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1
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Wick JM, Ni Y, Halmer N, Wong RJ, Chitnis AS, Jaganath D, Krueger AL, Skarbinski J. Tuberculosis and Chronic Hepatitis B Virus Infection Screening Among Non-US-Born Persons in an Integrated Health System in California. Open Forum Infect Dis 2024; 11:ofae484. [PMID: 39296340 PMCID: PMC11409871 DOI: 10.1093/ofid/ofae484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Accepted: 08/31/2024] [Indexed: 09/21/2024] Open
Abstract
Background Tuberculosis infection (TBI) and chronic hepatitis B virus (HBV) infection disproportionately affect non-US-born persons. Early identification and treatment are critical to reduce transmission, morbidity, and mortality, but little is known about screening in the United States. Methods We conducted a cross-sectional study in a large integrated California health system in September 2022 assessing TBI and HBV screening among persons aged ≥18 years who were born in countries with high TB burden (TB disease incidence rates ≥20/100 000 population) and/or HBV burden (hepatitis B surface antigen seroprevalence >2%). Results Of 510 361 non-US-born persons born in countries with high TB burden, 322 027 (63.1%) were born in countries with high HBV burden and 188 334 (36.9%) in countries with only high TB burden. Among persons born in countries with high TB and HBV burden, 29.6% were screened for TBI, 64.5% for HBV, and 23.4% for TBI and HBV; 9.9% had TBI and 3.1% had HBV infection. Among persons born in countries with high TB burden only, 27.9% were screened for TBI and 7.5% had TBI. Conclusions Among non-US-born persons from countries with high TB and HBV burden, we found low screening rates and elevated prevalence of TBI and chronic HBV infection. Cotesting for TBI and HBV infection in non-US-born persons from countries with high TB and HBV burden might improve outcomes by identifying persons who warrant TBI treatment, HBV treatment, or HBV vaccination. Increased screening is the first step in reducing health inequities and overall disease burden.
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Affiliation(s)
- Jenna M Wick
- Internal Medicine Residency Program, Oakland Medical Center, Kaiser Permanente Northern California, Oakland, California, USA
| | - Yuching Ni
- Division of Research, Kaiser Permanente Northern California, Oakland, California, USA
| | - Nicole Halmer
- Division of Research, Kaiser Permanente Northern California, Oakland, California, USA
| | - Robert J Wong
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA
- Gastroenterology and Hepatology Section, Veterans Affairs Palo Alto Healthcare System, Palo Alto, California USA
| | - Amit S Chitnis
- Tuberculosis Section, Division of Communicable Disease Control and Prevention, Alameda County Public Health Department, San Leandro, California, USA
| | - Devan Jaganath
- Division of Pediatric Infectious Disease, University of California San Francisco, San Francisco, California, USA
| | - Amy L Krueger
- Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Jacek Skarbinski
- Division of Research, Kaiser Permanente Northern California, Oakland, California, USA
- Department of Infectious Diseases, Oakland Medical Center, Kaiser Permanente Northern California, Oakland, California, USA
- Physician Researcher Program, Kaiser Permanente Northern California, Oakland, California, USA
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2
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Ward JW, Wanlapakorn N, Poovorawan Y, Shouval D. Hepatitis B Vaccines. PLOTKIN'S VACCINES 2023:389-432.e21. [DOI: 10.1016/b978-0-323-79058-1.00027-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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3
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Choi WM, Choi J, Lim YS. Hepatitis B: epidemiology, natural history, and diagnosis. COMPREHENSIVE GUIDE TO HEPATITIS ADVANCES 2023:183-203. [DOI: 10.1016/b978-0-323-98368-6.00007-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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4
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Chen CY, Hajinicolaou C, Walabh P, Ingasia LAO, Song E, Kramvis A. Molecular characterization of hepatitis B virus (HBV) isolated from a pediatric case of acute lymphoid leukemia, with a delayed response to antiviral treatment: a case report. BMC Pediatr 2022; 22:168. [PMID: 35361141 PMCID: PMC8969373 DOI: 10.1186/s12887-022-03204-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 03/09/2022] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Tenofovir disoproxil fumarate (TDF) is effectively used as the first-line antiviral for chronic hepatitis B virus (HBV) infection in adults and children older than 12 years. To date, no confirmed case of virologic breakthrough (VBT) in a pediatric case has been reported. CASE PRESENTATION Here we describe a case of a 5-year old, asymptomatically infected with HBV infection two months after chemotherapy for precursor B acute lymphoblastic leukemia (ALL). Although the 5-year old male is South African, his family originated from Guinea. At the end of the one-year follow-up, the infection progressed to chronic HBV infection, with a high viral load. At 36 weeks (8 months) post-treatment with lamivudine (LAM), there was a partial virologic response (PVR) and after 61 weeks (14 months), he was switched to TDF rescue monotherapy. Even with TDF treatment, he still experienced VBT and subsequent PVR. The full-length genome of HBV isolated 78 weeks after the switch to rescue TDF monotherapy was sequenced and belonged to genotype E. In addition to the LAM mutations (rtS256G and rtM267L), missense mutations in B-cell, T-cell, HLA class I and II-restricted epitopes emerged, which were to evade and escape host surveillance, leading to delayed viral clearance, persistence and disease progression. Two further events of VBT occurred between weeks 113 and 141 of TDF rescue-therapy. Viral loads and liver enzymes are normalizing progressively with long-term therapy. CONCLUSION Although the host immune reconstitution may be delayed, prolonged TDF treatment was effective in treating this pediatric case of HBV infection with VBT and PVR.
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Affiliation(s)
- Chien-Yu Chen
- Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, University of the Witwatersrand, Johannesburg, South Africa
| | - Christina Hajinicolaou
- Department of Paediatrics, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.,Paediatric Gastroenterology, Hepatology and Nutrition Unit, Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa.,Paediatric Gastroentrology, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Priya Walabh
- Paediatric Gastroenterology, Hepatology and Nutrition Unit, Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa
| | - Luicer Anne Olubayo Ingasia
- Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, University of the Witwatersrand, Johannesburg, South Africa
| | - Ernest Song
- Department of Internal Medicine, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa
| | - Anna Kramvis
- Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, University of the Witwatersrand, Johannesburg, South Africa.
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5
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Fawaz R, Jonas MM. Acute and Chronic Hepatitis. PEDIATRIC GASTROINTESTINAL AND LIVER DISEASE 2021:819-837.e6. [DOI: 10.1016/b978-0-323-67293-1.00075-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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6
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Lee HW, Chan HLY. Unresolved issues of immune tolerance in chronic hepatitis B. J Gastroenterol 2020; 55:383-389. [PMID: 32016713 PMCID: PMC7080668 DOI: 10.1007/s00535-020-01665-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2019] [Accepted: 01/07/2020] [Indexed: 02/07/2023]
Abstract
During the natural course of chronic hepatitis B virus infection, immune-tolerant phase is characterized by high viral replication, the presence of HBV e antigen (HBeAg), and normal or minimally elevated serum alanine aminotransferase. Immune-tolerant phase is usually regarded as a benign course of the disease. International guidelines recommend observation rather than treatment during immune-tolerant phase. In this article, we review unresolved issues related to the definition of true immune-tolerant phase and the benefit of antiviral treatment. Defining true immune-tolerant phase requires a careful approach and long-term follow-up. In previous studies, many patients were misclassified as being immune-tolerant phase. Noninvasive methods of assessing fibrosis are warranted for patients in the immune-tolerant phase. Yet, there has been controversy over the benefit and harm of antiviral treatment for immune-tolerant phase patients. Thus, further larger scale studies are needed to investigate the prognosis of patients in true immune-tolerant phase and their need for antiviral therapy.
