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Park J, Kim DY, Gee HY, Yu HC, Yang JD, Hwang S, Choi Y, Lee JG, Rhu J, Choi D, You YK, Ryu JH, Nah YW, Kim BW, Kim DS, Cho JY, Group TKOTR(KOTRYS. Genome-Wide Association Study to Identify Genetic Factors Linked to HBV Reactivation Following Liver Transplantation in HBV-Infected Patients. Int J Mol Sci 2024; 26:259. [PMID: 39796114 PMCID: PMC11719695 DOI: 10.3390/ijms26010259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Revised: 12/19/2024] [Accepted: 12/23/2024] [Indexed: 01/13/2025] Open
Abstract
This study utilized a genome-wide association study (GWAS) to investigate the genetic variations linked to the risk of hepatitis B virus (HBV) reactivation in patients who have undergone liver transplantation (LT), aiming to enhance understanding and improve clinical outcomes. Genotyping performed on a selected patients from the Korean Organ Transplantation Registry (KOTRY) data using high-throughput platforms with the Axiom Korea Biobank array 1.1. The discovery cohort included 21 patients who experienced HBV reactivation (cases) and 888 patients without HBV reactivation (controls) following LT. The replication cohort consisted of 5 patients with HBV reactivation (cases) and 312 patients without HBV reactivation (controls) after LT. Additive logistic regression analysis was conducted using PLINK software ver 1.9, with adjustments for age and gender. The GWAS findings from the discovery cohort were validated using the replication cohort. The GWAS identified several single-nucleotide polymorphisms (SNPs) in the RGL1, CDCA7L, and AQP9 genes that were significantly linked to HBV reactivation after LT, with genome-wide significance thresholds set at p < 10-7. Down-regulation of RGL1 cDNAs was observed in primary duck hepatocytes infected with duck HBV. Overexpression of CDCA7L was found to promote hepatocellular carcinoma cell proliferation and colony formation, whereas knocking down CDCA7L inhibited these processes. Additionally, the absence of AQP9 triggered immune and inflammatory responses, leading to mild and scattered liver cell pyroptosis, accompanied by compensatory liver cell proliferation. This study provides critical insights into the genetic factors influencing HBV reactivation after LT, identifying significant associations with SNPs in RGL1, CDCA7L, and AQP9. These findings hold promise for developing predictive biomarkers and personalized management strategies to improve outcomes for HBV-infected LT recipients.
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Affiliation(s)
- Joonhong Park
- Department of Laboratory Medicine, Jeonbuk National University College of Medicine and Hospital, Jeonju 54907, Republic of Korea;
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea;
| | - Dong Yun Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea;
| | - Heon Yung Gee
- Department of Pharmacology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Hee Chul Yu
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea;
- Department of Surgery, Jeonbuk National University College of Medicine and Hospital, Jeonju 54907, Republic of Korea
| | - Jae Do Yang
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea;
- Department of Surgery, Jeonbuk National University College of Medicine and Hospital, Jeonju 54907, Republic of Korea
| | - Shin Hwang
- Department of Surgery, Asan Medical Center, College of Medicine University of Ulsan, Seoul 05505, Republic of Korea;
| | - YoungRok Choi
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of Korea;
| | - Jae Geun Lee
- Department of Surgery, The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul 03722, Republic of Korea;
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea;
| | - Donglak Choi
- Department of Surgery, Daegu Catholic University School of Medicine, Daegu 42472, Republic of Korea;
| | - Young Kyoung You
- Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea;
| | - Je Ho Ryu
- Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea;
| | - Yang Won Nah
- Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, Republic of Korea;
| | - Bong-Wan Kim
- Department of Hepato-Biliary-Pancreatic Surgery, Ajou University School of Medicine, Suwon 16499, Republic of Korea;
| | - Dong-Sik Kim
- Department of Surgery, Korea University College of Medicine, Seoul 02841, Republic of Korea;
| | - Jai Young Cho
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Republic of Korea;
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Franzè MS, Pollicino T, Raimondo G, Squadrito G. Occult hepatitis B virus infection in hepatitis C virus negative chronic liver diseases. Liver Int 2022; 42:963-972. [PMID: 35246933 PMCID: PMC9310828 DOI: 10.1111/liv.15233] [Citation(s) in RCA: 2] [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: 05/11/2021] [Revised: 01/09/2022] [Accepted: 02/16/2022] [Indexed: 01/26/2023]
Abstract
Data concerning the prevalence of hepatitis B virus (HBV) occult infection (OBI) varies greatly in the different studies according to the sensitivity and specificity of the diagnostic approaches and the HBV prevalence in the different populations examined. The clinical implications of OBI are still debated. While the impact of OBI in HBV transmission as well as in HBV reactivation under immunosuppression are well established, the role of OBI in liver disease and hepatocellular carcinoma (HCC) development are still not definitively elucidated. It has been hypothesized that OBI might contribute to worsening the liver disease course when other causes of liver damage co-exist. Furthermore, much evidence suggests a role of OBI in the hepato-carcinogenesis processes through both indirect and direct oncogenic mechanisms that might favour HCC development. Data on the OBI clinical implications mainly come from studies performed in patients with hepatitis C virus (HCV) infection. However, HCV prevalence has dramatically fallen in the past years also because of the advent of specific and highly effective direct acting antivirals, with a consequent abrupt change of the worldwide scenario of chronic liver disease. Information about OBI prevalence and possible clinical impact in non-HCV-related liver disease are fragmentary, and the objective of this review is to critically summarize the available data in this field.
