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Leowattana W, Leowattana P, Leowattana T. Quantitative hepatitis B core antibody and quantitative hepatitis B surface antigen: Novel viral biomarkers for chronic hepatitis B management. World J Hepatol 2024; 16:550-565. [PMID: 38689745 PMCID: PMC11056893 DOI: 10.4254/wjh.v16.i4.550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 02/03/2024] [Accepted: 03/12/2024] [Indexed: 04/24/2024] Open
Abstract
The management of hepatitis B virus (HBV) infection now involves regular and appropriate monitoring of viral activity, disease progression, and treatment response. Traditional HBV infection biomarkers are limited in their ability to predict clinical outcomes or therapeutic effectiveness. Quantitation of HBV core antibodies (qAnti-HBc) is a novel non-invasive biomarker that may help with a variety of diagnostic issues. It was shown to correlate strongly with infection stages, hepatic inflammation and fibrosis, chronic infection exacerbations, and the presence of occult infection. Furthermore, qAnti-HBc levels were shown to be predictive of spontaneous or treatment-induced HBeAg and HBsAg seroclearance, relapse after medication termination, re-infection following liver transplantation, and viral reactivation in the presence of immunosuppression. qAnti-HBc, on the other hand, cannot be relied on as a single diagnostic test to address all problems, and its diagnostic and prognostic potential may be greatly increased when paired with qHBsAg. Commercial qAnti-HBc diagnostic kits are currently not widely available. Because many methodologies are only semi-quantitative, comparing data from various studies and defining universal cut-off values remains difficult. This review focuses on the clinical utility of qAnti-HBc and qHBsAg in chronic hepatitis B management.
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Affiliation(s)
- Wattana Leowattana
- Department of Clinical Tropical Medicine, Mahidol University, Rachatawee 10400, Bangkok, Thailand.
| | - Pathomthep Leowattana
- Department of Clinical Tropical Medicine, Mahidol University, Rachatawee 10400, Bangkok, Thailand
| | - Tawithep Leowattana
- Department of Medicine, Srinakharinwirot University, Wattana 10110, Bangkok, Thailand
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Yu HC, Huo WW, Lin KH, Sun WC, Lee CN. Trend patterns of HBsAg kinetics in chronic hepatitis B patients during nucleos(t)ide analogue therapy based on ARMA models. J Formos Med Assoc 2023; 122:458-469. [PMID: 36725372 DOI: 10.1016/j.jfma.2023.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 11/24/2022] [Accepted: 01/12/2023] [Indexed: 01/31/2023]
Abstract
BACKGROUND Trend pattern analysis are lacking for hepatitis B surface antigen (HBsAg) kinetics in chronic hepatitis B (CHB) patients during nucleos(t)ide analogue (Nuc) therapy. We evaluated the trend patterns of HBsAg kinetics by time series analysis and forecasting times to HBsAg seroclearance accordingly. METHODS A total of 116 CHB patients with documented three-month HBsAg levels during the previous more than five years of Nuc therapy were included. The piecewise linear trends of the autoregressive-moving average (ARMA) model were used for time series analysis of HBsAg kinetics trends. Best fitted models were created for each patient using HBsAg datasets with backtracking capability. Predicted time to HBsAg seroclearance was calculated accordingly. RESULTS Four trend patterns of HBsAg kinetics were found: no trend (n = 22, 19.0%), single trend (n = 16, 13.8%), biphasic trend with rapid-slow decline (n = 56, 48.2%) and biphasic trend with rise-decline (n = 22, 19.0%). Except for no-trend patients, the trend became slow reduction as HBsAg declined. Only 6.1% of patients continued rapid decline when the initial HBsAg of the last trend reached <100 IU/mL. Last trend slopes < -10 and rise-decline patterns indicate greater chances of achieving HBsAg seroclearance within two years. CONCLUSIONS Best fitted ARMA models of HBsAg kinetics can be created individually for patients during Nuc therapy. About 67.2% patients have biphasic trend patterns, suggesting the dynamic nature of HBsAg kinetics over time. Trend patterns and last trend slopes predict individual times to HBsAg seroclearance.