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Affiliation(s)
- Hye Won Lee
- grid.10784.3a0000 0004 1937 0482Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong ,grid.10784.3a0000 0004 1937 0482Insitute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong ,grid.15444.300000 0004 0470 5454Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Henry Lik-Yuen Chan
- grid.10784.3a0000 0004 1937 0482Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong ,grid.10784.3a0000 0004 1937 0482Insitute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
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7
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El-Shabrawi M, Abdelgawad M, Elgaddar O, Hassanin F, Khalil A, Mahfouz A, Elbanna B. A clinical and immunological study of children with chronic hepatitis B virus infection. PRZEGLAD GASTROENTEROLOGICZNY 2019; 14:211-216. [PMID: 31649794 PMCID: PMC6807666 DOI: 10.5114/pg.2019.88171] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Accepted: 02/14/2019] [Indexed: 01/16/2023]
Abstract
AIM To identify the clinical status and immunological profile of a cohort of children with chronic hepatitis B virus (HBV) infection to assess the short-term consequences of this infection. MATERIAL AND METHODS This prospective case-control study included 30 children in the age range 1-15 years with positive HBsAg attending the Hepatology clinic of Alexandria University Children's Hospital. Twenty children received lamivudine (3 mg/kg, oral, once a day), and 10 children were lamivudine-resistant and received entecavir treatment (10-11 kg/0.3 mg to > 30 kg/1 mg). They were followed up every 3 months for 1 year. RESULTS The study showed that 97% of the studied cases were discovered accidentally during routine investigations and only 3% presented by acute hepatitis. Ninety percent of them had family member infection with HBV, of which 70% were the mother. Eighty-seven percent of cases had no clinical signs, and only 13% of cases had hepatomegaly. All of the cases were HBsAg positive, 50% were HBeAg positive, 56.7% were HBeAb positive, 33.3% were HBcAb positive, and 100% were HBsAb negative. CONCLUSIONS Most of children with HBV infection had associated family member infection and were accidentally discovered. Despite a marked decrease in HBV DNA level after treatment, there was no clearance of HBsAg and no HBsAb seroconversion. Screening for the HBsAb level in children with family members with HBV is recommended.
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Affiliation(s)
| | - Manal Abdelgawad
- Paediatric Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Ola Elgaddar
- Medical Research Institute, Alexandria University, Alexandria, Egypt
| | | | - Ahmed Khalil
- Paediatric Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Aml Mahfouz
- Paediatric Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Basant Elbanna
- Paediatric Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
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8
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Coffin CS, Fung SK, Alvarez F, Cooper CL, Doucette KE, Fournier C, Kelly E, Ko HH, Ma MM, Martin SR, Osiowy C, Ramji A, Tam E, Villeneuve JP. Management of Hepatitis B Virus Infection: 2018 Guidelines from the Canadian Association for the Study of Liver Disease and Association of Medical Microbiology and Infectious Disease Canada. CANADIAN LIVER JOURNAL 2018; 1:156-217. [PMID: 35992619 PMCID: PMC9202759 DOI: 10.3138/canlivj.2018-0008] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Accepted: 04/17/2018] [Indexed: 08/01/2023]
Abstract
Hepatitis B virus (HBV) infection is an important public health problem in Canada. In keeping with evolving evidence and understanding of HBV pathogenesis, the Canadian Association for the Study of Liver Disease periodically publishes HBV management guidelines. The goals of the 2018 guidelines are to (1) highlight the public health impact of HBV infection in Canada and the need to improve diagnosis and linkage to care, (2) recommend current best-practice guidelines for treatment of HBV, (3) summarize the key HBV laboratory diagnostic tests, and (4) review evidence on HBV management in special patient populations and include more detail on management of HBV in pediatric populations. An overview of novel HBV tests and therapies for HBV in development is provided to highlight the recent advances in HBV clinical research. The aim and scope of these guidelines are to serve as an up-to-date, comprehensive resource for Canadian health care providers in the management of HBV infection.
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Affiliation(s)
- Carla S. Coffin
- Cumming School of Medicine, University of Calgary, Calgary, Alberta
| | - Scott K. Fung
- Faculty of Medicine, University of Toronto, Toronto, Ontario
| | - Fernando Alvarez
- Centre hospitalier de l’université de Montréal (CHUM)—CHU Sainte-Justine, Montreal, Québec
| | - Curtis L. Cooper
- Division of Infectious Diseases, Department of Medicine, University of Ottawa, Ottawa, Ontario
| | - Karen E. Doucette
- Division of Infectious Diseases, University of Alberta, Edmonton, Alberta
| | - Claire Fournier
- Department of Medicine, Université de Montréal, Montreal, Québec
| | - Erin Kelly
- Division of Gastroenterology, Department of Medicine, University of Ottawa, Ottawa, Ontario
| | - Hin Hin Ko
- Faculty of Medicine, University of British Columbia, Vancouver, British Columbia
| | - Mang M Ma
- Division of Gastroenterology, University of Alberta, Edmonton, Alberta
| | | | - Carla Osiowy
- Viral Hepatitis and Bloodborne Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba
| | - Alnoor Ramji
- St. Paul’s Hospital, Vancouver, British Columbia
| | - Edward Tam
- LAIR Centre, Vancouver, British Columbia
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9
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Colombatto P, Barbera C, Bortolotti F, Maina AM, Moriconi F, Cavallone D, Calvo P, Oliveri F, Bonino F, Brunetto MR. HBV pre-core mutant in genotype-D infected children is selected during HBeAg/anti-HBe seroconversion and leads to HBeAg negative chronic hepatitis B in adulthood. J Med Virol 2018; 90:1232-1239. [PMID: 29488227 DOI: 10.1002/jmv.25068] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2017] [Accepted: 02/23/2018] [Indexed: 12/26/2022]
Abstract
Selection of HBeAg defective HBV mutants (mt) during childhood might influence infection outcome in adults. Aim of this study was to correlate the dynamics of pre-core HBV mutant (pre-C mt) selection with virological/clinical outcomes in children followed-up until adulthood. Eighty subjects (50-M/30-F), 70 HBeAg-positive (87.5%), and 10 (12.5%) HBeAg-negative/anti-HBe-positive at the admission, mostly genotype D infected (91.2%), with median age of 6.5 (range: 0.2-17) years, were followed-up for 14.3 years (range: 1.1-24.5); 46 (57.5%) received IFN treatment. HBV-DNA and q-HBsAg were tested by commercial assays, Pre-Core 1896 mt by direct-sequence, oligo-hybridization-assay, and allele-specific-PCR (sensitivity: 30%, 10%, and 0.1% of total viremia). HBeAg/anti-HBe seroconversion (SC) occurred in 55/70 (78.6%) children. After SC, 8 (14.6%) developed HBeAg-negative chronic hepatitis (CHB), 41 (74.5%) remain with HBeAg-negative chronic infection, and 6 (10.9%) lost HBsAg. Baseline HBV-DNA and HBsAg were lower in SC than in no-SC children (median: 7.35 vs 8.95 Log IU/mL, P = 0.005, and 4.72 vs 5.04 Log IU/mL, P = 0.015). The prevalence of pre-C mt increased rapidly (10-40%) around SC. Eventually, pre-C mt was detected in 100% of CHB, in 33% of chronic infections without disease, and in 16% of subjects who cleared HBsAg (P < 0.001). HBV-DNA levels remained slightly higher in carriers of HBeAg negative infection with dominant/mixed pre-C mt populations, than in those with dominant pre-C wt (mean Log IU/mL: 3.83 and 3.42 vs 2.67, P = 0.007). In conclusion, pre-C-mt is selected during HBeAg/anti-HBe SC in children with poor control of HBV replication, leading to HBeAg-negative chronic-active-hepatitis during adulthood.
