|
1
|
Wang J, Qiu K, Zhou S, Gan Y, Jiang K, Wang D, Wang H. Risk factors for hepatocellular carcinoma: an umbrella review of systematic review and meta-analysis. Ann Med 2025; 57:2455539. [PMID: 39834076 PMCID: PMC11753015 DOI: 10.1080/07853890.2025.2455539] [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: 10/21/2024] [Revised: 01/09/2025] [Accepted: 01/10/2025] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND Numerous meta-analyses have identified various risk factors for hepatocellular carcinoma (HCC), prompting a comprehensive study to synthesize evidence quality and strength. METHODS This umbrella review of meta-analyses was conducted throughout PubMed, EMBASE, Web of Science, and Cochrane Database of Systematic Reviews. Evidence strength was evaluated according to the evidence categories criteria. RESULTS We identified 101 risk factors throughout 175 meta-analyses. 31 risk factors were classified as evidence levels of class I, II, or III. HBV and HCV infections increase HCC risk by 12.5-fold and 11.2-fold, respectively. These risks are moderated by antiviral treatments and virological responses but are exacerbated by higher HBsAg levels, anti-HBc positivity, and co-infection. Smoking, obesity, non-alcoholic fatty liver disease, diabetes, low platelet, elevated liver enzymes and liver fluke infection increase HCC risk, while coffee consumption, a healthy diet, and bariatric surgery lower it. Medications like metformin, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), aspirin, statins, and selective serotonin reuptake inhibitors reduce HCC risk, while acid suppressive agents, particularly proton pump inhibitors, elevate it. Blood type O reduces the risk of HCC, while male gender and older age increase the risk. CONCLUSIONS HBV and HCV are major HCC risk factors, with risk mitigation through antiviral treatments. Lifestyle habits such as smoking and alcohol use significantly increase HCC risk, highlighting the importance of cessation. Certain drugs like aspirin, statins, GLP-1 RAs, and metformin may reduce HCC occurrence, but further research is needed to confirm these effects.
Collapse
Affiliation(s)
- Jie Wang
- Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
| | - Kaijie Qiu
- Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
| | - Songsheng Zhou
- Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
| | - Yichao Gan
- Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
| | - Keting Jiang
- Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
| | - Donghuan Wang
- Operations Department, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
| | - Haibiao Wang
- Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
| |
Collapse
|
|
2
|
Detectability of Hepatitis B Virus in Peripheral Blood Mononuclear Cells Among Naive Chronic Hepatitis B Patients With Negative Viremia. INFECTIOUS DISEASES IN CLINICAL PRACTICE 2022. [DOI: 10.1097/ipc.0000000000001153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
|
|
3
|
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.
Collapse
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
| |
Collapse
|
|
4
|
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.
Collapse
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
| |
Collapse
|
|
5
|
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] [MESH Headings] [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.
Collapse
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
| |
Collapse
|
|
6
|
Sagnelli C, Sagnelli E. Towards the worldwide eradication of hepatitis B virus infection: A combination of prophylactic and therapeutic factors. World J Clin Infect Dis 2019; 9:11-22. [DOI: 10.5495/wjcid.v9.i2.11] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Revised: 07/10/2019] [Accepted: 07/17/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) is still a global health problem, mostly because of the intermediate/high rates of HBV chronic carriers living in most Asian, African and eastern European countries. The universal HBV vaccination of new-borns undertaken in most nations over the last 3 decades and effective HBV antiviral treatments (nucleos(t)ide analogue with high genetic barrier to viral resistance) introduced in the last decade have shown their beneficial effects in inducing a clear reduction of HBV endemicity in the countries where they have been extensively applied. Great hopes are now placed on new antiviral and immunotherapeutic drugs that are now at an advanced stage of study. It is in fact already conceivable that the synergistic use of new drugs targeting more than one HBV-lifecycle steps (covalent closed circular DNA destruction/silencing, HBV entry inhibitors, nucleocapsid assembly modulators targeting viral transcripts) and of some new immunotherapeutic agents might eliminate the intrahepatic covalent closed circular DNA and achieve the eradication of HBV infection. In spite of this, a strong effort should be given to extensive educational and screening programs for the at-risk population and to the implementation of HBV vaccination in developing countries.
Collapse
Affiliation(s)
- Caterina Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80131, Italy
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80131, Italy
| |
Collapse
|
|
7
|
|
|
8
|
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 2018; 7:443-453. [PMID: 30652089 PMCID: PMC6295390 DOI: 10.21037/hbsn.2018.10.01] [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: 07/30/2018] [Accepted: 10/09/2018] [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.
Collapse
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
| |
Collapse
|
|
9
|
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.
Collapse
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
| |
Collapse
|
|
10
|
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: 09/19/2017] [Accepted: 10/30/2017] [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.
Collapse
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
| | - 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
| | - 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
| |
Collapse
|
|
11
|
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]
|
|
12
|
Sagnelli C, Ciccozzi M, Coppola N, Minichini C, Lo Presti A, Starace M, Alessio L, Macera M, Cella E, Gualdieri L, Caprio N, Pasquale G, Sagnelli E. Molecular diversity in irregular or refugee immigrant patients with HBV-genotype-E infection living in the metropolitan area of Naples. J Med Virol 2016; 89:1015-1024. [PMID: 27805272 DOI: 10.1002/jmv.24724] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/29/2016] [Indexed: 12/12/2022]
Abstract
In a recent testing in the metropolitan area of Naples, Italy, on 945 irregular immigrants or refugees, 87 HBsAg chronic carriers were identified, 53 of whom were infected by HBV-genotype E. The aim of the present study was to identify the genetic diversity of HBV-genotype E in these 53 immigrants. The 53 immigrant patients with HBV-genotype-E infection were born in Africa, central or eastern Asia, eastern Europe or Latin America. These patients had been seen for a clinical consultation at one of the four first-level units from January 2012 to 2013. The first dataset contained 53 HBV-S gene isolates plus 128 genotype/subgenotype specific reference sequences downloaded from the National Center for Biotechnology Information. The second dataset, comprising the 53 HBV-S gene isolates, previously classified as HBV-genotype E, was used to perform the time-scaled phylogeny reconstruction using a Bayesian approach. Phylogenetic analysis showed that all 53 HBV-S isolates belonged to HBV-genotype E. Bayes factor analysis showed that the relaxed clock exponential growth model fitted the data significantly better than the other models. The time-scaled Bayesian phylogenetic tree of the second dataset showed that the root of the tree dated back to the year 1990 (95% HPD:1984-2000). Four statistically supported clusters were identified. Cluster A dated back to 2012 (95% HPD:1997-2012); cluster B dated back to 2008 (95% HPD:2001-2015); cluster C to 2006 (95% HPD:1999-2013); cluster D to 2004 (95% HPD:1998-2011). This study disclosed the genetic evolution and phylogenesis in a group of HBV-genotype-E-infected immigrants. J. Med. Virol. 89:1015-1024, 2017. © 2016 Wiley Periodicals, Inc.
Collapse
Affiliation(s)
- Caterina Sagnelli
- Department of Clinical and Experimental Medicine and Surgery, Second University of Naples, Naples, Italy.,Medical Center, Centro Sociale ex Canapificio, Caserta, Italy
| | - Massimo Ciccozzi
- Epidemiology Unit, Department of Infectious, Parasite and Immune-Mediated Diseases, Italian Institute of Health, Rome, Italy.,University of Biomedical Campus, Rome, Italy
| | - Nicola Coppola
- Medical Center, Centro Sociale ex Canapificio, Caserta, Italy.,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
| | - Alessandra Lo Presti
- Epidemiology Unit, Department of Infectious, Parasite and Immune-Mediated Diseases, Italian Institute of Health, Rome, Italy
| | - Mario Starace
- Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy
| | - Loredana Alessio
- Medical Center, Centro Sociale ex Canapificio, Caserta, Italy.,Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy
| | - Margherita Macera
- Medical Center, Centro Sociale ex Canapificio, Caserta, Italy.,Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy
| | - Eleonora Cella
- Epidemiology Unit, Department of Infectious, Parasite and Immune-Mediated Diseases, Italian Institute of Health, Rome, Italy.,Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | - Luciano Gualdieri
- Medical Center, Centro per la Tutela della Salute degli Immigrati, Naples, Italy
| | - Nunzio Caprio
- Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy.,Medical center, Centro Suore Missionarie della Carità, Naples, Italy
| | - Giuseppe Pasquale
- Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy
| |
Collapse
|
|
13
|
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.
Collapse
|
|
14
|
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.
