not significantly different between sexes; occult hepatitis B infections (OBI) were significantly more frequent in males. In Chinese blood donor anti-HBc+ and anti-HBs+, anti-HBs levels tended to be higher in males but vaccinated donors’ anti-HBs+ only, while anti-HBs levels were females > males. In areas where genotypes B-E are dominant, the prevalence of chronic HBV infection (HBsAg+) seems better controlled before age 16−18 by females infected vertically or horizontally. OBIs appear considerably more frequent in men, suggesting lower efficacy of HBV infection control. Female blood donors appear significantly safer from HBV than males, and their donation should be encouraged.
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Hsu PY, Wei YJ, Liang PC, Lee JJ, Niu SW, Huang JC, Hsu CT, Jang TY, Huang CI, Lin YH, Hsieh MY, Hsieh MH, Chen SC, Dai CY, Lin ZY, Chen SC, Huang JF, Chang JM, Yeh ML, Huang CF, Chiu YW, Hwang SJ, Chuang WL, Yu ML. Comorbidities in patients with chronic hepatitis C and hepatitis B on hemodialysis. J Gastroenterol Hepatol 2021; 36:2261-2269. [PMID: 33651428 DOI: 10.1111/jgh.15480] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 02/02/2021] [Accepted: 02/23/2021] [Indexed: 12/29/2022]
Abstract
BACKGROUND AND AIM Hemodialysis patients are at increased risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Both HBV and HCV infections lead to risks of end-stage liver diseases and extrahepatic manifestations. This study aimed to investigate hepatic and extrahepatic comorbidities in hemodialysis patients with HBV or HCV infections compared with those without viral hepatitis. METHODS A total of 1910 hemodialysis patients, including 159 HCV viremic patients (HCV group), 217 seropositive for HBV surface antigen (HBsAg, HBV group) and 1534 seronegative for both anti-HCV and HBsAg (non-B and non-C [NBNC] group), from 23 hemodialysis centers were enrolled. Comorbidities were classified into 10 categories by the International Classification of Diseases-10th Revision. RESULTS Among the 1910 patients, the mean age was 64.6 years, and 52.7% were male patients. A total of 1834 (96%) patients had at least one comorbidity, and the mean number of comorbidities was 2.9 ± 1.5 per person. The three most common comorbidities were hypertension, diabetes, and ischemic heart diseases. The mean number of comorbidities per person was significantly higher in the HCV group (3.3 ± 1.7) than in the HBV (2.7 ± 1.5, P < 0.001) and NBNC groups (2.9 ± 1.5, P = 0.004), mainly due to the higher prevalence of ischemic heart disease, respiratory disorders, and mental/behavioral disorders. The HBV and NBNC groups exhibited comparable burdens of comorbidities. CONCLUSIONS Hemodialysis patients had a high prevalence of multiple comorbidities. Hemodialysis patients with HCV exhibited a higher burden of comorbidities, especially ischemic heart diseases, respiratory disorders, and mental/behavioral disorders, than HBV and NBNC patients did.
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Affiliation(s)
- Po-Yao Hsu
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yu-Ju Wei
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Po-Cheng Liang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jia-Jung Lee
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Sheng-Wen Niu
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jiun-Chi Huang
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Cheng-Ting Hsu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Tyng-Yuan Jang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Hung Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Yen Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Meng-Hsuan Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Szu-Chia Chen
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shinn-Cherng Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jer-Ming Chang
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Wen Chiu
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shang-Jyh Hwang
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
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10
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Sugimoto R, Furukawa M, Senju T, Aratake Y, Shimokawa M, Tanaka Y, Inada H, Noguchi T, Lee L, Miki M, Maruyama Y, Hashimoto R, Hisano T. Risk factors for de novo hepatitis B during solid cancer treatment. World J Clin Cases 2020; 8:6264-6273. [PMID: 33392307 PMCID: PMC7760444 DOI: 10.12998/wjcc.v8.i24.6264] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 10/13/2020] [Accepted: 11/02/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Reactivation of hepatitis B virus (HBV) during anticancer treatment is a critical issue. When treating patients with solid tumors, it is unclear whether specific cancer types or treatments affect HBV reactivation in hepatitis B surface antigen (HBsAg)-negative and hepatitis B core antibody (HBcAb)-positive patients, so-called de novo hepatitis B patients. The risk of de novo hepatitis B may vary based on different background factors.
AIM To determine the frequency and risk factors for de novo hepatitis B during solid tumor treatment.
METHODS This retrospective cohort study comprised 1040 patients without HBsAgs and with HBcAbs and/or hepatitis B surface antibodies (HBsAbs). The patients were treated for solid cancer from 2008 to 2018 at the National Kyushu Cancer Center and underwent HBV DNA measurements. Patient characteristics and disease and treatment information were investigated. HBV DNA measurements were performed using TaqMan polymerase chain reaction (PCR). To identify the risk factors associated with HBV DNA expression, the age, sex, original disease, pathology, treatment method, presence or absence of hepatitis C virus (HCV), and HBsAb and/or HBcAb titers of all subjects were investigated. In patients with HBV DNA, the time of appearance, presence of HBsAgs and HBsAbs at the time of appearance, and course of the subsequent fluctuations in virus levels were also investigated.
RESULTS Among the 1040 patients, 938 were HBcAb positive, and 102 were HBcAb negative and HBsAb positive. HBV DNA expression was observed before the onset of treatment in nine patients (0.9%) and after treatment in 35 patients (3.7%), all of whom were HBcAb positive. The HBV reactivation group showed significantly higher median HBcAb values [9.00 (8.12-9.89) vs 7.22 (7.02-7.43), P = 0.0001] and significantly lower HBsAb values (14 vs 46, P = 0.0342) than the group without reactivation. Notably, the reactivated group showed a significantly higher proportion of cancers in organs related to digestion and absorption (79.0% vs 58.7%, P = 0.0051). A high HBcAb titer and cancers in organs involved in digestion and absorption were identified as independent factors for HBV reactivation (multivariate analysis, P = 0.0002 and P = 0.0095). The group without HBsAbs tended to have a shorter time to reactivation (day 43 vs day 193), and the frequency of reactivation within 6 mo was significantly higher in this group (P = 0.0459) than in the other group.
CONCLUSION A high HBcAb titer and cancers in organs involved in digestion and absorption are independent factors that contribute to HBV reactivation during solid tumor treatment.
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Affiliation(s)
- Rie Sugimoto
- Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka City 811-1395, Fukuoka Prefecture, Japan
| | - Masayuki Furukawa
- Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka City 811-1395, Fukuoka Prefecture, Japan
| | - Takeshi Senju
- Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka City 811-1395, Fukuoka Prefecture, Japan
| | - Yoshihusa Aratake
- Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka City 811-1395, Fukuoka Prefecture, Japan
| | - Mototsugu Shimokawa
- National Hospital Organization Kyushu Cancer Center, Clinical Research Institute, Fukuoka City 811-1395, Fukuoka Prefecture, Japan
- Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Ube City 755-8505, Yamaguchi Prefecture, Japan
| | - Yuki Tanaka
- Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka City 811-1395, Fukuoka Prefecture, Japan
| | - Hiroki Inada
- Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka City 811-1395, Fukuoka Prefecture, Japan
| | - Tatsuya Noguchi
- Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka City 811-1395, Fukuoka Prefecture, Japan
| | - Lingaku Lee
- Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka City 811-1395, Fukuoka Prefecture, Japan
| | - Masami Miki
- Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka City 811-1395, Fukuoka Prefecture, Japan
| | - Yuji Maruyama
- Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka City 811-1395, Fukuoka Prefecture, Japan
| | - Risa Hashimoto
- Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka City 811-1395, Fukuoka Prefecture, Japan
| | - Terumasa Hisano
- Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka City 811-1395, Fukuoka Prefecture, Japan
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11
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Yengo CK, Torimiro J, Kowo M, Lebon PA, Tiedeu BA, Luma H, Njoya O, Rowland-Jones S, Yindom LM. Variation of HLA class I (-A and -C) genes in individuals infected with hepatitis B or hepatitis C virus in Cameroon. Heliyon 2020; 6:e05232. [PMID: 33102855 PMCID: PMC7569220 DOI: 10.1016/j.heliyon.2020.e05232] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 09/10/2020] [Accepted: 10/08/2020] [Indexed: 12/22/2022] Open
Abstract
The Human Leucocyte Antigens (HLA) work in concert with other immune factors to modulate immunity to viral infections. Extensive variation has been reported in the genetic sequences and functions of classical HLA class I genes in many (mostly Western) populations, and several HLA associations with infectious disease outcomes have been reported. Little is known about their role in the susceptibility or resistance to hepatitis viruses in Central African populations. The aim of this study was to determine variants of two HLA class I genes (HLA-A and -C) in adults infected with hepatitis B (HBV)- or -C (HCV) virus in Cameroon. In this case-control study, a total of 169 unrelated adults comprising 68 HCV-infected, 38 HBV-infected and 63 uninfected (controls) individuals participated. Each consented participant was screened for HBV, HCV, and HIV infections and willingly donated a single blood sample for genomic DNA isolation and some clinical laboratory tests. HLA-A and HLA-C were genotyped using previously described sequence-based techniques (SBT). A total of 54 HLA alleles were identified in the study population (27 HLA-A and 27 HLA-C). HLA-A∗23:01 and HLA-C∗07:01 were the most common alleles with genotype frequencies of 31.4% and 29.3%, respectively. Hepatitis individuals were six times more likely to be HLA-A∗30:01 carriers than uninfected controls (OR = 6.30, p = 0.020 (HBV); OR = 6.21, p = 0.010 (HCV), respectively). Similarly, carriers of HLA-C∗17:01 were over-represented in the HBV-infected compared to the uninfected control group (21.9% vs. 6.4%, respectively) suggesting that this allele could play a role in the susceptibility to HBV infection. These findings demonstrate that carriers of HLA-A∗30:01 were over-represented in the hepatitis group compared to uninfected controls while HLA-C∗17:01 was completely absent in the HCV + group.
