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Chronic HBV Infection (chronic + hbv_infection)
Selected AbstractsSerum biomarkers of hepatitis B virus infected liver inflammation: A proteomic studyPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 5 2003Qing-Yu He Abstract Hepatitis B virus (HBV), a serious infectious and widespread human pathogen, represents a major health problem worldwide. Chronic HBV infection has a very high risk of evolving into hepatocellular carcinoma. Although considerable progress was made during the recent past, the pathogenesis of HBV infection is still elusive and a definite diagnosis of HBV infected liver information still relies on biopsy histological test. In this report, we used proteomics technology to globally examine HBV infected serum samples aiming at searching for disease-associated proteins that can be used as serological biomarkers for diagnosis and/or target proteins for pathogenetic study. By comparing with normal and HBV negative serum samples, we found that at least seven proteins were significantly changed in HBV infected sera. These greatly altered proteins were identified to be haptoglobin , and ,2 chain, apolipoprotein A-I and A-IV, ,1-antitrypsin, transthyretin and DNA topoisomerase II,. The alteration of these proteins is displayed not only in quantity but also in patterns (or specificity), which can be correlated with necroinflammatory scores. In particular, apolipoprotein A-I presents heterogeneous change in expression level with different isoforms and ,1-antitrypsin produces evidently different fragments implying diverse cleavage pathways. These unique phenomena appear specific to HBV infection. A combination simultaneously considering the quantities and isoforms of these proteins could be a useful serum biomarker (or index) for HBV diagnosis and therapy. [source] Novel mechanism of antibodies to hepatitis B virus in blocking viral particle release from cells,HEPATOLOGY, Issue 3 2010Avidan U. Neumann Antibodies are thought to exert antiviral activities by blocking viral entry into cells and/or accelerating viral clearance from circulation. In particular, antibodies to hepatitis B virus (HBV) surface antigen (HBsAg) confer protection, by binding circulating virus. Here, we used mathematical modeling to gain information about viral dynamics during and after single or multiple infusions of a combination of two human monoclonal anti-HBs (HepeX-B) antibodies in patients with chronic hepatitis B. The antibody HBV-17 recognizes a conformational epitope, whereas antibody HBV-19 recognizes a linear epitope on the HBsAg. The kinetic profiles of the decline of serum HBV DNA and HBsAg revealed partial blocking of virion release from infected cells as a new antiviral mechanism, in addition to acceleration of HBV clearance from the circulation. We then replicated this approach in vitro, using cells secreting HBsAg, and compared the prediction of the mathematical modeling obtained from the in vivo kinetics. In vitro, HepeX-B treatment of HBsAg-producing cells showed cellular uptake of antibodies, resulting in intracellular accumulation of viral particles. Blocking of HBsAg secretion also continued after HepeX-B was removed from the cell culture supernatants. Conclusion: These results identify a novel antiviral mechanism of antibodies to HBsAg (anti-HBs) involving prolonged blocking of the HBV and HBsAg subviral particles release from infected cells. This may have implications in designing new therapies for patients with chronic HBV infection and may also be relevant in other viral infections. (HEPATOLOGY 2010;) [source] Hepatitis B viral load predicts survival of HCC patients undergoing systemic chemotherapy,HEPATOLOGY, Issue 6 2007Winnie Yeo HCC is a common cause of morbidity and mortality. For patients who are not candidates for curative surgery, systemic chemotherapy is one of the standard treatments. In parts of China and the Far East, over 80% of HCC patients have chronic HBV infection. In this study, we aimed to assess the relationship between pre-chemotherapy HBV viral load and the survival of HCC patients. HBV infection status was determined prior to chemotherapy in 188 patients, 170 of whom had evidence of HBV chronic infection/exposure (160 hepatitis B surface antigen [HBsAg]-positive, 10 HBsAg-negative/hepatitis B core