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Affiliation(s)
- Maria Stella Franzè
- Department of Clinical and Experimental MedicineMessina UniversityMessinaItaly,Division of Medicine and HepatologyMessina University HospitalMessinaItaly
| | - Teresa Pollicino
- Department of Human PathologyMessina UniversityMessinaItaly,Division of Advanced Diagnostic LaboratoriesMessina University HospitalMessinaItaly
| | - Giovanni Raimondo
- Department of Clinical and Experimental MedicineMessina UniversityMessinaItaly,Division of Medicine and HepatologyMessina University HospitalMessinaItaly
| | - Giovanni Squadrito
- Department of Clinical and Experimental MedicineMessina UniversityMessinaItaly,Division of Internal MedicineMessina University HospitalMessinaItaly
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Man X, Wei R. Advancements in the prevention of hepatitis B recurrence by nucleos(t)ide analogue monotherapies after liver transplantation. EUR J INFLAMM 2022. [DOI: 10.1177/1721727x221139254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Previous studies have shown that the recurrence rate of HBV (hepatitis B virus) after liver transplantation (LT) can be as high as 80% without any preventive measures. Therefore, prevention of HBV recurrence after LT is always an essential part of clinical work worldwide. The NAs that have been approved for HBV treatment include lamivudine, adefovir dipivoxil, entecavir (ETV), and telbivudine, tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF). They are often combined with HBIG to prevent HBV recurrence after LT clinically. However, NAs with a higher genetic barrier, such as ETV, TDF, and TAF, can improve liver function by strongly inhibiting HBV replication and reducing the risks of HBV resistance. Recently, some NAs with a higher genetic barrier, such as ETV, TDF, and TAF, have been adopted as monotherapy for preventing the recurrence of hepatitis B after LT in multiple organ transplant centres and have achieved effective outcomes. This article aims to review the advances for NAs monotherapy in prophylaxis for HBV recurrence after LT.
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Affiliation(s)
- Xie Man
- Department of Gastroenterology, the Affiliated Hospital of Qingdao University, China
| | - Rao Wei
- Division of Hepatology, Liver Disease Center, the Affiliated Hospital of Qingdao University, China
- Department of Organ Transplantation, the Affiliated Hospital of Qingdao University, China
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Khiangte B, Kothakota SR, Sasidharan M, Kareem H, Nair AK, Kumar VV, Kanala JR, Kumar PC. Hepatitis B Reactivation in Liver Transplant Recipients With Hepatitis B Virus Core Antibody Positive Grafts: a Retrospective Study. J Clin Exp Hepatol 2020; 10:548-554. [PMID: 33311891 PMCID: PMC7719971 DOI: 10.1016/j.jceh.2020.05.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Accepted: 05/01/2020] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Liver grafts from hepatitis B core antibody (anti-HBc) positive donors increase the risk of hepatitis B virus (HBV) reactivation in recipients due to posttransplant immunosuppressive therapy. AIM AND OBJECTIVE to study the HBV reactivation in liver transplant recipients with anti-HBc-positive donors. METHODS This was a retrospective study. Liver transplant recipients who received grafts from anti-HBc-positive donors between January 2013 and December 2017 were included in analysis. Hospital records of all subjects for a 2-year posttransplantation period were studied to observe reactivation of hepatitis B. As per our institute protocol, prophylaxis for HBV was given to subjects with either positive hepatitis B surface antigens or hepatitis B surface antibody (anti-HBs) titre <100 mIU/ml, after transplantation with anti-HBc-positive donor grafts. Recipients with anti-HBs titre >100 mIU/mL were exempted from prophylaxis and kept on regular monitoring for HBV markers. RESULTS Of 85 liver transplant recipients, 20 subjects who received anti-HBc-positive grafts were included in analysis. The mean age of the study population was 46 years (range 2-68 years). The most common aetiology of cirrhosis in our study population was cryptogenic followed by ethanol. Among the study population, 16 (80%) transplant recipients had anti-HBs titre less than 100 mu/ml and 4 (20%) subjects had anti-HBs > 100 miu/ml. HBV reactivation occurred in 6 (30%) subjects. Reactivation was seen even in those who received HBV prophylaxis, while none of the subjects with anti-HBs titre >100 miu/ml developed HBV reactivation despite absence of prophylaxis. CONCLUSION HBV reactivation can occur even in the presence of target anti-HBs titre (i.e. >10 miu/ml) and HBV prophylaxis during postliver transplantation. However, HBV reactivation is not seen in recipients with anti-HBs titre of >100 miu/ml.