Collapse
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
| |
Collapse
|
|
15
|
Mohraz M, Jafari R, Poortahmasebi V, Sadeghi A, Hajabdolbaghi M, Rasoolinejad M, Forooghi M, Norouzi M, Poorebrahim M, Khamseh A, Karkhaneh M, Alavian SM, Ebrahimian A, Jazayeri SM. Molecular analysis of occult hepatitis B infection among Iranian HIV-positive patients. Future Virol 2016. [DOI: 10.2217/fvl-2016-0032] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Aim: The aims of this study were to find out the prevalence of occult hepatitis B infection (OBI) in HIV-1 patients, as well as to analyze the mutational patterns of OBI-positive individuals. Materials & methods: 172 HBsAg-negative, HIV-1-positive patients were selected according to data extracted from questionnaires. HBV serologic and molecular assays were performed. An extensive mutational analysis was applied using direct sequencing on HBsAg. Results: Thirty-one samples (18%) were OBI positive. Among 24 available OBI-positive samples, 17 (71%) contained at least one mutation only within ‘a’ determinant region of HBsAg. A stretch of mutations was found between amino acid positions 121 and 136. The physicochemical properties of individual amino acid substitutions and their potential impacts on 3D structure of ‘a’ determinant mutants were also determined. Conclusion: HBV serologic assays are not reliable markers to exclude occult HBV infection in HIV-positive patients.
Collapse
Affiliation(s)
- Minoo Mohraz
- Iranian Research Center for HIV AIDS, High Risk Reduction Institute, Tehran, Iran
| | - Rezvaneh Jafari
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Vahdat Poortahmasebi
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Ahmadreza Sadeghi
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Mehrnaz Rasoolinejad
- Iranian Research Center for HIV AIDS, High Risk Reduction Institute, Tehran, Iran
| | - Maryam Forooghi
- Iranian Research Center for HIV AIDS, High Risk Reduction Institute, Tehran, Iran
| | - Mehdi Norouzi
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Mansour Poorebrahim
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Azam Khamseh
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Masoud Karkhaneh
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed Moayed Alavian
- Middle East Liver Disease (MELD) Center, No 178, Sepahboud Gharanee St. Tehran 1598976516, Iran
| | - Arefeh Ebrahimian
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | | |
Collapse
|
|
16
|
Sagnelli C, Macera M, Pisaturo M, Zampino R, Coppola M, Sagnelli E. Occult HBV infection in the oncohematological setting. Infection 2016; 44:575-82. [PMID: 27076347 DOI: 10.1007/s15010-016-0891-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2015] [Accepted: 03/07/2016] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Occult hepatitis B infection (OBI), a virological condition characterized by a low release of Hepatitis B Virus (HBV) from liver cells and low HBV-DNA levels in serum and/or liver tissue of HBsAg-negative subjects, may reactivate in oncohematological patients undergoing immunosuppression by aggressive chemotherapy or hematopoietic stem cell transplantation. The entity of OBI reactivation varies from an increase in HBV replication without liver damage to an active HBV replication followed by liver cell necrosis, frequently severe and in some cases life threatening. Because of a possible severe outcome associated with OBI reactivation (hepatic failure or death due to the discontinuation of chemotherapy), prophylaxis with anti-HBV nucleot(s)ide analogues is recommended in relation to the foreseeable degree of immunosuppression. MATERIALS AND METHODS This review article focuses on the clinical impact of OBI in the oncohematological setting and is addressed to all health care workers having in care oncohematological patients or involved in the treatment of HBV infection and OBI prophylaxis. CONCLUSION International guidelines have indicated lamivudine prophylaxis in hematopoietic stem cell transplantation and when high-dose corticosteroids or anti-CD20 or anti-CD52 monoclonal antibodies are used. Entecavir or tenofovir should replace lamivudine for patients with advanced liver diseases for whom reactivation of OBI may be life threatening. When anti-CD20 or anti-CD52 sparing schedules or other non-aggressive chemotherapies are used, monitoring may be indicated, but very early treatment with highly effective antiviral drugs (entecavir or tenofovir) should be administered once a reactivation of OBI has occurred.
Collapse
Affiliation(s)
- C Sagnelli
- Department of Clinical and Experimental Medicine and Surgery "F. Magrassi e A. Lanzara", Second University of Naples, 80131, Naples, Italy
| | - M Macera
- Azienda Ospedaliera Universitaria-Second University of Naples, 80131, Naples, Italy
| | - M Pisaturo
- Division of Infectious Diseases, AORN Sant'Anna e San Sebastiano di Caserta, 81100, Caserta, Italy
| | - R Zampino
- Department of Medical, Surgical, Neurological, Metabolic and Geriatric Sciences, Second University of Naples, 80131, Naples, Italy
| | - M Coppola
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, Second University of Naples, Via: L. Armanni 5, 80131, Naples, Italy
| | - E Sagnelli
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, Second University of Naples, Via: L. Armanni 5, 80131, Naples, Italy.
| |
Collapse
|
|
17
|
Coppola N, Alessio L, Gualdieri L, Pisaturo M, Sagnelli C, Caprio N, Maffei R, Starace M, Angelillo IF, Pasquale G, Sagnelli E. Hepatitis B virus, hepatitis C virus and human immunodeficiency virus infection in undocumented migrants and refugees in southern Italy, January 2012 to June 2013. ACTA ACUST UNITED AC 2016; 20:30009. [PMID: 26530499 DOI: 10.2807/1560-7917.es.2015.20.35.30009] [Citation(s) in RCA: 69] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2014] [Accepted: 02/02/2015] [Indexed: 12/16/2022]
Abstract
Screening of undocumented migrants or refugees for hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections has been offered free of charge and free from bureaucratic procedures since 2012 at four primary-level clinical centres in Naples and Caserta, Italy. Of 926 undocumented migrants and refugees visiting one of the primary-level clinical centres from January 2012 to June 2013, 882 (95%) were screened for hepatitis B surface antigen (HBsAg), total hepatitis B core antibody (anti-HBc) and antibodies against HCV and HIV. Of the 882 individuals enrolled, 78 (9%) were HBsAg positive, 35 (4%) anti-HCV positive and 11 (1%) anti-HIV positive (single infections); seven (1%) had more than one infection (three were HBsAg positive). Of the 801 HBsAg-negative patients, 373 (47%) were anti-HBc positive. The HBsAg-positivity rate was high (14%; 62/444) in individuals from sub-Saharan Africa and intermediate in those from eastern Europe (6%; 12/198), northern Africa (2%; 2/80) and Bangladesh, India, Pakistan and Sri Lanka (the 'India-Pakistan area') (3%; 4/126). Anti-HCV was detected in 9/126 (7%) individuals originating from the India-Pakistan area, in 12/198 (6%) from eastern Europe, in 17/444 (4%) from sub-Saharan and in 2/80 (2%) from northern Africa. The HBV, HCV and HIV infections in the undocumented migrants and refugees screened serve as a reminder to the Italian healthcare authorities to carry out extensive screening and educational programmes for these populations.
Collapse
Affiliation(s)
- Nicola Coppola
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Italy
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
18
|
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.
Collapse
|
|
19
|
Ferrari TCA, Xavier MAP, Vidigal PVT, Amaral NS, Diniz PA, Resende AP, Miranda DM, Faria AC, Lima AS, Faria LC. Occult hepatitis B virus infection in liver transplant patients in a Brazilian referral center. ACTA ACUST UNITED AC 2014. [PMID: 25296362 PMCID: PMC4230290 DOI: 10.1590/1414-431x20143782] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Estimates of occult hepatitis B virus (HBV) infection prevalence varies among different studies depending on the prevalence of HBV infection in the study population and on the sensitivity of the assay used to detect HBV DNA. We investigated the prevalence of occult HBV infection in cirrhotic patients undergoing liver transplantation in a Brazilian referral center. Frozen liver samples from 68 adults were analyzed using a nested polymerase chain reaction assay for HBV DNA. The specificity of the amplified HBV sequences was confirmed by direct sequencing of the amplicons. The patient population comprised 49 (72.1%) males and 19 (27.9%) females with a median age of 53 years (range=18-67 years). Occult HBV infection was diagnosed in three (4.4%) patients. The etiologies of the underlying chronic liver disease in these cases were alcohol abuse, HBV infection, and cryptogenic cirrhosis. Two of the patients with cryptic HBV infection also presented hepatocellular carcinoma. Markers of previous HBV infection were available in two patients with occult HBV infection and were negative in both. In conclusion, using a sensitive nested polymerase chain reaction assay to detect HBV DNA in frozen liver tissue, we found a low prevalence of occult HBV infection in cirrhotic patients undergoing liver transplant, probably due to the low prevalence of HBV infection in our population.