antibody,positive). Of these, 125 had pretreatment HBV DNA levels determined via real-time PCR. Virological data were analyzed using conventional clinical variables to identify factors that influenced survival. Multivariate analysis revealed that high total bilirubin (P = 0.0016; hazard ratio = 1.040 per 1 ,M increase; 95% CI 1.015,1.065), HCV infection (P = 0.0095; hazard ratio = 6.955; 95% CI 1.606,30.129), and high HBV DNA level (P = 0.0217; hazard ratio = 1.650; 95% CI 1.076,2.531) affected survival significantly. Exploratory analysis revealed that high levels of pretreatment HBV DNA had a significantly higher incidence of severe hepatitis during chemotherapy. Conclusion: For HCC patients with HBV chronic infection/exposure, a high viral load prior to treatment is an adverse factor for survival and may be associated with a higher incidence of severe hepatitis during chemotherapy. Future strategies to improve the prognosis of HCC patients undergoing chemotherapy should consider supportive therapy that incorporates antiviral therapies to reduce HBV viral load. (HEPATOLOGY 2007;45:1382,1389.) [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] Combination therapy with lamivudine and famciclovir for chronic hepatitis B,infected Chinese patients: A viral dynamics studyHEPATOLOGY, Issue 2 2000George Ka Lau M.D. In vitro studies have shown that lamivudine and penciclovir (the active metabolite of famciclovir) act synergistically to inhibit hepatitis B virus (HBV) replication. We compared the effectiveness of HBV viral suppression by lamivudine monotherapy versus lamivudine plus famciclovir combination therapy in Chinese patients with chronic HBV infection. Twenty-one Chinese hepatitis B e antigen (HBeAg)-positive patients, with detectable HBV DNA (Digene Hybrid Capture II), were randomized to receive either lamivudine 150 mg/d orally (group 1, 9 patients) or lamivudine 150 mg/d plus famciclovir 500 mg 3 times a day orally (group 2, 12 patients) for 12 weeks, with a follow-up period of at least 16 weeks. Serial serum HBV-DNA levels were determined and a mathematical model with provision for incomplete inhibition of virus production during therapy was applied to analyze the dynamics of viral clearance. The mean antiviral efficacy was significantly greater in group 2 than in group 1 (0.988 ± 0.012 vs. 0.94 ± 0.03, P = .0012). HBV DNA returned to pretreatment level within 16 weeks after the end of initial treatment in 4 patients (66.7%) in group 1 and none in group 2 (P = .08), who remained HBeAg positive and received no further treatment after week 12. Hence, in Chinese chronic HBeAg-positive patients, combination therapy using lamivudine and famciclovir was superior to lamivudine monotherapy in inhibiting HBV replication. Further studies of longer duration are needed to define whether combination therapy will increase the HBeAg seroconversion rate and decrease the rate of emergence of lamivudine-resistant variants. [source] Effects of structural variations of APOBEC3A and APOBEC3B genes in chronic hepatitis B virus infectionHEPATOLOGY RESEARCH, Issue 12 2009Hiromi Abe Aim:, Human APOBEC3 deaminases induce G to A hypermutation in nascent DNA strand of hepatitis B virus (HBV) genomes and seem to operate as part of the innate antiviral immune system. We analyzed the importance of APOBEC3A (A3A) and APOBEC3B (A3B) proteins, which are potent inhibitors of adeno-associated-virus and long terminal repeat (LTR)-retrotransposons, in chronic HBV infection. Methods:, We focused on the common deletion polymorphism that spans from the 3, part of A3A gene to the 3, portion of A3B gene. An association study was carried out in 724 HBV carriers and 469 healthy control subjects. We also analyzed hypermutated genomes detected in deletion and insertion (non-deletion) homozygous patients to determine the effect of APOBEC3 gene deletion. Further, we performed functional analysis of A3A gene by transient transfection experiments. Results:, The association study showed no significant association between deletion polymorphism and chronic HBV carrier state. Context analysis also showed a negligible effect for the deletion. Rather, mild liver fibrosis was associated with APOBEC gene deletion homozygosity, suggesting that A3B deletion is not responsible for chronic HBV infection. Functional analysis of A3A showed that overexpression