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Affiliation(s)
- Piero Colombatto
- Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Reference Centre of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, Pisa, Italy
| | - Cristiana Barbera
- Paediatric Gastroenterology Unit, Regina Margherita Children Hospital, Torino, Italy
| | | | - Anna M Maina
- Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Reference Centre of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, Pisa, Italy
| | - Francesco Moriconi
- Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Reference Centre of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, Pisa, Italy
| | - Daniela Cavallone
- Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Reference Centre of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, Pisa, Italy
| | - Pierluigi Calvo
- Paediatric Gastroenterology Unit, Regina Margherita Children Hospital, Torino, Italy
| | - Filippo Oliveri
- Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Reference Centre of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, Pisa, Italy
| | - Ferruccio Bonino
- University of Pittsburgh Medical Center Institute for Health, Chianciano Terme, Siena, Italy
- Fondazione Italiana Fegato, AREA Science Park, Campus Basovizza, Trieste, Italy
| | - Maurizia R Brunetto
- Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Reference Centre of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, Pisa, Italy
- Internal Medicine, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
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10
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Li Q, Lu C, Li W, Huang Y, Chen L. Impact of age on the diagnostic performances and cut-offs of APRI and FIB-4 for significant fibrosis and cirrhosis in chronic hepatitis B. Oncotarget 2018; 8:45768-45776. [PMID: 28514753 PMCID: PMC5542225 DOI: 10.18632/oncotarget.17470] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2017] [Accepted: 04/15/2017] [Indexed: 12/14/2022] Open
Abstract
Aims Assessing the diagnostic performances of APRI and FIB-4 using age as a categorical marker. Methods 822 chronic hepatitis B (CHB) patients were included. Using METAVIR scoring system as a reference, the performances of APRI and FIB-4 were compared between patients aged≥30 and patients aged<30 years. Results The APRI AUROC in patients aged<30 years was lower than that in patients aged≥30 years for significant fibrosis (0.61 vs 0.70, p<0.001) and cirrhosis (0.64 vs 0.78, p<0.001). The FIB-4 AUROC in patients aged<30 years was lower than that in patients aged≥30 years for significant fibrosis (0.57 vs 0.65, p<0.001) and cirrhosis (0.63 vs 0.72, p<0.001). Using specificity≥90%, the APRI cut-off in patients aged<30 years was lower than patients aged≥30 years for significant fibrosis (1.0 vs 1.2) and cirrhosis (1.2 vs 1.5). Using sensitivity≥90%, the APRI cut-off in patients aged<30 years was also lower than patients aged≥30 years for significant fibrosis (0.2 vs 0.4) and cirrhosis (0.3 vs 0.5). Using specificity≥90%, the FIB-4 cut-off in patients aged<30 years was lower than that in patients aged≥30 years for significant fibrosis (1.2 vs 2.1) and cirrhosis (1.4 vs 2.6). Using sensitivity≥90%, the FIB-4 cut-off in patients aged<30 years was also lower than that in patients aged≥30 years for significant fibrosis (0.5 vs 0.8) and cirrhosis (0.8 vs 1.2). Conclusions Evaluation of the diagnostic performances of APRI and FIB-4 should take age into consideration.
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Affiliation(s)
- Qiang Li
- Department of Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.,Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Chuan Lu
- Department of Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
| | - Weixia Li
- Department of Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
| | - Yuxian Huang
- Department of Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.,Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Liang Chen
- Department of Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
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11
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Konerman MA, Lok AS. Epidemiology, Diagnosis, and Natural History of Hepatitis B. ZAKIM AND BOYER'S HEPATOLOGY 2018:474-484.e4. [DOI: 10.1016/b978-0-323-37591-7.00032-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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12
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13
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Heath RD, Tahan V. Natural History of Hepatitis B Virus. VIRAL HEPATITIS: CHRONIC HEPATITIS B 2018:1-10. [DOI: 10.1007/978-3-319-93449-5_1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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14
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Efficacy and safety of tenofovir disoproxil fumarate in preventing vertical transmission of hepatitis B in pregnancies with high viral load. Sci Rep 2017. [PMID: 28646142 PMCID: PMC5482834 DOI: 10.1038/s41598-017-04479-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
This study was a meta-analysis of the literature on the efficacy and safety of tenofovir disoproxil fumarate (TDF) in preventing vertical transmission of hepatitis B in pregnancies with high viral load. Four observational studies and one randomized controlled trial involving 585 pregnant women and 595 newborns were included in the meta-analysis. TDF was more effective than the placebo in reducing vertical transmission in HBeAg-positive chronic hepatitis B (CHB) pregnancies with high serum HBV-DNA levels (OR = 0.21, 95% CI = 0.07–0.61) at 4–12 months, infant HBV DNA seropositivity at delivery (OR = 0.16, 95% CI = 0.07–0.37), and a severe flair in maternal alanine aminotransferase (ALT) levels (OR = 0.43, 95% CI = 0.19–0.95) during pregnancy. In addition, TDF showed more improvement in HBV DNA suppression at delivery (OR = 254.46, 95% CI = 28.39–2280.79). No significant differences were found in HBeAg seroconversion or ALT normalization; or in rates of cesarean section, emergent cesarean section, postpartum hemorrhage, prematurity, congenital malformations, or infant death. However, TDF induced more drug-related adverse events (OR = 2.33, 95% CI = 1.39–3.89) and elevated creatine kinase (CK) (OR = 9.56, 95% CI = 1.17–78.09) than in controls. The available evidence suggests that TDF is effective and safe in preventing vertical transmission of hepatitis B in pregnancies exhibiting a high viral load.
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15
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Yu JH, Lee JI. Current role of transient elastography in the management of chronic hepatitis B patients. Ultrasonography 2017; 36:86-94. [PMID: 27956732 PMCID: PMC5381850 DOI: 10.14366/usg.16023] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2016] [Revised: 10/26/2016] [Accepted: 10/26/2016] [Indexed: 12/17/2022] Open
Abstract
Liver fibrosis is an important prognostic factor for chronic hepatitis B (CHB), and accurate evaluation of the stage of liver fibrosis is crucial in establishing management strategies. While liver biopsy is still considered the gold standard for staging liver fibrosis or cirrhosis, transient elastography (TE), a noninvasive means of assessing liver fibrosis, has come to play an increasing role in this process. After extensive validation, TE is now regarded as a reliable surrogate maker for grading the severity of liver fibrosis in CHB patients. It can detect the extent of fibrosis in a patient and can also be used to evaluate longitudinal changes in liver fibrosis over time with or without interventional management, such as antiviral therapy. However, several confounders hinder the effective assessment of liver fibrosis using TE, such as extensive liver necroinflammation, hepatic congestion, and cholestasis. TE has limited use in obese patients or patients with ascites. Although TE has several limitations, due to its accessibility and safety, it is a valuable tool for the initial evaluation and follow-up in patients with CHB.
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Affiliation(s)
- Jung Hwan Yu
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jung Il Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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16
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Fiorino S, Loggi E, Verucchi G, Comparcola D, Vukotic R, Pavoni M, Grandini E, Cursaro C, Maselli S, Bacchi Reggiani ML, Puggioli C, Badia L, Galli S, Viale P, Bernardi M, Andreone P. Vitamin E for the treatment of E-antigen-positive chronic hepatitis B in paediatric patients: results of a randomized phase 2 controlled study. Liver Int 2017; 37:54-61. [PMID: 27333382 DOI: 10.1111/liv.13192] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2016] [Accepted: 06/18/2016] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS The treatment of chronic hepatitis B infection (CHB) in children is still an area of great uncertainty. Vitamin E is an immunostimulating/antioxidant compound proven to be safe and effective for the treatment of adult CHB. The aim of this phase 2 controlled study was to evaluate the safety and efficacy of vitamin E for the treatment of paediatric HBeAg-positive CHB. METHODS Forty-six children were randomized in a 1:1 ratio to receive vitamin E at a dose of 15 mg/kg/day (in galenic preparation) or no treatment for 12 months and were monitored for the subsequent 12 months. Clinical, biochemical, haematological and serovirological evaluations were carried out every 3 months. RESULTS No significant side effects were associated with the vitamin E treatment. At the end of the study, anti-HBe seroconversion was obtained in 7 of 23 (30.4%) of vitamin E-treated versus 1 of 23 (4.3%) of the control patients (P = 0.05), while a virological response (≥2 log decrease in HBV-DNA from baseline) was observed in 9 of 23 (39.1%) vs. 2 of 23 (8.7%) respectively (P = 0.035). CONCLUSIONS Vitamin E administration for the treatment of paediatric CHB at the tested dosage has no significant side effects and may induce anti-HBe seroconversion. Vitamin E could represent a tool for the treatment of paediatric CHB.
