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Hepatitis B Virus (hepatitis + b_virus)
Kinds of Hepatitis B Virus Terms modified by Hepatitis B Virus Selected AbstractsTransgenic mice replicating hepatitis B virus but lacking expression of the major HBsAg,JOURNAL OF MEDICAL VIROLOGY, Issue 4 2008Leonie Halverscheid Abstract Hepatitis B Virus (HBV) transgenic mice replicating the viral genome at high level but lacking expression of the small envelope protein (HBsAg) have been produced using a terminally redundant viral DNA construct (HBV 1.4). The generation of viable infectious progeny was dependent on sex and age of mice. Viral mRNA was abundant in liver and kidneys and at low levels in other organs of the mice. No viral particles or HBV envelope proteins could be detected in sera of mice. Despite expression of non-secreted LHBs and MHBs proteins in the liver, there was no accumulation of viral particles in the endoplasmic reticulum of hepatocytes and no necroinflammatory hepatitis was observed. Therefore, these mice represent an excellent model for studies of the role of HBsAg in viral assembly, antiviral immune responses, the further understanding of HBV immunopathogenesis, and the development of antiviral vaccines. J. Med. Virol. 80:583,590, 2008. © 2008 Wiley-Liss, Inc. [source] Electrochemical Evaluation of Nucleoside Analogue Lamivudine in Pharmaceutical Dosage Forms and Human SerumELECTROANALYSIS, Issue 20 2005Burcu Dogan Abstract Lamivudine (LAM) is a synthetic nucleoside analogue with activity against human immunodeficiency virus-type 1 (HIV-1) and Hepatitis B virus (HBV). The aim of this study was to determine LAM levels in serum and pharmaceutical formulations, by means of electrochemical methods using hanging mercury drop electrode (HMDE). On this electrode, LAM undergoes irreversible reduction at the peak potential near Ep,1.26,V (vs. Ag/AgCl/3,M KCl). Reduction LAM signals were measured by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and square-wave voltammetry (OSW). DPV and OSW techniques for the determination of LAM in acetate buffer at pH,4.5, which allows quantitation over the 4×10,6 to 1×10,4,M range in supporting electrolyte for both methods, were proposed. The linear response was obtained in acetate buffer in the ranges of 2×10,6 to 2×10,4,M for spiked serum samples at pH,4.5 for both techniques. The repeatability and reproducibility of the methods for all media were determined. The standard addition method was used in serum. Precision and accuracy were also checked in all media. No electroactive interferences from the endogenous substances were found in serum. With respect to side effects of high doses and short half-life of LAM, a fast and simple detection method is described in this study. [source] Simply and reliably integrating micro heaters/sensors in a monolithic PCR-CE microfluidic genetic analysis systemELECTROPHORESIS, Issue 8 2009Runtao Zhong Abstract A novel fabrication process was presented to construct a monolithic integrated PCR-CE microfluidic DNA analysis system as a step toward building a total genetic analysis microsystem. Microfabricated Titanium/Platinum (Ti/Pt) heaters and resistance temperature detectors (RTDs) were integrated on the backside of a bonded glass chip to provide good thermal transfer and precise temperature detection for the drilled PCR-wells. This heater/RTD integration procedure was simple and reliable, and the resulting metal layer can be easily renewed when the Ti/Pt layer was damaged in later use or novel heater/RTD design was desired. A straightforward "RTD-calibration" method was employed to optimize the chip-based thermal cycling conditions. This method was convenient and rapid, comparing with a conventional RTD-calibration/temperature adjustment method. The highest ramping rates of 14°C/s for heating and 5°C/s for cooling in a 3-,L reaction volume allow 30 complete PCR cycles in about 33,min. After effectively passivating the PCR-well surface, successful ,-phage DNA amplifications were achieved using a two- or three-temperature cycling protocol. The functionality and performance of the integrated microsystem were demonstrated by successful amplification and subsequent on-line separation/sizing of ,-phage DNA. A rapid assay for Hepatitis B virus, one of the major human pathogens, was performed in less than 45,min, demonstrating that the developed PCR-CE microsystem was capable of performing automatic and high-speed genetic analysis. [source] Natural killer cells in viral hepatitis: facts and controversiesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2010Mario U. Mondelli Eur J Clin Invest 2010; 40 (9): 851,863 Abstract Background, Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major human hepatotropic pathogens responsible for a large number of chronic infections worldwide. Their persistence is thought to result from inefficiencies of innate and adaptive immune responses; however, very little information is available on the former. Natural killer (NK) cells are a major component of innate immunity and their activity is tightly regulated by several inhibitory and activating receptors. Design, In this review, we examine controversial findings regarding the role of NK cells in the pathogenesis of acute and chronic liver disease caused by HCV and HBV. Results, Recent studies built up on technical advances to identify NK receptors and their functional correlates in this setting. While NK cells seem to behave correctly during acute hepatitis, it would appear that the NK cytotoxic potential is generally conserved in chronic hepatitis, if not increased in the case of HCV. In contrast, their ability to secrete antiviral cytokines such as interferon ex vivo or after cytokine stimulation is severely impaired. Conclusions, Current evidence suggests the existence of an NK cell functional dichotomy, which may contribute to virus persistence, while maintaining low-level chronic liver inflammation. The study of liver-infiltrating NK cells is still at the very beginning, but it is likely that it will shed more light on the role of this simple and at the same time complex innate immune cell in liver disease. [source] Immunomodulatory therapy for chronic hepatitis B virus infectionFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2005D. Sprengers Abstract Hepatitis B virus (HBV) is one of the most prevalent viral pathogens of man with around 350 million chronically infected patients. It has been postulated that in persistently infected individuals the HBV-specific immune response is too weak to eliminate HBV from all infected hepatocytes, but sufficiently strong to continuously destroy HBV-infected hepatocytes and to induce chronic inflammatory liver disease. The primary aim in the treatment of chronic hepatitis B is to induce sustained disease remission and prevent serious complications like liver failure and/or hepatocellular carcinoma. The recent emergence of drug-resistant HBV mutants and post-treatment relapse as a consequence of nucleoside analogue monotherapy emphasizes that the principal goal should be to stimulate a successful immune response. In this paper we will focus on the immune response to HBV and we will review reported data on immunotherapeutic strategies like immunomodulatory drugs (cytokines and Thymic derivates) and vaccine therapies using currently available recombinant anti-HBV vaccines, lipopeptide-based T cell vaccine and newly developed genetic vaccines. [source] Chronic viral hepatitis in hemodialysis patientsHEMODIALYSIS INTERNATIONAL, Issue 2 2005Sydney Tang Abstract Ever since the first outbreaks of hepatitis in hemodialysis units in the late 1960s, a number of hepatotropic viruses transmitted by blood and other body fluids have been identified. This review summarizes the current state of knowledge regarding these blood-borne agents from an epidemiologic and preventive perspective. Data source and study selection were obtained from research and review articles related to the epidemiology of viral hepatitis in hemodialysis and indexed on Medline and Embase from 1965 to 2004. Hepatitis B virus (HBV) was the first significant hepatotropic virus to be identified in hemodialysis centers. HBV infection has been effectively controlled by active vaccination, screening of blood donors, the use of erythropoietin, and segregation of HBV carriers. To date, HBV remains an important cause of morbidity in endemic areas. Hepatitis delta virus is a defective virus that can only infect HBV-positive individuals. Hepatitis C virus is the most significant cause of non-A, non-B hepatitis and is mainly transmitted by blood transfusion. The introduction in 1990 of routine screening of blood donors for HCV contributed significantly to the control of HCV transmission. An effective HCV vaccine remains an unsolved challenge, however. Pegylation of interferon-, has made it possible to treat HCV-positive dialysis patients. Unexplained sporadic outbreaks of hepatitis by the mid-1990s prompted the discovery of hepatitis G virus and hepatitis GB virus C in 1995 and the TT virus in 1997. Although epidemiologic analyses revealed high prevalence rates of both viruses in the hemodialysis population, their exact role in liver disease has yet to be determined. The vigilant observation of guidelines on universal precaution and regular virologic testing are the cornerstones of the effective control of chronic hepatitis in the setting of hemodialysis. [source] Llama-derived single-domain intrabodies inhibit secretion of hepatitis B virions in mice,HEPATOLOGY, Issue 1 2009Benedikte Serruys Hepatitis B virus (HBV) infections cause 500,000 to 700,000 deaths per year as a consequence of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Efficient and safe antivirals to treat chronically infected patients and consequently to prevent development of hepatocellular carcinoma are still awaited. We isolated five single-domain antibodies (VHHs) that recognize the most abundant envelope protein (S) of HBV. VHHs, when expressed and retained in the endoplasmic reticulum as intrabodies, reduced levels of secreted hepatitis B surface antigen (HBsAg) particles in a cellular HBV model. In a hydrodynamics-based HBV mouse model, these intrabodies caused a marked reduction in HBsAg concentrations and a 10- to >100-fold reduction in the concentration of HBV virions in plasma. Conclusion: VHHs potently inhibited secretion of HBV virions in vivo, showing that this approach might be useful in the treatment of HBV. To our knowledge, this is the first report of intrabody-mediated inhibition of viral secretion in mammals. (HEPATOLOGY 2009;49:39-49.) [source] Longitudinal evaluation reveals a complex spectrum of virological profiles in hepatitis B virus/hepatitis C virus,coinfected patients,,HEPATOLOGY, Issue 1 2006Giovanni Raimondo Hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection is often associated with severe forms of liver disease. However, comprehensive studies are lacking, and scant information is available regarding the virological behavior over time in coinfected patients. This study enrolled 133 untreated HBV/HCV-positive patients (male/female = 102/31; median age 51 years [range: 22-83 years]) who were longitudinally followed up for 1 year with bimonthly evaluation of HBV/HCV viremia levels and liver biochemistry. Thirty of these patients had triple infection with hepatitis Delta virus (HDV), while 103 patients were HDV-negative. In the HDV-negative group, active infection with both HBV and HCV was revealed in 24 cases, inactive infection by both viruses was seen in 15 cases, active HBV/inactive HCV was seen in 15 cases, and inactive HBV/active HCV was seen in 49 cases. However, 32 subjects (31%) presented dynamic virological profiles characterized by fluctuation of HBV and/or HCV viremia levels that at different time points were over or under the cutoff limits. Consequently, a correct diagnosis could be performed in these subjects only by serially repeating the virological tests 1 year apart. Similarly, 15 of the 30 HDV-positive subjects showed active HBV and/or HCV infection, with fluctuating virological patterns in 8 cases. In conclusion, this study showed that the virological patterns in HBV/HCV coinfection are widely divergent and have dynamic profiles. A careful longitudinal evaluation of the viremia levels of both viruses is essential for making a correct diagnosis and tailoring the appropriate therapeutic schedule in coinfected patients. (HEPATOLOGY 