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Kim HS, Chen X, Xu M, Yan C, Liu Y, Deng H, Hoang BH, Thuy PTT, Wang T, Yan Y, Zeng Z, Gencay M, Westergaard G, Pabinger S, Kriegner A, Nauck M, Seffner A, Gohl P, Hübner K, Kaminski WE. Frequency of hepatitis B surface antigen variants (HBsAg) in hepatitis B virus genotype B and C infected East- and Southeast Asian patients: Detection by the Elecsys ® HBsAg II assay. J Clin Virol 2018; 103:48-56. [PMID: 29655170 DOI: 10.1016/j.jcv.2018.04.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Revised: 03/29/2018] [Accepted: 04/04/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND To avoid false negative results, hepatitis B surface antigen (HBsAg) assays need to detect samples with mutations in the immunodominant 'a' determinant region, which vary by ethnographic region. OBJECTIVE We evaluated the prevalence and type of HBsAg mutations in a hepatitis B virus (HBV)-infected East- and Southeast Asian population, and the diagnostic performance of the Elecsys® HBsAg II Qualitative assay. STUDY DESIGN We analyzed 898 samples from patients with HBV infection from four sites (China [Beijing and Guangzhou], Korea and Vietnam). HBsAg mutations were detected and sequenced using highly sensitive ultra-deep sequencing and compared between the first (amino acids 124-137) and second (amino acids 139-147) loops of the 'a' determinant region using the Elecsys® HBsAg II Qualitative assay. RESULTS Overall, 237 distinct amino acid mutations in the major hydrophilic region were identified; mutations were present in 660 of 898 HBV-infected patient samples (73.5%). Within the pool of 237 distinct mutations, the majority of the amino acid mutations were found in HBV genotype C (64.8%). We identified 25 previously unknown distinct mutations, mostly prevalent in genotype C-infected Korean patients (n = 18) followed by Chinese (n = 12) patients. All 898 samples were correctly identified by the Elecsys® HBsAg II Qualitative assay. CONCLUSIONS We observed 237 distinct (including 25 novel) mutations, demonstrating the complexity of HBsAg variants in HBV-infected East- and Southeast Asian patients. The Elecsys® HBsAg II Qualitative assay can reliably detect HBV-positive samples and is suitable for routine diagnostic use in East and Southeast Asia.
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Affiliation(s)
- Hyon Suk Kim
- Department of Laboratory Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul, South Korea
| | - Xinyue Chen
- Department of Liver Diseases, You'an Hospital, Capital Medical University, Beijing, China
| | - Min Xu
- Hepatology Department, Guangzhou No. 8 People's Hospital, Guangzhou, China
| | - Cunling Yan
- Department of Clinical Laboratory, Peking University First Hospital, Beijing, China
| | - Yali Liu
- Department of Liver Diseases, You'an Hospital, Capital Medical University, Beijing, China
| | - Haohui Deng
- Hepatology Department, Guangzhou No. 8 People's Hospital, Guangzhou, China
| | - Bui Huu Hoang
- Gastroenterology Department, Ho Chi Minh City University Medical Center, Ho Chi Minh City, Vietnam
| | - Pham Thi Thu Thuy
- Hepatology Department, Medic Medical Center, Ho Chi Minh City, Vietnam
| | | | - Yiwen Yan
- Roche Diagnostics Ltd., Shanghai, China
| | - Zhen Zeng
- Roche Diagnostics Ltd., Shanghai, China
| | - Mikael Gencay
- Roche Diagnostics International Ltd., Rotkreuz, Switzerland
| | | | - Stephan Pabinger
- AIT Austrian Institute of Technology, Molecular Diagnostics, Center for Health and Bioresources, Vienna, Austria
| | | | - Markus Nauck
- Bioscientia Institute for Medical Diagnostics GmbH, Ingelheim, Germany
| | - Anja Seffner
- MVZ Labor Dr. Limbach & Kollegen GbR, Department of Molecular Genetics and Microbiology, Heidelberg, Germany
| | - Peter Gohl
- Bioscientia Institute for Medical Diagnostics GmbH, Ingelheim, Germany
| | - Kirsten Hübner
- Bioscientia Institute for Medical Diagnostics GmbH, Ingelheim, Germany
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2
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Gencay M, Vermeulen M, Neofytos D, Westergaard G, Pabinger S, Kriegner A, Seffner A, Gohl P, Huebner K, Nauck M, Kaminski WE. Substantial variation in the hepatitis B surface antigen (HBsAg) in hepatitis B virus (HBV)-positive patients from South Africa: Reliable detection of HBV by the Elecsys HBsAg II assay. J Clin Virol 2018; 101:38-43. [DOI: 10.1016/j.jcv.2018.01.011] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Revised: 01/12/2018] [Accepted: 01/21/2018] [Indexed: 02/07/2023]
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3
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Basnayake SK, Easterbrook PJ. Wide variation in estimates of global prevalence and burden of chronic hepatitis B and C infection cited in published literature. J Viral Hepat 2016; 23:545-59. [PMID: 27028545 DOI: 10.1111/jvh.12519] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Accepted: 01/14/2016] [Indexed: 12/15/2022]
Abstract
To evaluate the extent of heterogeneity in global estimates of chronic hepatitis B (HBV) and C (HCV) cited in the published literature, we undertook a systematic review of the published literature. We identified articles from 2010 to 2014 that had cited global estimates for at least one of ten indicators [prevalence and numbers infected with HBV, HCV, HIV-HBV or HIV-HCV co-infection, and mortality (number of deaths annually) for HBV and HCV]. Overall, 488 articles were retrieved: 239 articles cited a HBV-related global estimate [prevalence (n = 12), number infected (n = 193) and number of annual deaths (n = 82)]; 280 articles had HCV-related global estimates [prevalence (n = 86), number infected (n = 203) and number of annual deaths (n = 31)]; 31 had estimates on both HBV and HCV; 54 had HIV-HBV co-infection estimates [prevalence (n = 42) and number co-infected (n = 12)]; and 68 had estimates for HIV-HCV co-infection [prevalence (n = 40) and number co-infected (n = 28)]. There was considerable heterogeneity in the estimates cited and also a lack of consistency in the terminology used. Although 40% of 488 articles cited WHO as the source of the estimate, many of these were from outdated or secondary sources. Our findings highlight the importance of clear and consistent communication from WHO and other global health agencies on current consensus estimates of hepatitis B and C burden and prevalence, the need for standardisation in their citation, and for regular updates.