of A3A induced hypermutation in HBV genome, although the levels of hypermutants were less than those introduced by A3G. However, overexpression of A3A did not decrease replicative intermediates of HBV. Conclusion:, These results suggest that A3A and A3B play little role in HBV elimination through anti-viral defense mechanisms. The significance of hypermutation induced by A3A should be investigated further. [source] Impact of determination of hepatitis B virus subgenotype and pre-core/core-promoter mutation for the prediction of acute exacerbation of asymptomatic carriersHEPATOLOGY RESEARCH, Issue 4 2009Tadashi Ikegami Aim:, A large cohort study in Japan revealed that the specific viral profile may influence the fulminant outcome in acute hepatitis B virus (HBV) infections, while the genetic influence on outcome has not been clarified in patients with acute exacerbation of chronic liver disease caused by HBV. We experienced a case of fatal liver failure that developed as the result of chronic HBV infection. To determine possible genetic factor involving acute exacerbation, genetic analysis of serum from the patient and his siblings was performed. Methods:, HBV subgenotype as well as pre-core/core-promoter mutations of samples mentioned above were determined. Results:, Patient had HBV-Bj with pre-core (1896/1899) and core-promoter (1762/1764) mutations, the genomic profile frequently seen in fulminant hepatitis caused by acute HBV infection. Conclusion:, This result suggests that determination of the HBV subgenotype and pre-core/core promoter mutations could provide a rationale for development of a treatment strategy in asymptomatic HBV carriers. [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] 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] Incidence of Sjögren's syndrome in Japanese patients with hepatitis C virus infectionJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 3 2003YUMIKO NAGAO Abstract Background and Aim: Hepatitis viruses induce not only chronic liver diseases but also the impairment of other organs and tissues as extrahepatic manifestations. In particular, hepatitis C virus (HCV) is involved in various extrahepatic manifestations. The purpose of the present study was to evaluate Sjögren's syndrome (SS) and lichen planus (LP) involvement, which are various extrahepatic manifestations in patients with liver diseases related to hepatitis B virus (HBV) or HCV. Methods: We examined a total of 110 Japanese patients with chronic liver disease: 29 with HBV infections and 81 HCV infections. Results: The prevalence of SS according to European and Japanese criteria in patients with chronic HCV infection was significantly higher than in patients with chronic HBV infection (European criteria: 25.9 vs 3.4%; P < 0.05, Japanese criteria: 21.0 vs 3.4%; P = 0.05). Lichen planus was observed in one (3.4%) of 29 patients with chronic HBV infection, and in 11 (13.6%) of 81 patients with chronic HCV infection. Simultaneously combined LP and SS occurred in 8.6% (seven of 81) of patients with HCV infection, but in none with HBV infection. Conclusions: Clinicians should routinely follow the HCV-infected patients, paying sufficient attention to the presence of SS and LP, and they should also carefully monitor their prognosis. [source] Chronic hepatitis B virus infection in Asian countriesJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 12 2000I Merican Of the estimated 50 million new cases of hepatitis B virus (HBV) infection diagnosed annually, 5,10% of adults and up to 90% of infants will become chronically infected, 75% of these in Asia where hepatitis B is the leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). In Indonesia, 4.6% of the population was positive for HBsAg in 1994 and of these, 21% were positive for HBeAg and 73% for anti-HBe; 44% and 45% of Indonesian patients with cirrhosis and HCC, respectively, were HBsAg positive. In the Philippines, there appear to be two types of age-specific HBsAg prevalence, suggesting different modes of transmission. In Thailand, 8,10% of males and 6,8% of females are HBsAg positive, with HBsAg also found in 30% of patients with cirrhosis and 50,75% of those with HCC. In Taiwan, 75,80% of patients with chronic liver disease are HBsAg positive, and HBsAg is found in 34% and 72% of patients with cirrhosis and