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Affiliation(s)
- Sirio Fiorino
- Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy
- Unità Operativa di Medicina Interna, Ospedale Maggiore, AUSL Bologna, Bologna, Italy
| | - Elisabetta Loggi
- Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy
| | - Gabriella Verucchi
- Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy
| | - Donatella Comparcola
- Unità Operativa Malattie Epatometaboliche, Ospedale Pediatrico del Bambin Gesù, Rome, Italy
| | - Ranka Vukotic
- Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy
| | - Michele Pavoni
- Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy
| | - Elena Grandini
- Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy
| | - Carmela Cursaro
- Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy
| | - Silvia Maselli
- Unità Operativa di Farmacia Clinica, Azienda Ospedaliero Universitaria di Bologna, Policlinico Sant'Orsola-Malpighi, Bologna, Italy
| | | | - Cristina Puggioli
- Unità Operativa di Farmacia Clinica, Azienda Ospedaliero Universitaria di Bologna, Policlinico Sant'Orsola-Malpighi, Bologna, Italy
| | - Lorenzo Badia
- Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy
| | - Silvia Galli
- Unità Operativa di Microbiologia e Virologia, Azienda Ospedaliero Universitaria di Bologna, Policlinico Sant'Orsola-Malpighi, Bologna, Italy
| | - Pierluigi Viale
- Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy
| | - Mauro Bernardi
- Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy
| | - Pietro Andreone
- Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy
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17
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Kramvis A. The clinical implications of hepatitis B virus genotypes and HBeAg in pediatrics. Rev Med Virol 2016; 26:285-303. [PMID: 27139263 PMCID: PMC5084815 DOI: 10.1002/rmv.1885] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2016] [Revised: 04/02/2016] [Accepted: 04/04/2016] [Indexed: 12/12/2022]
Abstract
Although a successful vaccine against HBV has been implemented in 184 countries, eradication of hepatitis B virus (HBV) is still not on the horizon. There are over 240 million chronic carriers of HBV globally. The risk of developing chronic hepatitis ranges from >90% in newborns of hepatitis Be antigen (HBeAg)‐positive mothers, 25%–35% in children under 5 years of age and <5% in adults. HBeAg, a non‐particulate viral protein, is a marker of HBV replication. This is the only HBV antigen to cross the placenta, leading to specific unresponsiveness of helper T cells to the capsid protein and HBeAg in newborns. HBeAg is tolerated in utero and acts as a tolerogen after birth. Perinatal transmission is frequent when mothers are HBeAg‐positive, whereas it occurs less frequently when mothers are HBeAg‐negative. Sequence heterogeneity is a feature of HBV. Based on an intergroup divergence >7.5% across the complete genome, HBV is classified phylogenetically into at least nine genotypes. With between ~4% and 8% intergroup nucleotide divergence, genotypes A–D, F, H and I are classified further into subgenotypes. HBV genotypes/subgenotypes may have distinct geographical distribution and can develop different mutations in the regions of the HBV genome that code for HBeAg. These differences can be related to the role of HBV genotypes to the natural history of infection and mode of transmission. Thus genotypes/subgenotypes of HBV can be responsible for the different natural history of infection and modes of transmission in children, found in various regions of the world, where different genotypes/subgenotypes prevail. Copyright © 2016 John Wiley & Sons, Ltd.
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Affiliation(s)
- Anna Kramvis
- Hepatitis Virus Diversity Research Unit (HVDRU), Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
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18
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The Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines: management of chronic hepatitis B. Clin Mol Hepatol 2016; 22:18-75. [PMID: 27044762 PMCID: PMC4825166 DOI: 10.3350/cmh.2016.22.1.18] [Citation(s) in RCA: 150] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2016] [Accepted: 02/22/2016] [Indexed: 01/10/2023] Open
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19
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Jonas MM, Lok ASF, McMahon BJ, Brown RS, Wong JB, Ahmed AT, Farah W, Mouchli MA, Singh S, Prokop LJ, Murad MH, Mohammed K. Antiviral therapy in management of chronic hepatitis B viral infection in children: A systematic review and meta-analysis. Hepatology 2016; 63:307-18. [PMID: 26566163 DOI: 10.1002/hep.28278] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2015] [Accepted: 10/04/2015] [Indexed: 12/13/2022]
Abstract
UNLABELLED Most individuals with chronic hepatitis B viral (HBV) infection acquired the infection around the time of birth or during early childhood. We aimed to synthesize evidence regarding the effectiveness of antiviral therapy in the management of chronic HBV infection in children. We conducted a comprehensive search of multiple databases from 1988 to December 2, 2014, for studies that enrolled children (<18 years) with chronic HBV infection treated with antiviral therapy. We included observational studies and randomized controlled trials (RCTs). Two independent reviewers selected studies and extracted data. In the 14 included studies, two cohort studies showed no significant reduction in the already low risk of hepatocellular carcinoma or cirrhosis and 12 RCTs reported intermediate outcomes. In RCTs with posttreatment follow-up <12 months, antiviral therapy compared to placebo improved alanine aminotransferase normalization (risk ratio [RR] = 2.3, 95% confidence interval [CI] 1.7-3.2), hepatitis B e antigen (HBeAg) clearance/loss (RR = 2.1, 95% CI 1.5-3.1), HBV DNA suppression (RR = 2.9, 95% CI 1.8-4.6), HBeAg seroconversion (RR = 2.1, 95% CI 1.4-3.3), and hepatitis B surface antigen clearance (RR = 5.8, 95% CI 1.1-31.5). In RCTs with posttreatment follow-up ≥12 months, antiviral therapy improved cumulative HBeAg clearance/loss (RR = 1.9, 95% CI 1.7-3.1), HBeAg seroconversion (RR = 2.1, 95% CI 1.3-3.5), alanine aminotransferase normalization (RR = 1.4, 95% CI 1.1-1.7), and HBV DNA suppression (RR = 1.4, 95% CI 1.1-1.8) but not hepatitis B surface antigen clearance or seroconversion. CONCLUSION In children with chronic HBV infection, antivirals compared to no antiviral therapy improve HBV DNA suppression and frequency of alanine aminotransferase normalization and HBeAg seroconversion.
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Affiliation(s)
- Maureen M Jonas
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA
| | - Anna S F Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI
| | - Brian J McMahon
- Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, AK
| | - Robert S Brown
- Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY
| | - John B Wong
- Department of Medicine, Tufts Medical Center, Boston, MA
| | - Ahmed T Ahmed
- Evidence-Based Practice Research Program, Mayo Clinic, Rochester, MN.,Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN
| | - Wigdan Farah
- Evidence-Based Practice Research Program, Mayo Clinic, Rochester, MN.,Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN
| | | | - Siddharth Singh
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | | | - Mohammad Hassan Murad
- Evidence-Based Practice Research Program, Mayo Clinic, Rochester, MN.,Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN.,Division of Preventive, Occupational and Aerospace Medicine, Mayo Clinic, Rochester, MN
| | - Khaled Mohammed
- Evidence-Based Practice Research Program, Mayo Clinic, Rochester, MN.,Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN.,Division of Preventive, Occupational and Aerospace Medicine, Mayo Clinic, Rochester, MN
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20
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Molecular Detection and Characterization of Hepatitis B Virus. Mol Microbiol 2016. [DOI: 10.1128/9781555819071.ch32] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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21
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Brown RS, McMahon BJ, Lok ASF, Wong JB, Ahmed AT, Mouchli MA, Wang Z, Prokop LJ, Murad MH, Mohammed K. Antiviral therapy in chronic hepatitis B viral infection during pregnancy: A systematic review and meta-analysis. Hepatology 2016; 63:319-33. [PMID: 26565396 DOI: 10.1002/hep.28302] [Citation(s) in RCA: 235] [Impact Index Per Article: 26.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2015] [Accepted: 10/15/2015] [Indexed: 12/11/2022]
Abstract
UNLABELLED Perinatal or mother-to-child transmission (MTCT) of hepatitis B virus (HBV) remains the major risk factor for chronic HBV infection worldwide. In addition to hepatitis B immune globulin and vaccination, oral antiviral therapies in highly viremic mothers can further decrease MTCT of HBV. We conducted a systematic review and meta-analysis to synthesize the evidence on the efficacy and maternal and fetal safety of antiviral therapy during pregnancy. A protocol was developed by the American Association for the Study of Liver Diseases guideline writing committee. We searched multiple databases for controlled studies that enrolled pregnant women with chronic HBV infection treated with antiviral therapy. Outcomes of interest were reduction of MTCT and adverse outcomes to mothers and newborns. Study selection and data extraction were done by pairs of independent reviewers. We included 26 studies that enrolled 3622 pregnant women. Antiviral therapy reduced MTCT, as defined by infant hepatitis B surface antigen seropositivity (risk ratio = 0.3, 95% confidence interval 0.2-0.4) or infant HBV DNA seropositivity (risk ratio = 0.3, 95% confidence interval 0.2-0.5) at 6-12 months. No significant differences were found in the congenital malformation rate, prematurity rate, and Apgar scores. Compared to control, lamivudine or telbivudine improved maternal HBV DNA suppression at delivery and during 4-8 weeks' postpartum follow-up. Tenofovir showed improvement in HBV DNA suppression at delivery. No significant differences were found in postpartum hemorrhage, cesarean section, and elevated creatinine kinase rates. CONCLUSIONS Antiviral therapy improves HBV suppression and reduces MTCT in women with chronic HBV infection with high viral load compared to the use of hepatitis B immunoglobulin and vaccination alone; the use of telbivudine, lamivudine, and tenofovir appears to be safe in pregnancy with no increased adverse maternal or fetal outcome.