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Affiliation(s)
| | - P J Easterbrook
- Global Hepatitis Programme, HIV Department, World Health Organization, Geneva, Switzerland
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Coppola N, Onorato L, Minichini C, Di Caprio G, Starace M, Sagnelli C, Sagnelli E. Clinical significance of hepatitis B surface antigen mutants. World J Hepatol 2015; 7:2729-2739. [PMID: 26644816 PMCID: PMC4663392 DOI: 10.4254/wjh.v7.i27.2729] [Citation(s) in RCA: 63] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Revised: 09/27/2015] [Accepted: 11/13/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) infection is a major public health problem in many countries, with nearly 300 million people worldwide carrying HBV chronic infection and over 1 million deaths per year due to cirrhosis and liver cancer. Several hepatitis B surface antigen (HBsAg) mutations have been described, most frequently due to a single amino acid substitution and seldom to a nucleotide deletion. The majority of mutations are located in the S region, but they have also been found in the pre-S1 and pre-S2 regions. Single amino acid substitutions in the major hydrophilic region of HBsAg, called the "a" determinant, have been associated with immune escape and the consequent failure of HBV vaccination and HBsAg detection, whereas deletions in the pre-S1 or pre-S2 regions have been associated with the development of hepatocellular carcinoma. This review article will focus on the HBsAg mutants and their biological and clinical implications.
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Affiliation(s)
- Nicola Coppola
- Nicola Coppola, Lorenzo Onorato, Carmine Minichini, Giovanni Di Caprio, Mario Starace, Evangelista Sagnelli, Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, 80131 Naples, Italy
| | - Lorenzo Onorato
- Nicola Coppola, Lorenzo Onorato, Carmine Minichini, Giovanni Di Caprio, Mario Starace, Evangelista Sagnelli, Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, 80131 Naples, Italy
| | - Carmine Minichini
- Nicola Coppola, Lorenzo Onorato, Carmine Minichini, Giovanni Di Caprio, Mario Starace, Evangelista Sagnelli, Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, 80131 Naples, Italy
| | - Giovanni Di Caprio
- Nicola Coppola, Lorenzo Onorato, Carmine Minichini, Giovanni Di Caprio, Mario Starace, Evangelista Sagnelli, Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, 80131 Naples, Italy
| | - Mario Starace
- Nicola Coppola, Lorenzo Onorato, Carmine Minichini, Giovanni Di Caprio, Mario Starace, Evangelista Sagnelli, Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, 80131 Naples, Italy
| | - Caterina Sagnelli
- Nicola Coppola, Lorenzo Onorato, Carmine Minichini, Giovanni Di Caprio, Mario Starace, Evangelista Sagnelli, Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, 80131 Naples, Italy
| | - Evangelista Sagnelli
- Nicola Coppola, Lorenzo Onorato, Carmine Minichini, Giovanni Di Caprio, Mario Starace, Evangelista Sagnelli, Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, 80131 Naples, Italy
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5
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Mohan M, James P, Valsalan R, Nazeem PA. Molecular docking studies of phytochemicals from Phyllanthus niruri against Hepatitis B DNA Polymerase. Bioinformation 2015; 11:426-31. [PMID: 26527851 PMCID: PMC4620619 DOI: 10.6026/97320630011426] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2015] [Accepted: 07/26/2015] [Indexed: 02/07/2023] Open
Abstract
Hepatitis B virus (HBV) infection is the leading cause for liver disorders and can lead to hepatocellular carcinoma, cirrhosis and liver damage which in turn can cause death of patients. HBV DNA Polymerase is essential for HBV replication in the host and hence is used as one of the most potent pharmacological target for the inhibition of HBV. Chronic hepatitis B is currently treated with nucleotide analogues that suppress viral reverse transcriptase activity and most of them are reported to have viral resistance. Therefore, it is of interest to model HBV DNA polymerase to dock known phytochemicals. The present study focuses on homology modeling and molecular docking analysis of phytocompounds from the traditional antidote Phyllanthus niruri and other nucleoside analogues against HBV DNA Polymerase using the software Discovery studio 4.0. 3D structure of HBV DNA Polymerase was predicted based on previously reported alignment. Docking studies revealed that a few phytochemicals from Phyllanthus niruri had good interactions with HBV DNA Polymerase. These compounds had acceptable binding properties for further in vitro validation. Thus the study puts forth experimental validation for traditional antidote and these phytocompounds could be further promoted as potential lead molecule.