Collapse
Affiliation(s)
- T C A Ferrari
- Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil
| | - M A P Xavier
- Departamento de Anatomia Patológica e Medicina Legal, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil
| | - P V T Vidigal
- Departamento de Anatomia Patológica e Medicina Legal, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil
| | - N S Amaral
- Laboratório de Genética Molecular, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil
| | - P A Diniz
- Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil
| | - A P Resende
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil
| | - D M Miranda
- Departamento de Pediatria, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil
| | - A C Faria
- Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil
| | - A S Lima
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil
| | - L C Faria
- Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil
| |
Collapse
|
|
20
|
Chenari M, Norouzi M, Ghalichi L, Rezaee A, Yari A, Alavian SM, Jazayeri SM. Characterization of overt and occult hepatitis B virus infection among HTLV-1 positive healthy carriers in the Northeast of Iran; AN HTLV-I endemic area. J Med Virol 2014; 86:1861-7. [PMID: 25132488 DOI: 10.1002/jmv.24046] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/15/2014] [Indexed: 12/23/2022]
Abstract
To date, no studies have provided data on hepatitis B virus (HBV) prevalence among asymptomatic, healthy human T-lymphotropic virus (HTLV-I) positive carriers. This sero- and molecular epidemiology study was performed on patients in the Northeast of Iran, which is an endemic area for HTLV-I infection. A total of 109 sera were collected from HTLV-I positive healthy carriers who were admitted to Ghaem Hospital, Mashhad City. All were tested for HBV serology and subsequently, real time PCR was carried out on the samples, regardless of the results of the serology. Standard PCR and direct sequencing were applied on positive samples. All cases were negative for HBsAg, Anti-HBc, and anti-HBs were positive in 34 (31.1%), and 35 (32%) individuals, respectively. There were 19 (17.4%) cases that were positive only for anti-HBs, and they had already received HBV vaccine. 16 (15%) were positive for both anti-HBs and anti-HBc, indicating a past-resolved HBV infection. 18 (16.5%) were isolated as anti-HBc, and 56 (51.3%) were negative for all HBV serological markers. Only one subject (0.9%) had detectable HBV DNA (2153 copy/ml), and assigned as being an occult HBV infection. The low prevalence of HBsAg, despite the high percentage of anti-HBc positive cases, might be related to the suppression effect of HTLV-I on surface protein expression. The low prevalence of HBV infection among HTLV-I positive healthy carriers from an endemic region, indicates that the epidemiology of HTLV-I and HBV coinfection is related to the endemicity of HBV in that region, rather than HTLV-I endemicity.
Collapse
Affiliation(s)
- Maryam Chenari
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | | | | | | | | | | | | |
Collapse
|
|
21
|
Sagnelli E, Pisaturo M, Martini S, Sagnelli C, Filippini P, Coppola N. Advances in the treatment of hepatitis B virus/hepatitis C virus coinfection. Expert Opin Pharmacother 2014; 15:1337-49. [PMID: 24773464 DOI: 10.1517/14656566.2014.913571] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Patients with chronic hepatitis B virus (HBV)/hepatitis C virus (HCV) coinfection are at a high risk of developing liver cirrhosis and hepatocellular carcinoma, and consequently, warrant effective treatment. AREAS COVERED Effective treatment should eradicate HCV infection and inhibit HBV replication but without serious adverse reactions. Careful evaluation of disease progression, predominance of one virus over another, comorbidities and concomitant hepatitis delta virus and/or HIV infection are essential for better therapy choices. In the case of HCV predominance, Peg-interferon plus ribavirin with or without a first-generation directly acting antiviral (DAA) should be the first choice, but future treatments will be DAA-based and interferon-free. In the case of HBV predominance, tenofovir or entecavir should be part of treatment. Patients should be closely monitored for early identification and treatment of HCV or HBV reactivation. EXPERT OPINION High potency and high genetic barrier nucleos(t)ide analogues to inhibit HBV replication have been used for years, with no urgency for new drugs. Several DAAs for interferon-free therapy for HCV eradication will be available in the near future. We hope that the high cost of these drugs will not be a limitation to their use in developing countries. Further investigation of HBV/HCV interaction is needed before and during the administration of new therapies.
Collapse
Affiliation(s)
- Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Division of Infectious Diseases, Second University of Naples , Naples , Italy +39 81 5560885 ; +39 81 5666207 ; ,
| | | | | | | | | | | |
Collapse
|
|
22
|
Sagnelli C, Ciccozzi M, Pisaturo M, Zehender G, Lo Presti A, Alessio L, Starace M, Lovero D, Sagnelli E, Coppola N. Molecular epidemiology of hepatitis B virus genotypes circulating in acute hepatitis B patients in the Campania region. J Med Virol 2014; 86:1683-93. [PMID: 24980631 DOI: 10.1002/jmv.24005] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/03/2014] [Indexed: 12/11/2022]
Abstract
Fifty-three HBV-DNA-positive patients with symptomatic acute hepatitis B were enrolled from 1999 to 2010 to evaluate molecular and phylogenetic changes in HBV in southern Italy. HBV polymerase region was evaluated by direct sequencing in plasma samples obtained at first observation. Different data sets were aligned and a phylogenetic tree was inferred using PhyML program. Statistical robustness was confirmed with a bootstrap analysis. A Bayesian Markov chain Monte Carlo method and a Bayesian skyline plot were used to estimate the evolution of our samples. The dN/dS rate (ω) was estimated by the maximum likelihood approach to investigate the presence of codons under positive selection. The MacClade program was used to test viral gene out/in flow only among HBV-D3 subgenotype patients with different risk factors. Of the 53 patients, 83% were born in Italy and 17% were foreigners. HBV genotype D was prevalent (64.1%), followed by genotype A (26.4%), E (3.8%), and F (5.7%). The prevalent subgenotype was D3 (70.6%). The Bayesian tree of the 24 D3 subgenotypes showed two main clades both dated 1994; 40% of viral gene flow observed was from intravenous drugs users and heterosexual patients. Phylogenetic analysis of HBV isolates showed that HBV-D3 remains the prevalent genotype, but also subgenotype A2 has become frequent in southern Italy. This may be of clinical relevance in years to come, since patients with HBV-genotype-A chronic infection less frequently than those with genotype D develop HBeAg-negative chronic hepatitis and respond more frequently to alfa-interferon treatment.
Collapse
Affiliation(s)
- Caterina Sagnelli
- Department of Clinical and Experimental Medicine and Surgery "F. Magrassi e A. Lanzara", Second University of Naples, Naples, Italy
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
23
|
Kitab B, Ezzikouri S, Alaoui R, Nadir S, Badre W, Trepo C, Chemin I, Benjelloun S. Occult HBV infection in Morocco: from chronic hepatitis to hepatocellular carcinoma. Liver Int 2014; 34:e144-e150. [PMID: 24502524 DOI: 10.1111/liv.12482] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2013] [Accepted: 01/30/2014] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS Morocco is one of low to intermediate endemic areas for hepatitis B virus (HBV) infection, but no reports have been published on Occult HBV infection (OBI). To determine the prevalence of OBI and its clinical impact among patients with cryptogenic and HCV-related chronic liver disease in Morocco. METHODS A total of 152 HBsAg-negative patients (60 patients with cryptogenic hepatitis and 92 HCV carriers) were enrolled in this study. Sera collected from all patients were tested for anti-HBc and anti-HBs antibodies. OBI was assessed in serum and liver tissue samples using highly sensitive PCR assays targeting Surface, X and core regions of the HBV genome and confirmed by Southern blot hybridization. RESULTS A high rate of anti-HBc positivity was found among patients with HCV infection (57/92, 61.95%) compared to those with cryptogenic hepatitis (24/60, 40%) (P = 0.034). A high prevalence of OBI was found among patients with HCV infection (42/92, 45.65%) compared to those with cryptogenic hepatitis (17/60, 28.3%) (P = 0.013). In both groups, the prevalence of OBI increased in parallel with advancing stage of liver disease (χ2 = 6.73; P = 0.0095). The highest proportion of OBI was reached among HCV-related HCC cases (62.5%). Multivariate Cox regression analysis revealed that older age (≥56 years), positivity for anti-HBc and presence of OBI were independent risk factors for the development of HCC in HCV-infected patients. CONCLUSION This study helps to understand the current status of OBI and its impact on the severity of liver disease in Moroccan patients.
Collapse
Affiliation(s)
- Bouchra Kitab
- Viral Hepatitis Laboratory, Pasteur Institute of Morocco, Casablanca, Morocco
| | | | | | | | | | | | | | | |
Collapse
|
|
24
|
Sagnelli E, Pisaturo M, Martini S, Filippini P, Sagnelli C, Coppola N. Clinical impact of occult hepatitis B virus infection in immunosuppressed patients. World J Hepatol 2014. [PMID: 25018849 DOI: 10.4254/wjh.v6i6.384] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Occult hepatitis B infection (OBI), is characterized by low level hepatitis B virus (HBV) DNA in circulating blood and/or liver tissue. In clinical practice the presence of antibody to hepatitis B core antigen in hepatitis B surface antigen (HBsAg)-/anti-HBs-negative subjects is considered indicative of OBI. OBI is mostly observed in the window period of acute HBV infection in blood donors and in recipients of blood and blood products, in hepatitis C virus chronic carriers, in patients under pharmacological immunosuppression, and in those with immunodepression due to HIV infection or cancer. Reactivation of OBI mostly occurs in anti-HIV-positive subjects, in patients treated with immunosuppressive therapy in onco-hematological settings, in patients who undergo hematopoietic stem cell transplantation, in those treated with anti-CD20 or anti-CD52 monoclonal antibody, or anti-tumor necrosis factors antibody for rheumatological diseases, or chemotherapy for solid tumors. Under these conditions the mortality rate for hepatic failure or progression of the underlying disease due to discontinuation of specific treatment can reach 20%. For patients with OBI, prophylaxis with nucleot(s)ide analogues should be based on the HBV serological markers, the underlying diseases and the type of immunosuppressive treatment. Lamivudine prophylaxis is indicated in hemopoietic stem cell transplantation and in onco-hematological diseases when high dose corticosteroids and rituximab are used; monitoring may be indicated when rituximab-sparing schedules are used, but early treatment should be applied as soon as HBsAg becomes detectable. This review article presents an up-to-date evaluation of the current knowledge on OBI.