2005.) [source] Occult hepatitis B virus infection in a North American adult hemodialysis patient populationHEPATOLOGY, Issue 5 2004Gerald Y. Minuk Hepatitis B virus (HBV) infections continue to occur in adult hemodialysis units. A possible contributing factor is the presence of occult HBV (serum hepatitis B surface antigen [HBsAg] negative but HBV DNA positive). Two hundred forty-one adult hemodialysis patients were screened for occult HBV. HBV DNA testing was performed by real-time polymerase chain reaction (PCR) with 2 independent primer sets (core promoter and surface). Two (0.8%) of the 241 patients were HBsAg positive. Of the remaining 239 HBsAg-negative patients, 9 (3.8%) were HBV DNA positive. Viral loads in these individuals were low (102 -104 viral copies/mL). Seven of the 9 (78%) were nt 587 mutation (sG145R mutant) positive. Demographic, biochemical, and HBV serological testing did not help to identify those with occult HBV. In conclusion, the prevalence of occult HBV in adult hemodialysis patients in this North American urban center is approximately 4 to 5 times higher than standard HBsAg testing would suggest. The majority of these infections are associated with low viral loads and a high prevalence of the sG145R mutant. Finally, the demographic, biochemical, and/or serological features of HBV DNA,positive subjects do not distinguish these individuals from the remainder of the dialysis patient population. (HEPATOLOGY 2004; 40:1072,1077.) [source] Tracking cccDNA in chronic HBV infectionHEPATOLOGY, Issue 6 2004Hans Christian Spangenberg M.D. Hepatitis B virus (hepadnavirus) infections are maintained by the presence of a small and regulated number of episomal viral genomes [covalently closed circular DNA (cccDNA)] in the nuclei of infected cells. Although a number of studies have measured the mean copy number of cccDNA molecules in hepadnaviral-infected cells, the distribution of individual copy numbers have not been reported. Using a PCR-based assay, we examined the number of cccDNA molecules of the duck hepatitis B virus in single nuclei isolated from the liver of a chronically infected duck over the course of 131 days of infection. Nuclei were isolated from frozen serial biopsies and individually deposited into PCR microplates by flow sorting. Each nucleus was assayed by nested PCR for cccDNA and for cellular IFN-, genes as an internal control. We found that 90% of the nuclei assayed contained between 1 and 17 cccDNA molecules, with the remaining 10% containing more (90% confidence), and that differences in the mean number of copies and distribution of copy numbers occurred within the same animal at different times postinfection. Overall, the data suggest (i) that the number of cccDNA molecules per cell may fluctuate over time, and (ii) that, according to these fluctuations, a substantial fraction of cells may contain only one or a few copies. We infer from the results that infected hepatocytes express virus at different levels and that during cell division it is possible to segregate cells containing no cccDNA. (Copyright 2003, National Academy of Sciences, U.S.A.) [source] Hepatitis B virus and HIV coinfection: relationship of different serological patterns to survival and liver diseaseHIV MEDICINE, Issue 5 2007MK Osborn Objectives Eighty per cent of HIV-positive patients show evidence of past or current infection with hepatitis B virus (HBV). The impact of chronic HBV infection or the presence of isolated HBV core antibody on survival in the era of highly active antiretroviral therapy (HAART) has not been well studied. Methods This retrospective analysis included patients from the HIV Atlanta Veterans Affairs Cohort Study (HAVACS). This cohort comprises 2818 HIV-positive patients followed since 1982. For this analysis, 1685 patients with available HBV serologies were included, based on laboratory records available since 1992. Adjusted survival analyses were performed for patients showing any of four serological patterns for HBV: (1) surface antigen positive (chronic HBV infection), (2) isolated core antibody, (3) surface antibody with or without core antibody (resolved/vaccinated) and (4) no HBV markers (negative group). Risk factors for liver disease were identified. Results A trend was seen for a lower survival rate from AIDS to death in the chronic HBV infection group compared with the negative group [hazard ratio (HR) 1.43; P=0.118]. The only independent predictor of lower survival rate was hepatitis C virus positivity (HR 1.62; P=0.008). Protective factors were use of HAART (HR 0.40; P=0.0003), use of lamivudine (HR 0.36; P<0.0001) and use of tenofovir (HR 0.23; P<0.0001). Survival from HIV diagnosis to death was not different among the HBV groups. Isolated core antibody patients did not have a lower survival rate compared with those with resolved HBV infection. Patients with chronic HBV infection were 3.5 times more likely to have liver disease than those with no HBV infection (P<0.02). Conclusions There is a trend towards a lower survival rate in patients with HIV and chronic HBV infection, but the difference did not reach statistical significance. The presence of isolated core antibody was not associated with a lower survival rate. [source] Evaluation of IL10, IL19 and IL20 gene polymorphisms and chronic hepatitis B infection outcomeINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 3 2008Ann L. Truelove Summary Hepatitis B virus (HBV) infection remains a serious global health problem despite the availability of a highly effective vaccine. Approximately 5% of HBV-infected adults develop chronic hepatitis B, which may result in liver cirrhosis or hepatocellular carcinoma. Variants of interleukin-10 (IL10) have been previously associated with chronic hepatitis B infection and progression to hepatocellular carcinoma. Single nucleotide polymorphisms (SNP; n = 42) from the IL10, IL19 and IL20 gene regions were examined for an association with HBV infection outcome, either chronic or recovered, in a nested case,control study of African Americans and European Americans. Among African Americans, three nominally statistically significant SNP associations in IL10, two in IL20, and one haplotype association were observed with different HBV infection