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Affiliation(s)
- Mekha Mohan
- Bioinformatics Centre (DIC), Kerala Agricultural University, India
| | - Priyanka James
- Bioinformatics Centre (DIC), Kerala Agricultural University, India
| | - Ravisankar Valsalan
- Bioinformatics Centre (DIC), Kerala Agricultural University, KAU P.O, Vellanikkara, Kerala, India -680656
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Abstract
For two decades, hepatitis B vaccine has been integrated into national routine childhood vaccination programs in almost all countries. The prevalence of HBsAg has decreased in children worldwide. However, there are children who miss the benefit of hepatitis B vaccine in some regions and countries. Long-term follow-up studies have revealed the clinical outcomes of chronic hepatitis B virus infection in children. A small percentage of chronically infected children develop liver cirrhosis and hepatocellular carcinoma. However, it is controversial who should be treated and when antiviral treatment should be initiated in children. Compared with adult studies, the data are insufficient to evaluate the pathogenesis of hepatitis B infection and the efficacy of antiviral treatment in childhood. New antiviral drugs have been approved for children and adults. Also, oral antiviral drugs are administered to pregnant women to reduce the hepatitis B virus mother-to-child transmission rate.
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Affiliation(s)
- Haruki Komatsu
- Department of Pediatrics, Toho University, Sakura Medical Center, 564-1 Shimoshizu Sakura, Chiba, 285-8741, Japan
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7
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Gentile I, Buonomo AR, Zappulo E, Borgia G. Interferon-free therapies for chronic hepatitis C: toward a hepatitis C virus-free world? Expert Rev Anti Infect Ther 2015; 12:763-73. [PMID: 24918116 DOI: 10.1586/14787210.2014.929497] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
About 2% of the world's population is estimated to be chronically infected with hepatitis C virus (HCV). These chronic carriers are at risk of developing liver cirrhosis and its complications. Successful treatment of HCV infection is associated with improved quality of life and increased survival. Antiviral approaches were formerly based on interferon and therefore all patients with a contraindication to interferon were excluded from treatment (e.g., patients with decompensated disease, severe impairment of other organs). Very recently, interferon-free combinations have become available for genotypes 2 and 3. This review focuses on the most recently reported data on the various interferon-free combinations used (namely, sofosbuvir-based combinations, the ABT-450/ombitasvir/dasabuvir/ribavirin combination, the daclatasvir/asunaprevir combination, and the MK-5172/MK-8742 combination). All these combinations yielded amazing results in terms of efficacy (90-100%), tolerability and safety. If the problem of the high cost is overcome, interferon-free therapies will lead to what has long been a chimera, namely, an HCV-free world.
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Affiliation(s)
- Ivan Gentile
- Department of Clinical Medicine and Surgery, University of Naples "Federico II", via S. Pansini 5, I-80131 Naples, Italy
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Coppola N, Sagnelli C, Pisaturo M, Minichini C, Messina V, Alessio L, Starace M, Signoriello G, Gentile I, Filippini P, Sagnelli E. Clinical and virological characteristics associated with severe acute hepatitis B. Clin Microbiol Infect 2014; 20:O991-O997. [PMID: 24930916 DOI: 10.1111/1469-0691.12720] [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] [Received: 04/27/2014] [Revised: 06/08/2014] [Accepted: 06/10/2014] [Indexed: 12/16/2022]
Abstract
To identify early predictors of a severe or fulminant course in patients with acute viral hepatitis B (AVH-B). One hundred and thirty-eight patients with symptomatic acute hepatitis B observed from 1999 to 2012 were enrolled. For each patient, the demographics, risk factors for the acquisition of hepatitis B virus (HBV) infection, clinical, biochemical and virological data (HBV DNA, HBV DNA sequences) were recorded and analysed. The HBV mutants in the polymerase region were sought in 110 (87%) patients by direct sequencing, and the rtM204V/I mutations also by an allele-specific PCR. AVH-B was severe in 13 (9.4%) of the 138 patients enrolled, fulminant in 6 (4.3%) and with a normal clinical course in 119. The 19 patients with severe or fulminant AVH-B more frequently than the 119 with a normal course stated intravenous drug use (63.2% versus 36.1%, p 0.04) and were HBV-DNA negative (31.6% versus 11.8%, p 0.03) and anti-hepatitis C virus (HCV) positive (57.9% versus 19.3%, p 0.0008); the prevalences of different HBV genotypes and of the rtM204V/I mutant were similar in these three forms of AVH-B. A multivariate logistic regression analysis identified a pre-existing HCV chronic infection as the only factor independently associated with a severe or fulminant clinical course of AVH-B (OR 4.89, 95% CI 1.5-15.94, p 0.01). A pre-existing HCV chronic infection was identified as the only factor independently associated with a severe clinical presentation of acute hepatitis B, an association most probably due to the combination of the liver lesions caused by acute hepatitis B and the pre-existing histological abnormalities related to HCV chronic infection.