Collapse
Affiliation(s)
- Evangelista Sagnelli
- Evangelista Sagnelli, Mariantonietta Pisaturo, Salvatore Martini, Pietro Filippini, Nicola Coppola, Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, 80131 Naples, Italy
| | - Mariantonietta Pisaturo
- Evangelista Sagnelli, Mariantonietta Pisaturo, Salvatore Martini, Pietro Filippini, Nicola Coppola, Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, 80131 Naples, Italy
| | - Salvatore Martini
- Evangelista Sagnelli, Mariantonietta Pisaturo, Salvatore Martini, Pietro Filippini, Nicola Coppola, Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, 80131 Naples, Italy
| | - Pietro Filippini
- Evangelista Sagnelli, Mariantonietta Pisaturo, Salvatore Martini, Pietro Filippini, Nicola Coppola, Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, 80131 Naples, Italy
| | - Caterina Sagnelli
- Evangelista Sagnelli, Mariantonietta Pisaturo, Salvatore Martini, Pietro Filippini, Nicola Coppola, Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, 80131 Naples, Italy
| | - Nicola Coppola
- Evangelista Sagnelli, Mariantonietta Pisaturo, Salvatore Martini, Pietro Filippini, Nicola Coppola, Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, 80131 Naples, Italy
| |
Collapse
|
|
25
|
Jang JY, Park EJ. [Occult hepatitis B virus infection in chronic hepatitis C]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2014; 62:154-9. [PMID: 24077625 DOI: 10.4166/kjg.2013.62.3.154] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Occult HBV infection is defined as the presence of HBV DNA in the liver (with or without detectable or undetectable HBV DNA in the serum) of individuals testing negative for HBsAg. Studies on occult HBV infection in hepatitis C patients have reported highly variable prevalence, because the prevalence of occult HBV infection varies depending on the hepatitis B risk factors and methodological approaches. The most reliable diagnostic approach for detecting occult HBV detection is through examination of liver DNA extracts. HCV has been suspected to strongly suppress HBV replication up to the point where it may be directly responsible for occult HBV infection development. However, more data are needed to arrive at a definitive conclusion regarding the role of HCV in inducing occult HBV infection. Occult HBV infection in chronic hepatitis C patients is a complex biological entity with possible relevant clinical implications. Influence of occult HBV infection on the clinical outcomes of chronic hepatitis C may be considered negative. However, recent studies have shown that occult HBV infection could be associated with the development of hepatocellular carcinoma and contribute to the worsening of the course of chronic liver disease over time in chronic hepatitis C patients. Nevertheless, the possible role of occult HBV infection in chronic hepatitis C is still unresolved and no firm conclusion has been made up until now. It still remains unclear how occult HBV infection affects the treatment of chronic hepatitis C. Therefore, in order to resolve current controversies and understand the pathogenic role and clinical impacts of occult HBV infection in chronic hepatitis C patients, well-designed clinical studies are needed.
Collapse
Affiliation(s)
- Jae Young Jang
- Institution for Digestive Research, Digestive Disease Center, Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea
| | | |
Collapse
|
|
26
|
Huang X, Hollinger FB. Occult hepatitis B virus infection and hepatocellular carcinoma: a systematic review. J Viral Hepat 2014; 21:153-62. [PMID: 24438677 DOI: 10.1111/jvh.12222] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2013] [Accepted: 12/08/2013] [Indexed: 12/13/2022]
Abstract
Occult hepatitis B (OHB) infection has been reported to play an important role in the development of hepatocellular carcinoma (HCC). In this systematic review, a significantly higher prevalence of OHB was observed in patients with HCC in the presence or absence of HCV infection when compared with control populations without HCC. Correspondingly, among adequately designed prospective studies, the cumulative probability of developing HCC was significantly greater among patients with OHB than among HBV DNA-negative patients in the presence or absence of HCV infection. Study design, inclusion criteria, treatment options, methodology and potential confounding variables were evaluated, and immunopathogenic mechanisms that could be involved in OHB as a risk factor in HCC were reviewed. From this analysis, we conclude that although OHB is an independent risk factor in HCC development in anti-HCV-negative patients, a synergistic or additive role in the occurrence of HCC in HCV-coinfected patients is more problematic due to the HCC risk attributable to HCV alone, especially in patients with advanced fibrosis and cirrhosis.
Collapse
Affiliation(s)
- X Huang
- Department of Blood Transfusion, The General Hospital of Jinan Military Command, Jinan, China
| | | |
Collapse
|
|
27
|
|
|
28
|
Macera M, Capoluongo N, Gambardella M, Starace M, Minichini C, Pisaturo M, Pasquale G, Coppola N. The reactivation of occult HBV infection emerging with the case of acute hepatitis B in the wife of a subject treated with rituximab-based chemotherapy. Antivir Ther 2014; 20:349-52. [DOI: 10.3851/imp2826] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/15/2014] [Indexed: 10/24/2022]
|
|
29
|
Sagnelli E, Pisaturo M, Stanzione M, Messina V, Alessio L, Sagnelli C, Starace M, Pasquale G, Coppola N. Clinical presentation, outcome, and response to therapy among patients with acute exacerbation of chronic hepatitis C. Clin Gastroenterol Hepatol 2013; 11:1174-1180.e11. [PMID: 23591280 DOI: 10.1016/j.cgh.2013.03.025] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2012] [Revised: 03/12/2013] [Accepted: 03/28/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The slow asymptomatic progression of chronic hepatitis C (CHC) can be interrupted by an acute exacerbation, characterized by increased serum levels of alanine aminotransferase (ALT) and bilirubin and other symptoms of acute hepatitis. We aimed to provide more information about the clinical presentation of acute exacerbation of CHC. METHODS We identified 82 consecutive patients, from 2 locations in Italy, who had an acute exacerbation of CHC from January 2005 through June 2010; we followed them up for a median period of 36 months. These cases were hepatitis C virus (HCV) RNA positive, hepatitis B surface antigen-negative, and had not received anti-HCV therapy. They were matched with 82 subjects with hepatitis C without reactivation for age, sex, and HCV genotype (controls). Sixty-nine cases and 73 controls were followed up for at least 2 years. Liver biopsy specimens had been taken from 23 cases and 31 controls-once before enrollment in the study and once during the follow-up period. RESULTS HCV genotype 2 was detected in 46.4% of cases, and HCV genotype 1 was detected in 43.9%. Among cases, the mean ALT level was 1063 ± 1038 IU/dL, and the mean total bilirubin level was 15.87 ± 7.15 mg/dL. A higher percentage of cases carried the interleukin-28B CC genotype than controls (40.2% vs 24.4%; P < .05). Among cases, 43.5% had a steady increase in ALT level (>2-fold baseline value); for 56.5% of these patients, ALT levels returned to baseline values before the acute exacerbation of chronic hepatitis. Based on comparisons of biopsy specimens, 18 cases (78.3%) and 11 controls (35.5%) had increasing fibrosis, with Ishak scores increasing by more than 2 (P < .005); 14 cases (60.9%) and 3 controls (9.6%) had increases in necroinflammation of more than 2 points (P < .005). Thirty-two cases (46.4%) and 38 controls (52%) received treatment with pegylated interferon and ribavirin; a sustained virologic response was achieved in 26 cases (81.2%) and 23 controls (60.5%). CONCLUSIONS Although an acute exacerbation of chronic hepatitis is a serious medical condition, most patients achieve a sustained virologic response after treatment with pegylated interferon and ribavirin.
Collapse
Affiliation(s)
- Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Naples, Italy.
| | | | | | | | | | | | | | | | | |
Collapse
|
|
30
|
Coppola N, Loquercio G, Tonziello G, Azzaro R, Pisaturo M, Di Costanzo G, Starace M, Pasquale G, Cacciapuoti C, Petruzziello A. HBV transmission from an occult carrier with five mutations in the major hydrophilic region of HBsAg to an immunosuppressed plasma recipient. J Clin Virol 2013; 58:315-7. [PMID: 23856167 DOI: 10.1016/j.jcv.2013.06.020] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2013] [Revised: 06/11/2013] [Accepted: 06/12/2013] [Indexed: 02/09/2023]
Abstract
We describe the case of transmission of an HBsAg-negative hepatitis B infection to an immunosuppressed patient by plasma donation from an HBsAg-negative subject, but with very low serum HBV DNA (about 50 IU/ml) and five mutations in the major hydrophilic region of HBsAg.