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Affiliation(s)
- Clauvis Kunkeng Yengo
- Department of Biochemistry, Faculty of Sciences, University of Yaoundé I, Yaoundé, Cameroon
| | - Judith Torimiro
- Molecular Biology Laboratory, Chantal Biya International Reference Centre for Research on Prevention and Management of HIV/AIDS (CIRCB), Yaoundé, Cameroon
- Department of Biochemistry, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon
| | - Mathurin Kowo
- Department of Internal Medicine, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon
| | - Patrick Awoumou Lebon
- Department of Biochemistry, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon
| | - Barbara Atogho Tiedeu
- Department of Biochemistry, Faculty of Sciences, University of Yaoundé I, Yaoundé, Cameroon
| | - Henry Luma
- Department of Internal Medicine, Douala General Hospital, Douala, Cameroon
| | - Oudou Njoya
- Department of Internal Medicine, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon
| | - Sarah Rowland-Jones
- Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Louis-Marie Yindom
- Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
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12
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Chen YY, Fang WH, Wang CC, Kao TW, Chang YW, Yang HF, Wu CJ, Sun YS, Chen WL. Crosssectional Assessment of Bone Mass Density in Adults with Hepatitis B Virus and Hepatitis C Virus Infection. Sci Rep 2019; 9:5069. [PMID: 30911051 PMCID: PMC6433944 DOI: 10.1038/s41598-019-41674-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2018] [Accepted: 03/13/2019] [Indexed: 12/13/2022] Open
Abstract
Osteoporosis is one of the major complications in chronic hepatitis B virus (HBV) and hepatitis C (HCV) infection. However, few studies had examined the relationship between hepatic viral infection with bone loss. Our aim was to investigate the association between hepatic viral infection with bone mineral density (BMD) in a cross-sectional study. Participants who attended the health examinations at the Tri-Service General Hospital (TSGH), Taiwan, were enrolled in the study. Diagnosis of viral hepatitis was confirmed by the serum viral markers of hepatitis B surface antigen (HBsAg) and anti-HCV, and BMD measurement was performed by the bone densitometry. Subjects were divided into four groups by the presence of viral markers. The association between hepatic viral infection and BMD was examined by a multivariate linear regression model. HBV infection was inversely associated with BMD after full adjusting with β values of -0.17 (95% CI: -0.29, -0.05) (p < 0.05). The relationship remained significant in males (β = -0.16, 95% CI = -0.31, -0.01) (p < 0.05). In subjects with body mass index less than 30 HBV infection was associated with reduced BMD (β = -0.16, 95% CI = -0.29, -0.02) (p < 0.05). However, HCV infection was only associated with an increase in BMD in patients with BMI less than 30 (β = 0.17, 95% CI = 0.21, 0.32) (p < 0.05). Chronic HBV infection was significantly associated with reduced BMD in males. The impact of viral hepatitis on bone health deserves further investigation for the potential pathophysiological mechanisms.
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Affiliation(s)
- Yuan-Yuei Chen
- Department of Internal Medicine, Tri-Service General Hospital Songshan Branch; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China.,Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China
| | - Wen-Hui Fang
- Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China
| | - Chung-Ching Wang
- Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China
| | - Tung-Wei Kao
- Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China.,Division of Geriatric Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China.,Graduate Institute of Clinical Medical, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China
| | - Yaw-Wen Chang
- Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China.,Division of Geriatric Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China
| | - Hui-Fang Yang
- Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China.,Division of Geriatric Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China
| | - Chen-Jung Wu
- Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China.,Division of Geriatric Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China.,Division of Family Medicine, Department of Community Medicine, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan, Republic of China
| | - Yu-Shan Sun
- Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China.,Division of Geriatric Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China
| | - Wei-Liang Chen
- Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China. .,Division of Geriatric Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China.
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13
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Ruggieri A, Gagliardi MC, Anticoli S. Sex-Dependent Outcome of Hepatitis B and C Viruses Infections: Synergy of Sex Hormones and Immune Responses? Front Immunol 2018; 9:2302. [PMID: 30349537 PMCID: PMC6186821 DOI: 10.3389/fimmu.2018.02302] [Citation(s) in RCA: 86] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Accepted: 09/17/2018] [Indexed: 01/19/2023] Open
Abstract
Hepatitis B virus (HBV) and hepatitis C virus (HCV) are hepatotropic viruses that differ in their genomic content, life cycle and molecular prognosis. HBV and HCV establish chronic lifespan infections that can evolve to fibrosis, cirrhosis and hepatocellular carcinoma (HCC). This malignant liver cancer affects more commonly male patients than females, with a male-to-female incidence ratio of <Capword>2</Capword>:1 up to 7:1. Sex significantly contributes to shape the immune responses, contributing to differences in the pathogenesis of infectious diseases, in males and females patients. Females usually develop more intense innate, humoral and cellular immune responses to viral infections and to vaccination compared to male subjects. Sex hormones, in turn, differentially affect the immune responses to viruses, by specific binding to the hormone receptors expressed on the immune cells. In general, estrogens have immune-stimulating effect, while androgens are immune-suppressing. However, sex hormones, such as androgen, can also directly interact with HBV genome integrated into the cell nucleus and activate transcription of HBV oncoproteins. On the other side, estradiol and estrogen receptors protect liver cells from inflammatory damage, apoptosis and oxidative stress, which contribute to fibrosis and malignant transformation preceding HCC. In HCV-associated cirrhosis and HCC the decreased expression of estrogen receptor alfa (ERα) in male patients may explain the worse outcome of HCV infection in men than in women. The synergistic action of male and female sex hormones and of immune responses, together with viral factors contribute to the mechanism of sex/gender disparity in the outcome and progression of hepatitis viruses infection.
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Affiliation(s)
- Anna Ruggieri
- Center for Gender Specific Medicine, Istituto Superiore di Sanità, Rome, Italy
| | | | - Simona Anticoli
- Center for Gender Specific Medicine, Istituto Superiore di Sanità, Rome, Italy
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14
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Mittal S, Kramer JR, Omino R, Chayanupatkul M, Richardson PA, El-Serag HB, Kanwal F. Role of Age and Race in the Risk of Hepatocellular Carcinoma in Veterans With Hepatitis B Virus Infection. Clin Gastroenterol Hepatol 2018; 16:252-259. [PMID: 28870660 DOI: 10.1016/j.cgh.2017.08.042] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2016] [Revised: 08/20/2017] [Accepted: 08/28/2017] [Indexed: 01/30/2023]
Abstract
BACKGROUND & AIMS Hepatocellular (HCC) surveillance guidelines for patients with chronic hepatitis B virus (HBV) infection are based on race- and age-specific estimates of HCC risk, derived from studies conducted in areas in which HBV is endemic. METHODS We conducted a retrospective cohort study using the national Veterans Administration data to identify patients with chronic HBV infection from 2001 through 2013. We examined the effect of race and age on HCC risk while adjusting for baseline clinical characteristics. RESULTS The study cohort had 8329 patients; 3498 patients (42.0%) were white, 3248 (39%) were African Americans, and 659 (7.9%) were Asian Pacific Islanders. The annual HCC incidence was highest in Asian Pacific Islanders (0.65%), followed by whites (0.57%) and African Americans (0.40%). After adjusting for clinical and viral factors, the risk of HCC was significantly higher in Asian Pacific Islanders compared with whites (adjusted hazard ratio [HR] = 2.04; 95% CI, 1.31-3.17). There was no difference in HCC risk between African Americans and whites (adjusted HR, 0.77; 95% CI, 0.58-1.02). HCC risk increased with age: adjusted HR was 1.97 (95% CI, 0.99-3.87) for 40-49 years; adjusted HR was 3.00 (95% CI, 1.55-5.81) for 50-59 years; and adjusted HR was 4.02 (95% CI, 2.03-7.94) for more than 60 years vs less than 40 years. Patients with cirrhosis had higher risk of HCC than patients without cirrhosis (adjusted HR = 3.69; 95% CI, 2.82-4.83). However, even among patients without cirrhosis, the annual incidence of HCC was more than 0.2% for all patients older than 40 years with high levels of alanine aminotransferase-regardless of race. CONCLUSIONS In a sample of male veterans with chronic HBV infection, risk of HCC is highest among Asian Pacific Islanders, followed by whites and African Americans. Cirrhosis increased HCC risk. Among patients without cirrhosis, male patients who are older than 40 years and have increased levels of alanine aminotransferase might benefit from HCC surveillance, regardless of race.