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Affiliation(s)
- N Coppola
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Naples, Italy
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9
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Sagnelli E, Sagnelli C, Pisaturo M, Macera M, Coppola N. Epidemiology of acute and chronic hepatitis B and delta over the last 5 decades in Italy. World J Gastroenterol 2014; 20:7635-7643. [PMID: 24976701 PMCID: PMC4069292 DOI: 10.3748/wjg.v20.i24.7635] [Citation(s) in RCA: 84] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2013] [Revised: 01/28/2014] [Accepted: 04/08/2014] [Indexed: 02/06/2023] Open
Abstract
The spread of hepatitis B virus (HBV) infection has gradually decreased in Italy in the last 5 decades as shown by the steady reduction in the incidence rates of acute hepatitis B, from 10/100000 inhabitants in 1984 to 0.85/100000 in 2012, and by the reduced prevalence of hepatitis B surface antigen (HBsAg)-positive cases among chronic hepatitis patients with different etiologies, from 60% in 1975 to about 10% in 2001. The prevalence of HBsAg chronic carriers in the general population also decreased from nearly 3% in the 1980s to 1% in 2010. Linked to HBV by its characteristics of defective virus, the hepatitis delta virus (HDV) has shown a similar epidemiological impact on the Italian population over time. The incidence of acute HDV infection decreased from 3.2/100000 inhabitants in 1987 to 0.8/100000 in 2010 and the prevalence of HDV infection in HBsAg chronic carriers decreased from 24% in 1990 to 8.5% in 2006. Before the beneficial effects of HBV mass vaccination introduced in 1991, the decreased endemicity of HBV and HDV infection in Italy paralleled the improvement in screening blood donations, the higher standard of living and impressive reduction in the birth rate associated with a marked reduction in the family size. A further contribution to the decline in HBV and HDV infections most probably came from the media campaigns to prevent the spread of human immunodeficiency virus infection by focusing the attention of the general population on the same routes of transmission of viral infections such as unsafe sexual intercourse and parenteral exposures of different kinds.
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Gentile I, Buonomo AR, Zappulo E, Minei G, Morisco F, Borrelli F, Coppola N, Borgia G. Asunaprevir, a protease inhibitor for the treatment of hepatitis C infection. Ther Clin Risk Manag 2014; 10:493-504. [PMID: 25061308 PMCID: PMC4079632 DOI: 10.2147/tcrm.s66731] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
According to the World Health Organization, approximately 150 million people worldwide are chronic carriers of hepatitis C virus (HCV). HCV infection can evolve into cirrhosis of the liver and its complications, which are ultimately responsible for more than 350,000 deaths every year. Antiviral therapy, when successful, is able to decrease the rate of progression and increase survival. Two types of therapies are currently available, ie, interferon-based therapies and interferon-free ones. The latter have several advantages in terms of safety and tolerability, and could be used even in the most advanced stages of the disease. However, their use is restricted to some viral genotypes (genotype 2 and 3) and they are expensive. Several molecules are in an advanced phase of development. This review deals with the pharmacokinetics, pharmacodynamics, tolerability, and safety of asunaprevir, an inhibitor of HCV nonstructural 3 protease. Asunaprevir exerts optimal in vitro activity particularly against HCV genotypes 1 and 4, and its pharmacokinetic profile enables twice daily administration. The drawback of asunaprevir, and of all protease inhibitors, is its low barrier to resistance. Consequently, it is used in association with other drugs to prevent resistance. Specifically, when combined with daclatasvir, an NS5A inhibitor, asunaprevir results in a very high rate of viral eradication in both treatment-naïve and treatment-experienced patients, with a sustained virological response rate of 80%-90%. Tolerability is fair; in fact, asunaprevir is associated with a transient increase in aminotransferase levels, which is mild in most cases. In conclusion, asunaprevir is a good candidate component of interferon-free combinations and may revolutionize the treatment of chronic HCV infection in the near future.
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Affiliation(s)
- Ivan Gentile
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Antonio Riccardo Buonomo
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Emanuela Zappulo
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Giuseppina Minei
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Filomena Morisco
- Section of Gastroenterology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Francesco Borrelli
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Nicola Coppola
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy
| | - Guglielmo Borgia
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
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11
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Frambo AAB, Atashili J, Fon PN, Ndumbe PM. Prevalence of HBsAg and knowledge about hepatitis B in pregnancy in the Buea Health District, Cameroon: a cross-sectional study. BMC Res Notes 2014; 7:394. [PMID: 24965844 PMCID: PMC4082373 DOI: 10.1186/1756-0500-7-394] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2013] [Accepted: 06/20/2014] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND Although infection with Hepatitis B Virus (HBV) remains a global public health problem, little is known about its epidemiology in pregnancy in sub-Saharan Africa. This study sought to determine the prevalence of, and identify factors associated with hepatitis B surface antigen (HBsAg) positivity among pregnant women in the Buea Health District (BHD) in rural Cameroon. We also assessed pregnant women's knowledge about hepatitis B. METHODS A cross-sectional, descriptive study was undertaken. Participants were evaluated using a structured questionnaire with clinical examination and were then screened for HBsAg using a commercial rapid diagnostic test. Assessment of knowledge was done using a hepatitis B basic knowledge summary score. RESULTS Of the 176 pregnant women studied, 9.7% (95% CI: 5.7%, 15%) tested positive for HBsAg. None of the risk factors assessed was significantly associated with HBsAg positivity. The hepatitis B knowledge summary score ranged from 0 to 12 with a mean of 1.5 (SD = 3.14, median = 0, IQR = 0 to 0). Only 16% of participants had scores greater than 6/12. The knowledge summary score of the participants was associated with the educational level (p-value = 0.0037). CONCLUSION The high prevalence of HBsAg (9.7%) among women of child bearing age suggests that vertical transmission of HBV may be a public health problem in Buea Health District. Knowledge of HBV among pregnant women was poor. We recommend that all pregnant women ought to be routinely screened for HBV and that health education on HBV should be provided to pregnant women especially during antenatal visits.