Collapse
Affiliation(s)
- Nicola Coppola
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Naples, Italy.
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
31
|
Nishikawa H, Osaki Y. Clinical significance of occult hepatitis B infection in progression of liver disease and carcinogenesis. J Cancer 2013; 4:473-80. [PMID: 23901347 PMCID: PMC3726709 DOI: 10.7150/jca.6609] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2013] [Accepted: 07/05/2013] [Indexed: 01/04/2023] Open
Abstract
Occult hepatitis B infection (OBI) is defined as long-lasting persistence of hepatitis B virus (HBV) DNA in the liver of patients with hepatitis B surface antigen (HBsAg)-negative status, with or without serological markers of previous exposure (antibodies to HBsAg and/or to hepatitis B core antigen). Over the past two decades, significant progress has been made in understanding OBI and its clinical implications. OBI as a cause of chronic liver disease in patients with HBsAg-negative status is becoming an important disease entity. In conditions of immunocompetence, OBI is inoffensive in itself and detection of HBV DNA in the liver does not always indicate active hepatitis. However, when other factors that cause liver damage, such as hepatitis C virus infection, obesity and alcohol abuse are present, the minimal lesions produced by the immunological response to OBI might worsen the clinical course of the underlying liver disease. Several lines of evidence suggest that OBI is associated with progression of liver fibrosis and the development of hepatocellular carcinoma in patients with chronic liver disease. The major interest in OBI is primarily associated with the growing, widely discussed evidence of its clinical impact. The aim of this review is to highlight recent data for OBI, with a major focus on disease progression or carcinogenesis in patients with chronic liver disease.
Collapse
Affiliation(s)
- Hiroki Nishikawa
- Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Osaka, Japan
| | | |
Collapse
|
|
32
|
Coppola N, Potenza N, Pisaturo M, Mosca N, Tonziello G, Signoriello G, Messina V, Sagnelli C, Russo A, Sagnelli E. Liver microRNA hsa-miR-125a-5p in HBV chronic infection: correlation with HBV replication and disease progression. PLoS One 2013; 8:e65336. [PMID: 23843939 PMCID: PMC3701058 DOI: 10.1371/journal.pone.0065336] [Citation(s) in RCA: 67] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2013] [Accepted: 04/24/2013] [Indexed: 02/06/2023] Open
Abstract
To study in HBsAg chronic carriers the expression of liver hsa-miR-125a-5p and its correlation with liver HBV-DNA values and clinical presentation, 27 consecutive Caucasian, HBsAg/anti-HBe/HBV-DNA-positive patients who were naive to nucleos(t)ide analogues and interferon therapy and had no marker of HCV, HDV or HIV infection and no history of alcohol intake were enrolled. For each patient, liver HBV DNA and liver hsa-miR-125a-5p were quantified by real-time PCR in relation to β-globin DNA or RNU6B, respectively. Liver fibrosis and necroinflammation were graded by applying Ishak's scoring system. Liver hsa-miR-125a-5p was detected in all patients enrolled and a correlation between its concentration and liver HBV DNA was demonstrated (p<0.0001). Higher liver hsa-miR-125a-5p concentrations were observed in patients with HBV-DNA plasma level >103 IU/ml (p<0.02), in those with HAI >6 (p = 0.02) and those with fibrosis score >2 (p<0.02) than in patients with lower scores. Higher HBV-DNA liver concentrations were found in patients with abnormal AST (p = 0.005) and ALT serum levels (p = 0.05), in those with serum HBV DNA higher than 10E3 IU/mL (p = 0.001) and those with fibrosis score >2 (p = 0.02) than in patients with a lower load. By multivariate logistic regression analysis, liver hsa-miR-125a-5p was identified as an independent predictor of disease progression: O.R. = 4.21, C.I. 95% = 1.08–16.43, p<0.05, for HAI >6; O.R. = 3.12, C.I. 95% = 1.17–8.27, p<0.05, for fibrosis score >2. In conclusion, in HBsAg/anti-HBe-positive patients, the liver hsa-miR-125a-5p level correlated with liver and plasma HBV-DNA values and was associated to a more severe disease progression.
Collapse
Affiliation(s)
- Nicola Coppola
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Naples, Italy
| | - Nicoletta Potenza
- Department of Life Sciences, Second University of Naples, Caserta, Italy
| | - Mariantonietta Pisaturo
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Naples, Italy
| | - Nicola Mosca
- Department of Life Sciences, Second University of Naples, Caserta, Italy
| | - Gilda Tonziello
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Naples, Italy
| | - Giuseppe Signoriello
- Department of Mental Health and Public Medicine, Section of Statistics, Second University of Naples, Naples, Italy
| | - Vincenzo Messina
- Division of Infectious and Tropical Diseases, AORN Sant'Anna e San Sebastiano di Caserta, Caserta, Italy
| | - Caterina Sagnelli
- Department of Clinical and Experimental Medicine and Surgery "F. Magrassi e A. Lanzara", Second University of Naples, Naples, Italy
| | - Aniello Russo
- Department of Life Sciences, Second University of Naples, Caserta, Italy
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Naples, Italy
- Division of Infectious and Tropical Diseases, AORN Sant'Anna e San Sebastiano di Caserta, Caserta, Italy
- * E-mail:
| |
Collapse
|
|
33
|
Coppola N, Tonziello G, Colombatto P, Pisaturo M, Messina V, Moriconi F, Alessio L, Sagnelli C, Cavallone D, Brunetto M, Sagnelli E. Lamivudine-resistant HBV strain rtM204V/I in acute hepatitis B. J Infect 2013; 67:322-8. [PMID: 23796869 DOI: 10.1016/j.jinf.2013.06.006] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2013] [Revised: 05/15/2013] [Accepted: 06/12/2013] [Indexed: 12/14/2022]
Abstract
AIMS To detect HBV rtM204V/I lamivudine-resistant strains in serum of patients with acute hepatitis B and to assess their biological and clinical significance. METHODS Eighty HBV DNA-positive patients with symptomatic acute hepatitis B observed from 1999 to 2010 were enrolled. A plasma sample obtained at the first observation was tested for HBV mutants in the polymerase region by direct sequencing; the antiviral drug-resistant rtM204V/I mutations, the most frequent HBV mutants in Italy, were also sought by the more sensitive allele-specific polymerase chain reaction (PCR). RESULTS No HBV mutation associated with resistance to nucleos(t)ide analogues was identified by direct sequencing, whereas allele-specific PCR identified HBV strains carrying the substitution rtM204V/I in 11 (13.7%) patients. Compared with those with the HBV wild strain, patients with rtM204V/I more frequently showed severe acute hepatitis B (36.4% vs 8.7%; p < 0.05) and lower values of serum HBV DNA (1.77 × 10(6) ± 4.76 × 10(6) vs. 1.68 × 10(8) ± 5.46 × 10(8)). In addition, a multivariate analysis identified the presence of a pre-existing HCV chronic infection as independently associated with severe acute hepatitis B (p < 0.05). CONCLUSIONS HBV rtM204V/I lamivudine-resistant strains were detected in serum of 11 (13.7%) patients with acute hepatitis B by allele-specific polymerase chain reaction. The frequent association of rtM204V/I with a more severe acute hepatitis B and with a lower viral load may suggest that greater and/or more prolonged immune pressure might have induced their selection.
Collapse
Affiliation(s)
- Nicola Coppola
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Italy
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
34
|
Vakili Ghartavol Z, Alavian SM, Amini S, Vahabpour R, Bahramali G, Mostafavi E, Aghasadeghi MR. Prevalence of occult hepatitis B virus in plasma and peripheral blood mononuclear cell compartments of patients with chronic hepatitis C infection in tehran-iran. HEPATITIS MONTHLY 2013; 13:e10134. [PMID: 23967017 PMCID: PMC3741907 DOI: 10.5812/hepatmon.10134] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/06/2013] [Revised: 02/27/2013] [Accepted: 04/15/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND Occult hepatitis B virus (HBV) infection (OBI) is frequently reported in patients with chronic hepatitis C virus (HCV) infection. An association between OBI and more liver damage, cirrhosis, hepatocellular carcinoma, and reduced response to interferon therapy in patients with HCV infection is suggested. OBJECTIVES The aim of this study was to determine the prevalence of occult HBV, and evaluate its clinical influence on patients with chronic HCV. PATIENTS AND METHODS A cohort study including50 patients with positive results for HCV, and negative results for HBsAg tests was performed. The patients were divided into two groups: one group had positive results for both HCV and occult HBV tests (n = 18), and the other had positive results for HCV, but negative findings for occult HBV (n = 32). All were treated with PEG-IFN alpha-2a and Ribavirin. Presence of HCV RNA was followed in these patients. RESULTS HBV-DNA was detected using nested-PCR in 20% of plasma and 32.6% of peripheral blood mononuclear cell (PBMC) compartments. No significant differences were observed between patients with and without occult HBV for sex, age, duration of HCV infection, histological markers, presence of anti-HBc, HCV viral load, and HCV genotype. The response rate was significantly higher in patients with positive results for HBV-DNA test compared to those with negative findings (100% vs. 71.9 %, P < 0.05). CONCLUSIONS In conclusion, occult HBV was found in 36% of patients with negative results for HBsAg, but positive results for HCV. Detection of HBV-DNA in both PBMCs and plasma together in comparison with plasma alone provided more true identification of OBI.The SVR rate was significantly higher in coinfected patients than mono-infected ones.