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Affiliation(s)
| | - Sunil R. Kothakota
- Address for correspondence. Sunil Raviraj K, Senior Resident, Department of Gastroenterology, KIMS hospital, Postal code/ P.O. Box: Anayara PO., Trivandrum, Kerala, 695029, India.
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Moayedi J, Moini M, Geramizadeh B, Malekhosseini SA, Yaghobi R. Seropositive Form of Occult Hepatitis B Virus Infection in Iranian Patients with Cryptogenic Liver Cirrhosis. HEPATITIS MONTHLY 2019; In Press. [DOI: 10.5812/hepatmon.84806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Wu CC, Chen YS, Cao L, Chen XW, Lu MJ. Hepatitis B virus infection: Defective surface antigen expression and pathogenesis. World J Gastroenterol 2018; 24:3488-3499. [PMID: 30131655 PMCID: PMC6102499 DOI: 10.3748/wjg.v24.i31.3488] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Revised: 06/01/2018] [Accepted: 06/25/2018] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) infection is a global public health concern. HBV causes chronic infection in patients and can lead to liver cirrhosis, hepatocellular carcinoma, and other severe liver diseases. Thus, understanding HBV-related pathogenesis is of particular importance for prevention and clinical intervention. HBV surface antigens are indispensable for HBV virion formation and are useful viral markers for diagnosis and clinical assessment. During chronic HBV infection, HBV genomes may acquire and accumulate mutations and deletions, leading to the expression of defective HBV surface antigens. These defective HBV surface antigens have been found to play important roles in the progression of HBV-associated liver diseases. In this review, we focus our discussion on the nature of defective HBV surface antigen mutations and their contribution to the pathogenesis of fulminant hepatitis B. The relationship between defective surface antigens and occult HBV infection are also discussed.
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MESH Headings
- DNA, Viral/genetics
- DNA, Viral/isolation & purification
- Disease Progression
- Genome, Viral/genetics
- Hepatitis B Surface Antigens/genetics
- Hepatitis B Surface Antigens/immunology
- Hepatitis B Surface Antigens/metabolism
- Hepatitis B virus/genetics
- Hepatitis B virus/immunology
- Hepatitis B, Chronic/immunology
- Hepatitis B, Chronic/pathology
- Hepatitis B, Chronic/prevention & control
- Hepatitis B, Chronic/virology
- Humans
- Liver/immunology
- Liver/pathology
- Liver/virology
- Liver Failure, Acute/immunology
- Liver Failure, Acute/pathology
- Liver Failure, Acute/prevention & control
- Liver Failure, Acute/virology
- Mutation
- Virus Replication/genetics
- Virus Replication/immunology
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Affiliation(s)
- Chun-Chen Wu
- State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, Hubei Province, China
| | - Ying-Shan Chen
- State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, Hubei Province, China
| | - Liang Cao
- State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, Hubei Province, China
- Department of Microbiology and Immunology, Feinberg School of Medicine Northwestern University, Chicago, IL 60611, United States
| | - Xin-Wen Chen
- State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, Hubei Province, China
| | - Meng-Ji Lu
- Institute of Virology, University Hospital of Essen, Essen 45122, Germany
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Chauhan R, Lingala S, Gadiparthi C, Lahiri N, Mohanty SR, Wu J, Michalak TI, Satapathy SK. Reactivation of hepatitis B after liver transplantation: Current knowledge, molecular mechanisms and implications in management. World J Hepatol 2018; 10:352-370. [PMID: 29599899 PMCID: PMC5871856 DOI: 10.4254/wjh.v10.i3.352] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2017] [Revised: 01/19/2018] [Accepted: 02/09/2018] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis B (CHB) is a major global health problem affecting an estimated 350 million people with more than 786000 individuals dying annually due to complications, such as cirrhosis, liver failure and hepatocellular carcinoma (HCC). Liver transplantation (LT) is considered gold standard for treatment of hepatitis B virus (HBV)-related liver failure and HCC. However, post-transplant viral reactivation can be detrimental to allograft function, leading