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Affiliation(s)
- Andreas A Besong Frambo
- Department of Public Health and Hygiene, Faculty of Health Sciences, University of Buea, P.O, Box, 63, Buea, Cameroon
| | - Julius Atashili
- Department of Public Health and Hygiene, Faculty of Health Sciences, University of Buea, P.O, Box, 63, Buea, Cameroon
| | - Peter Nde Fon
- Department of Public Health and Hygiene, Faculty of Health Sciences, University of Buea, P.O, Box, 63, Buea, Cameroon
| | - Peter Martins Ndumbe
- Department of Public Health and Hygiene, Faculty of Health Sciences, University of Buea, P.O, Box, 63, Buea, Cameroon
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12
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Gentile I, Borgia G. Vertical transmission of hepatitis B virus: challenges and solutions. Int J Womens Health 2014; 6:605-11. [PMID: 24966696 PMCID: PMC4062549 DOI: 10.2147/ijwh.s51138] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
More than 240 million people worldwide are chronically infected with hepatitis B virus (HBV). Mother-to-child transmission remains the most important mechanism of infection in countries with a high prevalence of HBV. Universal screening of all pregnant women, at-birth prophylaxis with specific anti-HBV immune globulin, as well as HBV vaccination for newborns of infected mothers are effective in reducing the risk of vertical transmission. However, in cases of a high viral load and hepatitis B e antigen positivity, there is a residual risk of HBV transmission to the newborn despite prophylaxis. This review focuses on the above-indicated strategies and on the efficacy and safety of antiviral drugs administered during the third trimester of pregnancy.
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Affiliation(s)
- Ivan Gentile
- Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy
| | - Guglielmo Borgia
- Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy
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13
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Gentile I, Zappulo E, Buonomo AR, Borgia G. Prevention of mother-to-child transmission of hepatitis B virus and hepatitis C virus. Expert Rev Anti Infect Ther 2014; 12:775-82. [PMID: 24840817 DOI: 10.1586/14787210.2014.920254] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
About 240 million people worldwide are chronically infected with hepatitis B virus (HBV). Vertical transmission is the most important mechanism of infection persistence in endemic areas. About 150 million people worldwide are chronically infected with hepatitis C virus (HCV). Mother-to-child transmission of HCV, which occurs in 3-10% of cases, is the leading route of infection in childhood. This review focuses on strategies to reduce the vertical transmission of HBV and HCV. The at-birth prophylaxis of newborns of HBV-infected mothers with specific immunoglobulin and vaccine plus administration of antivirals (tenofovir or telbivudine) in the third trimester of pregnancy (in case of high maternal viral load) greatly reduces the risk of transmission. In contrast, currently there is no drug able to reduce the vertical transmission of HCV infection. We discuss the possibility of reducing mother-to-child HCV transmission using newly available antivirals or antivirals in the pipeline for the treatment of hepatitis C.
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Affiliation(s)
- Ivan Gentile
- Department of Clinical Medicine and Surgery, University of Naples "Federico II", via S. Pansini 5, Naples, Italy
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Gentile I, Buonomo AR, Borgia F, Castaldo G, Borgia G. Ledipasvir: a novel synthetic antiviral for the treatment of HCV infection. Expert Opin Investig Drugs 2014; 23:561-71. [DOI: 10.1517/13543784.2014.892581] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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Wang J, Sánchez-Roselló M, Aceña JL, del Pozo C, Sorochinsky AE, Fustero S, Soloshonok VA, Liu H. Fluorine in Pharmaceutical Industry: Fluorine-Containing Drugs Introduced to the Market in the Last Decade (2001–2011). Chem Rev 2013; 114:2432-506. [DOI: 10.1021/cr4002879] [Citation(s) in RCA: 3607] [Impact Index Per Article: 300.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Jiang Wang
- Key
Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China
| | - María Sánchez-Roselló
- Department
of Organic Chemistry, Faculty of Pharmacy, University of Valencia, Av. Vicente Andrés Estellés, 46100 Burjassot, Valencia, Spain
- Laboratorio
de Moléculas Orgánicas, Centro de Investigación Príncipe Felipe, C/ Eduardo Primo Yúfera 3, 46012 Valencia, Spain
| | - José Luis Aceña
- Department
of Organic Chemistry I, Faculty of Chemistry, University of the Basque Country UPV/EHU, Paseo Manuel Lardizábal 3, 20018 San Sebastian, Spain
| | - Carlos del Pozo
- Department
of Organic Chemistry, Faculty of Pharmacy, University of Valencia, Av. Vicente Andrés Estellés, 46100 Burjassot, Valencia, Spain
| | - Alexander E. Sorochinsky
- Department
of Organic Chemistry I, Faculty of Chemistry, University of the Basque Country UPV/EHU, Paseo Manuel Lardizábal 3, 20018 San Sebastian, Spain
- IKERBASQUE, Basque Foundation for Science, Alameda Urquijo, 36-5 Plaza Bizkaia, 48011 Bilbao, Spain
- Institute
of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, Murmanska Street 1, 02660 Kyiv-94, Ukraine
| | - Santos Fustero
- Department
of Organic Chemistry, Faculty of Pharmacy, University of Valencia, Av. Vicente Andrés Estellés, 46100 Burjassot, Valencia, Spain
- Laboratorio
de Moléculas Orgánicas, Centro de Investigación Príncipe Felipe, C/ Eduardo Primo Yúfera 3, 46012 Valencia, Spain
| | - Vadim A. Soloshonok
- Department
of Organic Chemistry I, Faculty of Chemistry, University of the Basque Country UPV/EHU, Paseo Manuel Lardizábal 3, 20018 San Sebastian, Spain
- IKERBASQUE, Basque Foundation for Science, Alameda Urquijo, 36-5 Plaza Bizkaia, 48011 Bilbao, Spain
| | - Hong Liu
- Key
Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China
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16
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Kim SB, Song IH, Kim YM, Noh R, Kang HY, Lee HI, Yang HY, Kim AN, Chae HB, Lee SH, Kim HS, Lee TH, Kang YW, Lee ES, Kim SH, Lee BS, Lee HY. Long-term treatment outcomes of clevudine in antiviral-naive patients with chronic hepatitis B. World J Gastroenterol 2012; 18:6943-50. [PMID: 23322992 PMCID: PMC3531678 DOI: 10.3748/wjg.v18.i47.6943] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2012] [Revised: 10/22/2012] [Accepted: 10/30/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the treatment outcomes of clevudine compared with entecavir in antiviral-naive patients with chronic hepatitis B (CHB).