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Affiliation(s)
- Robert S Brown
- Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY
| | - Brian J McMahon
- Liver Diseases and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, AK
| | - Anna S F Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI
| | - John B Wong
- Division of Clinical Decision Making, Tufts Medical Center, Boston, MA
| | - Ahmed T Ahmed
- Evidence-Based Practice Research Program.,Center for the Science of Health Care Delivery
| | | | - Zhen Wang
- Evidence-Based Practice Research Program.,Center for the Science of Health Care Delivery
| | | | - Mohammad Hassan Murad
- Evidence-Based Practice Research Program.,Center for the Science of Health Care Delivery.,Division of Preventive, Occupational and Aerospace Medicine, Mayo Clinic, Rochester, MN
| | - Khaled Mohammed
- Evidence-Based Practice Research Program.,Center for the Science of Health Care Delivery.,Division of Preventive, Occupational and Aerospace Medicine, Mayo Clinic, Rochester, MN
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22
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Zhang YY, Hu KQ. Rethinking the pathogenesis of hepatitis B virus (HBV) infection. J Med Virol 2015; 87:1989-1999. [PMID: 25989114 DOI: 10.1002/jmv.24270] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2015] [Revised: 05/05/2015] [Accepted: 05/10/2015] [Indexed: 12/11/2022]
Abstract
Chronic hepatitis B virus (HBV) infection affects approximately 375 million people worldwide. Current antiviral treatment effectively controls, but rarely clears chronic HBV infection. In addition, a significant portion of chronic HBV infected patients are not suitable for currently available antiviral therapy, and still face higher risk for cirrhosis and hepatocellular carcinoma. The poorly understood pathogenesis of HBV infection is the main barrier for developing more effective treatment strategies. HBV has long been viewed as non-cytopathic and the central hypothesis for HBV pathogenesis lies in the belief that hepatitis B is a host specific immunity-mediated liver disease. However, this view has been challenged by the accumulating experimental and clinical data that support a model of cytopathic HBV replication. In this article we systematically review the pathogenic role of HBV replication in hepatitis B and suggest possible HBV replication related mechanisms for HBV-mediated liver injury. We propose that a full understanding of HBV pathogenesis should consider the following elements. I. Liver injury can be caused by high levels of HBV replication and accumulation of viral products in the infected hepatocytes. II. HBV infection can be either directly cytopathic, non-cytopathic, or a mix of both in an individual patient depending upon accumulation levels of viral products that are usually associated with HBV replication activity in individual infected hepatocytes.
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Affiliation(s)
| | - Ke-Qin Hu
- Division of Gastroenterology and Hepatology, University of California, Irvine Medical Center, Orange, California
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23
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Keshvari M, Alavian SM, Sharafi H. Comparison of Serum Hepatitis B Virus DNA and HBsAg Levels Between HBeAg-Negative and HBeAg-Positive Chronic Hepatitis B Patients. Jundishapur J Microbiol 2015; 8:e21444. [PMID: 25973160 PMCID: PMC4426187 DOI: 10.5812/jjm.21444] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2014] [Revised: 08/20/2014] [Accepted: 09/06/2014] [Indexed: 01/28/2023] Open
Abstract
BACKGROUND Chronic hepatitis B consists of different clinical phases. Laboratory and histological assessments can help differentiate the clinical phases of this disease and thus lead to better management. OBJECTIVES This study was conducted to determine laboratory and histological characteristics of HBeAg-negative and HBeAg-positive chronic hepatitis B patients. PATIENTS AND METHODS In this study, we evaluated 151 treatment naive chronic hepatitis B patients and grouped them according to their HBeAg status. Serum hepatitis B virus (HBV) DNA and HBsAg levels were measured, and liver function tests, and liver biopsy were performed for the study population. RESULTS There was a significant difference in age, and HBV DNA and HBsAg levels between HBeAg-negative and HBeAg-positive groups yet there was no statistically significant difference in sex, liver function tests, grading and staging of liver biopsy between the groups. Hepatitis B virus DNA and HBsAg levels were correlated in both HBeAg-negative and HBeAg-positive chronic hepatitis B patients. CONCLUSIONS We concluded that chronic hepatitis B patients had different HBV DNA and HBsAg levels according to their HBeAg status.
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Affiliation(s)
- Maryam Keshvari
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, IR Iran
- Middle East Liver Diseases (MELD) Center, Tehran, IR Iran
- Iran Hepatitis Network, Tehran, IR Iran
| | - Seyed Moayed Alavian
- Middle East Liver Diseases (MELD) Center, Tehran, IR Iran
- Iran Hepatitis Network, Tehran, IR Iran
| | - Heidar Sharafi
- Middle East Liver Diseases (MELD) Center, Tehran, IR Iran
- Iran Hepatitis Network, Tehran, IR Iran
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24
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Komatsu H, Inui A, Sogo T, Tsunoda T, Fujisawa T. Chronic hepatitis B virus infection in children and adolescents in Japan. J Pediatr Gastroenterol Nutr 2015; 60:99-104. [PMID: 25221937 DOI: 10.1097/mpg.0000000000000567] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Hepatitis B e antigen (HBeAg) seroconversion is an important event in patients with chronic hepatitis B virus (HBV) infection. This study aimed to clarify the outcome of long-term follow-up of chronic HBV infection and the factors affecting HBeAg seroconversion in children in Japan. METHODS Patients who were first examined at our institution between 1980 and 2012, who were <20 years of age at the time of this initial visit, and who were positive for hepatitis B surface antigen for at least 6 months were identified retrospectively. Sex, age at diagnosis, HBV genotype, maximum serum alanine aminotransferase (ALT) level, occurrence of hepatitis flare-ups (yes/no), and transmission route were evaluated to identify the predictors of HBeAg seroconversion. RESULTS A total of 205 children with chronic HBV were enrolled. Among them, 192 were positive for HBeAg upon diagnosis of chronic HBV infection. Out of this group, 95 (49%) achieved HBeAg seroconversion and 43 (21%) received treatment during the follow-up period. Only the maximum serum ALT level was significantly associated with the achievement of HBeAg seroconversion by multivariate analysis (P < 0.05). Kaplan-Meier analysis showed that the median times to HBeAg seroconversion (50% achievement of HBeAg seroconversion) of the treated and untreated children were 10.2 and 12.0 years, respectively. The cumulative proportion of HBeAg seroconversion was significantly higher in the treated children than in the untreated children (P = 0.02). CONCLUSIONS A higher serum ALT level was a predictor for HBeAg seroconversion. Antiviral treatment could accelerate the achievement of HBeAg seroconversion in HBV-infected children.
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Affiliation(s)
- Haruki Komatsu
- *Department of Pediatrics, Toho University, Sakura Medical Center, Chiba †Department of Pediatric Hepatology and Gastroenterology, Eastern Yokohama Hospital, Kanagawa, Japan
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25
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Lee JI. Reactivation of Hepatitis B Virus in Patients with Rheumatologic Disease Treated with Biologic Disease Modifying Anti-rheumatic Drugs: Screening and Treatment. JOURNAL OF RHEUMATIC DISEASES 2015. [DOI: 10.4078/jrd.2015.22.5.282] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Jung Il Lee
- Division of Gastroenterology, Deparmtment of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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26
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Okonkwo UC, Onyekwere CA. Challenges in the management of chronic HBV infection in West Africa: The clinician's perspective. Trop Doct 2014; 46:16-20. [PMID: 25505192 DOI: 10.1177/0049475514561822] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hepatitis B infection has become a public health issue in recent years. Approximately 350 million of the world's population are chronically infected reaching endemic proportions in West Africa. Guidelines for treatment are continuously improving but are becoming more complex. AIM To determine the challenges hepatologists experience in the management of patients with chronic hepatitis B. METHODS This was a cross-sectional descriptive study conducted among hepatologists in West Africa during a regional hepatitis conference in 2013. RESULTS Forty-six hepatologists completed the questionnaire. When evaluating a patient for chronic hepatitis B, the preferred investigations were: LFT (100%); abdominal ultrasound (93.5%); HBeAg (93.5%); HBV DNA (78%); HBsAg measure (22%); HBV genotype (15.2%); and liver biopsy (34.8%). Most had their patients on nucleoside/nucleotide analogue but follow-up visits after 1 year were problematic. CONCLUSION The majority of hepatologists had good intentions regarding the evaluation of their patients, but only a small percentage of patients are properly investigated.