outcomes (P = 0.005,0.04). A SNP (rs1518108) in IL20 deviated significantly from Hardy,Weinberg equilibrium in African Americans, with a large excess of heterozygotes in chronic HBV-infected cases (P = 0.0006), which suggests a strong genetic effect. Among European Americans, a nominally statistically significant SNP association in IL20 and an IL20 haplotype were associated with HBV recovery (P = 0.01,0.04). These results suggest that IL10 and IL20 gene variants influence HBV infection outcome and encourage the pursuit of further studies of these cytokines in HBV pathogenesis. [source] Molecular, immunological and clinical properties of mutated hepatitis B virusesJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1 2002C. Kreutz Abstract Hepatitis B virus (HBV) is at the origin of severe liver diseases like chronic active hepatitis, liver cirrhosis and hepatocellular carcinoma. There are some groups of patients with high risk of generation of HBV mutants: infected infants, immunosupressed individuals (including hemodialysis patients), patients treated with interferon and lamivudine for chronic HBV infection. These groups are the target for molecular investigations reviewed in this paper. The emergence of lamivudine- or other antiviral-resistant variants, rises concern regarding long term use of these drugs. Infection or immunization with one HBV subtype confers immunity to all subtypes. However, reinfection or reactivation of latent HBV infection with HBV mutants have been reported in patients undergoing transplant and those infected with HIV. Mutations of the viral genome which are not replicative incompetent can be selected in further course of infection or under prolonged antiviral treatment and might maintain the liver disease. Four open reading frames (ORF) which are called S-gene, C-gene, X-gene and P-gene were identified within the HBV genome. Mutations may affect each of the ORFs. Mutated S-genes were described to be responsible for HBV-infections in successfully vaccinated persons, mutated C-genes were found to provoke severe chronic liver diseases, mutated X-genes could cause serious medical problemes in blood donors by escaping the conventional test systems and mutated P-genes were considered to be the reason for chemotherapeutic drug resistance. This paper reviews molecular, immunological and clinical aspects of the HBV mutants. [source] Current therapeutic approaches in childhood chronic hepatitis B infection: A multicenter studyJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2004BUNYAMIN DIKICI Abstract Background and Aim:, The aim of the present study was to compare the therapeutic efficacy of three different regimens in childhood chronic hepatitis B (CHB) infection. Methods:, A total of 182 children with CHB infection were prospectively allocated to three random groups. Sixty-two patients in the first group received high-dose interferon (IFN)-, 2b (10 MU/m2) thrice/weekly alone for 6 months. In the second (n = 60) and third groups (n = 60), IFN-, was used for 6 months (5 MU/m2) thrice/weekly in combination with lamivudine (LAM) (4 mg/kg, maximum 100 mg/day) for 12 months. Lamivudine was started simultaneously with IFN in the second group, while it was started 2 months prior to IFN injections in the third group. Results:, The initial mean alanine aminotransferase (ALT) values for the first, second and third groups were 109 ± 93 IU/L, 101 ± 64 IU/L and 92 ± 42 IU/L, respectively (P > 0.05). At the end of the therapy, ALT values decreased to 82 ± 111 IU/L, 38 ± 41 IU/L and 29 ± 16 IU/L in groups 1, 2 and 3, respectively. The mean ALT value of the first group was significantly different to the second and third groups (P = 0.046 and P = 0.002, respectively) at the end of the therapy and these differences were found to be sustained after 18 months. However, results in the second and third groups were similar (P > 0.05). There were no significant differences in HBeAg clearance and anti-HBe seroconversion at the initial stage, 12 months and 18 months between the three groups (P > 0.05). Hepatitis B virus (HBV) DNA clearance in the first group was different from the second and third groups, while the second and third groups had similar HBV DNA clearance ratios at 12 and 18 months. No significant difference was found in the complete response (normalization of ALT, clearance of HBV DNA and seroconversion of anti HBe) ratios of all groups (at 12 months: 28.8, 45.5, 35.8% and at 18 months 33.3, 49 and 34% in groups 1, 2 and 3, respectively, P > 0.05). Conclusions:, Although the ALT normalization and HBV DNA clearance ratios of IFN plus LAM combination groups were better than the high-dose IFN-, monotherapy group, no significant difference was found in the complete response ratios of all three groups. [source] Public health measures to control hepatitis B virus infection in the developing countries of the Asia,Pacific regionJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2000Ding-Shinn Chen Hepatitis B virus (HBV) infection is prevalent in the Asia,Pacific region and the disease burden caused by chronic HBV infection has been enormous. Although vaccination programmes have been implemented in the past decade, and there are extremely successful countries in the region, many countries still cannot afford a control program. These countries are often populous and highly endemic for HBV infection. To overcome this, aid from developed countries or private foundations should be actively sought. In the developing countries of this region, HBV infection in early childhood is the main cause of chronic HBV status, and thus universal vaccination of all infants is the best way to control HBV infection. Because of the expense and extra costs of screening pregnant women, the use of hepatitis B immune globulin may not be essential. To achieve the goal of universal infant vaccination, public education should be done in parallel with education of health professionals and control measures. The Asia,Pacific region has more people with chronic hepatitis B than any other part of the world, and control of HBV infection in this region will no doubt be the most important and challenging task to be taken in the beginning of the new millennium. [source] Prevalence, whole