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1
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Fu MX, Elsharkawy A, Healy B, Jackson C, Bradshaw D, Watkins E, Ushiro-Lumb I, Griffiths J, Neuberger J, Maguire K, Desai M, McDougall N, Priddee N, Barclay ST, Blackmore S, Simmonds P, Irving WL, Harvala H. Occult hepatitis B virus infection: risk for a blood supply, but how about individuals' health? EClinicalMedicine 2025; 81:103095. [PMID: 39975699 PMCID: PMC11836515 DOI: 10.1016/j.eclinm.2025.103095] [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: 11/24/2024] [Revised: 01/14/2025] [Accepted: 01/20/2025] [Indexed: 02/21/2025] Open
Abstract
The implementation of effective blood donation screening for hepatitis B virus (HBV) anti-core antibodies with highly sensitive molecular HBV DNA detection in low-endemic countries like the United Kingdom has improved blood safety. However, the linkage to care and management for blood donors with occult HBV infection (OBI) is a complex dilemma involving virological, clinical, methodological, and social issues. Limited evidence suggests that OBI may accelerate the progression of liver disease and cancer. The need for a specialist referral for donors identified with OBI carries mixed opinions from blood establishments, hepatologists, and public health. Following extensive multidisciplinary discussions, experts agree upon a need for clear messaging for donors and to consider the oncogenic implications of OBI. Proposals for future studies are identified, and the applicability of the recommendations in low-resource, high-endemic regions is considered, as well as the inclusion of OBI in global hepatitis elimination targets.
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Affiliation(s)
- Michael X. Fu
- Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Ahmed Elsharkawy
- Liver Unit, Queen Elizabeth Hospital Birmingham, NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham, Birmingham, UK
| | - Brendan Healy
- Public Health Wales and Swansea Bay University Health Board, Swansea, UK
| | - Celia Jackson
- West of Scotland Specialist Virology Centre, Glasgow, UK
| | - Daniel Bradshaw
- Virus Reference Department, UK Health Security Agency, London, UK
| | - Emma Watkins
- Clinical Services, NHS Blood and Transplant, Birmingham, UK
| | | | | | - James Neuberger
- Liver Unit, Queen Elizabeth Hospital Birmingham, NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham, Birmingham, UK
| | | | - Monica Desai
- Blood Safety, UK Health Security Agency, London, UK
| | | | - Nicole Priddee
- Donor Services Division, Scottish National Blood Transfusion Service, Edinburgh, UK
| | | | | | - Peter Simmonds
- Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - William L. Irving
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, UK
| | - Heli Harvala
- Microbiology Services, NHS Blood and Transplant, Colindale, UK
- Radcliffe Department of Medicine, University of Oxford, Oxford, UK
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2
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Yasuura N, Suda G, Ohara M, Meno A, Sho T, Kohya R, Sasaki T, Yoda T, Yoshida S, Fu Q, Yang Z, Hosoda S, Maehara O, Ohnishi S, Saitou T, Sugiyama M, Fukuhara T, Baba M, Kitagataya T, Kawagishi N, Nakai M, Natsuizaka M, Ogawa K, Taketomi A, Sakamoto N. Positivity of high-sensitivity HBsAg test, not previous HBV infection, indicates poor prognosis in patients with non-HBV-related HCC. Aliment Pharmacol Ther 2024; 60:1315-1324. [PMID: 39228289 DOI: 10.1111/apt.18229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2024] [Revised: 06/26/2024] [Accepted: 08/15/2024] [Indexed: 09/05/2024]
Abstract
BACKGROUND AND AIMS The prognostic impact of previous-HBV-infection (pHBV) in non-HBV-related hepatocellular carcinoma (non-HBV-related-HCC) and the prevalence, characteristics and significance of recently developed high-sensitivity HBs antigen positivity (hHBsAg+) in these patients remain unclear. We aimed to close these gaps. METHODS We retrospectively screened patients with newly diagnosed non-HBV-related-HCC (standard HBsAg-test negative) at Hokkaido University. Patients with complete clinical information and preserved serum for hHBsAg+ were included. We evaluated the prevalence, characteristics and prognostic impact of pHBV and hHBsAg+ in non-HBV-related-HCC. RESULTS A total of 401 non-HBV-related-HCC patients were included (288 with pHBV/113 without pHBV). In non-HBV-related-HCC, pHBV did not affect overall survival (OS). Among non-HBV-related-HCC patients with pHBV, 11.8% (34/288) were hHBsAg+ and had more advanced stages of HCC, higher AFP levels, higher vascular invasion rates, and significantly shorter OS than others (OS: 19.3 vs. 61.4 months, p = 0.012). Comparison of OS among non-HBV-related-HCC patients without pHBV (group 1), those with pHBV and without hHBsAg+ (group 2), and those with pHBV and hHBsAg+ (group 3) revealed significantly shorter OS in group 3 (19.3, 56.6 and 66.4 months in groups 1, 2 and 3, respectively; p = 0.036). Multivariate Cox regression indicated that compared with group 1, only group 3 was significantly and independently associated with shorter OS (HR: 2.044, p = 0.011). Subgroup analysis revealed that this association was particularly evident in non-HBV-related-HCC patients with non-B-non-C aetiology and advanced HCC. CONCLUSIONS In non-HBV-related-HCC patients, hHBsAg+, not pHBV, is significantly and independently associated with poor prognosis.
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Grants
- JP24fk0210126,JP24fk0310501,JP24fk0210121,JP24fk0210112,JP24fk0210142,JP24fk0210111,JP24fk0310524,JP24fk0210123,JP24fk0210157,JP24fk0310518,JP24fk0210103,JP24fk0210104,JP24fk0210113,andJP24fk0210143 Japan Agency for Medical Research and Development
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Affiliation(s)
- Naohiro Yasuura
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Goki Suda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Masatsugu Ohara
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Akimitsu Meno
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Takuya Sho
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Risako Kohya
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Takashi Sasaki
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Tomoka Yoda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Sonoe Yoshida
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Qingjie Fu
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Zijian Yang
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Shunichi Hosoda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Osamu Maehara
- Laboratory of Molecular and Cellular Medicine, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
| | - Shunsuke Ohnishi
- Laboratory of Molecular and Cellular Medicine, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
| | - Tomoya Saitou
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Masaya Sugiyama
- Department of Viral Pathogenesis and Controls, National Center for Global Health Medicine, Tokyo, Japan
| | - Takasuke Fukuhara
- Department of Microbiology and Immunology, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Masaru Baba
- Center for Gastroenterology and Hepatology, Japan Community Healthcare Organization Hokkaido Hospital, Sapporo, Japan
| | - Takashi Kitagataya
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Naoki Kawagishi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Masato Nakai
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Mitsuteru Natsuizaka
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Koji Ogawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
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Morozov S, Batskikh S. Reactivation of hepatitis B virus infection - an important aspect of multifaceted problem. World J Gastroenterol 2024; 30:3193-3197. [PMID: 39086636 PMCID: PMC11287409 DOI: 10.3748/wjg.v30.i26.3193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Revised: 05/28/2024] [Accepted: 06/19/2024] [Indexed: 07/09/2024] Open
Abstract
In this editorial we comment on the article published in the recent issue of the World Journal of Gastroenterology. We focus specifically on the problem of occult hepatitis B virus (HBV) infection, that is a result of previous hepatitis B (PHB) and a source for reactivation of HBV. The prevalence of PHB is underestimated due to the lack of population testing programs. However, this condition not only complicate anticancer treatment, but may be responsible for the development of other diseases, like cancer or autoimmune disorders. Here we unveil possible mechanisms responsible for realization of these processes and suggest practical approaches for diagnosis and treatment.
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Affiliation(s)
- Sergey Morozov
- Department of Gastroenterology, Hepatology and Nutrition, Federal Research Center of Nutrition, Biotechnology and Food Safety, Moscow 115446, Russia
| | - Sergey Batskikh
- Department of Hepatology, Moscow Clinical Scientific Center N.A. A.S. Loginov, Moscow 111123, Russia
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Yano Y, Sato I, Imanishi T, Yoshida R, Matsuura T, Ueda Y, Kodama Y. Clinical Significance and Remaining Issues of Anti-HBc Antibody and HBV Core-Related Antigen. Diagnostics (Basel) 2024; 14:728. [PMID: 38611641 PMCID: PMC11011781 DOI: 10.3390/diagnostics14070728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 03/17/2024] [Accepted: 03/26/2024] [Indexed: 04/14/2024] Open
Abstract
Currently, hepatitis B virus (HBV) core antibody (anti-HBc antibody) and HBV core-related antigen (HBcrAg) are widely used as serum markers for diagnosis based on the HBV core region. This review focused on anti-HBc antibodies and HBcrAg and aimed to summarize the clinical significance of currently used assay systems and the issues involved. While anti-HBc is very significant for clinical diagnosis, the clinical significance of quantitative assay of anti-HBc antibody has been reevaluated with improvements in diagnostic performance, including its association with clinical stage and prediction of carcinogenesis and reactivation. In addition, concerning the new HBcrAg, a high-sensitivity assay method has recently been established, and its diagnostic significance, including the prediction of reactivation, is being reevaluated. On the other hand, the quantitative level of anti-HBc antibody expressed in different units among assay systems complicates the interpretation of the results. However, it is difficult to standardize assay systems as they vary in advantages, and caution is needed in interpreting the assay results. In conclusion, with the development of highly sensitive HBcrAg and anti-HBc antibody, a rapid and sensitive detection assay system has been developed and used in clinical practice. In the future, it is hoped that a global standard will be created based on the many clinical findings.
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Affiliation(s)
- Yoshihiko Yano
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; (R.Y.); (T.M.); (Y.U.); (Y.K.)
- Department of Clinical Laboratory, Kobe University Hospital, Kobe 650-0017, Japan; (I.S.); (T.I.)
| | - Itsuko Sato
- Department of Clinical Laboratory, Kobe University Hospital, Kobe 650-0017, Japan; (I.S.); (T.I.)
| | - Takamitsu Imanishi
- Department of Clinical Laboratory, Kobe University Hospital, Kobe 650-0017, Japan; (I.S.); (T.I.)
| | - Ryutaro Yoshida
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; (R.Y.); (T.M.); (Y.U.); (Y.K.)
| | - Takanori Matsuura
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; (R.Y.); (T.M.); (Y.U.); (Y.K.)
| | - Yoshihide Ueda
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; (R.Y.); (T.M.); (Y.U.); (Y.K.)
| | - Yuzo Kodama
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; (R.Y.); (T.M.); (Y.U.); (Y.K.)
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Conners EE, Panagiotakopoulos L, Hofmeister MG, Spradling PR, Hagan LM, Harris AM, Rogers-Brown JS, Wester C, Nelson NP. Screening and Testing for Hepatitis B Virus Infection: CDC Recommendations - United States, 2023. MMWR Recomm Rep 2023; 72:1-25. [PMID: 36893044 PMCID: PMC9997714 DOI: 10.15585/mmwr.rr7201a1] [Citation(s) in RCA: 75] [Impact Index Per Article: 37.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/10/2023] Open
Abstract
Chronic hepatitis B virus (HBV) infection can lead to substantial morbidity and mortality. Although treatment is not considered curative, antiviral treatment, monitoring, and liver cancer surveillance can reduce morbidity and mortality. Effective vaccines to prevent hepatitis B are available. This report updates and expands CDC's previously published Recommendations for Identification and Public Health Management of Persons with Chronic Hepatitis B Virus Infection (MMWR Recomm Rep 2008;57[No. RR-8]) regarding screening for HBV infection in the United States. New recommendations include hepatitis B screening using three laboratory tests at least once during a lifetime for adults aged ≥18 years. The report also expands risk-based testing recommendations to include the following populations, activities, exposures, or conditions associated with increased risk for HBV infection: persons incarcerated or formerly incarcerated in a jail, prison, or other detention setting; persons with a history of sexually transmitted infections or multiple sex partners; and persons with a history of hepatitis C virus infection. In addition, to provide increased access to testing, anyone who requests HBV testing should receive it, regardless of disclosure of risk, because many persons might be reluctant to disclose stigmatizing risks.
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Affiliation(s)
- Erin E. Conners
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, CDC
| | | | - Megan G. Hofmeister
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, CDC
| | - Philip R. Spradling
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, CDC
| | - Liesl M. Hagan
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, CDC
| | - Aaron M. Harris
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, CDC
| | - Jessica S. Rogers-Brown
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, CDC
| | - Carolyn Wester
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, CDC
| | - Noele P. Nelson
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, CDC
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Isolated Hepatitis B Core Antibody Positivity and Long-Term Liver-Related Mortality in Korea: A Cohort Study. Am J Gastroenterol 2023; 118:95-104. [PMID: 36087102 DOI: 10.14309/ajg.0000000000001994] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 08/23/2022] [Indexed: 01/28/2023]
Abstract
INTRODUCTION Whether isolated hepatitis B core antibody (anti-HBc) positivity is a risk factor for long-term liver-related outcomes in hepatitis B virus (HBV)-endemic areas remains unclear. We aimed to investigate liver-related and liver cancer mortality of isolated anti-HBc positivity in Korean adults. METHODS A cohort study comprised 609,299 Korean adults who underwent hepatitis B serologic markers, as a part of health examination. Liver-related and liver cancer mortality were determined using the National Death Records. RESULTS During a median follow-up of 9.0 years (interquartile range, 5.5-13.7 years), 554 liver-related deaths were identified (liver-related mortality, 9.6 cases per 10 5 person-years). The prevalence of isolated anti-HBc positivity was 3.8% (n = 23,399) and was age-dependent. After adjustment for age, sex, and other confounders, hazard ratios (95% confidence interval) for liver-related mortality in isolated anti-HBc-positive and hepatitis B surface antigen-positive subjects compared with HBV-unexposed subjects were 1.69 (1.22-2.33) and 27.02 (21.45-34.04), respectively. These associations were pronounced in the analyses using liver cancer mortality as an outcome. Among isolated anti-HBc-positive patients, the risks of liver-related and liver cancer mortality were significantly higher in those with high fibrosis-4 scores compared with patients unexposed to HBV with the multivariable-adjusted hazard ratios (95% confidence interval) of 15.59 (9.21-26.37) and 72.66 (36.96-142.86), respectively. DISCUSSION In this cohort of Korean adults, isolated anti-HBc positivity was associated with an increased risk of liver-related and liver cancer mortality, especially when accompanied by a high fibrosis score. Isolated anti-HBc positivity may be an independent risk factor for liver-related outcomes, especially in high-endemic areas.