HCC, respectively. In China, 73% of patients with chronic hepatitis and 78% and 71% of those with cirrhosis and HCC, respectively, are HBsAg positive. In Singapore, the prevalence of HBsAg has dropped since the introduction of HBV vaccination and the HBsAg seroprevalence of unvaccinated individuals over 5 years of age is 4.5%. In Malaysia, 5.24% of healthy volunteers, with a mean age of 34 years, were positive for HBsAg in 1997. In the highly endemic countries in Asia, the majority of infections are contracted postnatally or perinatally. Three phases of chronic HBV infection are recognized: phase 1 patients are HBeAg positive with high levels of virus in the serum and minimal hepatic inflammation; phase 2 patients have intermittent or continuous hepatitis of varying degrees of severity; phase 3 is the inactive phase during which viral concentrations are low and there is minimal inflammatory activity in the liver. In general, patients who clear HBeAg have a better prognosis than patients who remain HBeAg-positive for prolonged periods of time. The outcome after anti-HBe seroconversion depends on the degree of pre-existing liver damage and any subsequent HBV reactivation. Without pre-existing cirrhosis, there may be only slight fibrosis or mild chronic hepatitis, but with pre-existing cirrhosis, further complications may ensue. HBsAg-negative chronic hepatitis B is a phase of chronic HBV infection during which a mutation arises resulting in the inability of the virus to produce HBeAg. Such patients tend to have more severe liver disease and run a more rapidly progressive course. The annual probability of developing cirrhosis varies from 0.1 to 1.0% depending on the duration of HBV replication, the severity of disease and the presence of concomitant infections or drugs. The annual incidence of hepatic decompensation in HBV-related cirrhosis varies from 2 to 10% and in these patients the 5-year survival rate drops dramatically to 14,35%. The annual risk of developing HCC in patients with cirrhosis varies between 1 and 6%; the overall reported annual detection rate of HCC in surveillance studies, which included individuals with chronic hepatitis B and cirrhosis, is 0.8,4.1%. Chronic hepatitis B is not a static disease and the natural history of the disease is affected by both viral and host factors. The prognosis is poor with decompensated cirrhosis and effective treatment options are limited. Prevention of HBV infection thorough vaccination is still, therefore, the best strategy for decreasing the incidence of hepatitis B-associated cirrhosis and HCC. [source] Identification of a pre-S2 mutant in hepatocytes expressing a novel marginal pattern of surface antigen in advanced diseases of chronic hepatitis B virus infectionJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 5 2000Yu-Fen Fan Abstract Background and Aims: The expression of hepatitis B viral (HBV) antigens in liver tissue reflects the replicative status of chronic HBV infection. We have previously recognized a novel marginal pattern of hepatitis B surface antigen (HBsAg) in hepatocytes, which usually clusters in groups and emerges at the late non-replicative phase. This study was designed to investigate whether the marginal-type HBsAg represented the gene product of a specific HBV-surface mutant. Methods: Microdissection of cirrhotic nodules homogeneously expressing marginal HBsAg was performed on two of 12 resected livers from HBsAg-seropositive patients with hepatocellular carcinoma. The gene presumably encoding marginal HBsAg was polymerase chain reaction (PCR)-cloned, sequenced and analysed. In vitro transfection and expression of the cloned surface mutant plasmids were performed on the Huh7 cell line to illustrate intrahepatic HBsAg expression. Results: Immunohistochemical staining revealed that the marginal HBsAg was positive for pre-S1 and thus contained large surface proteins. The PCR cloning and sequencing of the genes presumably encoding marginal-type HBsAg in both cases revealed the same deletion at the 5, terminus (nt 2,55) of pre-S2. A point mutation on the small-surface (S) antigen was also found in one case. The pre-S2 deletion sequence and the mutation sites of the S gene coincide with human lymphocyte antigen-restricted T- and/or B-cell epitopes. In vitro transfection of the mutant plasmid revealed a blot-like retention