to poor survival. Prophylaxis with high-dose hepatitis B immunoglobulin (HBIG) and anti-viral drugs have achieved remarkable progress in LT by suppressing viral replication and improving long-term survival. The combination of lamivudine (LAM) plus HBIG has been for many years the most widely used. However, life-long HBIG use is both cumbersome and costly, whereas long-term use of LAM results in resistant virus. Recently, in an effort to develop HBIG-free protocols, high potency nucleos(t)ide analogues, such as Entecavir or Tenofovir, have been tried either as monotherapy or in combination with low-dose HBIG with excellent results. Current focus is on novel antiviral targets, especially for covalently closed circular DNA (cccDNA), in an effort to eradicate HBV infection instead of viral suppression. However, there are several other molecular mechanisms through which HBV may reactivate and need equal attention. The purpose of this review is to address post-LT HBV reactivation, its risk factors, underlying molecular mechanisms, and recent advancements and future of anti-viral therapy.
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Affiliation(s)
- Ranjit Chauhan
- Molecular Virology and Hepatology Research Group, Division of BioMedical Sciences, Health Sciences Centre, Memorial University, St. John’s, NL A1B 3V6, Canada
| | - Shilpa Lingala
- Division of Transplant Surgery, Methodist University Hospital Transplant Institute, University of Tennessee Health Sciences Center, Memphis, TN 38104, United States
| | - Chiranjeevi Gadiparthi
- Division of Transplant Surgery, Methodist University Hospital Transplant Institute, University of Tennessee Health Sciences Center, Memphis, TN 38104, United States
| | - Nivedita Lahiri
- Division of Rheumatology, Immunology and Allergy, Brigham Women’s Hospital, Harvard Medical School, Boston, MA 02115, United States
| | - Smruti R Mohanty
- Division of Gastroenterology and Hepatobiliary Disease, New York-Presbyterian Brooklyn Methodist Hospital, Brooklyn, NY 11215, United States
| | - Jian Wu
- Department of Medical Microbiology, Key Laboratory of Molecular Virology, Fudan University School of Basic Medical Sciences, Shanghai 200032, China
| | - Tomasz I Michalak
- Molecular Virology and Hepatology Research Group, Division of BioMedical Sciences, Health Sciences Centre, Memorial University, St. John’s, NL A1B 3V6, Canada
| | - Sanjaya K Satapathy
- Division of Transplant Surgery, Methodist University Hospital Transplant Institute, University of Tennessee Health Sciences Center, Memphis, TN 38104, United States
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Ryan K, Anderson M, Gyurova I, Ambroggio L, Moyo S, Sebunya T, Makhema J, Marlink R, Essex M, Musonda R, Gaseitsiwe S, Blackard JT. High Rates of Occult Hepatitis B Virus Infection in HIV-Positive Individuals Initiating Antiretroviral Therapy in Botswana. Open Forum Infect Dis 2017; 4:ofx195. [PMID: 29062862 PMCID: PMC5641381 DOI: 10.1093/ofid/ofx195] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Accepted: 09/12/2017] [Indexed: 12/16/2022] Open
Abstract
Background Hepatitis B surface antigen (HBsAg)–negative but hepatitis B virus (HBV) DNA-positive infection—known as occult hepatitis B infection (OBI)—occurs in 1% to >15% of HIV-positive individuals in the United States and South Africa, respectively. However, there are no data on OBI from Botswana, a country known to be hyperendemic for chronic HBV infection and to have a significant HIV burden. Methods Two hundred seventy-two adults enrolled in an HIV treatment study of tenofovir/emtricitabine as the nucleoside backbone who were previously determined to be HBsAg negative were tested for HBV DNA at baseline and 1 year after initiation of highly active antiretroviral therapy (HAART). Results HBV DNA was detected in 72 of 272 (26.5%). Six individuals (8.3%) had HBV DNA levels greater than 200 IU/mL, and the highest viral load was 3280 IU/mL. Of 65 participants with OBI evaluated at 12 months after initiating HAART, only 1 (1.5%) had detectable HBV DNA. Conclusions Occult HBV infection is quite common in HIV-infected patients in Botswana, although its impact on the course of HIV disease progression is unknown. The suppression of occult HBV DNA levels by tenofovir/emtricitabine suggests an effective therapeutic option, although the long-term suppressive abilities remain unstudied.