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Affiliation(s)
- Uchenna C Okonkwo
- Consultant Gastroenterologist/Lecturer, Department of Internal Medicine, University of Calabar Teaching Hospital, Calabar, Nigeria
| | - Charles A Onyekwere
- Chief Consultant Gastroenterologist/Reader, Department of Internal Medicine, Lagos State University Teaching Hospital, Lagos, Nigeria
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27
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Hong SJ, Park HJ, Chu MA, Choi BS, Choe BH. The Rate of Conversion from Immune-tolerant Phase to Early Immune-clearance Phase in Children with Chronic Hepatitis B Virus Infection. Pediatr Gastroenterol Hepatol Nutr 2014; 17:41-46. [PMID: 24749087 PMCID: PMC3990782 DOI: 10.5223/pghn.2014.17.1.41] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2014] [Revised: 03/03/2014] [Accepted: 03/10/2014] [Indexed: 01/10/2023] Open
Abstract
PURPOSE The spontaneous seroconversion rate of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) virus infection in children is lower than that in adults. However, few studies have investigated the rate of transition from the immune-tolerant to the early immune-clearance phase in children. METHODS From February 2000 to August 2011, we enrolled 133 children aged <18 years who had visited the Department of Pediatrics, Kyungpook National University Hospital. All subjects were in the immune-tolerant phase of HBeAg-positive CHB virus infection. The estimated transition rate into the early immune-clearance phase was calculated using the Kaplan-Meier method. RESULTS Among the 133 enrolled pediatric CHB virus infection patients in the HBeAg-positive immune-tolerant phase, only 21 children (15.8%) had converted to the early immune-clearance phase. The average age at entry into active hepatitis was 10.6±4.8 years. The incidence of transition from the immune-tolerant to the early immune-clearance phase in these children was 1.7 episodes/100 patient-years. When analyzed by age, the estimated transition rate was 4.6%, 7.1%, and 28.0% for patients aged <6, 6-12, >12 years, respectively. CONCLUSION In children with CHB virus infection, the estimated rate of entry into the early immune-clearance phase was 28.0% for patients aged 12-18 years, which was significantly higher than that observed for children aged <12 years (11.7%; p=0.001).
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Affiliation(s)
- Suk Jin Hong
- Department of Pediatrics, Catholic University of Daegu School of Medicine, Daegu, Korea
| | - Hyo Jung Park
- Department of Pediatrics, Kyungpook National University School of Medicine, Daegu, Korea
| | - Mi Ae Chu
- Department of Pediatrics, Kyungpook National University School of Medicine, Daegu, Korea
| | - Bong Seok Choi
- Department of Pediatrics, Kyungpook National University School of Medicine, Daegu, Korea
| | - Byung-Ho Choe
- Department of Pediatrics, Kyungpook National University School of Medicine, Daegu, Korea
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28
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Wong GLH, Chan HLY, Yu Z, Chan HY, Tse CH, Wong VWS. Liver fibrosis progression in chronic hepatitis B patients positive for hepatitis B e antigen: a prospective cohort study with paired transient elastography examination. J Gastroenterol Hepatol 2013; 28:1762-9. [PMID: 23808759 DOI: 10.1111/jgh.12312] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/16/2013] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND AIM Chronic hepatitis B patients in immune-reactive hepatitis B e antigen (HBeAg)-positive phase may have more rapid progression than those in immune-tolerant phase. We aimed to evaluate the risk of liver fibrosis progression in HBeAg-positive patients at different phases. METHODS Two hundred forty-seven HBeAg-positive patients without advanced fibrosis at baseline underwent liver stiffness measurement (LSM) by transient elastography in 2006-2008 and again in 2010-2012. Liver fibrosis progression was defined as increase in LSM by 30% or more to levels suggestive of advanced fibrosis at the second assessment. RESULTS At baseline, the mean age was 38 ± 11 years, 58% were males, alanine aminotransferase (ALT) was 65 ± 52 IU/L, hepatitis B virus DNA was 4.2 ± 1.2 log IU/mL, and LSM was 6.3 ± 2.1 kPa. At an interval of 42 ± 6 months, 13 patients (5.2%) developed liver fibrosis progression, and 106 patients (42.9%) required antiviral therapy. None of the clinical parameters (e.g., gender, age, ALT, hepatitis B virus DNA, hepatitis B surface antigen level, etc.) was associated with liver fibrosis progression. Among 74 and 137 patients in immune-tolerant and immune-reactive phase, 4.1% and 6.6% had liver fibrosis progression, and 12.2% and 67.2% received antiviral therapy respectively (P = 0.45 and P < 0.001). Immune-tolerant patients with low-normal (< 0.5× upper limit of normal) or high-normal ALT (0.5-1× upper limit of normal) also had similar risk of liver fibrosis progression (5.7% vs. 2.6%; P = 0.49). CONCLUSIONS Liver fibrosis progression is uncommon in HBeAg-positive patients. Patients in immune-reactive phase treated with antiviral therapy did not have increased risk of liver fibrosis progression.
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Affiliation(s)
- Grace Lai-Hung Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
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30
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Mansourian PG, Ghany MG, Thomas E. Spontaneous Mutations in the HBV Genome and their Clinical Implications. ACTA ACUST UNITED AC 2013. [DOI: 10.1007/s11901-013-0170-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
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Popalis C, Yeung LTF, Ling SC, Ng V, Roberts EA. Chronic hepatitis B virus (HBV) infection in children: 25 years' experience. J Viral Hepat 2013; 20:e20-6. [PMID: 23490385 DOI: 10.1111/jvh.12019] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2012] [Accepted: 09/01/2012] [Indexed: 12/19/2022]
Abstract
Whereas e-seroconversion represents the loss of hepatitis B e-antigen (HBeAg) followed by gain of antibody to HBeAg (anti-HBe), 'inactive chronic infection' extends this concept to include e-seroconversion with decreased serum viral load and biochemical remission. These events must be well-characterized before treatment outcomes can be evaluated. We examined the rates of e-seroconversion and achievement of inactive chronic infection among children with chronic HBV infection. Children who were HBsAg positive >6 months were identified retrospectively between 1983 and 2008 from the Hospital for Sick Children Liver Clinic. Inactive chronic infection was defined as loss of HBeAg, serum ALT ≤40 IU/mL, and HBV DNA <10(6 ) IU/mL. Both e-seroconversion and achievement of inactive chronic infection were characterized using survival analysis. The effect of transmission route, treatment, age at diagnosis, ethnicity, gender and baseline ALT on these rates was evaluated with univariate and multiple regression. Of 252 HBeAg-positive cases, 59.9% had HBV-infected mothers, 77% were Asian, and 33 received interferon-α. Untreated children were younger at last follow-up (mean 14.5 vs 17.6 years), had lower ALT (median 60 vs 116 IU/mL) and had shorter follow-up (6.6 vs 9.1 years, all P < 0.002) compared to treated children. Crude e-seroconversion rate was 41.7% over 0.5-19.1 years of follow-up, and this was not affected by transmission route (P = 0.93), gender (P = 0.62) nor treatment (P = 0.08). 49% achieved inactive chronic infection by age 19 years. Being non-Asian, age at diagnosis<3 years, and ALT ≥40 IU/mL were associated with a higher rate of e-seroconversion and achieving inactive chronic infection (P < 0.0001). Almost 50% of children achieved inactive chronic infection by early adulthood.
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Affiliation(s)
- C Popalis
- Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Toronto, ON, Canada
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32
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Affiliation(s)
- Maureen M. Jonas
- From the Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, MA
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Management of chronic hepatitis B: Canadian Association for the Study of the Liver consensus guidelines. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2013; 26:917-38. [PMID: 23248795 DOI: 10.1155/2012/506819] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Chronic hepatitis B (CHB) is a dynamic disease that is influenced by host and virological factors. The management of CHB has become more complex with the increasing use of long-term oral nucleos⁄tide analogue antiviral therapies and the availability of novel diagnostic assays. Furthermore, there is often a lack of robust data to guide optimal management such as the selection of therapy, duration of treatment, potential antiviral side effects and the treatment of special populations. In November 2011, the Canadian Liver Foundation and the Canadian Association for the Study of the Liver convened a consensus conference to review the literature and analyze published data, including other international expert guidelines on CHB management. The proceedings of the consensus conference are summarized and provide updated clinical practice guidelines to assist Canadian health care providers in the prevention, diagnosis, assessment and treatment of CHB.