or accumulation of HBsAg in the cytoplasm or at the periphery of hepatocytes, accompanied by a decreased secretion of HBsAg in the culture supernatant, mimicking intrahepatic expression. Conclusion: A natural pre-S2 deletion mutant was identified in hepatocytes expressing a novel marginal pattern of HBsAg, which probably contains mutant, large, surface proteins. The biological significance of the pre-S2 deletion mutant should be interesting in view of the clustering proliferation of hepatocytes expressing marginal HBsAg. [source] Epidemiology of hepatitis B virus infection in the Asia,Pacific regionJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2000Chien-Jen Chen There is a wide variation of hepatitis B virus (HBV) infection in the Asia,Pacific region. The prevalence of chronic HBV infection is lowest (< 1%) in North America, Australia and New Zealand, 2,4% in Japan, 5,18% in China and highest (15,20%) in Taiwan as well as several other countries in South East Asia. Perinatal transmission is common in HBV-hyperendemic areas. Geographical clusters of horizontal HBV infection have been reported in both high- and low-risk countries. Common sources of infection, including iatrogenic and sexual transmission, have been implicated. Migrant studies indicate the importance of childhood environments in the determination of HBV infection. Rural,urban and ethnic differences in the prevalence of HBV infection have also been reported. There has been a decrease in the prevalence of HBV infection after mass HBV vaccination programmes in some Asia, Pacific countries, which may be due to the intervention of possible transmission routes through the use of disposable syringes and needles, screening of HBV infection markers in blood banks, and prevention of high-risk tattooing, acupuncture, ear-piercing and sexual contact. A striking decrease in the incidence of HBV infection and hepatocellular carcinoma has been observed among children in Taiwan and other areas where mass vaccination programmes have been implemented. [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] Susceptibility of hepatitis B virus to lamivudine restored by resistance to adefovirJOURNAL OF MEDICAL VIROLOGY, Issue 3 2009H.L. Zaaijer Abstract Serial monotherapy and add-on regimes for treatment of chronic hepatitis B virus (HBV) infection may induce the accumulation of viral resistance mutations in patients, reducing the options for ongoing viral suppression. The induction of antiviral resistance by serial application of polymerase inhibitors does not necessarily imply that the subsequent combined use of the drugs will fail. Some HIV strains resistant to one polymerase inhibitor show increased susceptibility to another polymerase inhibitor. After failure of sequential lamivudine and adefovir monotherapy, two patients with hepatitis B changed to treatment with lamivudine plus adefovir and had renewed suppression of HBV. To study the mutational history of resistant HBV subpopulations in the two patients, a part of the HBV polymerase gene was amplified, cloned, sequenced, and analyzed for the presence of mutations, in sequential plasma samples. In both patients serial monotherapy caused the replacement in all HBV clones of wild-type virus by classical lamivudine resistant mutants (L180M and M204V/I), which were replaced subsequently by adefovir resistant mutants (A181V and N236T). When finally lamivudine was added to adefovir, the A181V adefovir mutation persisted in all clones and lamivudine-related mutations did not reappear. During 18 months of combination therapy, HBV-DNA levels decreased 10,000, respectively, 1,000-fold, despite the earlier resistance to lamivudine and adefovir. Although clinically insufficient, this effect indicates that HBV polymerase resistance mutations may be antagonistic, which is relevant if chronic HBV infection is to be treated by a combination of polymerase inhibitors. J. Med. Virol. 