Collapse
Affiliation(s)
- Zeinab Vakili Ghartavol
- Department of Basic Sciences, Science and Research Branch, Islamic Azad University, Tehran, IR Iran
| | - Seyed Moayed Alavian
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences and Tehran Hepatitis Center, Tehran, IR Iran
| | - Safieh Amini
- Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, IR Iran
- Corresponding author: Safieh Amini, Department of Hepatitis andAIDS, Pasteur Institute of Iran, Tehran, IR Iran. Tel: +98-2166969291, Fax: +98-2166969291, E-mail:
| | - Rouhollah Vahabpour
- Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, IR Iran
- Department of Virology, Tehran University of Medical Sciences, Tehran, IR Iran
| | - Golnaz Bahramali
- Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, IR Iran
| | - Ehsan Mostafavi
- Department of Epidemiology, Pasteur Institute of Iran, Tehran, IR Iran
| | | |
Collapse
|
|
35
|
Abd El Kader Mahmoud O, Abd El Rahim Ghazal A, El Sayed Metwally D, Elnour AM, Yousif GEA. Detection of occult hepatitis B virus infection among blood donors in Sudan. J Egypt Public Health Assoc 2013; 88:14-18. [PMID: 23528527 DOI: 10.1097/01.epx.0000427065.73965.c8] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/02/2023]
Abstract
BACKGROUND Sudan is classified among countries with a high hepatitis B surface antigen (HBsAg) endemicity of more than 8%. Cross-sectional studies have showed a marked increase in the prevalence of occult hepatitis B infection (OBI) in patients with cirrhosis or hepatocellular carcinoma. In terms of OBI infectivity by transfusion, it is largely unknown whether residual risk estimates translate into true rates of infection. AIM The current study aimed to determine the frequency of OBI among blood donors in Sudan. MATERIALS AND METHODS This study was carried out during the period between 2011 and 2012. It included 100 HBsAg-negative blood donors who attended the Central Blood Bank in Sudan. Sera collected from all donors were tested for HBsAg, antibodies against hepatitis B core antigen (anti-HBc), antibodies against hepatitis Be antigen (anti-HBe), and antibodies against hepatitis B surface antigen (anti-HBs) by enzyme-linked immunosorbant assay. Anti-HBc-positive patients were tested for hepatitis B virus (HBV)-DNA. RESULTS The anti-HBc was detected in 42% of the blood donors, among whom 90.5% were positive for HBV-DNA. Two main profiles have been detected, namely, the presence of the three genes (S, C, and X genes) together in 35.7% of the blood donors or the presence of the X gene in addition to the core gene. CONCLUSION AND RECOMMENDATIONS With the use of HBsAg as the sole detection marker for HBV, there is a danger of HBV transmission through blood transfusion. Anti-HBc testing should be added to the routine blood donor screening test if occult hepatitis B is to be diagnosed.
Collapse
Affiliation(s)
- Ola Abd El Kader Mahmoud
- aDepartment of Microbiology Medical Research Institute, University of Alexandria, Alexandria, Egypt bDepartment of Haematology, Faculty of Medicine, University of Elimam Elmahdi, Kosti cMedical Laboratory Science, University of Khartoum, Khartoum, Sudan
| | | | | | | | | |
Collapse
|
|
36
|
Cassini R, De Mitri MS, Gibellini D, Urbinati L, Bagaglio S, Morsica G, Domenicali M, Verucchi G, Bernardi M. A novel stop codon mutation within the hepatitis B surface gene is detected in the liver but not in the peripheral blood mononuclear cells of HIV-infected individuals with occult HBV infection. J Viral Hepat 2013; 20:42-9. [PMID: 23231083 DOI: 10.1111/j.1365-2893.2012.01623.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
To characterize occult HBV infection (OHB) in different compartments of HIV+ individuals. This retrospective study involved 38 consecutive HIV+ patients; 24 HBsAg negative (HBV-) and 14 HBsAg positive (HBV+). OHB was assessed in serum samples, liver tissue (LT) and peripheral blood mononuclear cells (PBMC) by genomic amplification of the partial S, X and precore/core regions. HBV genomic analysis was inferred by direct sequencing of PCR products. The intracellular HBV-DNA was measured by a quantitative real-time PCR. HBV+ patients were used as a control for HBV replication and genomic profile. In HBV- patients, HBV-DNA was undetectable in all serum samples, while it was found positive in 7/24 (29%) LT in which genotype D prevailed (57%). HBV-DNA was found in 6/7 (86%) PBMC of occult-positive and none of occult-negative LT. Significantly lower HBV-DNA load was present in both compartments in OHB+ with respect to the HBV+ group (LT: P = 0.002; PBMC: P = 0.026). In the occult-positive cases, HBV replication was significantly higher in LT than in PBMC (P = 0.028). A hyper-mutated S gene in PBMC and a nucleotide mutation at position C695 in LT that produces a translational stop codon at amino acid 181 of the HBs gene characterized OHB. In this group of HIV+ persons, OHB is frequent and exhibits lower replication levels than chronic HBV in the different compartments examined. HBV-DNA detection in PBMC may offer a useful tool to identify OHB in serum-negative cases. The novel HBs gene stop codon found in LT could be responsible for reduced production leading to undetectability of HBsAg.
Collapse
Affiliation(s)
- R Cassini
- Department of Clinical Medicine, University of Bologna, Bologna, Italy
| | | | | | | | | | | | | | | | | |
Collapse
|
|
37
|
Caviglia GP, Abate ML, Manzini P, Danielle F, Ciancio A, Rosso C, Olivero A, Pellicano R, Touscoz GA, Smedile A, Rizzetto M. Occult hepatitis B virus infection in patients with chronic hepatitis C treated with antiviral therapy. HEPATITIS MONTHLY 2012; 12:e7292. [PMID: 23300497 PMCID: PMC3539061 DOI: 10.5812/hepatmon.7292] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/01/2012] [Revised: 07/10/2012] [Accepted: 07/28/2012] [Indexed: 12/11/2022]
Abstract
BACKGROUND Occult hepatitis B virus infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in the liver and/or in the serum of patients with negative results of hepatitis B s antigen (HBsAg) test with or without serological markers of previous viral exposure. The impact of OBI in patients with chronic hepatitis C (CHC) is still unclear. OBJECTIVES The Aim of this study was to assess OBI prevalence and its potential implications on treatment outcome in a cohort of patients with CHC underwent standard antiviral therapy. PATIENTS AND METHODS Baseline serum samples from 137 HBsAg-negative CHC patients treated with pegylated-interferon and ribavirin (73 Responders/74 Non Responders),were retrospectively analyzed for HBV status. RESULTS Seventy-three patients (53.3%) showed markers of previous exposure to HBV. HBV DNA was detected in 2 of 137 serum samples (1.5%), both carrying HBV antibodies. Liver biopsies and post-therapy sera were available for 35 patients (12 Responders/23 Non Responders). HBV DNA sequences were found in 13 of 35 specimens (37.1%), all of patients with HBV DNA negativity in basal and post-therapy serum samples. Among OBI-positive patients, 5 (38.5%) carried serological markers of HBV infection. Regarding therapy outcome, in the OBI-positive group there were 5 of 13 (38.5%) sustained virological responders (SVR) compared to 7 of 22 (31.8%) in the OBI-negative one. CONCLUSIONS Despite the high prevalence rate of liver HBV DNA in patients with CHC, SVR was not affected by occult HBV infection.