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Affiliation(s)
- Hsien-Chung Yu
- Health Management Center, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan; Department of Nursing, Meiho Institute of Technology, Ping-Tung 912, Taiwan; Institute of BioPharmaceutical Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan.
| | - Wen-Wei Huo
- Health Management Center, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan; Institute of Economics, National Sun Yat-sen University, Kaohsiung 804, Taiwan
| | - Kung-Hung Lin
- Health Management Center, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan; Department of Nursing, Meiho Institute of Technology, Ping-Tung 912, Taiwan
| | - Wei-Chih Sun
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan
| | - Ching-Nun Lee
- Institute of Economics, National Sun Yat-sen University, Kaohsiung 804, Taiwan
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Osawa Y, Ohtake T, Suto D, Akita T, Yamada H, Kohgo Y, Murata K. Cases of Rapid Hepatitis B Surface Antigen Reduction after COVID-19 Vaccination. Intern Med 2023; 62:51-57. [PMID: 36261382 PMCID: PMC9876716 DOI: 10.2169/internalmedicine.0842-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Objective One of the therapeutic goals for chronic infection with hepatitis B virus is the clearance of hepatitis B surface antigen (HBsAg) from the blood, as a high load of HBsAg has been proposed to induce antigen-specific immunotolerance. To achieve HBsAg reduction, Pegylated interferon and nucleos (t) ide analogs are used to treat chronic hepatitis B. Following the coronavirus disease 2019 (COVID-19) outbreak, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has rapidly spread worldwide, and vaccination with mRNA COVID-19 vaccines has been conducted since 2021 in Japan. We experienced three clinical cases in which HBsAg levels rapidly decreased after injection of the COVID-19 vaccine without any incentive. Method To examine whether the vaccine administration was involved in the HBsAg reduction, the number of patients with chronic hepatitis B showing a change in the HBsAg levels during the period before the commencement of the COVID-19 vaccination program in Japan (i.e. until the end of 2020; pre-vaccination-program period) was compared to the number of those who showed a change in HBsAg levels after the initiation of the program (i.e. 2021 onwards; post-vaccination-program period). Results The number of patients whose HBsAg levels was reduced by >50% per year was prominent after the initiation of the vaccination program. Although the involvement of vaccination in HBsAg reduction was not statistically proven (p=0.0532), the result suggests that the administration of COVID-19 vaccines may have been involved in HBsAg reduction in patients with chronic hepatitis B. Conclusion COVID-19 vaccines may be involved in HBsAg reduction.
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Affiliation(s)
- Yosuke Osawa
- Department of Gastroenterology, International University of Health and Welfare Hospital, Japan
| | - Takaaki Ohtake
- Department of Gastroenterology, International University of Health and Welfare Hospital, Japan
| | - Daisuke Suto
- Department of Gastroenterology, International University of Health and Welfare Hospital, Japan
| | - Takayuki Akita
- Department of Gastroenterology, International University of Health and Welfare Hospital, Japan
| | - Hidehiko Yamada
- Department of Gastroenterology, International University of Health and Welfare Hospital, Japan
| | - Yutaka Kohgo
- Department of Gastroenterology, International University of Health and Welfare Hospital, Japan
| | - Kazumoto Murata
- Department of Gastroenterology, International University of Health and Welfare Hospital, Japan
- Division of Virology, Department of Infection and Immunity, Jichi Medical University, Japan
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Lee H, Jang S, Ahn SH, Kim BK. Cost-effectiveness of antiviral therapy in untreated compensated cirrhosis patient with serum HBV-DNA level < 2000 IU/mL. Hepatol Int 2022; 16:294-305. [PMID: 35322374 DOI: 10.1007/s12072-022-10310-1] [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: 11/04/2021] [Accepted: 01/28/2022] [Indexed: 11/26/2022]
Abstract
BACKGROUND Due to stringent reimbursement criteria, significant numbers of patients with compensated cirrhosis (CC) and low-level viremia [LLV; serum hepatitis B virus (HBV)-DNA levels of 20-2000 IU/mL] remain untreated especially in the East Asian countries, despite potential risk of disease progression. We analyzed cost-effectiveness to assess rationales for antiviral therapy (AVT) for this population. METHODS We compared cost and effectiveness (quality-adjusted life years, QALYs) in a virtual cohort including 10,000 54-year-old CC-LLV patients receiving AVT (Scenario I) versus no treatment (Scenario II). A Markov model, including seven HBV-related conditions, was used. Values for transition probabilities and costs were mostly obtained from recent real-world South Korean data. RESULTS As per a simulation of a base-case analysis, AVT reduced costs by $639 USD and yielded 0.108 QALYs per patient for 5 years among CC-LLV patients compared to no treatment. Thus, AVT is a cost-saving option with lower costs and better effectiveness than no treatment. If 10,000 patients received AVT, 815 incident cases of hepatocellular carcinoma (HCC) and 630 HBV-related deaths could be averted in 5 years compared to no treatment. In case of 10-year observation, AVT was consistently dominant. Even when the transition probabilities from CC-LLV vs. maintained virological response to HCC were same, fluctuation of results also lied within willingness-to-pay in South Korea. In the probabilistic sensitivity analysis with the willingness-to-pay threshold, the probability of AVT cost-effectiveness was 100%. CONCLUSION The extended application of AVT in CC-LLV patients may contribute positively to individual clinical benefits and national healthcare budgets.