81:413,416, 2009. © 2009 Wiley-Liss, Inc. [source] Change of hepatitis B virus genotypes in acute and chronic infections in JapanJOURNAL OF MEDICAL VIROLOGY, Issue 11 2008Mariko Kobayashi Abstract During 35 years from 1971 to 2005, 153 patients with acute and 4,277 with chronic HBV infection visited the Toranomon Hospital in Tokyo, Japan. They were grouped into seven 5-year periods, and HBV genotypes/subgenotypes were determined. Patients with acute HBV infection were younger (P,=,0.046), predominantly male (P,=,0.004), possessed higher alanine aminotransferase levels (P,<,0.001), positive more frequently for HBeAg (P,<,0.001), and had lower HBV DNA loads (P,=,0.014) than those with chronic infection. Sexual transmission was more frequent in patients with acute than chronic HBV infection (67% vs. 3%, P,<,0.001). The number of patients with acute infection increased throughout 1971,2005. Patients with chronic infection increased since 1971, peaked in 1986,1990 and then decreased. The number of patients increased since 1990,2000 again, however, reflecting recent boost of acute HBV infection. The distribution of HBV genotypes was considerably different between patients with acute and chronic infections (A, B, and C: 28.6%, 10.3%, and 59.5% vs. 3.0%, 12.3%, and 84.5%, respectively, P,<,0.001). Since 1991, genotype A foreign to Japan started to increase sharply in patients with acute infection, and gradually in those with chronic infection. There was a trend for the foreign subgenotype B2/Ba to increase recently (P,<,0.05). Despite immunoprophylaxis of high-risk babies born to carrier mothers with hepatitis B e antigen, implemented nationally since 1986, acute and chronic infections with HBV have been increasing in Japan. Based on genotypes/subgenotypes changing with time, the resurgence of hepatitis B could be attributed to infections, with foreign HBV genotypes/subgenotypes, spreading swiftly by sexual contact. J. Med. Virol. 80:1880,1884, 2008. © 2008 Wiley-Liss, Inc. [source] Role of hepatitis B virus genotypes and quantitative HBV DNA in metastasis and recurrence of hepatocellular carcinomaJOURNAL OF MEDICAL VIROLOGY, Issue 4 2008Yuehua Huang Abstract Identification of risk factors for recurrence and metastasis of HCC is important for the prognosis of HCC surveillance in chronic HBV infection. In this article, 125 HCC patients recruited were followed up prospectively for tumor metastasis and recurrence for a median of 104 (10,130) weeks. HBV DNA level was detected by LightCycler-based real-time fluorescence quantitative polymerase chain reaction-restriction system. HBV genotypes were determined by using PCR restriction-fragment length polymorphism. BCP and PC mutations were performed by PCR and direct sequencing of amplified products. Among 125 HCC patients, 19 patients were excluded because of the lack of follow-up data and the remaining 106 patients were followed up of 2 years and entered into analysis. Sixty-nine patients had tumor metastasis or recurrence during the follow-up and the cumulative probability of HCC metastasis or recurrence was 65.1%. On multivariate analysis, genotype C and HBV DNA level were the risk factors for HCC recurrence or metastasis. The incidence of recurrence or metastasis increased with baseline HBV DNA level in a dose-response relationship ranging from 22% for HBV DNA level of less than 3 log10 copies/ml to 80% for HBV DNA level of 5 log10 copies/ml or greater (P,=,0.012). Fifty-seven (74.0%) and 12 (41.4%) patients had metastasis or recurrence in patients with genotype C and B, respectively. The adjusted OR of recurrence or metastasis for genotype C compared with genotype B was 9.755 (P,=,0.009). In conclusion, elevated HBV DNA level and genotype C are strong risk predictors of HCC metastasis or recurrence. J. Med. Virol. 80:591,597, 2008. © 2008 Wiley-Liss, Inc. [source] Hepatitis B virus genotypes in children and adolescents in Japan: Before and after immunization for the prevention of mother to infant transmission of hepatitis B virusJOURNAL OF MEDICAL VIROLOGY, Issue 6 2007Ayano Inui Abstract The genotype distribution of hepatitis B virus (HBV) was investigated in 118 children in Japan. One hundred and sixteen children (98%) had chronic HBV infection, and the remainder had acute hepatitis. Genotyping of HBV was determined by PCR and sequencing analysis in the S gene. Genotype C (86%) was the most frequent, followed by genotype B (9%), D (2.5%), and A (1.0%). Transmission routes of HBV to children were from mothers in 91 patients (77%), fathers in 8 (6.5%), mother or father in 1 (1%), family members other than the parents in 5 (4%), and unknown in 13 (11.5%). The relationship between routes of HBV transmission and HBV genotypes was studied. Eighty-eight (97%) of 91 children of mother-to-infant transmission were genotype C, while 13 (49%) of 27 children of the routes other than the mother to infant transmission were genotype C. The number of children with genotype C who were infected from their mothers was significantly higher than those with genotype B, D, or A (P,<,0.01). In conclusion, HBV genotypes influence not only clinical characteristics but also the mechanisms of inter-personal HBV transmission. J. Med. Virol. 