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Affiliation(s)
- Sahil Mittal
- Center of Innovation, Effectiveness and Quality, Sections of Health Services Research, Section of Gastroenterology and Hepatology, Houston, Texas; Baylor College of Medicine, Houston, Texas.
| | - Jennifer R Kramer
- Center of Innovation, Effectiveness and Quality, Sections of Health Services Research, Section of Gastroenterology and Hepatology, Houston, Texas
| | | | | | - Peter A Richardson
- Center of Innovation, Effectiveness and Quality, Sections of Health Services Research, Section of Gastroenterology and Hepatology, Houston, Texas
| | - Hashem B El-Serag
- Center of Innovation, Effectiveness and Quality, Sections of Health Services Research, Section of Gastroenterology and Hepatology, Houston, Texas; Baylor College of Medicine, Houston, Texas; Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - Fasiha Kanwal
- Center of Innovation, Effectiveness and Quality, Sections of Health Services Research, Section of Gastroenterology and Hepatology, Houston, Texas; Baylor College of Medicine, Houston, Texas; Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
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15
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16
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Wong RJ, Nguyen MT, Trinh HN, Chan C, Huynh A, Ly MT, Nguyen HA, Nguyen KK, Torres S, Yang J, Liu B, Garcia RT, Bhuket T, Baden R, Levitt B, da Silveira E, Gish RG. Hepatitis B surface antigen loss and sustained viral suppression in Asian chronic hepatitis B patients: A community-based real-world study. J Viral Hepat 2017; 24:1089-1097. [PMID: 28581644 DOI: 10.1111/jvh.12736] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Accepted: 05/09/2017] [Indexed: 12/19/2022]
Abstract
Community-based real-world outcomes on effectiveness of antiviral therapies for chronic hepatitis B virus (CHB) in Asians are limited. Whether hepatitis B surface antigen (HBsAg) loss correlates with undetectable virus and alanine aminotransferase (ALT) normalization on treatment or what predicts risk of seroreversion or detectable virus after stopping therapy is unclear. We aim to evaluate rates and predictors of HBsAg loss, seroconversion, ALT normalization and undetectable HBV DNA, including HBsAg seroreversion or re-emergence of HBV DNA among Asian CHB patients. We retrospectively evaluated 1072 CHB adults on antiviral therapy at two community gastroenterology clinics from 1997 to 2015. Rates of HBsAg loss, ALT normalization, achieving undetectable HBV DNA and developing surface antibody (anti-HBs) were stratified by HBeAg status. Following HBsAg loss, HBsAg seroreversion or re-emergence of detectable HBV DNA was analysed. With median treatment of 76.7 months, the overall rate of HBsAg loss was 4.58%, with similar HBsAg loss rates between HBeAg-positive and HBeAg-negative patients (4.44% vs 4.71%, P=.85) in a predominantly Asian population (98.1%). Among HBsAg loss patients, 33.3% developed anti-HBs, 95.8% achieved undetectable virus and 66.0% normalized ALT. No significant baseline or on-treatment predictors of HBsAg loss were observed. While six patients who achieved HBsAg loss had seroreversion with re-emergence of HBsAg positivity, viral load remained undetectable, demonstrating the sustainability of viral suppression. Among a large community-based real-world cohort of Asian CHB patients treated with antiviral therapy, rate of HBsAg loss was 4.58%. Despite only 33.3% of HBsAg loss patients achieving anti-HBs, nearly all patients achieved sustained undetectable virus.
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Affiliation(s)
- R J Wong
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA, USA
| | - M T Nguyen
- Silicon Valley Research Institute, San Jose, CA, USA
| | - H N Trinh
- San Jose Gastroenterology, San Jose, CA, USA
| | - C Chan
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA, USA
| | - A Huynh
- Silicon Valley Research Institute, San Jose, CA, USA
| | - M T Ly
- Silicon Valley Research Institute, San Jose, CA, USA
| | - H A Nguyen
- San Jose Gastroenterology, San Jose, CA, USA
| | - K K Nguyen
- San Jose Gastroenterology, San Jose, CA, USA
| | - S Torres
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA, USA
| | - J Yang
- San Jose Gastroenterology, San Jose, CA, USA
| | - B Liu
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA, USA
| | - R T Garcia
- San Jose Gastroenterology, San Jose, CA, USA
| | - T Bhuket
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA, USA
| | - R Baden
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA, USA
| | - B Levitt
- San Jose Gastroenterology, San Jose, CA, USA
| | | | - R G Gish
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Stanford, CA, USA.,Hepatitis B Foundation, Doylestown, PA, USA
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17
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de Niet A, Jansen L, Stelma F, Willemse SB, Kuiken SD, Weijer S, van Nieuwkerk CMJ, Zaaijer HL, Molenkamp R, Takkenberg RB, Koot M, Verheij J, Beuers U, Reesink HW. Peg-interferon plus nucleotide analogue treatment versus no treatment in patients with chronic hepatitis B with a low viral load: a randomised controlled, open-label trial. Lancet Gastroenterol Hepatol 2017; 2:576-584. [PMID: 28522204 DOI: 10.1016/s2468-1253(17)30083-3] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2017] [Revised: 03/03/2017] [Accepted: 03/08/2017] [Indexed: 02/07/2023]
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Kosinska AD, Pishraft-Sabet L, Wu W, Fang Z, Lenart M, Chen J, Dietze KK, Wang C, Kemper T, Lin Y, Yeh SH, Liu J, Dittmer U, Yuan Z, Roggendorf M, Lu M. Low hepatitis B virus-specific T-cell response in males correlates with high regulatory T-cell numbers in murine models. Hepatology 2017; 66:69-83. [PMID: 28295453 DOI: 10.1002/hep.29155] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2016] [Revised: 02/06/2017] [Accepted: 03/08/2017] [Indexed: 12/18/2022]
Abstract
UNLABELLED Hepatitis B virus (HBV) infection shows significant gender-related differences in pathogenesis, disease progression, and development of hepatocellular carcinoma. The gender-associated differences in HBV replication and viral protein levels may be associated with distinct HBV-specific immune responses in the host. In the present study, we examined the impact of gender on HBV-specific immune responses in two different mouse models representing transient and persistent hepadnaviral infection; hydrodynamic injection with the HBV genome mimicked acute HBV infection, whereas the efficacy of therapeutic vaccination was studied in the woodchuck hepatitis virus transgenic mouse model. Consistent with previous reports, significantly higher HBV DNA and protein levels were detected in male compared to female mice. Although hydrodynamic injection with the HBV genome resulted in similar numbers of intrahepatic HBV-specific cluster of differentiation 8-positive (CD8+ ) T cells, their functionality was significantly reduced in males and correlated with higher numbers of intrahepatic regulatory T cells (Tregs). Similar effects were observed in woodchuck hepatitis virus transgenic mice immunized with a DNA prime-recombinant adenovirus boost vaccination protocol. Male mice showed functionally suppressed woodchuck hepatitis virus-specific CD8+ T-cell responses in the liver and significantly higher numbers of intrahepatic Tregs compared to females. Blockade of Treg responses in male mice led to augmented effector functions of specific CD8+ T cells and subsequently improved virus control in both models of transient and persistent hepadnaviral infection. CONCLUSION The functionality of virus-specific CD8+ T cells in male mice was suppressed by intrahepatic Tregs and inversely correlated with levels of hepadnaviral DNA and viral protein; the induction of intrahepatic Tregs by viral replication and/or protein levels may explain the gender-related differences in the outcomes of HBV infection and limit the success of immunotherapeutic strategies in male patients. (Hepatology 2017;66:69-83).