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Batskikh S, Morozov S, Dorofeev A, Borunova Z, Kostyushev D, Brezgin S, Kostyusheva A, Chulanov V. Previous hepatitis B viral infection–an underestimated cause of pancreatic cancer. World J Gastroenterol 2022; 28:4812-4822. [PMID: 36156926 PMCID: PMC9476854 DOI: 10.3748/wjg.v28.i33.4812] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 06/15/2022] [Accepted: 08/16/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The etiology of pancreatic cancer remains unclear. This limits the possibility of prevention and effective treatment. Hepatitis B virus (HBV) is responsible for the development of different types of cancer, but its role in pancreatic cancer is still being discussed.
AIM To assess the prevalence of previous HBV infection and to identify viral biomarkers in patients with pancreatic ductal adenocarcinoma (PDAC) to support the role of the virus in etiology of this cancer.
METHODS The data of 130 hepatitis B surface antigen-negative subjects were available for the final analysis, including 60 patients with PDAC confirmed by cytology or histology and 70 sex- and age-matched controls. All the participants were tested for HBV biomarkers in blood [antibody to hepatitis B core antigen (anti-HBc), antibody to hepatitis B surface antigen (anti-HBs) and HBV DNA], and for those with PDAC, biomarkers in resected pancreatic tissues were tested (HBV DNA, HBV pregenomic RNA and covalently closed circular DNA). We performed immunohistochemistry staining of pancreatic tissues for hepatitis B virus X antigen and Ki-67 protein. Non-parametric statistics were used for the analysis.
RESULTS Anti-HBc was detected in 18/60 (30%) patients with PDAC and in 9/70 (13%) participants in the control group (P = 0.029). Accordingly, the odds of PDAC in anti-HBc-positive subjects were higher compared to those with no previous HBV infection (odds ratio: 2.905, 95% confidence interval: 1.191-7.084, standard error 0.455). HBV DNA was detected in 8 cases of PDAC and in 6 of them in the pancreatic tumor tissue samples only (all patients were anti-HBc positive). Blood HBV DNA was negative in all subjects of the control group with positive results of the serum anti-HBc test. Among 9 patients with PDAC, 5 revealed signs of replicative competence of the virus (covalently closed circular DNA with or without pregenomic RNA) in the pancreatic tumor tissue samples. Hepatitis B virus X antigen expression and active cell proliferation was revealed by immunohistochemistry in 4 patients with PDAC in the pancreatic tumor tissue samples.
CONCLUSION We found significantly higher risks of PDAC in anti-HBc-positive patients. Detection of viral replication and hepatitis B virus X protein expression in the tumor tissue prove involvement of HBV infection in pancreatic cancer development.
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Affiliation(s)
- Sergey Batskikh
- Department of Hepatology, Moscow Clinical Scientific Center N.A. A.S. Loginov, Moscow 111123, Russia
| | - Sergey Morozov
- Department of Gastroenterology, Hepatology and Nutrition, Federal Research Center of Nutrition, Biotechnology and Food Safety, Moscow 115446, Russia
| | - Alexey Dorofeev
- Department of Scientific and Clinical Laboratory Research, Moscow Clinical Scientific Center N.A. A.S. Loginov, Moscow 111123, Russia
| | - Zanna Borunova
- Department of Scientific and Clinical Laboratory Research, Moscow Clinical Scientific Center N.A. A.S. Loginov, Moscow 111123, Russia
| | - Dmitry Kostyushev
- Laboratory of Genetic Technologies, Sechenov University, Moscow 119435, Russia
- Division of Biotechnology, Scientific Center for Genetics and Life Sciences, Sirius University of Science and Technology, Sochi 354340, Russia
| | - Sergey Brezgin
- Laboratory of Genetic Technologies, Sechenov University, Moscow 119435, Russia
- Division of Biotechnology, Scientific Center for Genetics and Life Sciences, Sirius University of Science and Technology, Sochi 354340, Russia
| | | | - Vladimir Chulanov
- Laboratory of Genetic Technologies, Sechenov University, Moscow 119435, Russia
- Division of Biotechnology, Scientific Center for Genetics and Life Sciences, Sirius University of Science and Technology, Sochi 354340, Russia
- Laboratory of Genetic Technologies and Translational Research, National Medical Research Center for Tuberculosis and Infectious Diseases of Ministry of Health of Russia, Moscow 127994, Russia
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Saitta C, Pollicino T, Raimondo G. Occult Hepatitis B Virus Infection: An Update. Viruses 2022; 14:v14071504. [PMID: 35891484 PMCID: PMC9318873 DOI: 10.3390/v14071504] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Revised: 06/28/2022] [Accepted: 06/29/2022] [Indexed: 11/16/2022] Open
Abstract
Occult hepatitis B virus (HBV) infection (OBI) refers to a condition in which replication-competent viral DNA is present in the liver (with detectable or undetectable HBV DNA in the serum) of individuals testing negative for the HBV surface antigen (HBsAg). In this peculiar phase of HBV infection, the covalently closed circular DNA (cccDNA) is in a low state of replication. Many advances have been made in clarifying the mechanisms involved in such a suppression of viral activity, which seems to be mainly related to the host's immune control and epigenetic factors. OBI is diffused worldwide, but its prevalence is highly variable among patient populations. This depends on different geographic areas, risk factors for parenteral infections, and assays used for HBsAg and HBV DNA detection. OBI has an impact in several clinical contexts: (a) it can be transmitted, causing a classic form of hepatitis B, through blood transfusion or liver transplantation; (b) it may reactivate in the case of immunosuppression, leading to the possible development of even fulminant hepatitis; (c) it may accelerate the progression of chronic liver disease due to different causes toward cirrhosis; (d) it maintains the pro-oncogenic properties of the "overt" infection, favoring the development of hepatocellular carcinoma.
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Affiliation(s)
- Carlo Saitta
- Division of Medicine and Hepatology, University Hospital of Messina, 98124 Messina, Italy;
- Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy
| | - Teresa Pollicino
- Department of Human Pathology, University Hospital of Messina, 98124 Messina, Italy;
| | - Giovanni Raimondo
- Division of Medicine and Hepatology, University Hospital of Messina, 98124 Messina, Italy;
- Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy
- Correspondence: ; Tel.: +39-(0)-902212392
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Çakal B, Çavuş B, Atasoy A, Poda M, Bulakçi M, Güllüoğlu M, Demirci M, Şener LT, Altunok D, Arslan AB, Akyüz F. What is the clinical impact of occult HBV infections and anti-HBc positivity in patients with chronic hepatitis C? Microbiol Immunol 2022; 66:386-393. [PMID: 35661243 DOI: 10.1111/1348-0421.13012] [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: 02/18/2022] [Revised: 05/20/2022] [Accepted: 06/01/2022] [Indexed: 11/29/2022]
Abstract
Occult hepatitis B infection (OBI) is defined by the persistence of the hepatitis B virus (HBV) genome in the liver of individuals testing negative for hepatitis B surface antigen (HBsAg). Hepatitis B core antibody (anti-HBc) is the serological marker that indicates HBV exposure. The impact of anti-HBc and OBI on patients with chronic hepatitis C remains unclear. The aim of the present study was to determine the prevalence of anti-HBc and OBI and to evaluate their impact on the clinical and pathological outcomes of patients with chronic hepatitis C. The study included 59 HBsAg-negative chronic hepatitis C patients who underwent a liver parenchymal biopsy. The presence of HBV DNA was investigated using an in-house nested PCR method. OBI was detected in 16 (27.1%) of the 59 cases and also in 10 (62.5%) of 22 (37.3%) anti-HBc-positive patients. None of the patients had positive serum HBV DNA. OBI was associated with the presence of anti-HBV antibodies (p<0.05). There was also an association between anti-HBc positivity and the activity grades and fibrosis stages of the liver and also a prevalence of liver steatosis (p<0.05). Positive anti-HBc results may predict OBI and also be associated with the progression of liver injury in HBsAg-negative patients with chronic hepatitis C. Therefore, it is suggested that patients with chronic hepatitis C should be screened for anti-HBc positivity, and anti-HBc-positive patients should be carefully evaluated for disease progression. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Bülent Çakal
- Department of Medical Microbiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Bilger Çavuş
- Division of Gastroenterohepatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Alp Atasoy
- Division of Gastroenterohepatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Mehveş Poda
- Department of Genetics, Aziz Sancar Institute for Experimental Medical Research, Istanbul University, Istanbul, Turkey
| | - Mesut Bulakçi
- Department of Radiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Mine Güllüoğlu
- Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Mehmet Demirci
- Department of Medical Microbiology, Faculty of Medicine, Kirklareli University, Kirklareli, Turkey
| | - Leyla Türker Şener
- Department of Biophysics Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Damla Altunok
- Division of Gastroenterohepatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | | | - Filiz Akyüz
- Division of Gastroenterohepatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
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Collis OA, Ashley PA, Chen LH, Pedula KL, Miyashiro SM, Yamashita SK. Hepatitis B Core Antibody Positivity Associated with Increased Risk of Liver Cancer in Patients with Chronic Hepatitis C: Analysis of a Large Patient Cohort in Hawai'i. HAWAI'I JOURNAL OF HEALTH & SOCIAL WELFARE 2022; 81:127-133. [PMID: 35528754 PMCID: PMC9077569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Chronic hepatitis C infection is a major cause of liver cancer in the United States. Hawai'i's incidence of liver cancer consistently ranks among the highest in the US, due in part to the high prevalence of hepatitis B in the state. To better understand the factors associated with liver cancer among patients in Hawai'i with hepatitis C virus (HCV) infection, the patient database of Kaiser Permanente's Hawai'i region was used to identify a cohort of 3198 patients with a history of chronic HCV infection, of whom 159 (5%) were diagnosed with liver cancer between the years 2004-2020. Multiple logistic regression was used to identify factors independently associated with liver cancer. Male sex (AOR 2.02, 95% CI 1.34-3.06), Asian race (AOR 1.78, 1.16 - 2.74) and hepatitis B core antibody (HBCAB) positivity (AOR 1.76, 95% CI 1.25 - 2.49) emerged as independent predictors of liver cancer among patients with chronic HCV infection. A history of diabetes (AOR 1.56, 1.07 - 2.27) and older age at the time of HCV diagnosis (AOR 1.19, 1.09-1.29) also emerged as significant associations. HBCAB-positive individuals did not differ significantly from those who were HBCAB-negative in regards to demographics or 5-year survival rate. In this cohort of patients with chronic HCV, a positive HBCAB without evidence of active hepatitis B infection was associated with 1.76 increased odds of liver cancer compared to those with negative HBCAB. This finding may have important implications for screening algorithms among individuals with hepatitis C infection.
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Affiliation(s)
| | - Patrycja A. Ashley
- Kaiser Permanente Internal Medicine Residency Program, Honolulu, HI (PAA, LC)
| | - Li-Hsieh Chen
- Kaiser Permanente Internal Medicine Residency Program, Honolulu, HI (PAA, LC)
| | - Kathryn L Pedula
- Hawai‘i Permanente Medical Group, Kaiser Permanente, Honolulu, HI (KLP)
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11
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Ji DZ, Pang XY, Shen DT, Liu SN, Goyal H, Xu HG. Global prevalence of occult hepatitis B: A systematic review and meta-analysis. J Viral Hepat 2022; 29:317-329. [PMID: 35253969 DOI: 10.1111/jvh.13660] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Revised: 11/30/2021] [Accepted: 02/05/2022] [Indexed: 12/13/2022]
Abstract
The study aimed to investigate the prevalence and risk factors associated with occult hepatitis B virus (HBV) infection (OBI) in the global population. We searched PubMed, Embase, CINAHL, Cochrane and Web of Science from database inception through 27 Dec, 2018. Studies reporting HBV-DNA serological data in previously undiagnosed hepatitis B patients were included. The data were further categorized according to the presence of risk factors. After an initial screening of 2,325 records, we finally included 98 articles about the prevalence of OBI from 34 countries and regions. The OBI prevalence was 0.82% (95% CI:0.69-0.96) in the general population, 16.26% (95% CI:10.97-22.34) in HIV patients, 13.99% (95% CI:8.33-20.79) in patients with other liver diseases, 4.25% (95% CI:1.64-7.87) in haemodialysis patients and 5.14% (95% CI:2.26-9.01) patients with other risk factors. In conclusion, OBI prevalence varies significantly across different populations and nations, which deserve attention from the public health authorities. Our results generate further epidemiological data to identify the population with OBI, which has important clinical implications in finding these high-risk populations to design preventive and management strategies.