Collapse
Affiliation(s)
| | | | - Paola Manzini
- Blood Bank, San Giovanni Battista University Hospital (Molinette), Turin, Italy
| | - Franca Danielle
- Blood Bank, San Giovanni Battista University Hospital (Molinette), Turin, Italy
| | - Alessia Ciancio
- Department of Gastroenterology and Hepatology, San Giovanni Battista University Hospital (Molinette), Turin, Italy
| | - Chiara Rosso
- Department of Internal Medicine, University of Turin, Turin, Italy
| | | | - Rinaldo Pellicano
- Department of Gastroenterology and Hepatology, San Giovanni Battista University Hospital (Molinette), Turin, Italy
- Corresponding author: Rinaldo Pellicano, Department of Gastroenterology and Hepatology, San Giovanni Battista University Hospital, C.so Bramante n.88/90, 10100, Turin, Italy. Tel.: +39-116333532, Fax: +39-116333976, E-mail:
| | - Giovanni Antonio Touscoz
- Department of Gastroenterology and Hepatology, San Giovanni Battista University Hospital (Molinette), Turin, Italy
| | - Antonina Smedile
- Department of Gastroenterology and Hepatology, San Giovanni Battista University Hospital (Molinette), Turin, Italy
| | - Mario Rizzetto
- Department of Gastroenterology and Hepatology, San Giovanni Battista University Hospital (Molinette), Turin, Italy
| |
Collapse
|
|
38
|
Occult Hepatitis B (OBH) in Clinical Settings. HEPATITIS MONTHLY 2012. [DOI: 10.5812/hapatmon.6126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
|
|
39
|
Tonziello G, Pisaturo M, Sica A, Ferrara MG, Sagnelli C, Pasquale G, Sagnelli E, Guastafierro S, Coppola N. Transient reactivation of occult hepatitis B virus infection despite lamivudine prophylaxis in a patient treated for non-Hodgkin lymphoma. Infection 2012; 41:225-9. [PMID: 22855434 DOI: 10.1007/s15010-012-0305-y] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2012] [Accepted: 07/12/2012] [Indexed: 12/16/2022]
|
|
40
|
Alavian SM, Miri SM, Hollinger FB, Jazayeri SM. Occult Hepatitis B (OBH) in Clinical Settings. HEPATITIS MONTHLY 2012; 12:e6126. [PMID: 23087749 PMCID: PMC3475016 DOI: 10.5812/hepatmon.6126] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/20/2012] [Revised: 06/20/2012] [Accepted: 07/08/2012] [Indexed: 12/11/2022]
Abstract
CONTEXT Occult hepatitis B (OHB), or persistent HBV DNA in patients who are hepatitis B surface antigen (HBsAg) negative, is a recently recognized entity. In an attempt to summarize the issues, this review presents an overview of the current proposed hypothesis on the clinical relevance and also updates the knowledge on the classification of OHB in different clinical settings. EVIDENCE ACQUISITION OHB COULD BE FOUND IN DIFFERENT POPULATION AND CLINICAL BACKGROUNDS INCLUDING: viral co-infections (with either human immunodeficiency or hepatitis C viruses), HBV chronic carriers, dialysis patients, transplantation settings and certain clinical situations (named in here: special clinical settings) with no apparent distinguishable clinical parameters. RESULTS The exact magnitude, pathogenesis, and clinical relevance of OHB are unclear. Even the possible role exerted by this cryptic infection on liver disease outcome, and hepatocellular carcinoma development remains unknown. CONCLUSIONS Monitoring of Individuals with positive anti-HBc, mass immunization programs and improvement in diagnostic tools seem to be important to control the probability of transmission of HBV through cryptic HBV infection.
Collapse
Affiliation(s)
- Seyed Moayed Alavian
- Baqiyatallah Research Center for Gastroenterology and Liver Disease, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
| | - Seyed Mohammad Miri
- Baqiyatallah Research Center for Gastroenterology and Liver Disease, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
| | | | - Seyed Mohammad Jazayeri
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran
| |
Collapse
|
|
41
|
Jang JY, Jeong SW, Cheon SR, Lee SH, Kim SG, Cheon YK, Kim YS, Cho YD, Kim HS, Jin SY, Kim YS, Kim BS. Clinical significance of occult hepatitis B virus infection in chronic hepatitis C patients. THE KOREAN JOURNAL OF HEPATOLOGY 2012; 17:206-12. [PMID: 22102387 PMCID: PMC3304657 DOI: 10.3350/kjhep.2011.17.3.206] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Background/Aims We investigated the frequency of occult hepatitis B virus (HBV) infection in anti-hepatitis C virus (HCV)-positive individuals and the effects of occult HBV infection on the severity of liver disease. Methods Seventy-one hepatitis B virus surface-antigen (HBsAg)-negative patients were divided according to their HBV serological status into groups A (anti-HBc positive, anti-HBs negative; n=18), B (anti-HBc positive, anti-HBs positive; n=34), and C (anti-HBc negative, anti-HBs positive/negative; n=19), and by anti-HCV positivity (anti-HCV positive; n=32 vs. anti-HCV negative; n=39). Liver biopsy samples were taken, and HBV DNA was quantified by real-time PCR. Results Intrahepatic HBV DNA was detected in 32.4% (23/71) of the entire cohort, and HBV DNA levels were invariably low in the different groups. Occult HBV infection was detected more frequently in the anti-HBc-positive patients. Intrahepatic HBV DNA was detected in 28.1% (9/32) of the anti-HCV-positive and 35.9% (14/39) of the anti-HCV-negative subjects. The HCV genotype did not affect the detection rate of intrahepatic HBV DNA. In anti-HCV-positive cases, occult HBV infection did not affect liver disease severity. Conclusions Low levels of intrahepatic HBV DNA were detected frequently in both HBsAg-negative and anti-HCV-positive cases. However, the frequency of occult HBV infection was not affected by the presence of hepatitis C, and occult HBV infection did not have a significant effect on the disease severity of hepatitis C.
Collapse
Affiliation(s)
- Jae Young Jang
- Institute for Digestive Research, Digestive Disease Center, Department of Gastroenterology, Soon Chun Hyang University Seoul Hospital, Soon Chun Hyang University College of Medicine, Seoul, Korea
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
42
|
Coppola N, Tonziello G, Pisaturo M, Messina V, Guastafierro S, Fiore M, Iodice V, Sagnelli C, Stanzione M, Capoluongo N, Pasquale G, Sagnelli E. Reactivation of overt and occult hepatitis B infection in various immunosuppressive settings. J Med Virol 2011; 83:1909-1916. [PMID: 21915865 DOI: 10.1002/jmv.22199] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/05/2011] [Indexed: 12/16/2022]
Abstract
The aim of the study was to evaluate clinical and virological differences in HBV reactivation between patients with overt and occult HBV infection. Twenty-three consecutive patients with symptomatic HBV reactivation occurring during or after immunosuppressive therapy were enrolled in a retrospective study: 10 with reactivation of overt HBV infection (overt group) and 13 of occult HBV infection (occult group). Twenty-one patients were treated with nucleot(s)ide analogues after HBV reactivation. Regimens including rituximab or fludarabine were administered more frequently in the occult group (61% vs. 31%, respectively). HBV reactivation was severe frequently in the overt (40%) and occult groups (38.4%). Patients in the overt group showed higher HBV-DNA titers (1.1 × 10(8) ± 1.4 × 10(8) vs. 5.1 × 10(5) ± 6.8 × 10(5) IU; P < 0.005). Seven patients died during HBV reactivation, two in the overt and five in the occult group. Of these seven patients, two remained untreated and five had been treated with Lamivudine; of the 16 patients showing remission of HBV reactivation, four had been treated with Lamivudine, four with Entecavir, two with Telbivudine, and six with Lamivudine plus Adefovir. It is concluded that HBV reactivation is life-threatening in patients with diseases inhibiting the immune response and/or receiving immunosuppressive drugs. Supportive therapy without antiviral drugs or Lamivudine monotherapy may not be effective for treating patients with HBV reactivation.
Collapse
Affiliation(s)
- Nicola Coppola
- Department of Public Medicine, Section of Infectious Diseases, Second University of Naples, Naples, Italy
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
43
|
Alavian SM, Jazayeri SM. Other views of occult hepatitis B in Hepatitis C infected patients. Eur J Intern Med 2011; 22:e67-8. [PMID: 21925047 DOI: 10.1016/j.ejim.2011.05.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2011] [Revised: 05/03/2011] [Accepted: 05/04/2011] [Indexed: 01/05/2023]
|
|
44
|
Taha HA, El Azab GI. Occult hepatitis B virus infection in patients with chronic hepatitis C: a hidden threat. Eur J Intern Med 2011; 22:e69-70. [PMID: 21925048 DOI: 10.1016/j.ejim.2011.06.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2011] [Revised: 06/07/2011] [Accepted: 06/13/2011] [Indexed: 10/18/2022]
|
|
45
|
Utsunomiya T, Shimada M. Molecular characteristics of non-cancerous liver tissue in non-B non-C hepatocellular carcinoma. Hepatol Res 2011; 41:711-21. [PMID: 21682827 DOI: 10.1111/j.1872-034x.2011.00818.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Although chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) are the most important risk factors for the development of hepatocellular carcinoma (HCC) worldwide, the proportion of HCC patients negative for the hepatitis B surface antigen and hepatitis C antibody, so-called "non-B non-C HCC", is rapidly increasing, especially in Japan. The background liver diseases of non-B non-C HCC patients can be multifactorial, including occult HBV infection and non-alcoholic steatohepatitis. It is reasonable to investigate the non-cancerous liver tissues to identify the potential molecular mechanisms responsible for the processes of hepatocarcinogenesis of non-B non-C HCC. However, to date, only a few studies have focused on this research concept based on the idea of "field cancerization". This review highlights the potential importance of the molecular analysis of non-cancerous liver tissues to clarify the molecular characteristics in patients with non-B non-C HCC. A better understanding of the molecular mechanisms underlying the individual predisposition to non-B non-C HCC will lead to improvements in the prevention, early diagnosis and treatment of this neoplastic disease.