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Affiliation(s)
- Anna D Kosinska
- Institute of Virology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany.,Key Laboratory of Medical Molecular Virology, Shanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, Shanghai, People's Republic of China
| | - Leila Pishraft-Sabet
- Institute of Virology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany
| | - Weimin Wu
- Institute of Virology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany
| | - Zhong Fang
- Key Laboratory of Medical Molecular Virology, Shanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, Shanghai, People's Republic of China.,Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, People's Republic of China
| | - Marzena Lenart
- Department of Clinical Immunology, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Cracow, Poland
| | - Jieliang Chen
- Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, People's Republic of China
| | - Kirsten K Dietze
- Institute of Virology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany
| | - Cong Wang
- Key Laboratory of Medical Molecular Virology, Shanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, Shanghai, People's Republic of China
| | - Thekla Kemper
- Institute of Virology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany
| | - Yong Lin
- Institute of Virology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany
| | - Shiou-Hwei Yeh
- Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan.,NTU Center for Genomic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jia Liu
- Institute of Virology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany
| | - Ulf Dittmer
- Institute of Virology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany
| | - Zhenghong Yuan
- Key Laboratory of Medical Molecular Virology, Shanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, Shanghai, People's Republic of China.,Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, People's Republic of China
| | - Michael Roggendorf
- Institute of Virology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany
| | - Mengji Lu
- Institute of Virology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany
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Guardiola Arévalo A, Gómez Rodríguez R, Romero Gutiérrez M, Gómez Moreno AZ, García Vela A, Sánchez Simón R, Gómez Hernando C, Andrés Esteban EM. Characteristics and course of chronic hepatitis B e antigen-negative infection. GASTROENTEROLOGIA Y HEPATOLOGIA 2016; 40:59-69. [PMID: 28007350 DOI: 10.1016/j.gastrohep.2016.11.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/06/2016] [Revised: 10/28/2016] [Accepted: 11/04/2016] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To describe the epidemiological, analytical and histological characteristics and clinical course of hepatitis B virus (HBV) carriers with negative HBe antigen. MATERIAL AND METHODS Observational, retrospective cohort study of HBV carriers with negative HBe antigen (2005-2012), with no other causes of liver disease. RESULTS One hundred and thirty-eight patients were included, with mean age 40.5±12.2 years; 54% were women, and 38% were of foreign origin; the number of foreign patients significantly increased (P<.001) over the years. Transaminases were normal in nearly 75% and HBV-DNA was <2,000IU/ml in 56% of patients at diagnosis. There was a gradual decrease in HBV-DNA levels in inactive carriers over the study period. Fibrosis study was performed in 47% of patients by Fibroscan® or liver biopsy: 55.4% normal histology and 6.1% cirrhosis. Just over three quarters of patients (77.77%) were inactive carriers. Treatment was required in 15.5% of patients (20% because of cirrhosis and 80% HBeAg-negative chronic hepatitis B). Five patients cleared HBsAg (annual rate .94%), all of whom presented HBV-DNA <2,000IU/ml at diagnosis. Five patients developed complications (3.6%), 4 of them hepatocellular carcinoma (HCC), of which only 2 had cirrhosis. There was 1 HBV-related death (.72%). CONCLUSION Among HBV carriers with negative HBe antigen, inactive HBs-Ag carriers are predominant. HBV-DNA gradually decreases in the first few years after diagnosis. Morbidity and mortality are low, especially if glutamic pyruvic transaminase (GPT) is normal and HBV-DNA levels are low at diagnosis. Treatment is needed in a considerable number of patients. HCC is the most frequent complication, even in the absence of cirrhosis.
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Affiliation(s)
- Antonio Guardiola Arévalo
- Servicio de Aparato Digestivo, Hospital Virgen de la Salud, Toledo, España; Servicio de Aparato Digestivo, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, España.
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Inoue T, Tanaka Y. Hepatitis B virus and its sexually transmitted infection - an update. MICROBIAL CELL (GRAZ, AUSTRIA) 2016; 3:420-437. [PMID: 28357379 PMCID: PMC5354569 DOI: 10.15698/mic2016.09.527] [Citation(s) in RCA: 72] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/04/2015] [Accepted: 05/17/2016] [Indexed: 12/12/2022]
Abstract
incidence and prevalence: About 5% of the world's population has chronic hepatitis B virus (HBV) infection, and nearly 25% of carriers develop chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The prevalence of chronic HBV infection in human immunodeficiency virus (HIV)-infected individuals is 5%-15%; HIV/HBV coinfected individuals have a higher level of HBV replication, with higher rates of chronicity, reactivation, occult infection, and HCC than individuals with HBV only. The prevalence of HBV genotype A is significantly higher among men who have sex with men (MSM), compared with the rest of the population. Molecular mechanisms of infection, pathology, and symptomatology: HBV replication begins with entry into the hepatocyte. Sodium taurocholate cotransporting polypeptide was identified in 2012 as the entry receptor of HBV. Although chronic hepatitis B develops slowly, HIV/HBV coinfected individuals show more rapid progression to cirrhosis and HCC. Transmission and protection: The most common sources of HBV infection are body fluids. Hepatitis B (HB) vaccination is recommended for all children and adolescents, and all unvaccinated adults at risk for HBV infection (sexually active individuals such as MSM, individuals with occupational risk, and immunosuppressed individuals). Although HB vaccination can prevent clinical infections (hepatitis), it cannot prevent 100% of subclinical infections. Treatment and curability: The goal of treatment is reducing the risk of complications (cirrhosis and HCC). Pegylated interferon alfa and nucleos(t)ide analogues (NAs) are the current treatments for chronic HBV infection. NAs have improved the outcomes of patients with cirrhosis and HCC, and decreased the incidence of acute liver failure.
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Affiliation(s)
- Takako Inoue
- Clinical Laboratory, Nagoya City University Hospital, Nagoya, Japan
| | - Yasuhito Tanaka
- Clinical Laboratory, Nagoya City University Hospital, Nagoya, Japan
- Department of Virology & Liver unit, Nagoya City University
Graduate School of Medical Sciences, Nagoya, Japan
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21
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Nguyen LH, Hoang J, Nguyen NH, Vu VD, Wang C, Trinh HN, Li J, Zhang JQ, Nguyen MH. Ethnic differences in incidence of hepatitis B surface antigen seroclearance in a real-life multicenter clinical cohort of 4737 patients with chronic hepatitis B infection. Aliment Pharmacol Ther 2016; 44:390-9. [PMID: 27363288 PMCID: PMC5316284 DOI: 10.1111/apt.13709] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2016] [Revised: 03/26/2016] [Accepted: 06/07/2016] [Indexed: 12/21/2022]
Abstract
BACKGROUND Hepatitis B surface antigen (HBsAg) positivity is associated with increased risk for cirrhosis and hepatocellular carcinoma (HCC). HBsAg seroclearance is thought to be rare in general, but cohort data from US patients are limited. AIM To determine the incidence of HBsAg seroclearance in a real-life US cohort. METHODS In total, 4737 patients with chronic hepatitis B from five primary care, gastroenterology and multispecialty centres, and a university medical centre were retrospectively enrolled between 2001 and 2014 with data obtained by manual review of individual patient medical records. Seroclearance was determined by loss of HBsAg seropositivity. Persistent HBsAg was confirmed by direct serology or by proxy with positive hepatitis B e-antigen (HBeAg) or HBV DNA levels. RESULTS HBsAg seroclearance occurred in 52 patients over 16 844 person-years (0.31% annually, 1.2% overall). Median follow-up was 32 months, and mean age 45 ± 14 years. Incidence of HBsAg seroclearance was higher in non-Asians, age >45, males, and those with baseline HBV DNA ≤10 000 IU/mL. On multivariate Cox proportional modelling, non-Asian ethnicity (HR 2.8), male sex (HR 2.1), baseline HBVDNA ≤10 000 (HR 2.0) and age >45 (HR 1.8) were significant independent predictors of seroclearance. CONCLUSION HBsAg seroclearance rates were lower than previously described in this real-life cohort of patients with chronic hepatitis B, especially among Asian, female and younger patients.
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Affiliation(s)
- Long H. Nguyen
- Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA.,Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA, USA
| | - Joseph Hoang
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Nghia H. Nguyen
- Department of Medicine, University of California, San Diego, San Diego, CA, USA
| | - Vinh D. Vu
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Christina Wang
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | | | - Jiayi Li
- Department of Gastroenterology, Palo Alto Medical Foundation, Mountain View, CA, USA
| | | | - Mindie H. Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
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Abstract
Chronic hepatitis B infection in the female population has implications not just for the individual but for her children as well. This article discusses the natural history of hepatitis B and how it plays an important role in hepatitis B virus (HBV) transmission, the current strategies and new strategies to control HBV and reduce transmission, and the updated guidelines for the management of HBV.
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Affiliation(s)
- Erica Cohen
- Division of Gastroenterology, Cedars Sinai Medical Center, 8730 Alden Dr, Los Angeles, CA 90025, USA
| | - Tram T Tran
- Liver Transplant, Cedars Sinai Medical Center, 8900 Beverly Boulevard, Los Angeles, CA 90048, USA.