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Affiliation(s)
- Dong-Ze Ji
- Department of Pathology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Xiao-Yu Pang
- Department of Laboratory Medicine, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Dan-Ting Shen
- Department of Laboratory Medicine, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Shu-Na Liu
- Department of Laboratory Medicine, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Hemant Goyal
- Department of Medicine, The Wright Center of Graduate Medical Education, Scranton, Pennsylvania, USA
| | - Hua-Guo Xu
- Department of Laboratory Medicine, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
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12
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Batskikh S, Morozov S, Vinnitskaya E, Sbikina E, Borunova Z, Dorofeev A, Sandler Y, Saliev K, Kostyushev D, Brezgin S, Kostyusheva A, Chulanov V. May Previous Hepatitis B Virus Infection Be Involved in Etiology and Pathogenesis of Autoimmune Liver Diseases? Adv Ther 2022; 39:430-440. [PMID: 34762287 DOI: 10.1007/s12325-021-01983-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 10/29/2021] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Viral infections, especially with hepatotropic viruses, may trigger autoimmune liver diseases (AILDs) and deteriorate their course. However, association of previous hepatitis B virus (HBV) infection (presence of anti-HBc with or without anti-HBs or HBV DNA in serum) with AILDs is poorly studied so far. The aim of the study was to assess the prevalence of previous hepatitis B virus infection markers and its clinical significance in patients with autoimmune liver diseases. METHODS The study was based on the data obtained from 234 consecutive HBsAg-negative patients with AILDs [81 with autoimmune hepatitis (AIH), 122 with primary biliary cholangitis (PBC) and 31 with primary sclerosing cholangitis (PSC)] and 131 subjects of the control group without liver diseases. Blood samples of the enrolled patients were tested for anti-HBc and HBV DNA. Samples of liver tissue were examined by standard morphologic protocol and, in anti-HBc positive subjects, for HBV DNA. We assessed estimated risks of AILDs according to anti-HBc positivity and association of anti-HBc positivity with stage of liver fibrosis. RESULTS Anti-HBc was detected in 14.5% participants in the control group vs 26.1% (p = 0.016) in patients with AILDs (including 27.1% subjects with PBC (p = 0.021 vs control group), in 29% of PSC and 23.5% in AIH. HBV DNA was detected in three patients with PBC and in one with AIH. Positive anti-HBc test result was associated with higher risk of AILDs-odds ratio (OR) = 2.078 [95% confidence interval (CI) 1.179-3.665], especially in PBC: OR (95% CI) 2.186 (1.165-4.101). Odds of advanced stage of liver fibrosis (F3-F4 by METAVIR) in anti-HBc-positive subjects with PBC were also higher compared to those who had no previous HBV infection: OR (95% CI) 2.614 (1.153-5.926). CONCLUSIONS Significant proportions of patients with AILDs are anti-HBc positive, and some of them have OBI. Among patients with AILDs, anti-HBc-positivity is most widespread in the PBC group and in subjects with advanced stage of liver fibrosis. Our data may support the idea of an important role of previous HBV infection in the etiology and pathogenesis of AILDs (namely PBC).
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Affiliation(s)
- Sergey Batskikh
- Moscow Clinical Scientific Center n.a. A.S. Loginov, Entuziastov Shosse, 86, 111123, Moscow, Russia
| | - Sergey Morozov
- Department Gastroenterology, Hepatology and Nutrition, Federal Research Center of Nutrition and Biotechnology, Kashirskoye Shosse, 21, 115446, Moscow, Russia.
| | - Elena Vinnitskaya
- Moscow Clinical Scientific Center n.a. A.S. Loginov, Entuziastov Shosse, 86, 111123, Moscow, Russia
| | - Evgeniya Sbikina
- Moscow Clinical Scientific Center n.a. A.S. Loginov, Entuziastov Shosse, 86, 111123, Moscow, Russia
| | - Zanna Borunova
- Moscow Clinical Scientific Center n.a. A.S. Loginov, Entuziastov Shosse, 86, 111123, Moscow, Russia
| | - Alexey Dorofeev
- Moscow Clinical Scientific Center n.a. A.S. Loginov, Entuziastov Shosse, 86, 111123, Moscow, Russia
| | - Yulia Sandler
- Moscow Clinical Scientific Center n.a. A.S. Loginov, Entuziastov Shosse, 86, 111123, Moscow, Russia
| | - Kirill Saliev
- Moscow Clinical Scientific Center n.a. A.S. Loginov, Entuziastov Shosse, 86, 111123, Moscow, Russia
| | - Dmitry Kostyushev
- National Medical Research Center of Tuberculosis and Infectious Diseases, Ministry of Health, 127994, Moscow, Russia
- Division of Biotechnology, Scientific Center for Genetics and Life Sciences, Sirius University of Science and Technology, 354340, Sochi, Russia
| | - Sergey Brezgin
- National Medical Research Center of Tuberculosis and Infectious Diseases, Ministry of Health, 127994, Moscow, Russia
- Division of Biotechnology, Scientific Center for Genetics and Life Sciences, Sirius University of Science and Technology, 354340, Sochi, Russia
| | - Anastasiya Kostyusheva
- National Medical Research Center of Tuberculosis and Infectious Diseases, Ministry of Health, 127994, Moscow, Russia
| | - Vladimir Chulanov
- National Medical Research Center of Tuberculosis and Infectious Diseases, Ministry of Health, 127994, Moscow, Russia
- Division of Biotechnology, Scientific Center for Genetics and Life Sciences, Sirius University of Science and Technology, 354340, Sochi, Russia
- Department of Infectious Diseases, Sechenov First Moscow State Medical University, 119146, Moscow, Russia
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13
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de Faria AC, Correa BHM, Faria LC, Vidigal PVT, Xavier MAP, Ferrari TCA. Occult hepatitis B virus infection in patients with chronic liver disease of different etiology in a Brazilian referral center: comparison of two different hepatitis B virus deoxyribonucleic acid amplification protocols: a cross-sectional study. SAO PAULO MED J 2022; 141:e2022147. [PMID: 36169566 PMCID: PMC10065104 DOI: 10.1590/1516-3180.2022.0147.r1.12072022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 07/12/2022] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Occult hepatitis B virus infection (OBI) is defined as the presence of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) in the liver of individuals with undetectable hepatitis B virus surface antigen (HBsAg) in the serum. The actual prevalence of OBI and its clinical relevance are not yet fully understood. OBJECTIVE To evaluate the prevalence of HBV DNA in liver biopsies of HBsAg-negative patients with chronic liver disease of different etiologies in a referral center in Brazil and compare two different HBV DNA amplification protocols to detect HBV. DESIGN AND SETTING This cross-sectional observational study was conducted at the Liver Outpatient Clinic, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil, between January 2016 and December 2019. METHODS HBV DNA was investigated in 104 liver biopsy samples from individuals with chronic liver disease of different etiologies, in whom HBsAg was undetectable in serum by nested-polymerase chain reaction (nested-PCR), using two different protocols. RESULTS OBI, diagnosed by detecting HBV DNA using both protocols, was detected in 6.7% of the 104 individuals investigated. Both protocols showed a good reliability. CONCLUSION In addition to the differences in the prevalence of HBV infection in different regions, variations in the polymerase chain reaction technique used for HBV DNA amplification may be responsible for the large variations in the prevalence of OBI identified in different studies. There is a need for better standardization of the diagnostic methods used to diagnose this entity.
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Affiliation(s)
- Alessandra Coutinho de Faria
- MD, MSc. Physician, Department of Internal Medicine, Faculty of
Medicine, Hospital das Clínicas, Universidade Federal de Minas Gerais (UFMG),
Belo Horizonte (MG), Brazil
| | - Bernardo Henrique Mendes Correa
- Research Associate, Undergraduate Student, Department of
Internal Medicine, Faculty of Medicine, Universidade Federal de Minas Gerais
(UFMG), Belo Horizonte (MG), Brazil
| | - Luciana Costa Faria
- MD, PhD. Professor Associate, Department of Internal Medicine,
Faculty of Medicine, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte
(MG), Brazil
| | - Paula Vieira Teixeira Vidigal
- MD, PhD. Professor Associate, Department of Pathological
Anatomy and Forensic Medicine, Faculty of Medicine, Universidade Federal de
Minas Gerais (UFMG), Belo Horizonte (MG), Brazil
| | - Marcelo Antônio Pascoal Xavier
- MD, PhD. Professor, Department of Pathological Anatomy and
Forensic Medicine, Faculty of Medicine, Universidade Federal de Minas Gerais
(UFMG), Belo Horizonte (MG), Brazil
| | - Teresa Cristina Abreu Ferrari
- MD, PhD. Professor, Department of Internal Medicine, Faculty of
Medicine, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte (MG),
Brazil
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14
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Lee HL, Bae SH, Lee J, Sung PS, Lee SW, Jang JW, Lee J, Choi JY, Han NI, Yoon SK. Effects of Positive Hepatitis B Core Antibody and Metabolic Disorders in Hepatocellular Carcinoma in an Endemic Area of Hepatitis B Virus. Cancer Control 2021; 28:10732748211039758. [PMID: 34569320 PMCID: PMC8481710 DOI: 10.1177/10732748211039758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND AND AIMS This retrospective study aimed to investigate the impact of positive hepatitis B core antibody (anti-HBc) and metabolic disorders on clinical characteristics of hepatocellular carcinoma (HCC) patients in an HBV-endemic area. METHODS A total of 1950 consecutive patients newly diagnosed with HCC between 2002 and 2015 were included. Patient records were reviewed. We compared non-viral and non-alcoholic HCC patients with other etiological groups for HCC. In addition, we compared HCC patients with negative hepatitis B surface antigen (HBsAg) and positive anti-HBc to those with negative HBsAg and negative anti-HBc, and to those with HBV. RESULTS The prevalence of non-viral and non-alcoholic HCC increased from 7% in 2002-2011 to 12% in 2012-2015. The proportion of non-viral and non-alcoholic HCC gradually increased with age. Patients with non-viral and non-alcoholic HCC exhibited higher rates of metabolic disorders and preserved liver function. The rate of anti-HBc positivity was similarly high in all HCC etiological groups. The clinical features of HCC patients with negative HBsAg and positive anti-HBc were similar to those with negative HBsAg and negative anti-HBc, but significantly different from those with HBV HCC. Regarding tumor characteristics, patients in the non-viral and non-alcoholic HCC group had more advanced stages of tumors (mUICC stage III-V and BCLC stage C/D). There was no significant difference in overall survival among the patient groups. The presence of anti-HBc did not affect patient survival. CONCLUSION Patients with non-viral and non-alcoholic HCC had a relatively high prevalence of metabolic disorders and preserved liver function. However, they had advanced tumor stage compared to patients from other etiological groups. Anti-HBc positivity did not affect the clinical characteristics or prognosis of non-HBV HCC patients in this study.
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Affiliation(s)
- Hae Lim Lee
- Department of Internal Medicine, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea.,The Catholic Liver Research Center, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea
| | - Si Hyun Bae
- Department of Internal Medicine, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea.,The Catholic Liver Research Center, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea
| | - Jaejun Lee
- Department of Internal Medicine, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea.,The Catholic Liver Research Center, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea
| | - Pil Soo Sung
- Department of Internal Medicine, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea.,The Catholic Liver Research Center, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea
| | - Sung Won Lee
- Department of Internal Medicine, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea.,The Catholic Liver Research Center, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea
| | - Jeong Won Jang
- Department of Internal Medicine, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea.,The Catholic Liver Research Center, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea
| | - Jungmin Lee
- Department of Internal Medicine, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea
| | - Jong Young Choi
- Department of Internal Medicine, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea.,The Catholic Liver Research Center, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea
| | - Nam Ik Han
- Department of Internal Medicine, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea.,The Catholic Liver Research Center, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea
| | - Seung Kew Yoon
- Department of Internal Medicine, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea.,The Catholic Liver Research Center, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea
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15
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Sinn DH, Kang D, Cho SJ, Paik SW, Guallar E, Cho J, Gwak GY. Risk of hepatocellular carcinoma in individuals without traditional risk factors: development and validation of a novel risk score. Int J Epidemiol 2021; 49:1562-1571. [PMID: 32725117 DOI: 10.1093/ije/dyaa089] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/30/2020] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Although hepatocellular carcinoma (HCC) occurs mostly in patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or heavy alcohol use or cirrhosis, some patients develop HCC without these risk factors. Our objective in this study was to develop and validate a new HCC risk score that could stratify HCC risk in patients who develop HCC without known risk factors. METHODS A new HCC risk score was developed using a nationwide, population-based cohort among individuals without chronic HBV infection, chronic HCV infection, heavy alcohol use or cirrhosis (n = 467 206, derivation cohort). The performance of the HCC risk score was validated using an independent Samsung Medical Center Health Promotion Center cohort (n = 91 357, validation cohort). RESULTS Multivariable Cox regression analysis identified six independent risk factors: age, sex, smoking, diabetes, total cholesterol level and serum alanine aminotransferase level. A 19-point scale for HCC risk score was developed, with 10-year risk of HCC ranging from 0.0% to 6.16% for the lowest and highest risk scores, respectively. The area under the receiver operating characteristics curve values (AUROCs) to predict HCC development were 0.83 [95% confidence interval (CI): 0.77, 0.88)] and 0.92 (95% CI: 0.89, 0.95) at 10 years in the derivation and validation cohorts, respectively. Predicted risk was well correlated with the Kaplan-Meier observed HCC risk. CONCLUSIONS A simple-to-use, novel HCC risk score was developed for predicting HCC development in individuals without alleged risk factors. It can be used to assess the risk of HCC in this population so that decisions about their clinical management, including risk reduction interventions, can be subsequently made.