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Affiliation(s)
- Kathleen Ryan
- University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Motswedi Anderson
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.,Department of Biological Sciences, University of Botswana, Gaborone, Botswana
| | - Ivayla Gyurova
- University of Cincinnati College of Medicine, Cincinnati, Ohio
| | | | - Sikhulile Moyo
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.,Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Teresa Sebunya
- Department of Biological Sciences, University of Botswana, Gaborone, Botswana
| | - Joseph Makhema
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.,Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Richard Marlink
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.,Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Max Essex
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.,Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Rosemary Musonda
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.,Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Simani Gaseitsiwe
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.,Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
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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: 102] [Impact Index Per Article: 11.3] [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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Sosa-Jurado F, Hilda Rosas-Murrieta N, Guzman-Flores B, Perez Zempoaltecalt C, Patricia Sanchez Torres A, Ramirez Rosete L, Bernal-Soto M, Marquez-Dominguez L, Melendez-Mena D, Angel Mendoza Torres M, Teresa Lopez Delgado M, Reyes-Leyva J, Vallejo-Ruiz V, Santos-Lopez G. Prevalence of Serologic Hepatitis B Markers in Blood Donors From Puebla, Mexico: The Association of Relatively High Levels of Anti-Core Antibodies With the Detection of Surface Antigen and Genomic DNA. HEPATITIS MONTHLY 2016; 16:e36942. [PMID: 27630726 PMCID: PMC5011399 DOI: 10.5812/hepatmon.36942] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/07/2016] [Revised: 04/02/2016] [Accepted: 04/20/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND The hepatitis B virus (HBV) causes chronic hepatitis, hepatic cirrhosis, and hepatocellular carcinoma. Surface antigen (HBsAg) detection is a definitive test that can confirm HBV infection, while the presence of antibodies against the core protein (anti-HBc) suggests either a previous or ongoing infection or occult hepatitis B infection (OBI). OBJECTIVES The aim of the present study was to determine the prevalence of anti-HBc and HBsAg in blood donors. Further, the study aimed to estimate the anti-HBc level at which HBV DNA is detected in putative OBI cases, as well as to search for mutations in the "a" determinant associated with the non-detection of HBsAg in serum. PATIENTS AND METHODS We conducted a cross-sectional study from 2003-2009. The study included 120,552 blood donors from the state of Puebla, Mexico. Different commercial systems based on microparticles (enzymatic (MEIA) or chemiluminescent (CMIA)) were used to determine the HBsAg and anti-HBc levels. For the detection of HBV DNA, a nested polymerase chain reaction (nested PCR) was used and the genotypes were determined using Sanger sequencing. RESULTS Of the 120,552 blood donors, 1437 (1.19%, 95% CI: 1.12 - 1.26) were reactive to anti-HBc, while 82 (0.066%, 95% CI: 0.053 - 0.079) were reactive to HBsAg. Some 156 plasma samples collected in 2009 from anti-HBc-positive/HBsAg-negative blood donors were submitted for HBV DNA detection in a search for probable OBI. Viral DNA was detected in 27/156 (17.3%, 95% CI: 11.5 - 23.1). Our results show an association between HBV DNA or HBsAg and anti-HBc S/CO levels ≥ 4.0. All DNA samples were identified as genotype H and some "a" determinant mutations were identified, although none corresponded to mutations previously reported to hinder the detection of HBsAg by commercial immunoassays. CONCLUSIONS We observed that as the anti-HBc levels increase, there is a higher prevalence of the viral protein HBsAg in blood donors. Samples testing positive for HBV-DNA were seen to exhibit a ten-fold higher presence of anti-HBc S/CO ≥ 4 than those with S/CO ≥ 1 and < 4.0, which highlights the relevance of anti-HBc determination in blood donor samples.