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Wang SH, Chen PJ, Yeh SH. Gender disparity in chronic hepatitis B: Mechanisms of sex hormones. J Gastroenterol Hepatol 2015; 30:1237-45. [PMID: 25708186 DOI: 10.1111/jgh.12934] [Citation(s) in RCA: 88] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/18/2015] [Indexed: 12/18/2022]
Abstract
Hepatitis B virus (HBV) is a common human pathogen transmitted worldwide, and its chronic infection is a well-known risk factor for hepatocellular carcinoma (HCC). The sex disparity of HBV-related liver diseases has been noticed for a long time, which could be attributed to sex hormone effects, other than gender behaviors or environmental impact. This difference is experimentally confirmed in HBV transgenic mice, as well as in immunocompetent mice receiving hydrodynamic delivery of HBV. Androgen and estrogen pathways were identified to play opposite regulations of HBV transcription by targeting viral enhancer I at molecular level. In addition to the direct effects on HBV life cycle, sex hormones may be also involved in the immune response to HBV infection and the progression of associated liver diseases, although the detailed mechanisms are still unclear. Besides, several unaddressed issues such as HBV entry, microRNA profiles, viral integration, and adaptability in which androgen and estrogen axes might be involved are warranted to be delineated. The comprehensive understanding of the sex disparity in HBV virology and pathogenesis will be helpful to provide newly biomarkers for clinical diagnosis and develop novel drugs to manage HBV-related HCC patients.
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Affiliation(s)
- Sheng-Han Wang
- Department of Microbiology, National Taiwan University Hospital and National Taiwan University, College of Medicine, Taipei, Taiwan
| | - Pei-Jer Chen
- Department of Microbiology, National Taiwan University Hospital and National Taiwan University, College of Medicine, Taipei, Taiwan.,NTU Center for Genomic Medicine, National Taiwan University Hospital and National Taiwan University, College of Medicine, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University Hospital and National Taiwan University, College of Medicine, Taipei, Taiwan.,Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University, College of Medicine, Taipei, Taiwan
| | - Shiou-Hwei Yeh
- Department of Microbiology, National Taiwan University Hospital and National Taiwan University, College of Medicine, Taipei, Taiwan.,NTU Center for Genomic Medicine, National Taiwan University Hospital and National Taiwan University, College of Medicine, Taipei, Taiwan
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25
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Xin G, Qin S, Wang S, Wang X, Zhang Y, Wang J. Sex hormone affects the severity of non-alcoholic steatohepatitis through the MyD88-dependent IL-6 signaling pathway. Exp Biol Med (Maywood) 2015; 240:1279-86. [PMID: 25790822 DOI: 10.1177/1535370215570189] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2014] [Accepted: 12/01/2014] [Indexed: 01/09/2023] Open
Abstract
Recent research has shown that the occurrence of gender disparity in liver cancer associated with sex differences in MyD88-dependent IL-6 production, but the role of this signaling pathway in sex differences of non-alcoholic steatohepatitis (NASH) remains unknown. To investigate the effects of sex hormone-specific intervention on pathology and progression of NASH, and on the inflammatory TLR-MyD88-IL-6 signaling pathway NASH was modeled in C57/BL6 mice by feeding a methionine and choline-deficient (MCD) diet for 4 weeks. Male mice were subjected to sex hormone-related interventions such as orchidectomy, and orchidectomy combined with administration of either testosterone propionate or estradiol benzoate. Next, the degree of non-alcoholic fatty liver disease activity score (NAS), serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and the expression level of MyD88 and IL-6, were compared between these groups. Males developed more serious inflammatory problems and had a higher NAS than the females. Sex-specific intervention in male mice by orchidectomy reduced NAS, ALT, and AST, and the expression level of MyD88 and IL-6. But administration of exogenous androgen had no influence on either NAS or the expression of ALT, AST, MyD88, and IL-6. On the other hand, exogenous estrogen could alleviate the pathological damage caused by NASH, as well as reduce NAS, ALT and AST, and the expression of MyD88 and IL-6. The result show different sex hormone-related interventions affected the severity of NASH, possibly by modulating the level of sex hormones and regulating the TLR-MyD88-IL-6 signaling pathway.
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Affiliation(s)
- Guangda Xin
- Department of Nephrology, China-Japan Union Hospital of Jilin University, Changchun 130033, PR China
| | - Shaoyou Qin
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, Changchun 130033, PR China
| | - Song Wang
- Department of Urology, The Second Hospital of Jilin University, Changchun 130041, PR China
| | - Xu Wang
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, Changchun 130033, PR China
| | - Yonggui Zhang
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, Changchun 130033, PR China
| | - Jiangbin Wang
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, Changchun 130033, PR China
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Børresen ML, Andersson M, Wohlfahrt J, Melbye M, Biggar RJ, Ladefoged K, Panum I, Koch A. Hepatitis B prevalence and incidence in Greenland: a population-based cohort study. Am J Epidemiol 2015; 181:422-30. [PMID: 25721415 DOI: 10.1093/aje/kwu287] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Greenland remains a highly endemic area for hepatitis B virus (HBV) infection. This is in sharp contrast to other modern societies, such as Denmark. To address this discrepancy, we investigated the natural history of HBV infection in Greenland by estimating the age-specific incidence of HBV infection, the proportion of chronic carriers, and the rates of hepatitis B surface antigen seroclearance. In total, 8,879 Greenlanders (16% of the population) from population-based surveys conducted in 1987 and 1998 were followed through March 2010. Data on HBV status were supplemented by HBV test results from all available HBV registries in Greenland to determine changes in HBV status over time. Incidence rates of HBV infection and hepatitis B surface antigen seroclearance were estimated after taking into account interval censoring. The incidence of HBV infection in 5-14-year-old subjects was less than 1 per 100 person-years and peaked at 5 per 100 person-years in persons 15-24 years of age. Overall, 17.5% of persons infected in adulthood were estimated to become chronic carriers. HBV is primarily transmitted in adolescence and adulthood in Greenland. In contrast to what is observed in most other populations, HBV-infected adults in Greenland have a high risk of progressing to chronic HBV carriage. This phenomenon might explain how the high rate of infection is maintained in Greenland.
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Abstract
It is now 50 years since the discovery of the hepatitis B virus (HBV), and, despite the availability of a prophylactic vaccine for more than 20 years, HBV infection remains a disease of significant global health burden. It is estimated that more than 240 million people are chronically infected with HBV and, therefore, are at risk for the development of cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). The risk of clinical complications has traditionally been higher in older males with hepatitis B e antigen (HBeAg)-positive disease, high-grade liver necroinflammation, and progressive fibrosis. Recent advances in the understanding of the natural history of chronic HBV infection have identified an important role for plasma HBV DNA levels as a marker of risk for clinical outcomes. Among adults, persistent high-level HBV replication is associated with an increased risk of cirrhosis, as well as HCC development. This has led to the therapeutic focus on achieving sustained viral suppression. There is an emerging role for quantitative hepatitis B surface antigen (HBsAg) levels as a marker of natural history. Low levels of HBsAg have been associated with sustained immune control, HBsAg seroclearance, as well as lower risk of HCC. In this work, we review the natural history of HBV infection, with a focus on the determinants of clinical outcomes in patients with chronic hepatitis B (CHB) infection.
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Huang FY, Wong DKH, Seto WK, Zhang AY, Lee CK, Lin CK, Fung J, Lai CL, Yuen MF. Sequence variations of full-length hepatitis B virus genomes in Chinese patients with HBsAg-negative hepatitis B infection. PLoS One 2014; 9:e99028. [PMID: 24901840 PMCID: PMC4047052 DOI: 10.1371/journal.pone.0099028] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2014] [Accepted: 05/09/2014] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND The underlying mechanism of HBsAg-negative hepatitis B virus (HBV) infection is notoriously difficult to elucidate because of the extremely low DNA levels which define the condition. We used a highly efficient amplification method to overcome this obstacle and achieved our aim which was to identify specific mutations or sequence variations associated with this entity. METHODS A total of 185 sera and 60 liver biopsies from HBsAg-negative, HBV DNA-positive subjects or known chronic hepatitis B (CHB) subjects with HBsAg seroclearance were amplified by rolling circle amplification followed by full-length HBV genome sequencing. Eleven HBsAg-positive CHB subjects were included as controls. The effects of pivotal mutations identified on regulatory regions on promoter activities were analyzed. RESULTS 22 and 11 full-length HBV genomes were amplified from HBsAg-negative and control subjects respectively. HBV genotype C was the dominant strain. A higher mutation frequency was observed in HBsAg-negative subjects than controls, irrespective of genotype. The nucleotide diversity over the entire HBV genome was significantly higher in HBsAg-negative subjects compared with controls (p = 0.008) and compared with 49 reference sequences from CHB patients (p = 0.025). In addition, HBsAg-negative subjects had significantly higher amino acid substitutions in the four viral genes than controls (all p<0.001). Many mutations were uniquely found in HBsAg-negative subjects, including deletions in promoter regions (13.6%), abolishment of pre-S2/S start codon (18.2%), disruption of pre-S2/S mRNA splicing site (4.5%), nucleotide duplications (9.1%), and missense mutations in "α" determinant region, contributing to defects in HBsAg production. CONCLUSIONS These data suggest an accumulation of multiple mutations constraining viral transcriptional activities contribute to HBsAg-negativity in HBV infection.