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Affiliation(s)
- Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Danbee Kang
- Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea
| | - Soo Jin Cho
- Center for Health Promotion, Samsung Medical Center, Seoul, South Korea
| | - Seung Woon Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Eliseo Guallar
- Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea.,Departments of Epidemiology and Medicine and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Juhee Cho
- Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea.,Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea.,Departments of Epidemiology and Medicine and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Geum-Youn Gwak
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
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16
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Lin S, Wang M, Liu Y, Huang J, Wu Y, Zhu Y, Wang X. Concurrence of HBV infection and non-alcoholic fatty liver disease is associated with higher prevalence of chronic kidney disease. Clin Res Hepatol Gastroenterol 2021; 45:101483. [PMID: 32646847 DOI: 10.1016/j.clinre.2020.06.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2020] [Revised: 05/22/2020] [Accepted: 06/11/2020] [Indexed: 02/04/2023]
Abstract
AIMS Coexistence of non-alcoholic fatty liver disease (NAFLD) and hepatitis B virus (HBV) infection is common in clinical practice. This study was to explore the prevalence of chronic kidney disease (CKD) in patients with NAFLD and/or HBV. METHODS Participants who received health examination in a physical examination center were included in this cross-sectional study. Binary logistic regression was used to estimate the odds ratios (ORs) for CKD. RESULTS A total of 32,578 cases were included in the final analysis, with 52.3% males and an average age of 44.01±13.09 years old. The positive rate of HBV surface antigen was 14.5% and NAFLD was diagnosed in 30.2% cases. The coexistence of NAFLD and HBV-infection was found in 1,275 (3.9%) cases. In overall population, 713 (2.2%) cases were diagnosed with CKD. The CKD prevalence were 1.4%, 2.1%, 3.5% and 5.0% in those without NAFLD or HBV, HBV-infection alone, NAFLD alone and those with concomitant HBV-infection and NAFLD, respectively. After adjustment for age, sex, body mass index, diabetes and hypertension, the correlation between CKD and liver disease was still significant in HBV group (OR=1.388, 95%CI: 1.055-1.809), yet no longer existed in patients with NAFLD (OR=1.183, 95%CI: 0.986-1.420). The concomitant of NAFLD and HBV infection was associated with a higher odds ratio for CKD compared to any other group (OR=1.961, 95%CI=1.454-2.645). CONCLUSIONS The coexistence of NAFLD and HBV increases the risk of CKD by 2-fold. The control of multiple liver diseases will be beneficial not only to liver but also to kidney.
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Affiliation(s)
- Su Lin
- Department of Gastroenterology, Union Hospital of Fujian Medical University, Fuzhou, Fujian
| | - Mingfang Wang
- Liver Research Center of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, China
| | - Yuxiu Liu
- Liver Research Center of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, China
| | - Jiaofeng Huang
- Liver Research Center of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, China
| | - Yinlian Wu
- Liver Research Center of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, China
| | - Yueyong Zhu
- Liver Research Center of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, China
| | - Xiaozhong Wang
- Department of Gastroenterology, Union Hospital of Fujian Medical University, Fuzhou, Fujian.
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17
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Tseng TC, Liu CJ. Occult Hepatitis B Infection. HEPATITIS B VIRUS AND LIVER DISEASE 2021:411-425. [DOI: 10.1007/978-981-16-3615-8_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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18
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Yang M, Parikh ND, Liu H, Wu E, Rao H, Feng B, Lin A, Wei L, Lok AS. Incidence and risk factors of hepatocellular carcinoma in patients with hepatitis C in China and the United States. Sci Rep 2020; 10:20922. [PMID: 33262356 PMCID: PMC7708980 DOI: 10.1038/s41598-020-77515-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Accepted: 11/09/2020] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection is the main cause of hepatocellular carcinoma (HCC) in the United States (US) and an increasingly common cause of HCC in China. We aimed to evaluate the incidence and risk factors of HCC in HCV patients in the US and China. 795 HCV RNA + patients without HCC from University of Michigan Health System (UMHS) in the US and 854 from Peking University Health Sciences Center (PUHSC) in China were prospectively followed for a median of 3.2 and 4.0 years, respectively. 45.4% UMHS and 16.2% PUHSC patients had cirrhosis. 57.6% UMHS and 52.0% PUHSC patients achieved SVR. 45 UMHS and 13 PUHSC patients developed HCC. Cumulative incidence of HCC at 5 years was 7.6% in UMHS and 1.8% in PUHSC cohort (P < 0.001). Ten patients not diagnosed with cirrhosis at enrollment but median APRI ≥ 2.0 developed HCC. Multivariate analysis showed age, gender, cirrhosis and APRI were predictors of HCC while study site and SVR were not. In this study of HCV patients, HCC incidence in the PUHSC cohort was lower than in the UMHS cohort, due to lower proportion of PUHSC patients with cirrhosis. APRI can identify risk of HCC among patients not diagnosed to have cirrhosis.
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Affiliation(s)
- Ming Yang
- Peking University People's Hospital, Peking University Hepatology Institute, Peking University Health Science Center, Beijing, China
| | - Neehar D Parikh
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Huixin Liu
- Department of Clinical Epidemiology and Biostatistics, Peking University People's Hospital, Beijing, China
| | - Elizabeth Wu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Huiying Rao
- Peking University People's Hospital, Peking University Hepatology Institute, Peking University Health Science Center, Beijing, China
| | - Bo Feng
- Peking University People's Hospital, Peking University Hepatology Institute, Peking University Health Science Center, Beijing, China
| | - Andy Lin
- The Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA
| | - Lai Wei
- Peking University People's Hospital, Peking University Hepatology Institute, Peking University Health Science Center, Beijing, China
| | - Anna S Lok
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
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19
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Pisaturo M, Onorato L, Russo A, Coppola N. Prevalence of occult HBV infection in Western countries. J Med Virol 2020; 92:2917-2929. [PMID: 32275083 DOI: 10.1002/jmv.25867] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Accepted: 03/19/2020] [Indexed: 12/11/2022]
Abstract
Due to a lack of standardized tests, it is difficult to obtain prevalence data and define the real impact of occult HBV infection (OBI) in Western countries. The present review article addresses the prevalence of OBI, defined as presence of hepatitis B virus (HBV) DNA in liver tissue or plasma in HBsAg-negative subjects, in Western countries. This varies in different studies according to the different methodologies used (based on serology vs virology), to the sample analyzed for the diagnosis (liver tissue vs plasma), to the different populations studied, to the different geographical variations in the HBV spread, to the host characteristics (age, gender, risk factors for acquiring HBV infection) and to the presence of other parenteral infections (hepatitis C virus and/or human immunodeficiency virus [HIV] infections). Considering the different liver diseases analyzed, that is in patients with cryptogenic cirrhosis or advanced liver fibrosis, the prevalence of OBI ranges 4% to 38%. Considering the different populations studied, in the case of parenteral blood exposure it is about 45%, in patients with chronic hepatitis C it is estimated at about 52%, in HIV-infected patients it ranges from 0% to 45%, in blood donors from 0% to 22.7% and in hemodialysis patients it ranges from 0% to 54%. In conclusion, OBI is a virological entity to be considered when performing the patient's evaluation for immunosuppressive diseases, liver pathologies, or for blood transfusions. Knowing the prevalence and clinical impact of OBI will allow better patient management.
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Affiliation(s)
- Mariantonietta Pisaturo
- Department of Mental Health and Public Medicine-Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Lorenzo Onorato
- Department of Mental Health and Public Medicine-Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Antonio Russo
- Department of Mental Health and Public Medicine-Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Nicola Coppola
- Department of Mental Health and Public Medicine-Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
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Occult hepatitis B infection and hepatocellular carcinoma: Epidemiology, virology, hepatocarcinogenesis and clinical significance. J Hepatol 2020; 73:952-964. [PMID: 32504662 DOI: 10.1016/j.jhep.2020.05.042] [Citation(s) in RCA: 128] [Impact Index Per Article: 25.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 05/21/2020] [Accepted: 05/25/2020] [Indexed: 12/12/2022]
Abstract
Occult hepatitis B infection (OBI) refers to a condition where replication-competent HBV DNA is present in the liver, with or without HBV DNA in the blood, in individuals with serum HBsAg negativity assessed by currently available assays. The episomal covalently closed circular DNA (cccDNA) in OBI is in a low replicative state. Viral gene expression is mediated by epigenetic control of HBV transcription, including the HBV CpG island methylation pathway and post-translational modification of cccDNA-bound histone, with a different pattern from patients with chronic HBV infection. The prevalence of OBI varies tremendously across patient populations owing to numerous factors, such as geographic location, assay characteristics, host immune response, coinfection with other viruses, and vaccination status. Apart from the risk of viral reactivation upon immunosuppression and the risk of transmission of HBV, OBI has been implicated in hepatocellular carcinoma (HCC) development in patients with chronic HCV infection, those with cryptogenic or known liver disease, and in patients with HBsAg seroclearance after chronic HBV infection. An increasing number of prospective studies and meta-analyses have reported a higher incidence of HCC in patients with HCV and OBI, as well as more advanced tumour histological grades and earlier age of HCC diagnosis, compared with patients without OBI. The proposed pathogenetic mechanisms of OBI-related HCC include the influence of HBV DNA integration on the hepatocyte cell cycle, the production of pro-oncogenic proteins (HBx protein and mutated surface proteins), and persistent low-grade necroinflammation (contributing to the development of fibrosis and cirrhosis). There remain uncertainties about exactly how, and in what order, these mechanisms drive the development of tumours in patients with OBI.
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Kardani K, Basimi P, Fekri M, Bolhassani A. Antiviral therapy for the sexually transmitted viruses: recent updates on vaccine development. Expert Rev Clin Pharmacol 2020; 13:1001-1046. [PMID: 32838584 DOI: 10.1080/17512433.2020.1814743] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION The sexually transmitted infections (STIs) caused by viruses including human T cell leukemia virus type-1 (HTLV-1), human immunodeficiency virus-1 (HIV-1), human simplex virus-2 (HSV-2), hepatitis C virus (HCV), hepatitis B virus (HBV), and human papillomavirus (HPV) are major public health issues. These infections can cause cancer or result in long-term health problems. Due to high prevalence of STIs, a safe and effective vaccine is required to overcome these fatal viruses. AREAS COVERED This review includes a comprehensive overview of the literatures relevant to vaccine development against the sexually transmitted viruses (STVs) using PubMed and Sciencedirect electronic search engines. Herein, we discuss the efforts directed toward development of effective vaccines using different laboratory animal models including mice, guinea pig or non-human primates in preclinical trials, and human in clinical trials with different phases. EXPERT OPINION There is no effective FDA approved vaccine against the sexually transmitted viruses (STVs) except for HBV and HPV as prophylactic vaccines. Many attempts are underway to develop vaccines against these viruses. There are several approaches for improving prophylactic or therapeutic vaccines such as heterologous prime/boost immunization, delivery system, administration route, adjuvants, etc. In this line, further studies can be helpful for understanding the immunobiology of STVs in human. Moreover, development of more relevant animal models is a worthy goal to induce effective immune responses in humans.
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Affiliation(s)
- Kimia Kardani
- Department of Hepatitis and AIDS, Pasteur Institute of Iran , Tehran, Iran
| | - Parya Basimi
- Department of Hepatitis and AIDS, Pasteur Institute of Iran , Tehran, Iran
| | - Mehrshad Fekri
- Department of Hepatitis and AIDS, Pasteur Institute of Iran , Tehran, Iran
| | - Azam Bolhassani
- Department of Hepatitis and AIDS, Pasteur Institute of Iran , Tehran, Iran
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Positive Hepatitis B Core Antibody Is Associated With Cirrhosis and Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease. Am J Gastroenterol 2020; 115:867-875. [PMID: 32149781 DOI: 10.14309/ajg.0000000000000588] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Previous exposure to hepatitis B virus (HBV) may increase the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. We aim to study the impact of previous HBV infection on the severity and outcomes of patients with nonalcoholic fatty liver disease (NAFLD). METHODS This was a multicenter study of 489 patients with biopsy-proven NAFLD and 69 patients with NAFLD-related or cryptogenic HCC. Antihepatitis B core antibody (anti-HBc) was used to detect the previous HBV infection. RESULTS In the biopsy cohort, positive anti-HBc was associated with lower steatosis grade but higher fibrosis stage. 18.8% and 7.5% of patients with positive and negative anti-HBc had cirrhosis, respectively (P < 0.001). The association between anti-HBc and cirrhosis remained significant after adjusting for age and metabolic factors (adjusted odds ratio 2.232; 95% confidence interval, 1.202-4.147). At a mean follow-up of 6.2 years, patients with positive anti-HBc had a higher incidence of HCC or cirrhotic complications (6.5% vs 2.2%; P = 0.039). Among patients with NAFLD-related or cryptogenic HCC, 73.9% had positive anti-HBc. None of the patients had positive serum HBV DNA. By contrast, antihepatitis B surface antibody did not correlate with histological severity. DISCUSSION Positive anti-HBc is associated with cirrhosis and possibly HCC and cirrhotic complications in patients with NAFLD. Because a significant proportion of NAFLD-related HCC may develop in noncirrhotic patients, future studies should define the role of anti-HBc in selecting noncirrhotic patients with NAFLD for HCC surveillance.