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Hepatitis B vaccines. Vaccines (Basel) 2013. [DOI: 10.1016/b978-1-4557-0090-5.00025-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
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Mufti AR, Reau N. A pregnant patient with a positive hepatitis B surface antigen. Frontline Gastroenterol 2013; 4:12-19. [PMID: 28839696 PMCID: PMC5369788 DOI: 10.1136/flgastro-2012-100147] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2012] [Revised: 04/22/2012] [Accepted: 05/30/2012] [Indexed: 02/04/2023] Open
Abstract
Hepatitis B is a major cause of liver disease worldwide. The highest rates of chronic infection occur in subjects who are infected early in life and these patients are also at the greatest risk of developing complications such as hepatocellular carcinoma and cirrhosis from the disease. There has been a concerted worldwide effort to immunise newborns that are at the highest risk of acquiring infection. In 1992, when WHO recommended global vaccination against hepatitis B, only 31 countries elected to participate in the programme. By 2009, 177 countries were part of WHO national infant immunisation programme. Consequently, maternal screening and infant immunoprophylaxis have significantly reduced vertical transmission of hepatitis B. In this paper, we will review the management of hepatitis B in the pregnant population and identify some of the challenges that are encountered in this specialised population.
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Affiliation(s)
- Arjmand Rasool Mufti
- Department of Gastroenterology, Hepatology and Nutrition, University of Chicago Medical Center, Chicago, Illinois, USA
| | - Nancy Reau
- Center for Liver Disease, University of Chicago Medical Center, Chicago, Illinois, USA
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Brown RS, Verna EC, Pereira MR, Tilson HH, Aguilar C, Leu CS, Buti M, Fagan EA. Hepatitis B virus and human immunodeficiency virus drugs in pregnancy: findings from the Antiretroviral Pregnancy Registry. J Hepatol 2012; 57:953-9. [PMID: 22766470 DOI: 10.1016/j.jhep.2012.06.031] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2012] [Revised: 06/14/2012] [Accepted: 06/26/2012] [Indexed: 12/19/2022]
Abstract
BACKGROUND & AIMS Fetal safety of antiviral therapies is important given the long-term treatment of women with chronic hepatitis B (CHB) infection who may become pregnant. We analyzed neonatal safety data from the Antiretroviral Pregnancy Registry (APR), the largest safety database in pregnancy for antivirals used for HIV and CHB. METHODS Data were extracted from APR cases prospectively enrolled between 1989 and 2011. Primary outcomes were major birth defects rates with exposure to all antivirals, individual classes, and drugs compared to population-based controls. Relevant to CHB, only lamivudine (LAM) and tenofovir disoproxil fumarate (TDF) had sufficient individual data for review (≥200 cases). RESULTS Of 13,711 cases analyzed, the overall birth defect prevalence (2.8%, 95% CI 2.6-3.1%) was comparable to Centers for Disease Control population-based data (2.72%, 2.68-2.76%, p=0.87) and two prospective antiretroviral exposed newborn cohorts (2.8%, 2.5-3.2%, p=0.90 and 1.5%, 1.1-2.0%, p<0.001). The birth defects prevalence between first and second/third trimesters exposure was similar (3.0% vs. 2.7%). No increased risk of major birth defects with LAM or TDF exposure compared to population-based controls was observed. No specific pattern of major birth defects was observed for individual antivirals or overall. CONCLUSIONS No increased risk of major birth defects including in non-live births was observed for pregnant women exposed to antivirals relevant to CHB treatment overall or to LAM or TDF compared to population-based controls. Continued safety and efficacy reporting on antivirals in pregnancy are essential to inform patients on their risks and benefits during pregnancy.
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Affiliation(s)
- Robert S Brown
- Center for Liver Disease and Transplantation, Columbia University Medical Center, New York, NY 10032, United States.
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Abstract
UNLABELLED The guideline on the management of chronic hepatitis B (CHB) was first developed in 2004 and revised in 2007 by the Korean Association for the Study of the Liver (KASL). Since then there have been many developments, including the introduction of new antiviral agents and the publications of many novel research results from both Korea and other countries. In particular, a large amount of knowledge on antiviral resistance--which is a serious issue in Korea--has accumulated, which has led to new strategies being suggested. This prompted the new guideline discussed herein to be developed based on recent evidence and expert opinion. TARGET POPULATION The main targets of this guideline comprise patients who are newly diagnosed with CHB and those who are followed or treated for known CHB. This guideline is also intended to provide guidance for the management of patients under the following special circumstances: malignancy, transplantation, dialysis, coinfection with other viruses, pregnancy, and children.
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MESH Headings
- Acute Disease
- Adolescent
- Adult
- Aged
- Alanine Transaminase/blood
- Antiviral Agents/therapeutic use
- Asian People
- Aspartate Aminotransferases/blood
- Carcinoma, Hepatocellular/diagnosis
- Carcinoma, Hepatocellular/etiology
- Child
- Child, Preschool
- Coinfection/drug therapy
- DNA, Viral/blood
- Drug Resistance, Viral
- Drug Therapy, Combination
- Female
- Hepatitis B Surface Antigens/blood
- Hepatitis B e Antigens/blood
- Hepatitis B virus/genetics
- Hepatitis B, Chronic/complications
- Hepatitis B, Chronic/diagnosis
- Hepatitis B, Chronic/drug therapy
- Humans
- Immunosuppression Therapy
- Infectious Disease Transmission, Vertical/prevention & control
- Liver/pathology
- Liver/physiology
- Liver Cirrhosis/physiopathology
- Liver Neoplasms/diagnosis
- Liver Neoplasms/etiology
- Liver Transplantation
- Male
- Middle Aged
- Pregnancy
- Renal Dialysis
- Republic of Korea
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Lok ASF, Negro F. Hepatitis B and D. SCHIFF'S DISEASES OF THE LIVER 2011:537-581. [DOI: 10.1002/9781119950509.ch24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Kwon SY, Lee CH. Epidemiology and prevention of hepatitis B virus infection. THE KOREAN JOURNAL OF HEPATOLOGY 2011; 17:87-95. [PMID: 21757978 PMCID: PMC3304633 DOI: 10.3350/kjhep.2011.17.2.87] [Citation(s) in RCA: 76] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Hepatitis B virus (HBV) infection has been a major global cause of morbidity and mortality. The recognition of the problem led to a worldwide effort to reduce transmission of HBV through routine infant vaccination. HBV infection is the most common cause of chronic liver diseases and hepatocellular carcinoma in Korea. After hepatitis B vaccine era, seroprevalence of hepatits B surface antigen is decreasing, particularly in children. Hepatitis B vaccine is remarkably safe and shows high immunogenicity. Universal childhood immunization with three doses of hepatitis B vaccine in the first year of life is a highly effective method for prevention and control of hepatitis B.
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Affiliation(s)
- So Young Kwon
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
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Yokosuka O, Kurosaki M, Imazeki F, Arase Y, Tanaka Y, Chayama K, Tanaka E, Kumada H, Izumi N, Mizokami M, Kudo M. Management of hepatitis B: Consensus of the Japan Society of Hepatology 2009. Hepatol Res 2011; 41:1-21. [PMID: 21070536 DOI: 10.1111/j.1872-034x.2010.00739.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Recently, much progress has been made in the field of hepatitis B, such as natural history of the disease in relation to the amount of hepatitis B virus (HBV) DNA, genotypes of HBV influencing the natural course and treatment effects, mutations of HBV influencing the severity of the disease and development of hepatocellular carcinoma, and antiviral treatment such as nucleos(t)ide analogues and pegylated interferon. To make the consensus for the diagnosis, management and treatment of hepatitis B, a meeting was held during 45th annual meeting of Japan Society of Hepatology (JSH) in June 2009. In the meeting, recommendations and informative statements were discussed on the following subjects: (i) natural history of HBV infection; (ii) clinical implication of HBV genotypes; (iii) HBV mutations and their potential impact on pathogenesis of HBV infection; (iv) indications for antiviral treatment of chronic hepatitis B; (v) nucleos(t)ide analogues for chronic hepatitis B; and (vi) interferon therapy for chronic hepatitis B. The presenters reviewed the data on these subjects and proposed the consensus statements and recommendations. These statements were discussed among the organizers and presenters, and were approved by the participants of the meeting. In the current report, the relevant data were reviewed and the 12 consensus statements and nine recommendations on chronic hepatitis B were described.