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Affiliation(s)
- Fung-Yu Huang
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
| | - Danny Ka-Ho Wong
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
- State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
| | - Wai-Kay Seto
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
| | - An-Ye Zhang
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
| | - Cheuk-Kwong Lee
- Hong Kong Red Cross Blood Transfusion Service, Hospital Authority, Hong Kong, China
| | - Che-Kit Lin
- Hong Kong Red Cross Blood Transfusion Service, Hospital Authority, Hong Kong, China
| | - James Fung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
- State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
| | - Ching-Lung Lai
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
- State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
| | - Man-Fung Yuen
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
- State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
- * E-mail:
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Hepatitis B vaccines. Vaccines (Basel) 2013. [DOI: 10.1016/b978-1-4557-0090-5.00025-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
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Cost-Effectiveness Analysis of Hepatitis B Immunization in Vietnam: Application of Cost-Effectiveness Affordability Curves in Health Care Decision Making. Value Health Reg Issues 2012; 1:7-14. [PMID: 29702830 DOI: 10.1016/j.vhri.2012.03.007] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
OBJECTIVES To perform a cost-effectiveness analysis and to identify the cost-effectiveness affordability levels for a newborn universal vaccination program against hepatitis B virus (HBV) in Vietnam. METHODS By using a Markov model, we simulated a Vietnamese birth cohort using 1,639,000 newborns in 2002 and estimated the incremental cost-effectiveness ratios for quality-adjusted life-year gained following universal newborn HBV vaccination. Two types of analyses were performed, including and excluding expenditures on the treatment of chronic hepatitis B and its complications. We used Monte Carlo simulations to examine cost-effectiveness acceptability and affordability from the payer's perspective and constructed a cost-effectiveness affordability curve to assess the costs and health effects of the program. RESULTS In the base-case analysis, newborn universal HBV vaccination reduced the carrier rate by 58% at a cost of US $42 per carrier averted. From the payer's perspective, incremental cost-effectiveness ratio per quality-adjusted life-year gained was US $3.77, much lower than the 2002 per-capita gross domestic product of US $440. Vaccination could potentially be affordable starting at a US $2.1 million budget. At the cost-effectiveness threshold of US $3.77 per quality-adjusted life-year and an annual budget of US $5.9 million, the probability that vaccination will be both cost-effective and affordable was 21%. CONCLUSIONS Universal newborn HBV vaccination is highly cost-effective in Vietnam. In low-income, high-endemic countries, where funds are limited and the economic results are uncertain, our findings on the cost-effectiveness affordability options may assist decision makers in proper health investments.
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Yan Z, Tan S, Dan Y, Sun X, Deng G, Wang Y. Relationship between HLA-DP gene polymorphisms and clearance of chronic hepatitis B virus infections: case-control study and meta-analysis. INFECTION GENETICS AND EVOLUTION 2012; 12:1222-8. [PMID: 22543033 DOI: 10.1016/j.meegid.2012.03.026] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/18/2012] [Revised: 03/28/2012] [Accepted: 03/29/2012] [Indexed: 01/02/2023]
Abstract
Hepatitis B virus (HBV) infection is a serious public health problem worldwide. Two common genetic variants (rs3077 and rs9277535) of human leukocyte antigen DP (HLA-DP) have been reported to be associated with persistent HBV infection in populations of Japan and Thailand. To confirm whether the association can be replicated in Chinese populations, an independent case-control study were conducted, and two polymorphisms (rs3077 and rs9277535) were genotyped using the TaqMan SNP genotyping assay in 282 persistent chronic HBV carriers and 64 spontaneously HBV recovered carriers. To provide a more definitive conclusion, a meta-analysis combining and summarizing five studies was performed by random-effects model using the DerSimonian and Laird's method. By using logistic regression analysis with adjustment for covariates, including age, sex, and alcohol consumption, the results of our independent case-control study showed that the minor allele's homozygote (AA genotype) of rs3077 and rs9277535 was significantly associated with decreasing risk/protection of HBV persistent chronic infection (for rs3077: P=0.0017, OR=0.29, 95% CI=0.13-0.62; for rs9277535, P=0.0004, OR=0.26, 95% CI=0.12-0.54). The results of meta-analysis pooling all eligible studies also showed that rs3077-A and rs9277535-A alleles were associated with an increased clearance rate to HBV infection (rs3077: OR=0.57, 95% CI=0.44-0.75; rs9277535: OR=0.56, 95% CI=0.47-0.63). These results further confirmed the strong influence of HLA-DP gene variants on risk of spontaneous HBV clearance from persistent HBV infection. Both A alleles of HLA-DP SNP rs3077 and rs9277535 showed strong protective effects for spontaneous HBV clearance from persistent HBV infection in the Han Chinese population.
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Affiliation(s)
- Zehui Yan
- Institute of Infectious Diseases, Southwest Hospital, Third Military Medical University, 30 Gao Tan Yan Street, Sha Ping Ba District, Chongqing 400038, PR China
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Kim BK, Revill PA, Ahn SH. HBV genotypes: relevance to natural history, pathogenesis and treatment of chronic hepatitis B. Antivir Ther 2012; 16:1169-86. [PMID: 22155900 DOI: 10.3851/imp1982] [Citation(s) in RCA: 115] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Although chronic HBV infection is the leading cause of chronic liver disease and death worldwide, there are substantial differences in its clinical courses regarding prevalence, mode of transmission, characteristics of each phase, responses to antiviral therapy, and development of cirrhosis and hepatocellular carcinoma, according to geographical areas (Asia versus Western Europe and North America versus Africa). Furthermore, the clinical course in infected individuals depends on a complex interplay among various factors including viral, host, environmental and other factors. Recently, understanding of molecular characteristics of the prevailing HBV genotypes, frequently accompanied mutations and their clinical implications might explain these geographical differences more pertinently. Hence, in this article, we review the global epidemiology and the natural history of HBV infection, with emphasis on summarizing the different HBV genotypes according to regions.
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Affiliation(s)
- Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
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Hung HF, Chen HH. Cost-effectiveness analysis of prophylactic lamivudine use in preventing vertical transmission of hepatitis B virus infection. PHARMACOECONOMICS 2011; 29:1063-1073. [PMID: 22077578 DOI: 10.2165/11586470-000000000-00000] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
Abstract
BACKGROUND As neonates born to mothers with positive hepatitis B e antigen may not be completely protected by hepatitis B vaccination, prophylactic lamivudine use in mothers with high viraemia has been proposed. However, the overall effectiveness and the balance between cost and benefit for such a prophylactic strategy have rarely been addressed. OBJECTIVE Using a review of recent literature, we aimed to assess the cost effectiveness, from the Taiwanese societal perspective, of administering prophylactic lamivudine to mothers to reduce vertical transmission of hepatitis B virus and its long-term sequelae in neonates. METHODS A meta-analysis of three randomized controlled trials was conducted to evaluate the efficacy of lamivudine versus placebo. A Markov decision model was constructed in which in both treatment arms infants received active and passive immunoprophylaxis. An economic evaluation was performed to calculate costs, acute infections averted, and QALYs gained. Probabilistic sensitivity analyses were conducted and a cost-effectiveness acceptability curve drawn. All these analyses were from the societal perspective. Costs ($US) were valued in year 2008 prices. RESULT Supplemental lamivudine use gained an additional 0.0024 QALYs and averted 0.23 acute infections per birth compared with the routine active-passive immunization without lamivudine. The cost-effectiveness analysis suggested that the use of additional prophylactic lamivudine dominated the routine strategy. The acceptability curve suggested that the probability of being cost effective under the willingness-to-pay threshold of $US20,000 was 94%. CONCLUSION This analysis suggests that supplemental use of lamivudine in mothers with high hepatitis B viraemia is effective in reducing vertical transmission and may be cost effective, from a Taiwanese societal perspective, compared with the routine active-passive immunization without lamivudine.
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Affiliation(s)
- Hui-Fang Hung
- Hsin-Chu General Hospital, Department of Health, Executive Yuan, Taipei, Taiwan
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36
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Kwon SY, Lee CH. Epidemiology and prevention of hepatitis B virus infection. THE KOREAN JOURNAL OF HEPATOLOGY 2011; 17:87-95. [PMID: 21757978 PMCID: PMC3304633 DOI: 10.3350/kjhep.2011.17.2.87] [Citation(s) in RCA: 76] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Hepatitis B virus (HBV) infection has been a major global cause of morbidity and mortality. The recognition of the problem led to a worldwide effort to reduce transmission of HBV through routine infant vaccination. HBV infection is the most common cause of chronic liver diseases and hepatocellular carcinoma in Korea. After hepatitis B vaccine era, seroprevalence of hepatits B surface antigen is decreasing, particularly in children. Hepatitis B vaccine is remarkably safe and shows high immunogenicity. Universal childhood immunization with three doses of hepatitis B vaccine in the first year of life is a highly effective method for prevention and control of hepatitis B.