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Pisaturo M, Onorato L, Russo A, Chiodini P, Coppola N. An estimation of the prevalence of occult HBV infection in Western Europe and in Northern America: A meta-analysis. J Viral Hepat 2020; 27:415-427. [PMID: 31834645 DOI: 10.1111/jvh.13248] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Revised: 11/05/2019] [Accepted: 11/30/2019] [Indexed: 12/12/2022]
Abstract
Data on the prevalence of occult HBV infection (OBI) in Western Europe and in Northern America are few; hence, we conducted a systematic review and meta-analysis. All studies included had to fulfil the following inclusion criteria: (a) they investigated the prevalence of OBI (HBV DNA in liver tissue in HBsAg-negative subjects), (b) were carried out in Western Europe and in Northern America; (c) were available as a full-text manuscript, (d) written in English and (e) published up to December 2018. The exclusion criteria were as follows: (a) meta-analyses, letters, reviews, meeting abstracts or editorial comments; (b) studies investigating HBsAg-positive patients; (c) those investigating OBI outside Western Europe and in Northern America; and (d) to avoid small sample bias in the random-effects model, those enrolling less than five subjects. Thirty-four studies met the inclusion criteria, allowing a meta-analysis on 2729 patients. The overall prevalence of OBI was 34% (95% CI = 26%-42%), 28% (CI 95%: 12%-48%) in 329 subjects without chronic liver disease and 35% (95% CI 26%-44%) in 2400 patients with chronic liver disease. The prevalence of OBI was 51% (95% CI 40%-62%) in the 823 anti-HBc-positive subjects and 19% (95% CI 10%-30%) in the 1,041 anti-HBc-negative subjects. Evaluating the data from 17 studies comparing anti-HBc-positive and negative subjects, the prevalence of OBI was higher in the 641 anti-HBc-positive subjects than in the 1041 anti-HBc-negative (prevalence ratio = 2.29; 95% CI = 1.61-3.26, P < .001). This meta-analysis showed that in HBsAg-negative subjects the prevalence of OBI was high and was associated with anti-HBc positivity.
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Affiliation(s)
- Mariantonietta Pisaturo
- Department of Mental Health and Public Medicine - Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Lorenzo Onorato
- Department of Mental Health and Public Medicine - Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Antonio Russo
- Department of Mental Health and Public Medicine - Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Paolo Chiodini
- Department of Mental Health and Public Medicine - Medical Statistics Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Nicola Coppola
- Department of Mental Health and Public Medicine - Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
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Huang J, Jing M, Wang C, Wang M, You S, Lin S, Zhu Y. The impact of hepatitis B virus infection status on the prevalence of nonalcoholic fatty liver disease: A population-based study. J Med Virol 2019; 92:1191-1197. [PMID: 31691993 DOI: 10.1002/jmv.25621] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2019] [Accepted: 10/31/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND We aimed to explore the impact of hepatitis B virus (HBV) infection on the prevalence of nonalcoholic fatty liver disease (NAFLD) based on clinical big data. METHODS Data were collected from the health examination center of the First Affiliated Hospital of Fujian Medical University. Univariate and multivariate analysis were applied to investigate the relationship between HBV and NAFLD. RESULTS A total of 14 452 patients were included, with an average age of 43.84 ± 13.03 years. Cases of HBV current infection, past infection, and noninfection were 21 102 110 (14.6%), 90 039 003 (62.3%), and 33 393 339 (23.1%), respectively. The prevalence of NAFLD was significantly lower in the current infection group (29.9%) than in the past infection group (35.8%) and noninfection group (31.9%) (P < .001). After adjusting for age, the prevalence of NAFLD in the current infection group remained the lowest across all of the age groups. Multivariate analysis showed that current infection was at a lower risk of NAFLD (odds ratio [OR] = 0.717, 95% CI: 0.608-0.846), whereas past infection had no effect on NAFLD. CONCLUSIONS Current HBV infection may lower the risk of NAFLD. This effect becomes insignificant when the patient is no longer infected.
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Affiliation(s)
- Jiaofeng Huang
- Department of Liver Research Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Mengli Jing
- Department of Physical Examination Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Ciyang Wang
- Department of Physical Examination Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Mingfang Wang
- Department of Liver Research Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Shunjie You
- Department of Physical Examination Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Su Lin
- Department of Liver Research Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Yueyong Zhu
- Department of Liver Research Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
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Midorikawa Y, Takayama T, Nakayama H, Higaki T, Moriguchi M, Moriya K, Kanda T, Matsuoka S, Moriyama M. Prior hepatitis B virus infection as a co-factor of chronic hepatitis C patient survival after resection of hepatocellular carcinoma. BMC Gastroenterol 2019; 19:147. [PMID: 31426746 PMCID: PMC6700986 DOI: 10.1186/s12876-019-1069-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Accepted: 08/15/2019] [Indexed: 02/07/2023] Open
Abstract
Background Prior hepatitis B virus infection (PBI) may increase the risk of developing hepatocellular carcinoma (HCC), but the impact of PBI on clinical outcomes following treatment for HCC remains unknown. The aim of this study was to clarify whether PBI affects clinical outcomes after liver resection for hepatitis C virus (HCV)-related HCC by retrospective cohort study. Methods PBI patients were defined as those negative for hepatitis B surface antigen and positive for anti-hepatitis B core antibody. Surgical outcomes of HCV-related HCC patients with PBI were compared to those without PBI. Survival of patients with non-B non-C HCC with and without PBI were also compared. Results In the HCV group, the median overall survival of 165 patients with PBI was 4.7 years (95% confidence interval [CI], 3.9–5.9), and was significantly shorter compared with 263 patients without PBI (6.6 years [5.3–9.8]; p = 0.015). Conversely, there was no significant difference in recurrence-free survival between the two groups (1.8 years [95% CI, 1.4–2.0] vs 2.0 years [1.7–2.3]; p = 0.205). On Cox proportional hazards regression model, independent factors for overall survival were PBI (hazard ratio 1.38 [95% CI, 1.02–1.87]; p = 0.033), multiple tumors (p = 0.007), tumor size (p = 0.002), and liver cirrhosis (p < 0.001). On the other hand, in the non-B non-C HCC group, both the median overall survival (6.5 years [95% CI, 4.8–7.1]) and recurrence-free survival (2.4 years, [95% CI, 1.5–3.3]) in 104 patients with PBI were not significantly different from those (7.5 years [5.5 − NA; p = 0.932]; and 2.2 years [1.7–2.7; p = 0.983]) in 213 patients without PBI. Conclusions PBI and HCV in conjunction with each other affect the survival of patients that have undergone resection for HCC.
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Affiliation(s)
- Yutaka Midorikawa
- Department of Digestive Surgery, Nihon University School of Medicine, 30-1, Oyaguchikami-cho, Itabashi-ku, Tokyo, 173-8610, Japan.
| | - Tadatoshi Takayama
- Department of Digestive Surgery, Nihon University School of Medicine, 30-1, Oyaguchikami-cho, Itabashi-ku, Tokyo, 173-8610, Japan.
| | - Hisashi Nakayama
- Department of Digestive Surgery, Nihon University School of Medicine, 30-1, Oyaguchikami-cho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Tokio Higaki
- Department of Digestive Surgery, Nihon University School of Medicine, 30-1, Oyaguchikami-cho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Masamichi Moriguchi
- Department of Digestive Surgery, Nihon University School of Medicine, 30-1, Oyaguchikami-cho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Kyoji Moriya
- Department of Infectious Diseases, University of Tokyo Faculty of Medicine, Tokyo, Japan
| | - Tatsuo Kanda
- Department of Gastroenterology and Hepatology, Nihon University School of Medicine, Tokyo, Japan
| | - Shunichi Matsuoka
- Department of Gastroenterology and Hepatology, Nihon University School of Medicine, Tokyo, Japan
| | - Mitsuhiko Moriyama
- Department of Gastroenterology and Hepatology, Nihon University School of Medicine, Tokyo, Japan
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Raimondo G, Locarnini S, Pollicino T, Levrero M, Zoulim F, Lok AS. Update of the statements on biology and clinical impact of occult hepatitis B virus infection. J Hepatol 2019; 71:397-408. [PMID: 31004683 DOI: 10.1016/j.jhep.2019.03.034] [Citation(s) in RCA: 335] [Impact Index Per Article: 55.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Revised: 03/20/2019] [Accepted: 03/28/2019] [Indexed: 02/06/2023]
Abstract
In October 2018 a large number of international experts with complementary expertise came together in Taormina to participate in a workshop on occult hepatitis B virus infection (OBI). The objectives of the workshop were to review the existing knowledge on OBI, to identify issues that require further investigation, to highlight both existing controversies and newly emerging perspectives, and ultimately to update the statements previously agreed in 2008. This paper represents the output from the workshop.
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Affiliation(s)
- Giovanni Raimondo
- Division of Clinical and Molecular Hepatology, University of Messina, Messina, Italy; Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
| | - Stephen Locarnini
- Victorian Infectious Diseases Reference Laboratory at the Doherty Institute, Melbourne, Victoria, Australia
| | - Teresa Pollicino
- Division of Clinical and Molecular Hepatology, University of Messina, Messina, Italy; Department of Human Pathology, University of Messina, Messina, Italy
| | - Massimo Levrero
- Cancer Research Center of Lyon, INSERM U1052, Hospices Civils de Lyon, Lyon University, Lyon, France
| | - Fabien Zoulim
- Cancer Research Center of Lyon, INSERM U1052, Hospices Civils de Lyon, Lyon University, Lyon, France
| | - Anna S Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
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27
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El-Maksoud MA, Habeeb MR, Ghazy HF, Nomir MM, Elalfy H, Abed S, Zaki MES. Clinicopathological study of occult hepatitis B virus infection in hepatitis C virus-associated hepatocellular carcinoma. Eur J Gastroenterol Hepatol 2019; 31:716-722. [PMID: 30870221 DOI: 10.1097/meg.0000000000001388] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Occult hepatitis B virus infection (OBI) frequently occurs in patients with chronic hepatitis C (CHC) infection, but the influence of OBI on CHC outcome is still uncertain. The aim of the present study was to clarify the clinical and pathological characteristics of OBI in CHC-related hepatocellular carcinoma (HCC). PATIENTS AND METHODS DNA was obtained from serum and tumor tissue of patients with hepatitis C virus (HCV)-related HCC with negative HBsAg and from patients with HCV-related liver cirrhosis. HBV-DNA was detected using qPCR. Clinicopathological features were compared between patients with HCC with and without OBI. RESULTS On the basis of positive serum and tissue HBV-DNA typing, the overall frequency of OBI was 50% in patients with HCV-related HCC. HBV genotype D was the most dominant, constituting 35.3% of HCC cases. Almost 80% of patients with OBI had anti-HBc, whereas 20% of patients had no serological markers. Tissue HBV-DNA showed significant association with positive serum HBV-DNA, anti-HBc, and genotype D. There were no clinical differences between patients with HCC with and without OBI; however, patients with OBI tended to be younger. HCC cases with positive OBI were significantly associated with positive anti-HBc antibodies and late histological grades (3-4). Multivariate logistic regression analysis revealed that the presence of OBI was a predictor of more advanced HCC histological grades in patients with HCV infection. CONCLUSION OBI was detected in 50% of HCV-infected patients with HCC. OBI was strongly associated with the presence of anti-HBc antibodies. Patients with HCC with positive OBI were younger and had more advanced HCC histological grades.
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Affiliation(s)
| | | | | | - Manal M Nomir
- Clinical Pathology Student's Hospital, Mansoura University, Mansoura, Egypt
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28
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Chang JJ, Mohtashemi N, Bhattacharya D. Significance and Management of Isolated Hepatitis B Core Antibody (Anti-HBc) in HIV and HCV: Strategies in the DAA Era. Curr HIV/AIDS Rep 2019; 15:172-181. [PMID: 29572624 DOI: 10.1007/s11904-018-0379-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
PURPOSE OF REVIEW The purpose of this review is to summarize the prevalence and clinical implications of the isolated anti-HBc serologic profile in HIV-infected individuals. We highlight the rare but important issue of HBV reactivation in the setting of HCV therapy and describe an approach to management. RECENT FINDINGS The isolated anti-HBc pattern, a profile that most often indicates past exposure to HBV with waning anti-HBs immunity, is found commonly in HIV-infected individuals, particularly those with HCV. Some large cohort studies demonstrate an association with advanced liver disease, while others do not. Conversely, meta-analyses have found an association between occult HBV infection (a component of the isolated anti-HBc pattern) and advanced liver disease and hepatocellular carcinoma in HIV-uninfected individuals. In HIV-uninfected individuals with anti-HBc positivity, HBV reactivation has been reported in patients receiving HCV therapy. This phenomenon is likely the result of disinhibition of HBV with HCV eradication. In HIV-infected patients, the long-term liver outcomes associated with the isolated anti-HBc pattern remain to be fully elucidated, supporting the need for large cohort studies with longitudinal follow-up. HBV reactivation during HCV DAA therapy has been well-described in HIV-uninfected cohorts and can inform algorithms for the screening and management of the isolated anti-HBc pattern in this population.
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Affiliation(s)
- Jennifer J Chang
- UCLA CARE Center, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Avenue, 37-121 CHS, Los Angeles, CA, 90095, USA.,Department of Infectious Diseases, Kaiser Permanente at Los Angeles Medical Center, 1505 N. Edgemont St., 2nd Floor, Los Angeles, CA, 90027, USA
| | - Neaka Mohtashemi
- UCLA CARE Center, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Avenue, 37-121 CHS, Los Angeles, CA, 90095, USA
| | - Debika Bhattacharya
- UCLA CARE Center, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Avenue, 37-121 CHS, Los Angeles, CA, 90095, USA.