METHODS: We retrospectively analyzed the clinical data of CHB patients treated with clevudine 30 mg/d and compared their clinical outcomes with patients treated with entecavir 0.5 mg/d. The biochemical response, as assessed by serum alanine aminotransferase (ALT) activity, virologic response, as assessed by serum hepatitis B virus DNA (HBV DNA) titer, serologic response, as assessed by hepatitis B e antigen (HBeAg) status, and virologic breakthrough with genotypic mutations were assessed.
RESULTS: Two-hundred and fifty-four patients [clevudine (n = 118) vs entecavir (n = 136)] were enrolled. In clevudine-treated patients, the cumulative rates of serum ALT normalization were 83.9% at week 48 and 91.5% at week 96 (80.9% and 91.2% in the entecavir group, respectively), the mean titer changes in serum HBV DNA were -6.03 and -6.55 log10 copies/mL (-6.35 and -6.86 log10 copies/mL, respectively, in the entecavir group), and the cumulative non-detection rates of serum HBV DNA were 72.6% and 83.1% (74.4% and 83.8%, respectively, in the entecavir group). These results were similar to those of entecavir-treated patients. The cumulative rates of HBeAg seroconversion were 21.8% at week 48 and 25.0% at week 96 in patients treated with clevudine, which was similar to patients treated with entecavir (22.8% and 27.7%, respectively). The virologic breakthrough in the clevudine group occurred in 9 (7.6%) patients at weeks 48 and 15 (12.7%) patients at week 96, which primarily corresponded to genotypic mutations of rtM204I and/or rtL180M. There was no virologic breakthrough in the entecavir group.
CONCLUSION: In antiviral-naive CHB patients, long-term treatment outcomes of clevudine were not inferior to those of entecavir, except for virologic breakthrough.
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17
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Wang M, Da Y, Cai H, Lu Y, Wu L, Jia J. Telbivudine myopathy in a patient with chronic hepatitis B. Int J Clin Pharm 2012; 34:422-5. [PMID: 22527478 DOI: 10.1007/s11096-012-9633-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2011] [Accepted: 03/29/2012] [Indexed: 12/11/2022]
Abstract
CASE A 25-year-old man with hepatitis B virus (HBV) infection received antiviral treatment with telbivudine 600 mg daily. Six months after starting treatment, the patient developed progressive weakness and myalgia. Physical examination showed symmetrical proximal weakness. Blood tests at admission revealed positive hepatitis b surface antigen (HBs Ag), and, elevated creatine kinase (CK) level (1,614 U/L, normal range: 38-174 U/L). Aspartate aminotransferase was 64.7 U/L (normal range: 8-40 U/L), and LDH was 293 U/L (normal range: 80-285 U/L). Electrodiagnostic studies indicated myopathic changes. A muscle biopsy revealed myositis and no mitochondrial changes were found. Drug-induced myopathy was suspected and telbivudine was changed to entecavir. The muscle weakness and laboratory findings improved. CONCLUSION A patient developed drug-induced myopathy during long-term treatment with telbivudine for chronic HBV. To promptly detect this reversible adverse event, monitoring of serum CK level and recognition of myopathic signs and symptoms are necessary. Further investigations are needed to clarify the possible mechanism of telbivudine-induced myopathy.