genome characterization and phylogenetic analysis of hepatitis B virus in captive orangutan and gibbonJOURNAL OF MEDICAL PRIMATOLOGY, Issue 6 2008Pattaratida Sa-nguanmoo Abstract Background, Hepatitis B virus (HBV) is a public health problem worldwide and apart from infecting humans, HBV has been found in non-human primates. Methods, We subjected 93 non-human primates comprising 12 species to ELISA screening for the serological markers HBsAg, antiHBs and antiHBc. Subsequently, we detected HBV DNA, sequenced the whole HBV genome and performed phylogenetic analysis. Results, HBV infection was detected in gibbon (4/15) and orangutan (7/53). HBV DNA isolates from two gibbons and seven orangutans were chosen for complete genome amplification. We aligned the Pre-S/S, Pre-C/C and entire genomes with HBV sequences and performed phylogenetic analysis. The gibbon and orangutan viruses clustered within their respective groups. Conclusions, Both geographic location and host species influence which HBV variants are found in gibbons and orangutans. Hence, HBV transmission between humans and non-human primates might be a distinct possibility and additional studies will be required to further investigate this potential risk. [source] Relationship between serum hepatitis B virus DNA and surface antigen with covalently closed circular DNA in HBeAg-negative patients,JOURNAL OF MEDICAL VIROLOGY, Issue 9 2010L.Y. Lin Abstract Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is responsible for viral persistence. This study aimed to investigate the serum surrogate markers for cccDNA and to evaluate the intrahepatic viral events associated with disease activity in HBeAg-negative chronic hepatitis B patients. Thirty-three treatment-naïve patients with a negative HBeAg who had a liver biopsy were studied. Active disease was defined as a serum alanine aminotransferase >40,IU/L and a serum HBV DNA >10,000,copies/ml. This study showed significant correlation between serum HBV DNA and both log cccDNA (r,=,0.41, P,=,0.018) and log total intrahepatic HBV DNA (r,=,0.71, P,<,0.0001). No significant correlation was observed between serum HBsAg and log cccDNA (P,=,0.15) or log total intrahepatic HBV DNA (P,=,0.97). Fourteen and 19 patients had inactive and active disease, respectively. The median log cccDNA and log total intrahepatic HBV DNA (copies/106 cells) were significantly higher in patients with active disease compared with those with inactive disease (4.11 vs. 3.53, P,=,0.03 and 5.46 vs. 4.64, P,<,0.001, respectively). The HBV replicative efficiency, defined as the ratio of serum HBV DNA to cccDNA, was approximately 20% higher in patients with active disease. No significant difference was observed in the HBsAg levels and the ratio of serum HBsAg to cccDNA between the two groups. In conclusion, serum HBV DNA, but not HBsAg, reflects the amount of cccDNA and the replication efficiency of HBV in patients with HBeAg-negative chronic hepatitis B. J. Med. Virol. 82:1494,1500, 2010. © 2010 Wiley-Liss, Inc. [source] Hepatitis B virus X protein upregulates expression of calpain small subunit 1 via nuclear facter-,B/p65 in hepatoma cellsJOURNAL OF MEDICAL VIROLOGY, Issue 6 2010Feng Zhang Abstract Hepatitis B virus (HBV) infection is closely correlated with the development of hepatocellular carcinoma (HCC), in which hepatitis B virus X protein (HBx) plays crucial roles. HBx is believed to be a multifunctional oncoprotein. It has been reported that the calpain small subunit 1 (Capn4) is upregulated in the HCC tissues and involved in the metastasis of HCC. Therefore, we suppose that HBx may promote hepatoma cell migration through Capn4. In the present study, we investigated the effect of HBx on regulating Capn4 expression in human HCC cells. Our data showed that HBx could increase promoter activity of Capn4 and upregulate the expression of Capn4 at the levels of mRNA and protein in human hepatoma HepG2 (or H7402) cells using luciferase reporter gene assay, real-time quantitative RT-PCR assay and Western blot analysis. While, the RNA interference targeting HBx mRNA was able to abolish the upregulation. Interestingly, we found that the inhibition of nuclear factor-,B (NF-,B) mediated by siRNA targeting NF-,B/p65 mRNA or PDTC (an inhibitor of NF-,B) could attenuate the upregulation of Capn4. While, HBx failed to increase the promoter activity of Capn4 in hepatoma cells when the putative NF-,B binding site of the Capn4 promoter was mutant, suggesting that NF-,B is involved in the activation of Capn4 mediated by HBx. In function, wound healing assay showed that HBx could significantly enhance the migration ability of HepG2 cells through upregulating Capn4. Thus, we conclude that HBx upregulate Capn4 through NF-,B/p65 to promote migration of hepatoma cells. J. Med. Virol. 82:920,928, 2010. © 2010 Wiley-Liss, Inc. [source] Molecular characterization of a variant virus that caused de novo hepatitis B without elevation of hepatitis B surface antigen after chemotherapy with rituximabJOURNAL OF MEDICAL VIROLOGY, Issue 12 2008Masami Miyagawa Abstract Hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-negative patients following treatment with rituximab has been reported increasingly. The aim of this study was to investigate the molecular mechanisms underlying HBV reactivation in an HBsAg-negative patient. HBV was reactivated in a 75-year-old man following chemotherapy with rituximab, without elevation of HBsAg. The patient's full-length HBV genome was cloned and the entire sequence was determined. Transfection studies were performed in vitro using recombinant wild-type HBV (wild-type), the patient's HBV (patient), and two chimeric HBV constructs, in which the preS/S region of the patient and wild-type virus had been exchanged with one another. Secreted HBsAg and intra- and extra-cellular HBV DNA were measured. The number of amino acid substitutions in HBV from this patient was much higher than in previous reports of HBV mutants, such as occult HBV and vaccine escape HBV mutants. Levels of HBsAg and HBV DNA production in vitro were significantly lower in the patient compared to wild-type transfections. From analyses of the chimeric constructs, the altered preS/S region was responsible mainly for this impairment. These results show that highly mutated HBV can reactivate after chemotherapy with rituximab, despite an unusually large number of mutations, resulting in impaired viral replication in vitro. Severe immune suppression, probably caused by rituximab, may permit reactivation of highly mutated HBV. These findings have important clinical implications for the prevention and management of HBV reactivation and may explain partially the mechanism of recent, unusual cases of HBV reactivation. J. Med. Virol. 