79: 670,675, 2007. © 2007 Wiley-Liss, Inc. [source] Infection with hepatitis A, B, C, and delta viruses among patients with acute hepatitis in Mongolia,JOURNAL OF MEDICAL VIROLOGY, Issue 5 2006Bira Tsatsralt-Od Abstract One hundred ten consecutive patients (60 males and 50 females; age, mean,±,standard deviation [SD], 22.6,±,6.4 years; range 16,48 years) who were clinically diagnosed with sporadic acute hepatitis between December 2004 and January 2005 in Ulaanbaatar, Mongolia, were studied. IgM antibodies to hepatitis A virus were detected in 18 patients (16.4%), IgM antibodies to hepatitis B core (anti-HBc IgM) in 38 patients (34.5%) including two patients with concurrent hepatitis delta virus (HDV) infection, and hepatitis C virus RNA in nine patients (8.2%). There were 30 hepatitis B virus (HBV) carriers who had detectable hepatitis B surface antigen and antibodies to HDV but were negative for anti-HBc IgM, suggesting that they acquired type D acute hepatitis due to superinfection of HDV on a background of chronic HBV infection. None had IgM antibodies to hepatitis E virus (HEV). Consequently, 16.4, 32.7, 6.4, 1.8, and 27.3% of the patients were diagnosed as having acute hepatitis of type A, B, C, type B,+,D (HBV/HDV coinfection), and type D (superinfection of HDV), respectively. The cause of hepatitis was not known in the remaining 17 patients (15.5%). All 18 HAV isolates were genotyped as IA, all 9 HCV isolates were genotyped as 1b, and all 32 HDV isolates were classified into genotype I. The distribution of HBV genotypes among the 67 HBV isolates was A (1.5%, n,=,1) and D (98.5%, n,=,66). The present study indicates that de novo infections of HAV, HBV, HCV, and HDV are prevalent among young adults in Mongolia. J. Med. Virol. 78:542,550, 2006. © 2006 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 infection in dentistry: a forgotten topicJOURNAL OF VIRAL HEPATITIS, Issue 5 2010N. Mahboobi Summary., More than two billion people have been infected with hepatitis B virus (HBV). Globally, 350,400 million suffer from chronic HBV infection. It is postulated that dentists and dental staff are infected and transmit the virus to their patients more than any other occupation. The aim of this article is to review the HBV incidence in dental society, the points of view of dentists and their patients regarding transmission of the virus during dental procedures, the occurrence of HBV outbreaks in dental clinics and the importance of methods of preventing HBV infection in dentistry. [source] B7-H1 expression is upregulated in peripheral blood CD14+ monocytes of patients with chronic hepatitis B virus infection, which correlates with higher serum IL-10 levelsJOURNAL OF VIRAL HEPATITIS, Issue 11 2006L. Geng Summary., Chronicity in hepatitis B virus (HBV) infection is maintained by increased type 2 T-helper cell response, possibly because of increased interleukin-10 (IL-10) productions. B7-H1 can negatively regulate T-cell responses via its receptor, programmed death 1. Ligation of B7-H1 to T-cells can result in the preferential secretion of IL-10. In this study, we investigated whether there was an upregulated expression of B7-H1 in peripheral blood mononuclear cells in patients chronically infected by HBV and further explored the correlation between B7-H1 expression and serum interleukin 2, interferon- ,, IL-10, HBeAg, alanine aminotransferase (ALT) levels and viral load. Fifty-five patients with chronic HBV infection and 20 healthy controls (HCs) were enrolled in the present study. The results showed that in patients with chronic hepatitis B CD14+ monocytes but not CD3+ and CD19+ cells had a significantly increased expression of B7-H1 compared with HCs, which positively correlates with serum IL-10 levels and the presence of HBeAg and negatively correlates with serum ALT levels. In conclusion, chronic HBV patients harbour an increased B7-H1 