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Affiliation(s)
- So Young Kwon
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
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Abstract
Chronic hepatitis B (CHB) is a major public health problem affecting up to 400 million people globally. Complications of CHB including liver failure and hepatocellular carcinoma result in 1.2 million deaths per year, making CHB the 10th leading cause of mortality worldwide. The natural history of CHB is variable and complex. The past decade witnessed important developments for the therapy of hepatitis B and marked the new era of oral therapy. The ultimate goal of CHB therapy is to arrest the progression of liver injury and to prevent the development of liver failure and hepatocellular carcinoma. Currently, six agents are approved for the treatment of CHB. Each of these agents, given as monotherapy, has been shown to produce virological, biochemical, and histological benefits for both HBeAg positive and negative CHB. There are, however, limitations in spite of their efficacy. The significant side-effect profile of interferon, for example, limits its long-term use. The approved oral agents are tolerable with prolonged use but drug resistance could limit long-term monotherapy. To date, combination therapy with nucleoside analogue and pegylated interferon or two nucleos(t)ide analogues given for one year does not show superiority in durability of response compared to monotherapy. Ongoing research effort is critical to identify the ideal hepatitis B therapy that is safe, effective, and produces durable response with a finite course of therapy. It is equally important to conduct a well designed, prospective natural history study to identify predictors of disease progression. This will accurately guide treatment strategy for this important disease.
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Affiliation(s)
- Daryl T-Y Lau
- Associate Professor of Medicine, Harvard Medical School (HMS), Director of Translational Liver Research, Beth Israel Deaconess Medical Center, HMS Liver Center, Division of Gastroenterology, Department of Medicine, 110 Francis Street, Suite 4A, Boston, MA 02215.
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38
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An P, the HBV Study Consortium, Winkler C, the HBV Study Consortium, Guan L, the HBV Study Consortium, O'Brien SJ, the HBV Study Consortium, Zeng Z, the HBV Study Consortium. A Common HLA–DPA1 Variant is a Major Determinant of Hepatitis B Virus Clearance in Han Chinese. J Infect Dis 2011; 203:943-947. [DOI: https:/doi.org/10.1093/infdis/jiq154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/02/2023] Open
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An P, Winkler C, Guan L, O'Brien SJ, Zeng Z. A common HLA-DPA1 variant is a major determinant of hepatitis B virus clearance in Han Chinese. J Infect Dis 2011; 203:943-947. [PMID: 21402545 PMCID: PMC3068033 DOI: 10.1093/infdis/jiq154] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2010] [Accepted: 11/12/2010] [Indexed: 12/27/2022] Open
Abstract
A recent genome-wide study showed that the single nucleotide polymorphisms (SNPs) in the HLA-DP region were associated with chronic hepatitis B virus (HBV) infection in Japanese and Thai persons. We tested the effects of HLA-DP SNPs for all major HBV outcomes in Han Chinese (n = 1742): HBV resistance, clearance, chronic infection, cirrhosis, and hepatocellular carcinoma. HLA - DPA1 rs3077 T was strongly associated with decreased risk of chronic HBV infection (odds ratio, .62; P = .001), consistent with the previous report. We showed for the first time to our knowledge that it is a predictor for HBV clearance (odds ratio, 2.41; P < .001). However, rs3077 was not associated with the development of cirrhosis or hepatocellular carcinoma.
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Affiliation(s)
| | | | - Li Guan
- Laboratory of Genomic Diversity, SAIC-Frederick
| | - Stephen J. O'Brien
- Laboratory of Genomic Diversity, National Cancer Institute-Frederick, Maryland
| | - Zheng Zeng
- Department of Infectious Diseases, Peking University First Hospital, Beijing, People’s Republic of China
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40
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[HBsAg seroclearance: prognostic value for the response to treatment and the long-term outcome]. ACTA ACUST UNITED AC 2011; 34 Suppl 2:S119-25. [PMID: 21095515 DOI: 10.1016/s0399-8320(10)70031-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Chronic hepatitis B is a major cause of liver disease worldwide, ranking as the first cause of cirrhosis and hepatocellular carcinoma. Hepatitis B surface antigen (HBsAg) is usually used as a qualitative marker for the diagnosis of hepatitis B virus (HBV) infection. HBsAg clearance is the closest to cure outcome as one can expect to achieve in hepatitis B. Support for this comes from natural history studies demonstrating increased length of survival, lower rates of hepatic decompensation, reduction in the frequency of hepatocellular carcinoma, and regression of liver fibrosis in patients who clear HBsAg. HBsAg seroclearance may occur spontaneously at a yearly incidence of 1-2%, preceded usually by a long period of inactive disease. Interferon treatment enhanced HBsAg seroclearance by approximately three-fold in western studies and sixfold in Asian studies compared with non-treated patients. Pegylated interferon induced a 10-15% yearly rate of HBsAg seroclearance in patients who developed sustained virological response in clinical trials. By contrast, treatment with nucleos (t) ides analogues did not significantly affect the rate of HBsAg seroclearance, especially in patients with hepatitis B e antigen (HBeAg) - negative disease. Recently, serum HBsAg has been shown to be a surrogate marker of covalently closed circular DNA (cccDNA) concentration in the liver. Quantification of serum HBsAg has also been recently shown to be a promising tool for monitoring virologic response in HBeAg-negative patients treated with pegylated interferon.
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Abstract
GOALS AND BACKGROUND The long-term clinical course, including the development of hepatocellular carcinoma (HCC) after hepatic B surface antigen (HBsAg) seroclearance is not established. We discovered that the incidence of HCC and the risk factors for HCC in chronic hepatitis B (CHB) patients after HBsAg seroclearance. STUDY During 28 years, 96 CHB patients with HBsAg seroclearance were retrospectively reviewed. These patients continued to undergo HCC surveillance. The median follow-up time from initial visit was 166.5 months (range, 7 to 321 mo). RESULTS The mean age at the initial visit and at the time of seroclearance was 39.2 ± 10.6 years and 46.4 ± 9.9 years, respectively. The mean age at the time of HBsAg seroclearance was significantly lower (P=0.03) in patients with spontaneous HBsAg seroclearance than patients with treatment-associated HBsAg seroclearance. During a median of 56 months (range, 7 to 238 mo) of follow-up after HBsAg seroclearance, 6 (6.5%) patients developed HCC. The mean age at the time of developing HCC was 55.8 ± 10.3 years. On univariate analysis, the evidence of liver cirrhosis from the time of HBsAg seroclearance and age more than 45 years at the time of HBsAg seroclearance were significant risk factors for HCC development. In multivariate analysis, the evidence of liver cirrhosis at HBsAg seroclearance was the only significant risk factor for HCC development. CONCLUSIONS HCC can develop after HBsAg seroclearance in patients with known cirrhosis. Patients who achieved HBsAg seroclearance at older age (>45) may have undiagnosed cirrhosis and hence remain at risk for HCC. HCC surveillance should be carried out for both of those patient populations.
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42
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Siddiqui MR, Gay N, Edmunds WJ, Ramsay M. Economic evaluation of infant and adolescent hepatitis B vaccination in the UK. Vaccine 2010; 29:466-75. [PMID: 21073988 DOI: 10.1016/j.vaccine.2010.10.075] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2009] [Revised: 10/08/2010] [Accepted: 10/27/2010] [Indexed: 12/17/2022]
Abstract
A Markov model of hepatitis B virus (HBV) disease progression in the UK estimated that 81% of predicted HBV-associated morbidity and mortality could be prevented by universal infant vaccination at a cost of approximately £ 260,000 per QALY gained. Universal adolescent vaccination would be less effective (45% prevented) and less cost-effective (£ 493,000 per QALY gained). Higher HBV incidence rates in males and intermediate/high risk ethnic populations meant it was approximately 3 times more cost-effective to vaccinate these groups. At current vaccine costs a selective infant vaccination programme, based on vaccinating intermediate/high risk ethnic populations would not be considered cost effective. The threshold cost per vaccinated child at which the programme would be considered cost-effective was investigated. Universal infant vaccination would be cost-effective if the average cost of vaccinating each child against HBV, including vaccine and administration costs of all doses, was less than £ 4.09. Given the low cost of vaccination required to make a universal programme cost-effective the most feasible policy in the UK would be to use a suitably priced combined vaccine that included the other antigens in the current infant vaccination schedule.
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Affiliation(s)
- M Ruby Siddiqui
- Health Protection Agency, Centre for Infections, 61 Colindale Avenue, London NW9 5EQ, UK
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43
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Chu CM, Liaw YF. Hepatitis B surface antigen seroclearance during chronic HBV infection. Antivir Ther 2010; 15:133-43. [PMID: 20386068 DOI: 10.3851/imp1497] [Citation(s) in RCA: 142] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Hepatitis B surface antigen (HBsAg) seroclearance in chronic HBV infection occurs at an annual incidence of 1-2%. The long-term outcome after HBsAg seroclearance is excellent if there is no pre-existing cirrhosis or viral superinfection. For this reason, HBsAg seroclearance has attracted recent interest in both long-term studies of the natural history of HBV infection and in patients receiving antiviral therapy. Here, we review a diverse range of studies investigating spontaneous HBsAg seroclearance in varied groups of patients and consider the many predictive factors - of both viral and host origin - for seroclearance. Studies to assess the effects of antiviral therapy, and in particular interferon treatment, are also discussed together with virological, biochemical and histological profiles following HBsAg seroclearance and the long-term outcomes.