80:2069,2078, 2008. © 2008 Wiley-Liss, Inc. [source] Comparison of hepatitis B virus subgenotypes in patients with acute and chronic hepatitis B and absence of lamivudine-resistant strains in acute hepatitis B in JapanJOURNAL OF MEDICAL VIROLOGY, Issue 4 2007Kazuhiko Hayashi Abstract Hepatitis B virus (HBV) has been classified into eight genotypes and can be further divided into several subgenotypes that have different geographic distributions. Because of increased human migration, the prevalence of rare subgenotypes is increasing in Japanese patients with acute hepatitis B. Lamivudine-resistant strains of HBV have begun to emerge in association with chronic hepatitis B. The aim of this study was to investigate the distribution of HBV subgenotypes and lamivudine-resistant strains in patients in Japan with acute hepatitis B. One hundred twenty-three patients with acute hepatitis B and 123 with chronic hepatitis B were studied. HBV subgenotypes and lamivudine-resistance mutations were determined by direct sequencing of the preS and polymerase region, respectively. HBV subgenotypes Aa (n,=,3), Ae (n,=,23), Ba (n,=,7), Bj (n,=,3), Cs (n,=,7), Ce (n,=,76), D (n,=,2), and H (n,=,2) were detected in patients with acute hepatitis. In patients with chronic hepatitis, HBV subgenotypes Ae (n,=,4), Ba (n,=,1), Bj (n,=,18), and Ce (n,=,100) were found. Non-common Japanese subgenotypes, that is, non-Bj and non-Ce, were detected more frequently in patients with acute hepatitis (35.8%) than in patients with chronic hepatitis (4.1%) (Odds ratio, 0.076; 95%CI, 0.029,0.200; P,<,0.0001). Lamivudine-resistance mutations were detected in chronic hepatitis patients with breakthrough hepatitis but not in other patients. In conclusion, the prevalence of uncommon Japanese HBV subgenotypes is expected to increase, although lamivudine-resistant strains have not yet been found in patients with acute hepatitis B. J. Med. Virol. 79:366,373, 2007. © 2007 Wiley-Liss, Inc. [source] Gene expression profile of transgenic mouse kidney reveals pathogenesis of hepatitis B virus associated nephropathy,JOURNAL OF MEDICAL VIROLOGY, Issue 5 2006J. Ren Abstract Hepatitis B virus (HBV)-associated nephritis has been reported worldwide. Immune complex deposition has been accepted as its pathogenesis, although the association between the presence of local HBV DNA and viral antigen and the development of nephritis remains controversial. To understand better the roles played by HBV protein expression in the kidney, the global gene expression profile was studied in the kidney tissue of a lineage of HBV transgenic mouse (#59). The mice expressed HBsAg in serum, and HBsAg and HBcAg in liver and kidney, but without virus replication. Full-length HBV genome (adr subtype, C genotype) isolated from a chronic HBV carrier was used to establish the transgenic mice #59. Similarly manipulated mice that did not express HBV viral antigens served as controls. Southern blotting, hybridization with HBV probe, and immuno-histochemical staining were used to study HBV gene expression. mRNA extracted from the kidney tissue was analyzed using Affymetrix microarrays. HBsAg and HBcAg were located mainly in the cytoplasm of tubular epithelium. Altogether 520 genes were "up-regulated" more than twofold and 76 genes "down-regulated" more than twofold in the kidney. The complement activation, blood coagulation, and acute-phase response genes were markedly "up-regulated". Compared to the controls, the level of serum C3 protein was decreased in #59 mice, while the level of C3 protein from kidney extract was increased. Results indicate that expression of HBsAg and HBcAg in tubular epithelial cells of the kidney per se can up-regulate complement-mediated inflammatory gene pathways, in addition to immune complex formation. J. Med. Virol. 78:551,560, 2006. © 2006 Wiley-Liss, Inc. [source] Characterization of seven genotypes (A to E, G and H) of Hepatitis B virus recovered from Japanese patients infected with human immunodeficiency virus type 1,JOURNAL OF MEDICAL VIROLOGY, Issue 1 2005Takao Shibayama Abstract To investigate the prevalence of hepatitis B virus (HBV) genotypes and characteristics of HBV isolates among Japanese patients infected with human immunodeficiency virus type 1 (HIV), serum samples collected between September 1990 and March 2002 from 471 HIV-infected patients (age, 38.8,±,11.4 [mean,±,standard deviation] years; male, 90%) were tested for hepatitis B surface antigen (HBsAg) and HBV DNA. Positivity for HBsAg and HBV DNA was seen in 42 patients (8.9%), 41 of whom had contracted HIV infection through sexual activity and 1 had hemophilia. Genotypes of HBV were determined by comparative and phylogenetic analyses of the S gene sequence (396 nucleotides [nt]). The distribution of HBV genotypes among the 42 HBV-viremic patients was: A (50%), B (5%), C (24%), D (5%), E (2%), H (10%), A plus D (2%), A plus G (2%). The hemophilia patient had HBV genotype D. Genotypes E, G, and H which had not been reported in Japan, were found in one patient each who had traveled to Zambia, the US, and South America, respectively. Genotypes A and D, which are rare in Japan, were found in patients who had no history of traveling abroad. The entire genome of the HB-JI411 (genotype E [3,212 nt]), HB-JI444G (genotype G [3,248 nt]), and HB-JI260 (genotype H [3,218 nt]) isolates had the highest identity of 98.3%, 99.9%, and 98.5%, respectively, with reported HBV isolates of the same genotype. Most Japanese patients coinfected with HIV and HBV had HBV genotypes that are found rarely or had not been reported in Japan. J. Med. Virol. 