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Affiliation(s)
- Hankil Lee
- College of Pharmacy, Ajou University, Suwon, Gyeonggi-do, Republic of Korea
| | - Sungin Jang
- Institute of Health Services Research, Yonsei University, Seoul, Republic of Korea
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea.
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Zeng W, Liu M, Peng S, Yu G, Zhai X, Chen X, Lu F. Is the life-long entecavir treatment really inevitable in chronic hepatitis B patients? J Viral Hepat 2020; 27:1509-1510. [PMID: 32741086 DOI: 10.1111/jvh.13369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Accepted: 07/21/2020] [Indexed: 12/09/2022]
Affiliation(s)
- Wanjia Zeng
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Mingchen Liu
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Siwen Peng
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Guangxin Yu
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Xiangwei Zhai
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Xiangmei Chen
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Fengmin Lu
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.,Hepatology Institute, Peking University People's Hospital, Beijing, China
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Lu YX, He CZ, Wang YX, Ai ZS, Liang P, Yang CQ. Effect of Entecavir on the Intestinal Microflora in Patients with Chronic Hepatitis B: A Controlled Cross-Sectional and Longitudinal Real-World Study. Infect Dis Ther 2020; 10:241-252. [PMID: 33111216 PMCID: PMC7954982 DOI: 10.1007/s40121-020-00355-w] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Accepted: 10/08/2020] [Indexed: 02/07/2023] Open
Abstract
Introduction This study aimed to analyze the diversity of intestinal flora in patients with chronic hepatitis B (CHB) and investigate the effect of entecavir on the intestinal flora in these patients. Methods Thirty patients with CHB and 30 healthy controls were recruited from the Department of Infectious Diseases and Department of Gastroenterology of Shanghai Tongji Hospital between January 2017 and December 2018. Stool samples were collected for the detection of intestinal flora by high-throughput sequencing. Patients with CHB received antivirus therapy with entecavir for 8 weeks. The biochemical and virological responses were assessed and the intestinal flora were compared. Results After entecavir treatment, the blood levels of alanine aminotransferase (ALT), interleukin-6 (IL-6), IL-8, tumor necrosis factor (TNF), and hepatitis B virus (HBV) DNA reduced significantly in patients with CHB and the species abundance of intestinal flora increased markedly. In patients with CHB, the unique genera included Butyrivibrio, Phaseolus acutifolius, and Prevotellaceae NK3B31 group before treatment and Howardella, Candidatus Stoquefichus, Citrobacter, Dysgonomonas, Faecalicoccus, Methanobrevibacter, Mitsuokella, Mobilitalea, Succinivibrio, Gluconobacter, and Plesiomonas after treatment. The abundance of the following genera increased significantly after entecavir treatment in patients with CHB: Clostridium sensu stricto 1, Erysipelotrichaceae UCG-007, and Intestinibacter. The abundance of Streptococcus, Atopobium, and Murdochiella reduced markedly after entecavir treatment in patients with CHB. Conclusion After 8-week entecavir treatment, the blood biochemical, immunological, and virological responses improved significantly, the species abundance of intestinal flora increased markedly, and there were unique genera in patients with CHB before and after treatment. Electronic supplementary material The online version of this article (10.1007/s40121-020-00355-w) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Yu-Xia Lu
- Department of Gastroenterology and Hepatology, Institution of Digestive Diseases, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.,Department of Infectious Diseases, Institution of Digestive Diseases, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Cheng-Zhi He
- Department of Gastroenterology and Hepatology, Institution of Digestive Diseases, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.,Department of Infectious Diseases, Institution of Digestive Diseases, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Ying-Xin Wang
- Department of Gastroenterology and Hepatology, Institution of Digestive Diseases, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.,Department of Infectious Diseases, Institution of Digestive Diseases, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Zi-Sheng Ai
- Department of Statistics, Tongji University School of Medicine, Shanghai, China
| | - Ping Liang
- Department of Laboratory Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Chang-Qing Yang
- Department of Gastroenterology and Hepatology, Institution of Digestive Diseases, Tongji Hospital, Tongji University School of Medicine, Shanghai, China. .,Department of Infectious Diseases, Institution of Digestive Diseases, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
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