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Affiliation(s)
- Min Wang
- Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, 100053, People's Republic of China
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18
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El-Shabrawi MHF, Kamal NM. Medical management of chronic liver diseases in children (part I): focus on curable or potentially curable diseases. Paediatr Drugs 2011; 13:357-370. [PMID: 21999649 DOI: 10.2165/11591610-000000000-00000] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The management of children with chronic liver disease (CLD) mandates a multidisciplinary approach. CLDs can be classified into 'potentially' curable, treatable non-curable, and end-stage diseases. Goals pertaining to the management of CLDs can be divided into prevention or minimization of progressive liver damage in curable CLD by treating the primary cause; prevention or control of complications in treatable CLD; and prediction of the outcome in end-stage CLD in order to deliver definitive therapy by surgical procedures, including liver transplantation. Curative, specific therapies aimed at the primary causes of CLDs are, if possible, best considered by a pediatric hepatologist. Medical management of CLDs in children will be reviewed in two parts, with part I (this article) specifically focusing on 'potentially' curable CLDs. Dietary modification is the cornerstone of management for galactosemia, hereditary fructose intolerance, and certain glycogen storage diseases, as well as non-alcoholic steatohepatitis. It is also essential in tyrosinemia, in addition to nitisinone [2-(nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione] therapy, as well as in Wilson disease along with copper-chelating agents such as D-penicillamine, triethylenetetramine dihydrochloride, and ammonium tetrathiomolybdate. Zinc and antioxidants are adjuvant drugs in Wilson disease. New advances in chronic viral hepatitis have been made with the advent of oral antivirals. In children, currently available drugs for the treatment of chronic hepatitis B virus infection are standard interferon (IFN)-α-2, pegylated IFN-α-2 (PG-IFN), and lamivudine. In adults, adefovir and entecavir have also been licensed, whereas telbivudine, emtricitabine, tenofovir disoproxil fumarate, clevudine, and thymosin α-1 are currently undergoing clinical testing. For chronic hepatitis C virus infection, the most accepted treatment is PG-IFN plus ribavirin. Corticosteroids, with or without azathioprine, remain the basic strategy for inducing remission in autoimmune hepatitis. Ciclosporin (cyclosporine) and other immune suppressants may be used for patients who do not achieve remission, or who have significant side effects, with corticosteroid/azathioprine therapy. The above therapies can prevent, or at least minimize, progression of liver damage, particularly if started early, leading to an almost normal quality of life in affected children.
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19
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Dang S, Gao N, Zhang X, Jia X. Rhabdomyolysis in a 48-Year-Old Man With Hepatitis B-Induced Cirrhosis. Am J Med Sci 2011; 342:73-75. [DOI: 10.1097/maj.0b013e31821a520e] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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20
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Daga PR, Duan J, Doerksen RJ. Computational model of hepatitis B virus DNA polymerase: molecular dynamics and docking to understand resistant mutations. Protein Sci 2010; 19:796-807. [PMID: 20162615 DOI: 10.1002/pro.359] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Hepatitis B virus (HBV) DNA polymerase (HDP) is a pharmacological target of intense interest. Of the seven agents approved in USA for the treatment of HBV infections, five are HDP inhibitors. However, resistance development against HDP inhibitors, such as lamivudine and adefovir, has severely hurt their efficacy to treat HBV. As a step toward understanding the mechanism of resistance development and for gaining detailed insights about the active site of the enzyme, we have built a homology model of HDP which is an advance over previously reported ones. Validation using various techniques, including PROSTAT, PROCHECK, and Verify-3D profile, proved the model to be stereochemically significant. The stability of the model was studied using a 5 ns molecular dynamics simulation. The model was found to be sufficiently stable after the initial 2.5 ns with overall root mean squared deviation (RMSD) of 4.13 A. The homology model matched the results of experimental mutation studies of HDP reported in the literature, including those of antiviral-resistant mutations. Our model suggests the significant role of conserved residues, such as rtLys32, in binding of the inhibitors, contrary to previous studies. The model provides an explanation for the inactivity of some anti-HIV molecules which are inactive against HDP. Conformational changes which occurred in certain binding pocket amino acids helped to explain the better binding of some of the inhibitors in comparison to the substrates.
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Affiliation(s)
- Pankaj R Daga
- Department of Medicinal Chemistry, School of Pharmacy, University of Mississippi, Mississippi 38677-1848, USA
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21
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Reynaud L, Carleo MA, Talamo M, Borgia G. Tenofovir and its potential in the treatment of hepatitis B virus. Ther Clin Risk Manag 2009; 5:177-85. [PMID: 19436619 PMCID: PMC2697525 DOI: 10.2147/tcrm.s3335] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Recent literature is reviewed about treatment of chronic hepatitis B virus (CHB), focusing on tenofovir disoproxil fumarate (TDF; Viread((R))), among the nucleotide and nucleoside analogs. TDF pharmacokinetics and pharmacodynamics, activity in respect of hepatitis B virus (HBV) multi-drug-resistant mutations, efficacy in treatment-naïve and treatment-experienced patients, and side effects are described. The most predictive response factors to TDF therapy are discussed and all available combination therapies to optimize clinical outcome in the various patient profiles are analyzed, such as compensated and/or decompensated cirrhotic patients. The use of TDF in pregnancy, and prophylaxis after exposure to HBV and post-liver transplantation are also evaluated.