76:24,32, 2005. © 2005 Wiley-Liss, Inc. [source] Hepatitis B virus genotypes and spontaneous hepatitis B e antigen seroconversion in Taiwanese hepatitis B carriersJOURNAL OF MEDICAL VIROLOGY, Issue 3 2004Jia-Horng Kao MD Abstract Hepatitis B virus (HBV) is classified into eight genotypes (A,H), and genotype C is associated with more aggressive liver disease compared to genotype B. However, the mechanisms responsible for the clinical differences remain unclear. To test whether genotype C patients had with lower rates of spontaneous hepatitis B ge antigen (HBeAg) seroconversion than genotype B patients, stored serum samples from 146 Taiwanese adult HBeAg-positive hepatitis B carriers followed-up for a mean of 52 months (range, 12,120 months) were tested for HBV genotype by a molecular method. Genotype C patients were significantly older than genotype B patients (mean age, 37,±,12 vs. 29,±,10 years, P,<,0.001). During the follow-up period, genotype C patients had a significantly lower rate of spontaneous HBeAg seroconversion than genotype B patients (27 vs. 47%, P,<,0.025). Spontaneous HBeAg seroconversion occurred one decade later in genotype C patients compared with genotype B patients. Multivariate analyses identified age ,35 years (odds ratio: 2.08; 95% confidence interval [CI], 1.07,4.0; P,<,0.05), high baseline serum alanine aminotransferase level (odds ratio: 2.34; 95%CI, 1.39,4.09; P,<,0.005), and HBV genotype B (odds ratio: 1.94; 95%CI, 1.03,3.63; P,<,0.05) as independent factors associated with spontaneous HBeAg seroconversion. In conclusion, genotype C patients, compared to genotype B patients, have a delayed HBeAg seroconversion in the immune clearance phase of chronic HBV infection, which may contribute to a more progressive liver disease and more refractory to antiviral therapy. J. Med. Virol. 72:363,369, 2004. © 2004 Wiley-Liss, Inc. [source] Hepatitis B virus genotypes and HBsAg subtypes in refugees and injection drug users in the United States determined by LiPA and monoclonal EIAJOURNAL OF MEDICAL VIROLOGY, Issue 3 2001Paul D. Swenson Abstract Hepatitis B virus (HBV) genotyping and hepatitis B surface antigen (HBsAg) subtyping were carried out on sera from 196 HBsAg-positive patients, including 151 refugees entering the United States and 45 injection drug users in Seattle. HBsAg subtyping was performed by enzyme immunoassay (EIA) using a panel of monoclonal antibodies and the HBV genotype was determined by polymerase chain reaction (PCR) followed by detection of amplified HBV DNA by a reverse-phase hybridization line probe assay (LiPA) using genotype-specific probes. HBV DNA was detected by PCR in 155 (79%) of the 196 sera and all 155 were genotyped by LiPA. Samples from Southeast Asia were predominantly genotype B/subtype ayw1 and genotype C/adr; samples from the former Soviet Union and eastern Europe were mostly genotype D/ayw2 and genotype D/ayw3; samples from east Africa were mainly genotype A/adw2 and genotype D/ayw2; and samples from injection drug users were mostly genotype D/ayw3 and genotype A/adw2. Some strains of ayw3 gave atypical monoclonal antibody reactivity patterns in the subtyping assay due to a Val/Ala instead of a Thr at amino acid residue 118 and a Thr instead of a Met at residue 125. A strain of ayw2 also gave an atypical monoclonal antibody reactivity pattern due to an Ala instead of a Thr at amino acid residue 123. LiPA genotyping and monoclonal EIA subtyping can provide useful information for epidemiological studies. J. Med. Virol. 64:305,311, 2001. © 2001 Wiley-Liss, Inc. [source] Screening for hepatitis B in chemotherapy patients: survey of current oncology practicesALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010T. T. TRAN Summary Background, Hepatitis B virus (HBV) reactivation occurs in up to 78% of patients receiving cytotoxic chemotherapy for nonhepatic malignancies. Reactivation can lead to hepatic dysfunction, jaundice and fulminant hepatic failure. Current recommendations include screening patients at risk for HBV prior to immunosuppressive therapy and initiating antiviral prophylaxis in patients with chronic HBV. Aim, To investigate current practice among oncologists regarding HBV screening and antiviral prophylaxis in candidates for chemotherapy. Methods, A survey was sent to American Medical Association registered oncologists assessing demographics and HBV screening practices. Statistical analysis was performed using Fisher's exact test. Results, In all, 265 responses were received. Office-based physicians were less likely to screen for HBV prior to chemotherapy (P < 0.001). Years in practice varied: 51% with <5 years, 29% with 5,15 years and 18% with >15 years, with no difference in screening practices between groups (P = N.S.). Responders screen for HBV as follows: never , 20%, only in the presence of abnormal liver biochemistries , 30%, risk factors or history of hepatitis , 38%. In patients with known HBV, 75% of oncologists refer to specialists, 7% initiate therapy, while 15% do not refer or initiate therapy, most of whom are in an office setting (P = 0.02). Conclusions, Twenty per cent of oncologists never screen for HBV prior to initiating chemotherapy. Office-based physicians were less likely to screen, treat or refer to a specialist prior to chemotherapy. Greater education regarding risk of HBV reactivation is needed for clinicians treating patients with immunosuppressive therapies. Aliment Pharmacol Ther,31, 240,246 [source] Hepatitis D outbreak among children in a hepatitis B hyper-endemic settlement in GreenlandJOURNAL OF VIRAL HEPATITIS, Issue 3 2010M. L. Børresen Summary., Hepatitis B virus (HBV) infection is endemic in Greenland with 5,10% of the population being HBsAg-positive (chronic carriers). Surprisingly, despite of the high prevalence of HBV infection, acute and chronic hepatitis B, liver cirrhosis and primary hepatocellular carcinoma appear much less frequently than expected. The reasons for the low frequencies are unknown, but as a consequence implementation of a childhood HBV vaccination programme, though debated for years, has never been instituted. We describe an outbreak of hepatitis D (HDV) infection among children in a hepatitis B hyper-endemic settlement of 133 inhabitants on the west coast of Greenland. In 2006 a total of 27% of the inhabitants were HBsAg-positive (chronic carriers) and 83% were