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Affiliation(s)
- Chia-Ming Chu
- Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan
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44
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Suen SSH, Lao TT, Sahota DS, Lau TK, Leung TY. Implications of the relationship between maternal age and parity with hepatitis B carrier status in a high endemicity area. J Viral Hepat 2010; 17:372-8. [PMID: 19780946 DOI: 10.1111/j.1365-2893.2009.01195.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
This study aimed to examine the prevalence of maternal hepatitis B virus (HBV) infection in the past 10 years and the age- and parity-specific incidences for evidence of control of HBV infection in the female reproductive population. We conducted a retrospective cohort study on 58 736 consecutive pregnant women delivered from July 1998 to June 2008. Maternal HBV status and demographic data were retrieved from a computerized database for analysis by year, age, year of birth and parity. A total of 5788 (10.1%) women had HBV infection, and the annual prevalence was around 10% throughout. When categorized by maternal age into six 5-year cohorts, the incidence increased from 6.8% in the <20 years cohort to 10.8% in the 20-24 and 25-29 year cohorts, then declined to 9.3% in the > or =40 years cohort (P < 0.001). When categorized by year of birth into 5-year cohorts, the incidence varied from 9.2% for the 1965-1969 cohort to 11.3% in the 1980-1984 cohort, which then declined to 7.3% in the > or =1985 cohort (P < 0.001). Multiparas had higher incidence when compared with nulliparas overall (10.5% vs 9.6%, P = 0.001), and significantly higher incidences for the 25-29 year (P = 0.009), 30-34 year (P < 0.001) and 35-39 year (P = 0.032) cohorts when analysed by age. In conclusion, the prevalence of maternal HBV infection remained constant at 10% for the past decade. The changes in relation to age and parity suggested that horizontal transmission, probably by sexual contact, had played an important role in maintaining the same prevalence as reported from Hong Kong 20 years ago.
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Affiliation(s)
- S S H Suen
- Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.
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Polo P, Castañeda C, Sierra M, Alvis N. Hepatitis B oculta en pacientes VIH positivos de una institución de salud en Barranquilla Colombia. INFECTIO 2010. [DOI: 10.1016/s0123-9392(10)70091-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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Gish RG, Chang TT, Lai CL, de Man R, Gadano A, Poordad F, Yang J, Brett-Smith H, Tamez R. Loss of HBsAg antigen during treatment with entecavir or lamivudine in nucleoside-naïve HBeAg-positive patients with chronic hepatitis B. J Viral Hepat 2010; 17:16-22. [PMID: 19622117 DOI: 10.1111/j.1365-2893.2009.01146.x] [Citation(s) in RCA: 92] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
This retrospective analysis was conducted to describe the characteristics of nucleoside-naïve hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B, who achieved hepatitis B surface antigen (HBsAg) loss during entecavir or lamivudine therapy. HBeAg-positive adults with chronic hepatitis B, elevated serum alanine aminotransferase, and compensated liver disease were randomized to double-blind treatment for up to 96 weeks with entecavir 0.5 mg/day or lamivudine 100 mg/day. HBsAg and hepatitis B virus (HBV) DNA were measured at regular intervals during and off-treatment follow-up. Through a maximum duration of 96 weeks on-treatment and 24 weeks off-treatment, HBsAg loss was confirmed in 18/354 (5.1%) patients treated with entecavir and 10/355 (2.8%) patients treated with lamivudine. Among the 28 patients with confirmed HBsAg loss, 27 (96%) achieved HBV DNA <300 copies/mL, and 27 (96%) achieved confirmed HBeAg loss. All entecavir recipients with HBsAg loss had HBV DNA <300 copies/mL. Caucasian patients, and those infected with HBV genotype A or D, were significantly more likely to lose HBsAg. This retrospective analysis of data from a randomized, global phase three trial shows that confirmed loss of HBsAg occurred in 5% of nucleoside-naïve HBeAg-positive patients treated with entecavir, and that HBsAg loss is associated with sustained off-treatment suppression of HBV DNA.
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Affiliation(s)
- R G Gish
- Division of Hepatology and Complex GI, Physicians Foundation California Pacific Medical Center, San Francisco, CA 94115-1932, USA.
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Hung HF, Chen THH. Probabilistic cost-effectiveness analysis of the long-term effect of universal hepatitis B vaccination: An experience from Taiwan with high hepatitis B virus infection and Hepatitis B e Antigen positive prevalence. Vaccine 2009; 27:6770-6. [PMID: 19735755 DOI: 10.1016/j.vaccine.2009.08.082] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2008] [Revised: 08/19/2009] [Accepted: 08/22/2009] [Indexed: 01/05/2023]
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Kim JM, Choe BH, Chu MA, Cho SM. [Comparison of lamivudine-induced HBsAg loss rate according to age in children with chronic hepatitis B]. THE KOREAN JOURNAL OF HEPATOLOGY 2009; 15:168-178. [PMID: 19581769 DOI: 10.3350/kjhep.2009.15.2.168] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND/AIMS The aim of this study was to establish the characteristics of children with hepatitis B e antigens (HBeAg) positive chronic hepatitis B who were cleared of hepatitis B surface antigens (HBsAg) as a result of lamivudine treatment. METHODS Seventy-six children with chronic hepatitis B who were seropositive for HBeAg were treated with lamivudine for at least 6 months. HBeAg seroconversion occurred during treatment in 49 of these children, who were then followed up to assess their clearance of serum HBsAg. Various clinical variables were compared between those patients who were cleared of HBsAg and those who were not, including age, pretreatment serum levels of alanine aminotransferase (ALT) and hepatitis B virus (HBV) DNA, treatment duration, the time elapsed between initiation of treatment and ALT normalization, HBV DNA negativization, HBeAg seroconversion, and HBsAg clearance. RESULTS HBsAg disappeared in 13 of the 49 (26.5%) patients who experienced lamivudine-induced HBeAg seroconversion; HBsAg did not reappear during follow-up period (1-86 months). The time that elapsed between initiation of lamivudine treatment and total HBsAg clearance was 25.9+/-27.1 months (mean+/-SD; range: 5-104 months). The age at which treatment was initiated was the only factor associated with HBsAg clearance. Children who were cleared of HBsAg were significantly younger than those who were not (5.1+/-4.3 years vs. 7.9+/-4.9 years, respectively; P=0.006). All 13 of these patients eventually produced antibodies to HBsAg. CONCLUSIONS Younger children (age <7 years old) have a higher chance of HBsAg clearance than older children after the treatment of HBeAg-positive chronic hepatitis B with lamivudine.
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Affiliation(s)
- Jung-mi Kim
- Department of Pediatrics, Kyungpook National University School of Medicine, Daegu, Korea
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Herrine SK, Rossi S, Navarro VJ. INFECTIOUS HEPATITIS. PHARMACOLOGY AND THERAPEUTICS 2009:527-547. [DOI: 10.1016/b978-1-4160-3291-5.50039-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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50
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Miriti MK, Billah K, Weinbaum C, Subiadur J, Zimmerman R, Murray P, Gunn R, Buffington J. Economic benefits of hepatitis B vaccination at sexually transmitted disease clinics in the U.S. Public Health Rep 2008; 123:504-13. [PMID: 18763413 DOI: 10.1177/003335490812300412] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
OBJECTIVE This study assessed the long-term economic implications of a national program to vaccinate all adults treated at sexually transmitted disease (STD) clinics in a single year. METHODS A model was developed to track the long-term disease outcomes and costs among a hypothetical cohort of 2 million STD clinic clients accessing services in one year, using data from published sources and demonstration projects at STD clinics in San Diego (California), Illinois, and Denver (Colorado). The model estimated net economic benefits of a routine hepatitis B vaccination policy at STD clinics nationwide compared with no vaccination. RESULTS Without a vaccination program, an estimated 237,021 new hepatitis B virus (HBV) infections would occur over the lifetimes of the 2 million STD clinic clients seen in a single year. HBV-related medical costs and productivity losses would be $1.6 billion. In a national program for routine vaccination at STD clinics, 1.3 million adults would be expected to receive at least one vaccine dose, and an estimated 45% of the new HBV infections expected without vaccination would be prevented. The vaccination program would cost $138 million, HBV infections occurring despite the program would cost $878 million, and clients' time and travel would cost $45 million. The net economic benefit (savings) of routine vaccination would be $526 million. If the indirect costs of lost productivity due to HBV infection are not considered, routine vaccination would have a net cost of $28 million. CONCLUSIONS Estimates from this model suggest a national program for routine hepatitis B vaccination of adults at STD clinics would be a cost saving to society.
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Affiliation(s)
- M'Kiaira K Miriti
- Division of Viral Hepatitis, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA
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