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Yamaji K, Kai K, Komukai S, Koga H, Ide T, Kawaguchi A, Noshiro H, Aishima S. Occult HBV infection status and its impact on surgical outcomes in patients with curative resection for HCV-associated hepatocellular carcinoma. Hepatobiliary Surg Nutr 2019; 7:443-453. [PMID: 30652089 DOI: 10.21037/hbsn.2018.10.01] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Background We sought to clarify the prevalence of occult hepatitis B virus (HBV) infection (OBI) and to determine whether OBI affects the surgical outcomes in curatively resected Japanese patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). Methods A total of 257 patients with HCV-related HCC who underwent curative surgical resection were enrolled. All enrolled patients were serologically negative for HBV surface antigen and positive for HCV antibody. DNA was extracted from formalin-fixed paraffin-embedded liver tissue. OBI was determined by the HBV-DNA amplification of at least two different sets of primers by TaqMan real-time polymerase chain reaction. Surgical outcomes were evaluated according to overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). Results OBI was identified in 15 of the 257 (5.8%) cases. In the multivariate analyses, the factors significantly correlated with OS were BMI >25 (P=0.0416), portal vein invasion (P=0.0065), and multiple tumors (P=0.0064). The only factor significantly correlated with DSS was T-stage (P=0.0275). The factors significantly correlated with DFS were liver fibrosis (P=0.0017) and T-stage (P=0.0001). The status of OBI did not show any significant correlation with OS, DSS or DFS, but a weak association with DSS (P=0.0603) was observed. Conclusions The prevalence of OBI was 5.8% in 257 cases of HCV-related HCC. Although a weak association between DSS and OBI was observed, and statistical analyses were limited by small number of OBI cases, no significant correlation between OBI and surgical outcomes was detected.
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Affiliation(s)
- Koutaro Yamaji
- Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan.,Department of Pathology & Microbiology, Saga University Faculty of Medicine, Saga 849-8501, Japan
| | - Keita Kai
- Department of Pathology, Saga University Hospital, Saga 849-8501, Japan
| | - Sho Komukai
- Clinical Research Center, Saga University Hospital, Saga 849-8501, Japan
| | - Hiroki Koga
- Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan
| | - Takao Ide
- Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan
| | - Atsushi Kawaguchi
- Center for Comprehensive Community Medicine, Saga University Faculty of Medicine, Saga 849-8501, Japan
| | - Hirokazu Noshiro
- Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan
| | - Shinichi Aishima
- Department of Pathology & Microbiology, Saga University Faculty of Medicine, Saga 849-8501, Japan.,Department of Pathology, Saga University Hospital, Saga 849-8501, Japan
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30
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Zhong GC, Wu YL, Hao FB, Rao XW, Yuan XW, Zhao Y, Gong JP. Current but not past hepatitis B virus infection is associated with a decreased risk of nonalcoholic fatty liver disease in the Chinese population: A case-control study with propensity score analysis. J Viral Hepat 2018; 25:842-852. [PMID: 29406564 DOI: 10.1111/jvh.12878] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Accepted: 01/04/2018] [Indexed: 12/11/2022]
Abstract
The relation between hepatitis B virus (HBV) infection and fatty liver has been addressed by several observational studies, but their results remain controversial. To date, no study has precisely investigated the association of current and past HBV infection with the risk of nonalcoholic fatty liver disease (NAFLD) in the Chinese population. Therefore, we conducted a hospital-based case-control study in southwestern China to clarify this issue. A total of 631 newly ultrasound-diagnosed NAFLD cases and 2357 controls were selected from 123 243 consecutive patients admitted to a tertiary-care hospital between January 2015 and December 2016. Multivariate logistic regression was employed to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). A propensity score was developed for adjustment and matching. Subgroup analysis was conducted to identify potential effect modifiers. Current and past HBV infection had an overall prevalence of 9.7% and 55.2%, respectively. In the fully adjusted model, current HBV infection was associated with a decreased risk of NAFLD (OR 0.64; 95% CI 0.42-0.95). A similar inverse association was observed in both propensity-score-adjusted (OR 0.58; 95% CI 0.40-0.86) and propensity-score-matched analyses (OR 0.61; 95% CI 0.40-0.92).The inverse association was stronger in patients with hypertension than in those without (Pinteraction = .018).No significant association between past HBV infection and NAFLD risk was found. In conclusion, current but not past HBV infection is associated with a decreased risk of NAFLD in the Chinese population. The corresponding biological mechanisms remain to be elucidated.
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Affiliation(s)
- G C Zhong
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Y L Wu
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - F B Hao
- Department of Pediatric Surgery, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - X W Rao
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - X W Yuan
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Y Zhao
- School of Public Health and Management, Chongqing Medical University, Chongqing, China
| | - J P Gong
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Muto J, Sugiyama M, Shirabe K, Mukaide M, Kirikae-Muto I, Ikegami T, Yoshizumi T, Yamashita YI, Maehara Y, Mizokami M. Frequency and Characteristics of Occult Hepatitis B Infection Among Hepatocellular Carcinoma Patients in Japan. Ann Hepatol 2018; 17:596-603. [PMID: 29893701 DOI: 10.5604/01.3001.0012.0927] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM Occult hepatitis B virus (HBV) infection (OBI) represents a state without detectable hepatitis B surface antigen, but positive for HBV DNA. The correlation between OBI and hepatocellular carcinoma (HCC) carcinogenesis is controversial. We studied the frequency and characteristics of OBI among HCC patients and metastatic liver cancer patients. MATERIAL AND METHODS DNA was obtained from tumor and non-tumor tissues from 75 HCC patients (15 chronic hepatitis B (CHB), 39 chronic hepatitis C (CHC), 21 cryptogenic) and 15 metastatic liver cancer patients who underwent liver resection. HBV DNA and covalentlyclosed circular (ccc) DNA were detected using real-time polymerase chain reaction (PCR), and four HBV DNA regions were detected by nested PCR. Clinicopathological factors were compared between patients with and without OBI. RESULTS HBV DNA was detected in 14 (93.3%) CHB, five (22.7%) cryptogenic and four (10.3%) CHC patients. cccDNA was detected in 12 (80.0%) CHB, three (14.3%) cryptogenic and two (5.1%) CHC patients. All CHB, eight (38.1%) cryptogenic and ten (25.6%) CHC patients tested positive with nested PCR. No metastatic liver cancer patients were positive for any HBV DNA regions. OBI patients had shorter prothrombin times (P = 0.0055), and lower inflammation activity score in non-tumor liver (P = 0.0274). There were no differences in anti-HBV antibodies. CONCLUSIONS OBI was detected in 38% of cryptogenic and 25.6% of CHC patients. There was no correlation between OBI and anti-HBV antibodies, but fewer patients with OBI had high inflammatory activity, suggesting that factors other than inflammation may be involved in HCC carcinogenesis in patients with OBI.
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Affiliation(s)
- Jun Muto
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Masaya Sugiyama
- The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan
| | - Ken Shirabe
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Motokazu Mukaide
- The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan
| | - Ikue Kirikae-Muto
- The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan
| | - Toru Ikegami
- Global Health and Medicine, Ichikawa, Chiba, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yo-Ichi Yamashita
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshihiko Maehara
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Masashi Mizokami
- The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan
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Coppola N, Onorato L, Iodice V, Starace M, Minichini C, Farella N, Liorre G, Filippini P, Sagnelli E, de Stefano G. Occult HBV infection in HCC and cirrhotic tissue of HBsAg-negative patients: a virological and clinical study. Oncotarget 2018; 7:62706-62714. [PMID: 27486882 PMCID: PMC5308760 DOI: 10.18632/oncotarget.10909] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2016] [Accepted: 06/18/2016] [Indexed: 12/19/2022] Open
Abstract
Aim To evaluate the virological and clinical characteristics of occult HBV infection (OBI) in 68 consecutive HBsAg-negative patients with biopsy-proven cirrhosis and HCC. Methods HBV DNA was sought and sequenced in plasma, HCC tissue and non-HCC liver tissue by PCRs using primers for HBV core, surface and x regions. OBI was identified by the presence of HBV DNA in at least two different PCRs. Results OBI was detected in HCC tissue of 13 (20%) patients and in non-HCC liver tissue of 3 of these 13. OBI was detected in HCC tissue of 54.5% of 11 anti-HBs- negative/anti-HBc-positive patients, in 29.4% of 17 anti-HBs/anti-HBc-positive and in 5% of 40 anti-HBs/anti-HBc-negative (p < 0.0005). The 13 patients with OBI in HCC tissue more frequently than the 55 without showed Child-B or -C cirrhosis (53.9% vs. 5.5%, p < 0.0001) and BCLC-B or -C stages (46.1% vs. 1.8%, p < 0.0001). The pre-S1, pre-S2 and S region sequences in HCC tissue showed amino acid (AA) substitutions (F19L, P24L, S59F, T131I, Q129H) and deletions (in positions 4,8, 17 and 86) in the S region, AA substitutions (T40S, P124K, L54P, G76A, N222T and I273L) in pre-S1 region and AA substitutions in pre-S2 region (P41H and P66L). In the 3 patients showing OBI also in non-HCC liver tissue the S, pre-S1 and pre-S2 sequencing displayed patterns of mutations different. Conclusions The study showed a significant correlation between OBI and the severity of liver damage, several patterns of mutations in the S, pre-S1 and pre-S2 regions in HCC tissue, some at their first description.
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Affiliation(s)
- Nicola Coppola
- Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy
| | - Lorenzo Onorato
- Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy
| | - Valentina Iodice
- Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy.,Ninth Interventional Ultrasound Unit for Infectious Diseases, Cotugno Hospital, Naples, Italy
| | - Mario Starace
- Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy
| | - Carmine Minichini
- Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy
| | - Nunzia Farella
- Ninth Interventional Ultrasound Unit for Infectious Diseases, Cotugno Hospital, Naples, Italy
| | - Giulia Liorre
- Ninth Interventional Ultrasound Unit for Infectious Diseases, Cotugno Hospital, Naples, Italy
| | - Pietro Filippini
- Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy.,Infectious Diseases Unit, Caserta Hospital, Caserta, Italy
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy
| | - Giorgio de Stefano
- Ninth Interventional Ultrasound Unit for Infectious Diseases, Cotugno Hospital, Naples, Italy
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Itoh S, Yoshizumi T, Tomino T, Nagatsu A, Motomura T, Harada N, Harimoto N, Ikegami T, Soejima Y, Maehara Y. Associations between antibody to hepatitis B core antigen positivity and outcomes in hepatocellular carcinoma patients undergoing hepatic resection. Hepatol Res 2018; 48:E155-E161. [PMID: 28710825 DOI: 10.1111/hepr.12939] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2017] [Revised: 07/11/2017] [Accepted: 07/12/2017] [Indexed: 02/08/2023]
Abstract
AIM We aimed to evaluate the effect of antibody to hepatitis B core antigen (HBcAb) positivity on clinical outcomes after hepatic resection in hepatocellular carcinoma (HCC) patients with negative hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (HCVAb), termed non-B, non-C HCC (NBNC-HCC), or with HCV-related HCC. METHODS Two hundred and sixty-three patients who underwent hepatic resection for HCC and measurements of HBsAg, HCVAb, and HBcAb were enrolled in this study. RESULTS The percentages of HBcAb positivity were 52.3% (n = 57) and 56.9% (n = 66) in patients with NBNC- and HCV-related HCC, respectively. The proportion of multiple NBNC-HCCs was significantly greater in patients with HBcAb positivity compared to HBcAb negativity (P = 0.028). There were no significant differences in the recurrence-free and overall survival rates between NBNC-HCC patients with HBcAb positivity versus negativity (P = 0.461 and P = 0.190, respectively). Furthermore, for HCV-related HCC patients, there were no significant differences in the baseline factors between patients with positive versus negative HBcAb. The proportion of patients with HBcAb-positive HCV-related HCC who underwent anatomical resection of the liver was significantly greater than that of HBcAb-negative patients, whereas the recurrence-free and overall survival rates were not significantly different (P = 0.158 and P = 0.191, respectively). CONCLUSION In our study, the presence of HBcAb had no impact on surgical outcomes after hepatic resection in patients with NBNB- and HCV-related HCC. Occult HBV infection might be associated with hepatocarcinogenesis in patients with NBNC-related HCC.
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Affiliation(s)
- Shinji Itoh
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takahiro Tomino
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Akihisa Nagatsu
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takashi Motomura
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Noboru Harada
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Norifumi Harimoto
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Toru Ikegami
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yuji Soejima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshihiko Maehara
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Koga H, Kai K, Aishima S, Kawaguchi A, Yamaji K, Ide T, Ueda J, Noshiro H. Occult hepatitis B virus infection and surgical outcomes in non-B, non-C patients with curative resection for hepatocellular carcinoma. World J Hepatol 2017; 9:1286-1295. [PMID: 29290910 PMCID: PMC5740092 DOI: 10.4254/wjh.v9.i35.1286] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2017] [Revised: 09/14/2017] [Accepted: 10/31/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the prevalence, clinicopathological characteristics and surgical outcomes of occult hepatitis B virus (HBV) infection (OBI) in patients with non-B, non-C (NBNC) hepatocellular carcinoma (HCC).
METHODS This study retrospectively examined the cases of 78 NBNC patients with curative resection for HCC for whom DNA could be extracted from formalin-fixed paraffin-embedded tissue. OBI was determined by the HBV-DNA amplification of at least two different sets of primers by TaqMan real-time polymerase chain reaction. Possibly carcinogenetic factors such as alcohol abuse, diabetes mellitus, obesity and non-alcoholic steatohepatitis (NASH) were examined. Surgical outcomes were evaluated according to disease-free survival (DFS), overall survival (OS) and disease-specific survival (DSS).
RESULTS OBI was found in 27/78 patients (34.6%) with NBNC HCC. The OBI patients were significantly younger than the non-OBI cases at the time of surgery (average age 63.0 vs 68.1, P = 0.0334) and the OBI cases overlapped with other etiologies significantly more frequently compared to the non-OBI cases (P = 0.0057). OBI had no impact on the DFS, OS or DSS. Only tumor-related factors affected these surgical outcomes.
CONCLUSION Our findings indicate that OBI had no impact on surgical outcomes. The surgical outcomes of NBNC HCC depend on early tumor detection; this reconfirms the importance of a periodic medical examination for individuals who have NBNC HCC risk factors.