HBcAb-positive (previously exposed). Forty-six percent of the HBsAg-positive persons were below 20 years of age. On follow-up 1 year later a total of 68% of the HBsAg-positive persons were HDV-IgG positive. Five children, who were HBsAg-positive in 2006, had HDV-seroconverted from 2006 to 2007, indicating a HDV-super-infection. Most of the HDV-IgG positive children had markedly elevated liver enzymes. In the multivariate analysis, among the HBV and HDV markers, presence of HDV-IgG was most strongly associated with elevation of liver enzymes. In conclusion, the HBV-HDV super-infection and presumed HDV outbreak in this settlement challenges the notion that HBV infection may not be as harmless in Greenland as previously anticipated. The findings strongly suggest that HBV vaccination should be included in the child-immunization program in Greenland. [source] Virological, serological and biochemical outcomes through 3 years of entecavir treatment in nucleoside-naive Chinese chronic hepatitis B patientsJOURNAL OF VIRAL HEPATITIS, Issue 2010G. B. Yao Summary., Hepatitis B virus (HBV) infection has a high prevalence in China. Entecavir has shown superior efficacy over lamivudine in Chinese nucleoside-naive chronic hepatitis B (CHB) patients over 48 weeks, with continued clinical benefit to 96 weeks. The present study evaluates the long-term efficacy of entecavir in Chinese CHB patients who continued entecavir treatment for 144 weeks. Patients receiving either entecavir 0.5 mg/day (n = 258) or lamivudine 100 mg/day (n = 261) entered the initial 96-week randomized, double-blind, controlled efficacy study. Patients who did not achieve a consolidated response [HBV DNA <0.7 MEq/mL; alanine aminotransferase (ALT) <1.25 × upper limit of normal; and if hepatitis B e antigen (HBeAg) positive at baseline, loss of HBeAg for ,24 weeks] or who experienced viral breakthrough or relapse entered a 48-week entecavir rollover study. A total of 160 patients received continuous entecavir for 144 weeks; of these, 89% had undetectable serum HBV DNA, 86% showed ALT normalization, 20% reported HBeAg loss and 8% experienced HBeAg seroconversion. The cumulative rates of HBeAg loss and seroconversion were 36% and 27% at Week 144, respectively. The development of resistance was low, with three patients up to Week 96 and an additional two patients in Weeks 96,144 showing evidence of associated genotypic mutations. Entecavir was well tolerated. Adverse event rates were similar to those in lamivudine-treated patients, but patients receiving entecavir experienced fewer ALT flares. This study demonstrates that entecavir provides durable, long-term suppression of HBV DNA and ALT normalization in Chinese CHB patients, and is associated with low rates of emerging resistance. The results are consistent with the findings using entecavir globally and in Japan. [source] Hepatitis B virus (HBV) DNA levels and the management of HBV-infected health care workersJOURNAL OF VIRAL HEPATITIS, Issue 1 2006A. A. Van Der Eijk Summary., Different guidelines exist for the management of hepatitis B virus (HBV)-infected health care workers (HCWs). Various HBV DNA levels are used as a cutoff level to determine whether an HBV-infected HCW is allowed to perform exposure-prone procedures (EPPs) or not. In this paper we discuss the factors that determine HBV DNA levels and the implications of different HBV DNA cutoff levels for EPP performing HCWs. If the level of HBV DNA in the serum of HCWs is used to determine acceptability for the conduct of EPPs, it is necessary to take into account the variability in time of HBV DNA levels in HBV carriers and the reliability and reproducibility of the molecular diagnostic test involved. The issue of standardization has to be addressed, before a universal, maximum level of viraemia for EPP performing HCWs can be introduced. [source] Inhibition of hepatitis B virus replication in 2.2.15 cells by expressed shRNAJOURNAL OF VIRAL HEPATITIS, Issue 3 2005X.-R. Ren Summary., Hepatitis B virus (HBV) infection is a worldwide health problem. To determine whether RNA interference (RNAi) could inhibit ongoing HBV replication in 2.2.15 cells, we constructed shRNA-producing vector pU6P based on the mouse U6 RNA promoter and cloned 12 targeted sequences against HBV into the vector, resulting in a series of pU6-siHBV vectors. The recombinant vectors were transfected into 2.2.15 cells, HBsAg and HBeAg in cultured media were assayed using enzyme-linked immunosorbent assay at various days after transfection. The amount of HBV DNA in the culture medium was quantitated by real-time polymerase chain reaction. HBsAg and HBeAg expression were inhibited by 72.8 ± 5.4% (P = 0.00003) and 55.8 ± 6.2% (P = 0.000026), respectively, 4 days after transfection with pU6-siHBV5. The greatest inhibition of HBV DNA was decreased by approximately 1.9-fold (P = 0.013) on day 6 post transfection with pU6-siHBV11 compared with that of empty vector. No change was found for HBV protein expression and DNA replication on pU6-siGFP (negative control) transfected cells. Our data demonstrate that the transfection of HBV-targeted shRNA-producing vector in 2.2.15 cells could inhibit the HBV protein expression and HBV DNA replication specifically. RNAi may be considered as a potential antiviral approach for human HBV infection. [source] Hepatitis B and hepatitis C in 2009LIVER INTERNATIONAL, Issue 2009Patrick Marcellin Abstract Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are among the most frequent viral infections in humans, and represent a major global public health problem. HBV- and HCV-related chronic hepatitis are the main causes of cirrhosis and hepatocellular carcinoma (HCC) that are responsible for a high rate of morbidity and mortality. End-stage HBV- and HCV-related liver disease and HCC are the main causes of liver transplantation. In the last few years, knowledge of the epidemiology and the natural history of HBV and HCV infection has markedly improved. Furthermore, considerable progress has been made in the efficacy of therapy. New drugs and new therapeutic strategies that are currently under evaluation could further improve the efficacy of therapy in the near future. [source] | |||||||||||||||||||||||||||||||||||||||||||