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Affiliation(s)
- Laura Reynaud
- Department of Public Medicine and Social Security – Section of Infectious Disease University of Naples “Federico II”, Italy
| | - Maria Aurora Carleo
- Department of Public Medicine and Social Security – Section of Infectious Disease University of Naples “Federico II”, Italy
| | - Maria Talamo
- Department of Public Medicine and Social Security – Section of Infectious Disease University of Naples “Federico II”, Italy
| | - Guglielmo Borgia
- Department of Public Medicine and Social Security – Section of Infectious Disease University of Naples “Federico II”, Italy
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22
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Zhang JC, Nie QH. New antiviral choice for chronic hepatitis B: tenofovir disoproxil fumarate. Shijie Huaren Xiaohua Zazhi 2008; 16:2679-2688. [DOI: 10.11569/wcjd.v16.i24.2679] [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
Tenofovir disoproxil fumarate (TDF) is an oral prodrug of tenofovir, a novel, acyclic nucleotide analogue with in vitro activity against HIV-1 and HIV-2. TDF is licensed by American Food and Drug Administration (FDA) in 2001 for the treatment of HIV infection. TDF is currently one of the most widely used nucleotide reverse transcriptase inhibitors (NRTIs) for the treatment of HIV infection. Its efficacy, favorable toxicity profile, and convenient dosing have made this drug one of the most popular first-line treatment. Numerous studies have demonstrated the use of TDF in the treatment of HIV infection. It also has been shown to be effective in HIV/HBV coinfected patients and in patients with wild-type and lamivudine-resistant strains. Accumulating evidence suggests that TDF is more potent in suppressing HBV replication. In this review, we summarize the study progress of TDF in treating HBV infection.
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23
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Zhang XS, Jin R, Zhang SB, Tao ML. Clinical features of adverse reactions associated with telbivudine. World J Gastroenterol 2008; 14:3549-53. [PMID: 18567085 PMCID: PMC2716619 DOI: 10.3748/wjg.14.3549] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [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
AIM: To analyze the clinical features and risk factors of adverse reactions associated with telbivudine.
METHODS: Clinical data were collected from cases that presented with serious adverse reactions to telbivudine. We analyzed general information and medicine status, clinical features, results of examination, and misdiagnosis.
RESULTS: Out of 105 patients who were treated with telbivudine for hepatitis B in an outpatient department from January, 2007 to January, 2008, five presented with serious adverse drug reactions. Most of these five patients had used other nucleoside analogues in the past. Four were treated with a combination of telbivudine and interferon or another nucleoside analogue, while the other received an increased dose of telbivudine. The main adverse reactions were myalgia and general weakness. This was accompanied by cardiac arrhythmia in one patient, and nervous symptoms in three. Serum creatine kinase was elevated. The rate of misdiagnosis was high.
CONCLUSION: The adverse reactions were related to telbivudine, but the biological mechanism of the reactions is not yet clear. Combination therapy with interferon or another nucleoside analogue and a high dose may increase the risk of adverse reactions.
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24
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Luxembourg A, Hannaman D, Wills K, Bernard R, Tennant BC, Menne S, Cote PJ. Immunogenicity in mice and rabbits of DNA vaccines expressing woodchuck hepatitis virus antigens. Vaccine 2008; 26:4025-33. [PMID: 18556096 DOI: 10.1016/j.vaccine.2008.05.021] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2008] [Revised: 05/04/2008] [Accepted: 05/09/2008] [Indexed: 02/07/2023]
Abstract
The licensed vaccine against hepatitis B virus (HBV) is an effective means to prevent infection, but is not an effective therapeutic strategy to treat established chronic infections when used alone. In an animal model of chronic HBV infection (the woodchuck experimentally infected with woodchuck hepatitis virus (WHV)), the combination of conventional vaccine and potent antiviral drugs has shown promise as a potential therapeutic intervention. This approach might be improved further through the application of newer vaccine technologies. In the present study, we evaluated electroporation (EP)-based intramuscular (i.m.) delivery of a codon-optimized DNA vaccine for the WHV surface antigen (WHsAg) in mice and rabbits. In mice, this immunization procedure compared favorably to vaccination by i.m. injection of the DNA vaccine or i.m. administration of a recombinant WHsAg-alum vaccine, exhibiting characteristics expected to be beneficial for a therapeutic vaccine strategy. These included dose efficiency, consistency, vigorous induction of antibody responses to WHsAg, as well as a Th1 bias. Following scale-up to rabbits, a species that approximates the size of the woodchuck, the EP dosing regimen was markedly more effective than conventional i.m. injection of the DNA vaccine. Taken together, these results provide the foundation for studies of EP-based DNA immunization in the woodchuck in order to further assess its potential as an immunotherapeutic approach for treatment of chronic HBV infection in humans.
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Affiliation(s)
- Alain Luxembourg
- Ichor Medical Systems, 6310 Nancy Ridge Drive, San Diego, CA 92121, USA.
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25
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Peng X, Zhang P, Wang X, Chan J, Zhu M, Jiang M, Tuthill C, Wan Y, Dragoi AM, Chu WM. Signaling pathways leading to the activation of IKK and MAPK by thymosin alpha1. Ann N Y Acad Sci 2007; 1112:339-50. [PMID: 17567943 DOI: 10.1196/annals.1415.025] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Thymosin alpha 1 (Talpha1) has therapeutic potential in the treatment of infectious diseases and cancer. However, the exact molecular pathways for Talpha1 action are not fully understood. We found that Talpha1 induces the production of interleukin-6 (IL-6), IL-10, and IL-12 in murine bone marrow-derived macrophages (BMDMs) through IKK and MAPK pathways. Talpha1 triggers the activation of AP-1 and the phosphorylation of JNK and p38. Inhibition of p38 impairs IL-6 production in response to Talpha1. Further, TRAF6 is involved in the activation of JNK and IRAK4 is involved for the activation of IKK and PKCzeta in a Talpha1-induced system. Loss of IRAK4 largely blocked induction of IL-6. Thus, our studies define early signal events that are critical for the Talpha1-induced immune responses.
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Affiliation(s)
- Xiao Peng
- Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA
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