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Affiliation(s)
- Osamu Yokosuka
- Department of Medicine and Clinical Oncology, Postgraduate School of Medicine, Chiba University, Japan
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Fawaz R, Jonas MM. Acute and Chronic Hepatitis. PEDIATRIC GASTROINTESTINAL AND LIVER DISEASE 2011:811-828.e5. [DOI: 10.1016/b978-1-4377-0774-8.10075-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Abstract
Hepatitis B and its complications are one of the major global health problems. Around 2 billion individuals are infected by hepatitis B virus (HBV) worldwide, more than 350 million are chronically infected, and approximately 15 to 40 percents of them will develop serious complications such as liver cirrhosis, hepatic failure, or hepatocellular carcinoma (HCC). The worldwide prevalence of chronic HBV infection ranges from 0.1 to 20 percent and varies widely in different geographic areas. According to the prevalence rate, WHO has classified countries into 3 levels: high areas (>8%) such as Africa, Asia, Western Pacific and Middle East; intermediate areas (2–8%) such as South America and Eastern Europe, and low areas (<2%) such as Western Europe, North America, and Australia.
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Gui HL, Wang H, Yang YH, Wu YW, Zhou HJ, Guo SM, Lin LY, Wang L, Cai W, Chen R, Guo Q, Zhou XQ, Bao SS, Xie Q. Significant histopathology in Chinese chronic hepatitis B patients with persistently high-normal alanine aminotransferase. J Viral Hepat 2010; 17 Suppl 1:44-50. [PMID: 20586933 DOI: 10.1111/j.1365-2893.2010.01270.x] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Current guidelines recommend antiviral therapy for chronic hepatitis B (CHB) patients with elevated alanine aminotransferase (ALT) and high viral load. Scant histological data exist for CHB patients with persistently normal ALT (PNALT) because disease progression is thought to be rare. To identify potential predictors of significant histology in the presence of PNALT, we compared the clinical characteristics and histology of Chinese CHB PNALT patients to those in patients with elevated ALT. Percutaneous liver biopsy was performed in 522 CHB patients with Chinese ethnicity who had not had antiviral treatment. Differences in age, ALT, viral load, hepatitis B e antigen (HBeAg) status and liver histology were compared between eligible PNALT (252) and elevated ALT (270) patients. Of the PNALT patients, 38.5% had normal liver histology, 25.4% had significant necroinflammation and/or fibrosis and 8.4% had established cirrhosis. Furthermore, histopathological differences between patients with high-normal ALT (0.5-1.0 x the upper limit of normal (ULN)) and low-normal ALT (≤ 0.5 x ULN) were evaluated. There was a significantly greater prevalence of histopathology in the high-normal group (40.0%) than in the low-normal group (16.6%) (P < 0.001). Multiple logistic regression identified that significant histopathology findings in PNALT patients correlated with age (P < 0.001) and ALT level (P < 0.001), with age >40 years and ALT >0.5 x ULN predicting significant histopathology. Our data indicate that liver biopsy is recommended in CHB patients >40 years of age, particularly when their ALT is 0.5-1.0 x ULN. The findings above provide evidence for indication of antiviral therapy in patients with PNALT and significant histopathological change.
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Affiliation(s)
- H L Gui
- Department of Infectious Diseases, Ruijin Hospital, Jiaotong University School of Medicine, Shanghai, China
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Mizokami M, Tanaka E, Chayama K, Tanaka Y, Kurosaki M, Izumi N, Arase Y, Kumada H, Imazeki F, Yokosuka O, Kudo M. JSH Consensus Kobe 2009: Diagnosis and Treatment of Hepatitis B. KANZO 2010; 51:243-260. [DOI: 10.2957/kanzo.51.243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/10/2023]
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Lindh M, Uhnoo I, Bläckberg J, Duberg AS, Friman S, Fischler B, Karlström O, Norkrans G, Reichard O, Sangfeldt P, Söderström A, Sönnerborg A, Weiland O, Wejstål R, Wiström J. Treatment of chronic hepatitis B infection: An update of Swedish recommendations. ACTA ACUST UNITED AC 2009; 40:436-50. [PMID: 18584530 DOI: 10.1080/00365540802154769] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Söderström A, Lindh M, Ekholm K, Conradi N, Horal P, Krantz M, Hultgren C, Norkrans G. Predictive factors and virological response to interferon treatment in children with chronic hepatitis B. ACTA ACUST UNITED AC 2009; 37:40-7. [PMID: 15764189 DOI: 10.1080/00365540410026031] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Further knowledge about factors predicting response to interferon treatment for chronic hepatitis B in children is required, in particular as the benefits of therapy are uncertain. In the present study, baseline characteristics were related to virological and histological responses in 27 children given interferon-alpha for 24 weeks after steroid priming. HBe seroconversion was seen in 8 of 27 HBeAg positive patients and was accompanied by a sustained virological response (SR), with a median 4.1 log HBV DNA reduction. Pretreatment viraemia level was the only baseline parameter associated with SR. After 12 weeks of IFN (mid-treatment), viraemia was significantly reduced in all patients, with a median of 3.0 (range 0.6-5.2) log decline in SR compared with 0.6 (range -0.5-3.6) log decline in non-sustained responders (NSR). HBV DNA levels below 1 million copies/ml at week 12 predicted sustained response with a positive predictive value of 75% and a negative predictive value of 89%. During the latter half of the IFN treatment HBV DNA tended to increase by a mean of 0.4-0.5 log for all patient groups. Flares during IFN treatment were rare or mild as measured by ALT. Pretreatment anti-HBc IgM was associated with liver damage but not with response. Histological inflammation scores were improved in SR. Thus, pretreatment HBV DNA levels were associated with IFN response, and the virological response at week 12 predicts SR and may be useful in the decision to continue or modify therapy.
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Affiliation(s)
- Ann Söderström
- Department of Infectious Diseases, Göteborg University, Sweden
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[Natural history and clinical manifestations of chronic hepatitis B virus]. Enferm Infecc Microbiol Clin 2009; 26 Suppl 7:11-8. [PMID: 19100227 DOI: 10.1016/s0213-005x(08)76515-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Hepatitis B virus (HBV) infection is a serious public health problem worldwide. In the last few decades, major advances have been achieved that have contributed to greater understanding of the natural history and clinical manifestations of this infection. The fluctuation between viral replication and the host's immune response has implications in the pathogenesis and progression of the hepatic lesion. In immunocompetent adults, most HBV infections resolve spontaneously in contrast with progression to chronic infection in most infants. Patients with chronic hepatitis due to HBV or chronic hepatitis B can present at four phases: 1) the immune tolerance phase, 2) HBeAg-positive chronic hepatitis B, 3) inactive HBsAg carrier state, and 4) HBeAg-negative chronic hepatitis. HBeAg-positive or -negative chronic hepatitis can progress to cirrhosis, liver failure and hepatocellular carcinoma. Progression to these complications is more frequent in HBeAg-negative forms, associated with mutations that affect the pre-core region and maintain active viral replication. Risk factors are HBV-DNA positive serum levels, an increase in serum transaminase levels and some genotypes. These factors highlight the need to evaluate and monitor all HBV carriers to identify those who could benefit from early antiviral treatment, thus avoiding progression to more advanced forms of liver disease. These measures could improve prevention and treatment of hepatitis B.
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Abstract
This article summarizes the meta-analyses of interventions for viral hepatitis A, B, and C. Some of the interventions assessed are described in small trials with unclear bias control. Other interventions are supported by large, high-quality trials. Although attempts have been made to adjust for unclear bias control, analysis of publication bias and other biases is difficult when only few trials are available. It is possible that some of the meta-analyses presented in this article are biased. Furthermore, performing updated cumulative meta-analyses also may introduce random error.3,4 The extent and direction of bias may vary. On average, however, bias leads to overestimated intervention benefits.1 Accordingly, the benefit of some of the interventions suggested in this article may be exaggerated by systematic and random errors. Additional research including large, randomized trials is necessary to clarify the true intervention effects.
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Affiliation(s)
- Lise L Gluud
- Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
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