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Affiliation(s)
- Hiroki Koga
- Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan
| | - Keita Kai
- Department of Pathology, Saga University Hospital, Saga 849-8501, Japan
| | - Shinichi Aishima
- Department of Pathology, Saga University Hospital, Saga 849-8501, Japan
- Department of Pathology and Microbiology, Saga University Faculty of Medicine, Saga 849-8501, Japan
| | - Atsushi Kawaguchi
- Center for Comprehensive Community Medicine, Saga University Faculty of Medicine, Saga 849-8501, Japan
| | - Koutaro Yamaji
- Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan
- Department of Pathology and Microbiology, Saga University Faculty of Medicine, Saga 849-8501, Japan
| | - Takao Ide
- Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan
| | - Junji Ueda
- Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan
| | - Hirokazu Noshiro
- Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan
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Torres HA, Shigle TL, Hammoudi N, Link JT, Samaniego F, Kaseb A, Mallet V. The oncologic burden of hepatitis C virus infection: A clinical perspective. CA Cancer J Clin 2017; 67:411-431. [PMID: 28683174 PMCID: PMC5591069 DOI: 10.3322/caac.21403] [Citation(s) in RCA: 75] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2016] [Revised: 05/09/2017] [Accepted: 05/10/2017] [Indexed: 12/18/2022] Open
Abstract
Answer questions and earn CME/CNE Chronic hepatitis C virus (HCV) infection affects millions of people worldwide and is associated with cancer. Direct-acting antivirals (DAAs) have changed HCV treatment paradigms, but little is known about the management of HCV infection in patients with cancer. The substantial burden of HCV infection and the inconclusive evidence regarding its detection and management in patients with cancer prompted the authors to review the literature and formulate recommendations. Patients for whom HCV screening is recommended included all patients with hematologic malignancies, hematopoietic cell transplantation candidates, and patients with liver cancer. There is a lack of consensus-based recommendations for the identification of HCV-infected patients with other types of cancer, but physicians may at least consider screening patients who belong to groups at heightened risk of HCV infection, including those born during 1945 through 1965 and those at high risk for infection. Patients with evidence of HCV infection should be assessed by an expert to evaluate liver disease severity, comorbidities associated with HCV infection, and treatment opportunities. DAA therapy should be tailored on the basis of patient prognosis, type of cancer, cancer treatment plan, and hepatic and virologic parameters. HCV-infected patients with cancer who have cirrhosis (or even advanced fibrosis) and those at risk for liver disease progression, especially patients with HCV-associated comorbidities, should have ongoing follow-up, regardless of whether there is a sustained virologic response, to ensure timely detection and treatment of hepatocellular carcinoma. HCV infection and its treatment should not be considered contraindications to cancer treatment and should not delay the initiation of an urgent cancer therapy. CA Cancer J Clin 2017. © 2017 American Cancer Society. CA Cancer J Clin 2017;67:411-431. © 2017 American Cancer Society.
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Affiliation(s)
- Harrys A. Torres
- H. A. Torres: Department of Infectious Diseases, Infection Control
and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX,
USA
| | - Terri Lynn Shigle
- T. L. Shigle: Division of Pharmacy, Section of Clinical Pharmacy
Services, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Nassim Hammoudi
- N. Hammoudi and V. Mallet: Université Paris
Descartes-Sorbonne Paris Cité; Assistance Publique-Hôpitaux de
Paris, Groupe Hospitalier Cochin Port Royal, Hepatology service; Institut National
de la Santé et de la Recherche Médicale unité 1223; Institut
Pasteur; all in Paris, France
| | - J. T. Link
- J. T. Link and A. Kaseb: Department of Gastrointestinal Medical
Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Felipe Samaniego
- F. Samaniego: Department of Lymphoma & Myeloma, The University
of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ahmed Kaseb
- J. T. Link and A. Kaseb: Department of Gastrointestinal Medical
Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Vincent Mallet
- N. Hammoudi and V. Mallet: Université Paris
Descartes-Sorbonne Paris Cité; Assistance Publique-Hôpitaux de
Paris, Groupe Hospitalier Cochin Port Royal, Hepatology service; Institut National
de la Santé et de la Recherche Médicale unité 1223; Institut
Pasteur; all in Paris, France
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Li X, Gu Y, Guo X, Gu L, Zhou L, Wu X, Wang X, Stamataki Z, Huang Y. A Practical Model Evaluating Antiviral Cytokines by Natural Killer Cells in Treatment Naïve Patients with Chronic Hepatitis B Virus Infection. Sci Rep 2017; 7:5866. [PMID: 28725030 PMCID: PMC5517634 DOI: 10.1038/s41598-017-06192-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2017] [Accepted: 06/21/2017] [Indexed: 12/23/2022] Open
Abstract
Natural killer (NK) cells play a major role in anti-viral immunity as first line defense during hepatitis B infection, particularly in untreated patients whose T cells functions are profoundly impaired. Cytokine interferon (IFN)-γ and tumor necrosis factor (TNF)-α produced by NK cells are important anti-viral factors. However, there is lack of a quantifiable model to evaluate cytokine responses by NK cells. In this study, almost half of the patients (47.9%) beyond treatment criteria had high cytokine activity, although it was lower than those recommended for antiviral therapy (78.2%). Moreover, we developed a model that low levels of HBsAg, HBcAb, and albumin and high fibrosis values predicted strong antiviral cytokine production by NK cells. Based on the cut-off score (0.361) obtained from the multivariable model, patients with 67%, 8%, 92%, and 74% in immune-active (IA), immune-tolerant (IT), immune-inactive (IC), and grey zone (GZ), respectively, showed active antiviral cytokines produced by NK cells. These results suggest that those who possess activated cytokine responses beyond the current treatment criteria may have potential implications for the timing of antiviral therapy to achieve better virus control.
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Affiliation(s)
- Xiaoyan Li
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yurong Gu
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiaobo Guo
- Department of Statistical Science, School of Mathematics, Sun Yat-Sen University, Guangzhou, China.,Southern China Center for Statistical Science, Sun Yat-Sen University, Guangzhou, China.,Department of Ophthalmology, University of Melbourne, Melbourne, Australia
| | - Lin Gu
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Liang Zhou
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiaojuan Wu
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xueqin Wang
- Department of Statistical Science, School of Mathematics, Sun Yat-Sen University, Guangzhou, China.,Southern China Center for Statistical Science, Sun Yat-Sen University, Guangzhou, China.,Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
| | - Zania Stamataki
- Institute for Immunology and Immunotherapy and NIHR Biomedical Research Centre, University of Birmingham, Birmingham, United Kingdom
| | - Yuehua Huang
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. .,Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
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37
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Mittal M, Hu KQ. Clinical Implications and Management of Chronic Occult Hepatitis B Virus Infection. CURRENT HEPATOLOGY REPORTS 2017; 16:90-96. [DOI: 10.1007/s11901-017-0339-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/16/2025]
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Cho J, Lee SS, Choi YS, Jeon Y, Chung JW, Baeg JY, Si WK, Jang ES, Kim JW, Jeong SH. Occult hepatitis B virus infection is not associated with disease progression of chronic hepatitis C virus infection. World J Gastroenterol 2016; 22:9427-9436. [PMID: 27895431 PMCID: PMC5107707 DOI: 10.3748/wjg.v22.i42.9427] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Revised: 08/18/2016] [Accepted: 09/06/2016] [Indexed: 02/07/2023] Open
Abstract
AIM To clarify the prevalence of occult hepatitis B virus (HBV) infection (OBI) and the association between OBI and liver disease progression, defined as development of liver cirrhosis or hepatocellular carcinoma (HCC), worsening of Child-Pugh class, or mortality in cases of chronic hepatitis C virus (HCV) infection.
METHODS This prospective cohort study enrolled 174 patients with chronic HCV infection (chronic hepatitis, n = 83; cirrhosis, n = 47; HCC, n = 44), and evaluated disease progression during a mean follow-up of 38.7 mo. OBI was defined as HBV DNA positivity in 2 or more different viral genomic regions by nested polymerase chain reaction using 4 sets of primers in the S, C, P and X open reading frame of the HBV genome.
RESULTS The overall OBI prevalence in chronic HCV patients at enrollment was 18.4%, with 16.9%, 25.5% and 13.6% in the chronic hepatitis C, liver cirrhosis and HCC groups, respectively (P = 0.845). During follow-up, 52 patients showed disease progression, which was independently associated with aspartate aminotransferase > 40 IU/L, Child-Pugh score and sustained virologic response (SVR), but not with OBI positivity. In 136 patients who were not in the SVR state during the study period, OBI positivity was associated with neither disease progression, nor HCC development.
CONCLUSION The prevalence of OBI in chronic HCV patients was 18.4%, and OBI was not associated with disease progression in South Koreans.
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Abstract
Hepatitis B virus (HBV) infection is a major global health challenge. HBV can cause significant morbidity and mortality by establishing acute and chronic hepatitis. Approximately 250 million people worldwide are chronically infected, and more than 2 billion people have been exposed to HBV. Since the discovery of HBV, the advances in our understanding of HBV virology and immunology have translated into effective vaccines and therapies for HBV infection. Although current therapies successfully suppress viral replication but rarely succeed in viral eradication, recent discoveries in HBV virology and immunology provide exciting rationales for novel treatment strategies aiming at HBV cure.
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Affiliation(s)
- Bertram Bengsch
- Department of Microbiology and Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, 331 Biomedical Research Building II/III, 421 Curie Boulevard, Philadelphia, PA 19104, USA
| | - Kyong-Mi Chang
- Medical Research, Philadelphia Corporal Michael J. Crescenz VA Medical Center (CMC VAMC), A424, University and Woodland Avenue, Philadelphia, PA 19104, USA; Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, 421 Curie Boulevard, Philadelphia, PA 19104, USA.
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40
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Makvandi M. Update on occult hepatitis B virus infection. World J Gastroenterol 2016; 22:8720-8734. [PMID: 27818588 PMCID: PMC5075547 DOI: 10.3748/wjg.v22.i39.8720] [Citation(s) in RCA: 105] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2016] [Revised: 06/13/2016] [Accepted: 07/20/2016] [Indexed: 02/06/2023] Open
Abstract
The event of mutations in the surface antigen gene of hepatitis B virus (HBV) results in undetectable hepatitis B surface antigen with positive/negative anti-hepatitis B core (anti-HBc) antibody status in serum and this phenomenon is named occult hepatitis B infection (OBI). The presence of anti-HBc antibody in serum is an important key for OBI tracking, although about 20% of OBI cases are negative for anti-HBc antibody. The diagnosis of OBI is mainly based on polymerase chain reaction (PCR) and real-time PCR assays. However, real-time PCR is a more reliable method than PCR. OBI is a great issue for the public health problem and a challenge for the clinical entity worldwide. The persistence of OBI may lead to the development of cirrhosis and hepatocellular carcinoma. With regard to OBI complications, the screening of HBV DNA by the highly sensitive molecular means should be implemented for: (1) patients with a previous history of chronic or acute HBV infection; (2) patients co-infected with hepatitis C virus/human immunodeficiency virus; (3) patients undergoing chemotherapy or anti-CD20 therapy; (4) recipients of organ transplant; (5) blood donors; (6) organ transplant donors; (7) thalassemia and hemophilia patients; (8) health care workers; (9) patients with liver related disease (cryptogenic); (10) hemodialysis patients; (11) patients undergoing lamivudine or interferon therapy; and (12) children in time of HBV vaccination especially in highly endemic areas of HBV. Active HBV vaccination should be implemented for the close relatives of patients who are negative for OBI markers. Thus, the goal of this review is to evaluate the rate of OBI with a focus on status of high risk groups in different regions of the world.
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Coppola N, Onorato L, Sagnelli C, Sagnelli E, Angelillo IF. Association between anti-HBc positivity and hepatocellular carcinoma in HBsAg-negative subjects with chronic liver disease: A meta-analysis. Medicine (Baltimore) 2016; 95:e4311. [PMID: 27472708 PMCID: PMC5265845 DOI: 10.1097/md.0000000000004311] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
A meta-analysis was performed to ascertain to what extent hepatitis B surface antigen (HBsAg)-negative/anti-hepatitis B core (anti-HBc)-positive subjects with chronic liver disease are at a higher risk of developing hepatocellular carcinoma (HCC) than the anti-HBc-negative.All studies included had to fulfill the following characteristics and inclusion criteria: they investigated the relationship between HBsAg-negative/anti-HBc-positive serology and the occurrence of HCC, whether a case-control or cohort study, they provided relative risk (RR) or odds ratios (ORs) and 95% confidence intervals (CIs), were available as a full text written in English, and were published and indexed up to April 2015.Twenty-six original studies met the inclusion criteria, allowing a meta-analysis on 44,553 patients. The risk of HCC among the 9986 anti-HBc-positive subjects was 67% higher than in the 34,567 anti-HBc-negative (95% CI = 1.44-1.95, P < 0.0001). The results were similar when groups of patients with a different stage of liver disease (patients with chronic liver disease, patients with cirrhosis), with different ethnicity (Asian and non-Asian) and etiology (HCV and non-HCV) were considered. The risk of HCC was significantly higher in the 651 anti-HBs/anti-HBc-positive patients (RR = 1.36; 95% CI = 1.17-1.58, P = 0.03) and in the 595 anti-HBs-negative/anti-HBc-positive subjects (RR = 2.15; 95% CI = 1.58-2.92, P < 0.0001) than in the 1242 anti-HBs/anti-HBc negative. However, the RR from 8 studies indicated that the risk of HCC was 35% lower among the anti-HBs/anti-HBc-positive subjects compared to the anti-HBs-negative/anti-HBc-positive (RR = 0.65; 95% CI = 0.52-0.8, P < 0.0001).This meta-analysis shows that in HBsAg-negative subjects with chronic liver disease, anti-HBc positivity is strongly associated with the presence of HCC, an association observed in all subgroups according to the stage of the disease, etiology, and ethnicity.