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Affiliation(s)
- Francisca Sosa-Jurado
- Laboratory of Virology and Molecular Biology, Eastern Biomedical Research Center, Mexican Social Security Institute, Puebla, Mexico
- Corresponding Authors: Francisca Sosa-Jurado, Laboratory of Virology and Molecular Biology, Eastern Biomedical Research Center, Mexican Social Security Institute, Puebla, Mexico. Tel/Fax: +52-2444440122, E-mail: ; Gerardo Santos-Lopez, Laboratory of Virology and Molecular Biology, Eastern Biomedical Research Center, Mexican Social Security Institute, Puebla, Mexico. Tel/Fax: +52-2444440122, E-mail:
| | - Nora Hilda Rosas-Murrieta
- Laboratory of Biochemistry and Molecular Biology, Chemistry Center, Institute of Science, Autonomous University of Puebla, Puebla, Mexico
| | - Belinda Guzman-Flores
- Blood Bank Hospital, National Medical Center Manuel Avila Camacho, Mexican Social Security Institute, Puebla, Mexico
| | - Cintia Perez Zempoaltecalt
- Laboratory of Virology and Molecular Biology, Eastern Biomedical Research Center, Mexican Social Security Institute, Puebla, Mexico
| | - Ana Patricia Sanchez Torres
- Blood Bank Hospital, National Medical Center Manuel Avila Camacho, Mexican Social Security Institute, Puebla, Mexico
| | - Leticia Ramirez Rosete
- Blood Bank Hospital, National Medical Center Manuel Avila Camacho, Mexican Social Security Institute, Puebla, Mexico
| | - Maribel Bernal-Soto
- Blood Bank Hospital, National Medical Center Manuel Avila Camacho, Mexican Social Security Institute, Puebla, Mexico
| | - Luis Marquez-Dominguez
- Laboratory of Virology and Molecular Biology, Eastern Biomedical Research Center, Mexican Social Security Institute, Puebla, Mexico
| | - Daniel Melendez-Mena
- Department of Gastroenterology, Specialized Hospital, Medical Unit of High Specialty, National Medical Center Manuel Avila Camacho, Mexican Social Security Institute, Puebla, Mexico
| | - Miguel Angel Mendoza Torres
- Department of Gastroenterology, Specialized Hospital, Medical Unit of High Specialty, National Medical Center Manuel Avila Camacho, Mexican Social Security Institute, Puebla, Mexico
| | | | - Julio Reyes-Leyva
- Laboratory of Virology and Molecular Biology, Eastern Biomedical Research Center, Mexican Social Security Institute, Puebla, Mexico
| | - Veronica Vallejo-Ruiz
- Laboratory of Virology and Molecular Biology, Eastern Biomedical Research Center, Mexican Social Security Institute, Puebla, Mexico
| | - Gerardo Santos-Lopez
- Laboratory of Virology and Molecular Biology, Eastern Biomedical Research Center, Mexican Social Security Institute, Puebla, Mexico
- Corresponding Authors: Francisca Sosa-Jurado, Laboratory of Virology and Molecular Biology, Eastern Biomedical Research Center, Mexican Social Security Institute, Puebla, Mexico. Tel/Fax: +52-2444440122, E-mail: ; Gerardo Santos-Lopez, Laboratory of Virology and Molecular Biology, Eastern Biomedical Research Center, Mexican Social Security Institute, Puebla, Mexico. Tel/Fax: +52-2444440122, E-mail:
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Ferrarese A, Zanetto A, Gambato M, Bortoluzzi I, Nadal E, Germani G, Senzolo M, Burra P, Russo FP. Liver transplantation for viral hepatitis in 2015. World J Gastroenterol 2016; 22:1570-1581. [PMID: 26819523 PMCID: PMC4721989 DOI: 10.3748/wjg.v22.i4.1570] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2015] [Accepted: 11/19/2015] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation (LT) is a life-saving treatment for patients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis viruses are between the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. Before the availability of antiviral prophylaxis, hepatitis B virus (HBV) recurrence was universal in patients who were HBV DNA-positive before transplantation. The natural history of recurrent HBV was accelerated by immunosuppression, and it progressed rapidly to graft failure and death. Introduction of post-transplant prophylaxis with immunoglobulin alone first, and associated to antiviral drugs later, drastically reduced HBV recurrence, resulting in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Overall, patient and graft survival after LT for hepatitis C virus (HCV)-associated cirrhosis is inferior compared with other indications. However, successful pretransplant or post transplant antiviral therapy has been associated with increased graft and overall survival. Until recently, the combination of pegylated interferon and ribavirin was the standard of care for the treatment of patients with chronic hepatitis C. Highly active antiviral compounds have been developed over the past decade, thanks to new in vitro systems to study HCV entry, replication, assembly, and release.
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