Collapse
Affiliation(s)
- Tohru Utsunomiya
- Department of Surgery, The University of Tokushima, Tokushima, Japan
| | | |
Collapse
|
|
46
|
Tan YW. Antiviral treatment of hepatitis B virus and hepatitis C virus co-infection. Shijie Huaren Xiaohua Zazhi 2011; 19:1614-1619. [DOI: 10.11569/wcjd.v19.i15.1614] [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] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are among the most common causes of advanced chronic liver disease worldwide. HBV/HCV co-infection is not uncommon with an estimated 7-20 million individuals affected worldwide. Patients with HBV/HCV co-infection have an increased risk of cirrhosis, hepatocellular carcinoma (HCC), and even death. The pathophysiology of HBV/HCV co-infection is complex, as different patterns of virological dominance may occur, which can even fluctuate over time. Recently, combination of pegylated interferon (PEG-IFN) plus ribavirin has been explored in HBV/HCV-coinfected patients who are positive for HCV-RNA. In this paper, we summarize the epidemiology, viral interaction and clinical features of HBV/HCV co-infection and the available treatment options. Detailed serological and virological evaluations are required for HBV/HCV-co-infected patients before initiation of antiviral therapy. At present, PEG-IFN-a plus ribavirin should be the treatment of choice in patients with dominant HCV replication. However, HBV rebound may occur after elimination of HCV, and thus close monitoring for both viruses is recommended even for patients with initially suppressed HBV DNA.
Collapse
|
|
47
|
Fernandez-Rodriguez CM, Gutierrez ML, Lledó JL, Casas ML. Influence of occult hepatitis B virus infection in chronic hepatitis C outcomes. World J Gastroenterol 2011; 17:1558-62. [PMID: 21472121 PMCID: PMC3070126 DOI: 10.3748/wjg.v17.i12.1558] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2010] [Revised: 10/26/2010] [Accepted: 11/02/2010] [Indexed: 02/06/2023] Open
Abstract
Persistence of hepatitis B virus-DNA in the sera, peripheral blood mononuclear cells or in the liver of hepatitis B surface antigen (HBsAg)-negative patients with or without serological markers of previous exposure (antibodies to HBsAg and/or to HB-core antigen) defines the entity called occult hepatitis B infection (OBI). Co-infection with hepatitis B and hepatitis C viruses is frequent in highly endemic areas. While this co-infection increases the risk of liver disease progression, development of cirrhosis and hepatocellular carcinoma and also increases the rate of therapeutic failure to interferon-based treatments than either virus alone, a potentially negative effect of OBI on clinical outcomes and of therapeutic response to current antiviral regimes of patients with chronic hepatitis C remains inconclusive.
Collapse
|
|
48
|
Lisboa Neto G, Tengan FM, Cavalheiro NDP, Barone AA. [Influence of previous hepatitis B virus infection on liver fibrosis in patients with chronic hepatitis C: a retrospective case series evaluation]. Rev Soc Bras Med Trop 2010; 43:416-20. [PMID: 20802942 DOI: 10.1590/s0037-86822010000400016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2009] [Accepted: 05/25/2010] [Indexed: 01/05/2023] Open
Abstract
INTRODUCTION Hepatitis C is a major cause of liver disease worldwide. Its evolutionary course is dynamics and may be influenced by several cofactors. Among them, previous hepatitis B virus infection (anti-HBcAg [+] and HBsAg [-]) has been associated with worse histological and therapeutic prognosis. This study had the objective of independently assessing the relationship between previous hepatitis B infection and liver fibrosis in patients with chronic hepatitis C. METHODS The medical records of patients chronically infected with the hepatitis C virus who had been seen consecutively during a one-year period at the infectious and parasitic diseases outpatient clinic of HC FMUSP were retrospectively reviewed in relation to epidemiological, clinical and histological data. Analysis on the independence of the previous hepatitis B infection was performed using the statistical model of multivariate logistic regression. Detection of anti-HBcAg was taken to be the independent variable. The outcome was taken to be grade 3 and 4 histopathological abnormality (septa with nodule formation and cirrhosis). RESULTS 145 subjects were evaluated in this study. 47.2% of them were anti-HBcAg (+). The main risk factor for infection was blood and blood derivative transfusion (35.9%). Findings of anti-HBcAg (+) were not related to advanced liver fibrosis, although piecemeal necrosis has been found frequently in patients with this serological marker. CONCLUSIONS Previous hepatitis B infection does not seem to increase the structural liver damage triggered by chronic hepatitis C virus infection, after statistical control for other co-factors capable to impact the natural history of this infection.
Collapse
Affiliation(s)
- Gaspar Lisboa Neto
- Departamento de Doenças Infecciosas e Parasitárias, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP.
| | | | | | | |
Collapse
|
|
49
|
Bhargava A, Khan S, Panwar H, Pathak N, Punde RP, Varshney S, Mishra PK. Occult hepatitis B virus infection with low viremia induces DNA damage, apoptosis and oxidative stress in peripheral blood lymphocytes. Virus Res 2010; 153:143-50. [PMID: 20667493 DOI: 10.1016/j.virusres.2010.07.023] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2010] [Revised: 07/17/2010] [Accepted: 07/19/2010] [Indexed: 12/23/2022]
Abstract
Occult HBV infections (OHBI) are often associated with poor therapeutic response and increased risk of developing hepatocellular carcinoma. Despite a decade of research, OHBI still remains an intricate issue and much is yet to be defined about their possible immune implications. As HBV is known to infect peripheral blood lymphocytes, the present study aimed to explore the molecular mechanisms underlying DNA damage response triggered due to OHBI in host cells. The study was divided into three groups i.e. group A (OHBI patients n=30, viral load <or=100 IU/mL); group B (chronic HBV patients, n=30) and group C (controls, n=30). Peripheral blood lymphocytes were isolated and DNA damage response, apoptosis and oxidative stress were the studied parameters. A significant increase in the phosphorylation of DNA damage response proteins (ATM, ATR, H2AX and p53) in OHBI in comparison to controls suggested that OHBI induces DNA damage in peripheral blood lymphocytes and elicit a PI3 kinase mediated cellular response. In addition, increased DNA fragmentation, circulating nucleosome levels and mitochondrial membrane depolarization observed in OHBI group indicated that this damage might lead to cellular demise and immune hypo-responsiveness. Moreover, OHBI was also observed to be strongly associated with oxidative stress as suggested by the augmented levels of DCF fluorescence and depleted GR activity. Collectively, these results provide the basic knowledge about the genotoxic effects of OHBI in peripheral blood lymphocytes. Such studies may possibly open up new avenues for identifying novel therapeutic targets for viral hepatitis.
Collapse
Affiliation(s)
- Arpit Bhargava
- Bhopal Memorial Hospital & Research Centre, Bhopal, India
| | | | | | | | | | | | | |
Collapse
|
|
50
|
Abstract
IMPORTANCE OF THE FIELD Hepatitis B (HBV) and hepatitis C (HCV) virus infections are among the most common causes of advanced chronic liver disease worldwide. HBV/HCV coinfection is not uncommon with an estimated 7 - 20 million individuals affected worldwide. Patients with HBV/HCV coinfection have an increased risk for cirrhosis, hepatocellular carcinoma (HCC) and even death. AREAS COVERED IN THIS REVIEW The pathophysiology of HBV/HCV coinfection is complex, as different patterns of virological dominance may occur, which can even fluctuate over time. Recently, combination of pegylated interferon (PEG-IFN) plus ribavirin has been explored in HBV/HCV coinfected patients who are positive for HCV-RNA. HBV polymerase inhibitors may be indicated if HBV-DNA concentrations are above 2000 IU/ml. In this review, we summarize the epidemiology, viral interaction, its clinical features and the available treatment options. WHAT THE READER WILL GAIN Insights into viral interaction of HBV/HCV coinfection and treatment individualization strategies are provided in the review. TAKE HOME MESSAGE Detailed serological and virological evaluations are required for HBV/HCV coinfected patients before initiation of antiviral therapy. At present, PEG-IFN-alpha plus ribavirin should be the treatment of choice in patients with dominant HCV replication. However, HBV rebound may occur after elimination of HCV, and thus close monitoring for both viruses is recommended even for patients with initially suppressed HBV-DNA.
Collapse
Affiliation(s)
- Andrej Potthoff
- Hannover Medical School, Medizinische Hochschule Hannover, Department of Gastroenterology, Hepatology and Endocrinology, Carl Neuberg Str. 1, D-30625 Hannover, Germany
| | | | | |
Collapse
|