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Affiliation(s)
- Nicola Coppola
- Department of Mental Health and Public Medicine, Section of Infectious Diseases
- Correspondence: Nicola Coppola, Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Via L. Armanni 5, 80131 Naples, Italy (e-mail: )
| | - Lorenzo Onorato
- Department of Mental Health and Public Medicine, Section of Infectious Diseases
| | - Caterina Sagnelli
- Department of Clinical and Experimental Medicine and Surgery “F. Magrassi e A. Lanzara”
| | | | - Italo F. Angelillo
- Department of Experimental Medicine, Second University of Naples, Naples, Italy
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Coppola N, Onorato L, Pisaturo M, Macera M, Sagnelli C, Martini S, Sagnelli E. Role of occult hepatitis B virus infection in chronic hepatitis C. World J Gastroenterol 2015; 21:11931-11940. [PMID: 26576082 PMCID: PMC4641115 DOI: 10.3748/wjg.v21.i42.11931] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2015] [Revised: 06/28/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023] Open
Abstract
The development of sensitive assays to detect small amounts of hepatitis B virus (HBV) DNA has favored the identification of occult hepatitis B infection (OBI), a virological condition characterized by a low level of HBV replication with detectable levels of HBV DNA in liver tissue but an absence of detectable surface antigen of HBV (HBsAg) in serum. The gold standard to diagnose OBI is the detection of HBV DNA in the hepatocytes by highly sensitive and specific techniques, a diagnostic procedure requiring liver tissue to be tested and the use of non-standardized non-commercially available techniques. Consequently, in everyday clinical practice, the detection of anti-hepatitis B core antibody (anti-HBc) in serum of HBsAg-negative subjects is used as a surrogate marker to identify patients with OBI. In patients with chronic hepatitis C (CHC), OBI has been identified in nearly one-third of these cases. Considerable data suggest that OBI favors the increase of liver damage and the development of hepatocellular carcinoma (HCC) in patients with CHC. The data from other studies, however, indicate no influence of OBI on the natural history of CHC, particularly regarding the risk of developing HCC.
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Pondé RAA. Molecular mechanisms underlying HBsAg negativity in occult HBV infection. Eur J Clin Microbiol Infect Dis 2015; 34:1709-31. [PMID: 26105620 DOI: 10.1007/s10096-015-2422-x] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2015] [Accepted: 06/03/2015] [Indexed: 02/06/2023]
Abstract
Although genomic detection is considered the gold standard test on HBV infection identification, the HBsAg investigation is still the most frequent clinical laboratory request to diagnose HBV infection in activity. However, the non-detection of HBsAg in the bloodstream of chronic or acutely infected individuals has been a phenomenon often observed in clinical practice, despite the high sensitivity and specificity of screening assays standardized commercially and adopted in routine. The expansion of knowledge about the hepatitis B virus biology (replication/life cycle, genetic variability/mutability/heterogeneity), their biochemical and immunological properties (antigenicity and immunogenicity), in turn, has allowed to elucidate some mechanisms that may explain the occurrence of this phenomenon. Therefore, the negativity for HBsAg during the acute or chronic infection course may become a fragile or at least questionable result. This manuscript discusses some mechanisms that could explain the negativity for HBsAg in a serological profile of individuals with HBV infection in activity, or factors that could compromise its detection in the bloodstream during HBV infection.
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Affiliation(s)
- R A A Pondé
- Laboratory of Human Virology, Institute of Tropical Pathology and Public Health, Federal University of Goiás, Goiânia, Goiás, Brazil,
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Kwak MS, Kim YJ. Occult hepatitis B virus infection. World J Hepatol 2014; 6:860-869. [PMID: 25544873 PMCID: PMC4269905 DOI: 10.4254/wjh.v6.i12.860] [Citation(s) in RCA: 71] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2014] [Revised: 09/23/2014] [Accepted: 10/29/2014] [Indexed: 02/06/2023] Open
Abstract
Occult hepatitis B virus (HBV) infection (OBI) refers to the presence of HBV DNA in the absence of detectable hepatitis B surface antigen. Since OBI was first described in the late 1970s, there has been increasing interest in this topic. The prevalence of OBI varies according to the different endemicity of HBV infection, cohort characteristics, and sensitivity and specificity of the methods used for detection. Although the exact mechanism of OBI has not been proved, intra-hepatic persistence of viral covalently closed circular DNA under the host’s strong immune suppression of HBV replication and gene expression seems to be a cause. OBI has important clinical significance in several conditions. First, OBI can be transmitted through transfusion, organ transplantation including orthotopic liver transplantation, or hemodialysis. Donor screening before blood transfusion, prophylaxis for high-risk organ transplantation recipients, and dialysis-specific infection-control programs should be considered to reduce the risk of transmission. Second, OBI may reactivate and cause acute hepatitis in immunocompromised patients or those receiving chemotherapy. Close HBV DNA monitoring and timely antiviral treatment can prevent HBV reactivation and consequent clinical deterioration. Third, OBI may contribute to the progression of hepatic fibrosis in patients with chronic liver disease including hepatitis C. Finally, OBI seems to be a risk factor for hepatocellular carcinoma by its direct proto-oncogenic effect and by indirectly causing persistent hepatic inflammation and fibrosis. However, this needs further investigation. We review published reports in the literature to gain an overview of the status of OBI and emphasize the clinical importance of OBI.
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Is previous exposure to hepatitis B a risk factor for pancreatic cancer or hepatocellular carcinoma? J Clin Gastroenterol 2014; 48:729-33. [PMID: 24618505 DOI: 10.1097/mcg.0000000000000111] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
GOALS We evaluated whether prior infection with the hepatitis B virus (HBV) influences the development of pancreatic cancer or hepatocellular carcinoma (HCC). BACKGROUND Prior infection with HBV may predispose patients to developing pancreatic cancer or HCC. STUDY We conducted a retrospective cohort study using administrative data from an integrated health care system. We identified all patients who had HBV testing over a 13-year period. These patients were divided into 1 of 3 cohorts based on HBV status: negative infection (n=28,719), previous exposure (n=5141), or active infection (n=404). Pancreatic cancer and HCC data were obtained from pathology reports in the health system's cancer registry. RESULTS In a multivariable model, age [hazards ratio (HR), 1.08; confidence interval (CI), 1.06-1.09; P<0.001)] and presence of diabetes (HR, 1.88; CI, 1.27-2.80; P=0.002) were identified to have significant influence on pancreatic cancer development, whereas previous HBV exposure did not have a significant influence (HR, 1.41; CI, 0.88-2.27; P=0.16). In a separate multivariable model, male sex (HR, 2.05; CI, 1.35-3.11; P<0.001), age (HR, 1.08; CI, 1.06-1.09; P<0.001), being hepatitis C positive (HR, 5.40; CI, 3.51-8.33; P<0.001), and presence of cirrhosis (HR, 27.84; CI, 17.43-44.46, P<0.001) were all significant predictors of HCC. However, previous HBV exposure was not associated with HCC development (HR, 1.03; CI, 0.68-1.56; P=0.88). CONCLUSIONS Data from this study indicate that previous HBV exposure is not a risk factor for the development of either pancreatic cancer or HCC.
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Pollicino T, Saitta C. Occult hepatitis B virus and hepatocellular carcinoma. World J Gastroenterol 2014; 20:5951-5961. [PMID: 24876718 PMCID: PMC4033435 DOI: 10.3748/wjg.v20.i20.5951] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 01/15/2014] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
Occult hepatitis B virus (HBV) infection (OBI) is a challenging pathobiological and clinical issue that has been widely debated for several decades. By definition, OBI is characterized by the persistence of HBV DNA in the liver tissue (and in some cases also in the serum) in the absence of circulating HBV surface antigen (HBsAg). Many epidemiological and molecular studies have indicated that OBI is an important risk factor for hepatocellular carcinoma (HCC) development. OBI may exert direct pro-oncogenic effects through the activation of the same oncogenic mechanisms that are activated in the course of an HBsAg-positive infection. Indeed, in OBI as in HBV-positive infection, HBV DNA can persist in the hepatocytes both integrated into the host genome as well as free episome, and may maintain the capacity to produce proteins-mainly X protein and truncated preS-S protein - provided with potential transforming properties. Furthermore, OBI may indirectly favor HCC development. It has been shown that the persistence of very low viral replicative activity during OBI may induce mild liver necro-inflammation continuing for life, and substantial clinical evidence indicates that OBI can accelerate the progression of liver disease towards cirrhosis that is considered the most important risk factor for HCC development.
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48
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Snow KK, Bell MC, Stoddard AM, Curto TM, Wright EC, Dienstag JL. Processes to manage analyses and publications in a phase III multicenter randomized clinical trial. Trials 2014; 15:159. [PMID: 24886378 PMCID: PMC4040510 DOI: 10.1186/1745-6215-15-159] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2013] [Accepted: 04/24/2014] [Indexed: 02/07/2023] Open
Abstract
Background The timely publication of findings in peer-reviewed journals is a primary goal of clinical research. In clinical trials, the processes leading to publication can be complex from choice and prioritization of analytic topics through to journal submission and revisions. As little literature exists on the publication process for multicenter trials, we describe the development, implementation, and effectiveness of such a process in a multicenter trial. Methods The Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial included a data coordinating center (DCC) and clinical centers that recruited and followed more than 1,000 patients. Publication guidelines were approved by the steering committee, and the publications committee monitored the publication process from selection of topics to publication. Results A total of 73 manuscripts were published in 23 peer-reviewed journals. When manuscripts were closely tracked, the median time for analyses and drafting of manuscripts was 8 months. The median time for data analyses was 5 months and the median time for manuscript drafting was 3 months. The median time for publications committee review, submission, and journal acceptance was 7 months, and the median time from analytic start to journal acceptance was 18 months. Conclusions Effective publication guidelines must be comprehensive, implemented early in a trial, and require active management by study investigators. Successful collaboration, such as in the HALT-C trial, can serve as a model for others involved in multidisciplinary and multicenter research programs. Trial registration The HALT-C Trial was registered with clinicaltrials.gov (NCT00006164).
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Affiliation(s)
| | | | | | - Teresa M Curto
- New England Research Institutes, 9 Galen Street, Watertown, MA 02472, USA.
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Abstract
BACKGROUND Chronic hepatitis B has been shown to increase mortality, but association of past exposure to hepatitis B and mortality has not been studied well. The aim of this study was to evaluate the risk of overall and liver-related mortality in individuals with past exposure to hepatitis B. METHODS The National Health and Nutrition Examination Survey III (NHANES III) and its related public linked mortality files were used for this study. The participants with presence of anti-HBc ± anti-HBs, in absence of hepatitis B surface antigen were considered to have previous exposure to hepatitis B. The overall mortality from past exposure to hepatitis B was assessed in participants without any chronic liver diseases (CLD) and in participants with chronic hepatitis C, alcoholic liver disease (ALD), and nonalcoholic fatty liver disease. The Cox proportional regression analysis was used to calculate adjusted hazard ratios. RESULTS A total of 15,650 individuals were included in the analyses. Past exposure to hepatitis B was an independent predictor of increase in overall mortality in individuals without CLD [adjusted hazard ratio (aHR)=1.29; 95% confidence interval (CI), 1.06-1.56; P=0.012] and those with ALD (aHR=2.25; 95% CI, 1.20-4.23; P=0.013). It was also an independent predictor of liver-related mortality in ALD cohort (aHR=7.75; 95% CI, 2.56-23.48; P<0.001). Past exposure to hepatitis B did not correlate with a significant increase in overall or liver-related mortality in chronic hepatitis C or nonalcoholic fatty liver disease cohorts. CONCLUSION Past exposure to hepatitis B is associated with significant increase in overall mortality among individuals with ALD and those without CLD.
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Shlomai A, de Jong YP, Rice CM. Virus associated malignancies: the role of viral hepatitis in hepatocellular carcinoma. Semin Cancer Biol 2014; 26:78-88. [PMID: 24457013 DOI: 10.1016/j.semcancer.2014.01.004] [Citation(s) in RCA: 130] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2013] [Revised: 12/29/2013] [Accepted: 01/09/2014] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) is the third leading fatal cancer worldwide and its incidence continues to increase. Chronic viral hepatitis involving either hepatitis B virus (HBV) or hepatitis C virus (HCV) infection is the leading etiology for HCC, making HCC prevention a major goal of antiviral therapy. While recent clinical observations and translational research have enhanced our understanding of the molecular mechanisms driving the initiation and progression of HCC, much remains unknown. Current data indicates that HCC tumors are highly complex and heterogeneous resulting from the aberrant function of multiple molecular pathways. This complex biology is responsible, at least in part, for the absence of highly efficient target-directed therapies for this deadly cancer. Additionally, the direct or indirect effect of HBV and HCV infection on the development of HCC is still a contentious issue. Thus, the question remains whether viral hepatitis-associated HCC stems from virus-specific factors, and/or from a general mechanism involving inflammation and tissue regeneration. In this review we summarize general mechanisms implicated in HCC, emphasizing data generated by new technologies available today. We also highlight specific pathways by which HBV and HCV could be involved in HCC pathogenesis. However, improvements to current in vitro and in vivo systems for both viruses will be needed to rigorously define the temporal sequence and specific pathway dysregulations that drive the strong clinical link between chronic hepatitis virus infection and HCC.
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Affiliation(s)
- Amir Shlomai
- Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY, USA.
| | - Ype P de Jong
- Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY, USA; Division of Gastroenterology and Hepatology, Center for the Study of Hepatitis C, Weill Cornell Medical College, New York, NY, USA
| | - Charles M Rice
- Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY, USA.
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