expression in CD14+ monocytes compared with controls, which may be responsible for the increased serum IL-10 levels. This might be an important way by which HBV evades an adequate immune response, leading to viral persistence and disease chronicity. [source] Inhibition of hepatitis B virus by lentiviral vector delivered antisense RNA and hammerhead ribozymesJOURNAL OF VIRAL HEPATITIS, Issue 4 2005K. L. Nash Summary., Chronic hepatitis B virus (HBV) infection is an important cause of cirrhosis and hepatocellular carcinoma. Current treatments are limited and may be ineffective. Nucleic acid-mediated targeting of viral mRNA is an attractive and specific approach for viral infection and lentiviral vectors provide a means to express antisense sequences or ribozymes stably in target cells permitting continuous production within that cell and its progeny. To demonstrate long-term gene expression by lentiviral vectors in hepatocytes and to introduce lentiviral vectors expressing anti-HBV genes to assess their effect against HBV, lentiviral vectors expressing a reporter gene were assessed for longevity of gene expression in hepatocytes in vitro. Hammerhead ribozymes and antisense sequences targeting the HBV encapsidation signal (,), X or surface antigen on mRNAs were cloned into lentiviral vectors and used to transduce HBV expressing hepatocytes where the effect on HBV mRNA level was assessed using ribonuclease protection. Gene expression in hepatocytes from integrated vectors continued for over 4 months without selection. Antisense RNA targeting HBs mRNA reduced this transcript, whilst antisense RNA to HBX mRNA was ineffective. Sense RNAs corresponding to , and HBX mRNA also reduced HBV mRNA levels. Ribozymes targeting HBs and HBX mRNA effectively reduced HBV mRNA levels compared with inactive constructs indicating their effect to be enzymatic rather than antisense. Lentiviral vectors can produce long-term gene expression in hepatocytes and thus permit prolonged expression of antiviral genes targeting the HBV encapsidation signal, surface and X mRNAs as treatments for chronic HBV infection. [source] Clinical outcome and virological characteristics of hepatitis B-related acute liver failure in the United StatesJOURNAL OF VIRAL HEPATITIS, Issue 2 2005C.-T. Wai Summary., The role of hepatitis B virus (HBV) genotypes in the outcome of acute HBV infection is unclear. In this study, we aimed to evaluate the clinical and virological features of patients with hepatitis B-related acute liver failure (HBV-ALF) in the US. Clinical and laboratory features of consecutive patients with HBV-ALF from the US ALF Study Group were analysed. Prevalence of HBV genotypes, precore stop (G1896A) and core promoter dual (T1762A, A1764T) variants among patients with HBV-ALF were compared with a cohort of 530 patients with chronic HBV infection. Thirty-four HBV-ALF patients were studied: mean age 41 years, 56% men, 25 had detectable HBV-DNA. HBV genotypes A, B, C and D were found in 36, 24, 8 and 32% patients, respectively. Precore stop and core promoter dual variants were detected in 32 and 44% of patients, respectively. Twenty-three (68%) patients survived: 14 after liver transplant, nine without transplant. Older age was the only independent factor associated with poor outcome. Compared with patients with chronic HBV infection, patients with ALF were more likely to be non-Asians (88%vs 44%, P = 0.005) and to have genotype D (32%vs 10%, P < 0.01). A higher prevalence of HBV genotype D persisted even after matching for race and HBeAg status (32%vs 16%, P = 0.007). We concluded that HBV genotype D was more frequently found in patients with HBV-ALF than those with chronic HBV infection in the US. Further studies are needed to determine if HBV genotypes play a role in the outcome of acute HBV infection. [source] The role of intrahepatic immune effector cells in inflammatory liver injury and viral control during chronic hepatitis B infectionJOURNAL OF VIRAL HEPATITIS, Issue 3 2003T. J. Tang Summary. Cytotoxic T lymphocytes (CTL) and Kupffer cells play an important role in the immune control of hepatitis B virus (HBV), but may also induce liver injury during infection. We investigated the intrahepatic immune response in liver biopsies of chronic HBV patients in relation to inflammatory liver injury and viral control. Forty-seven liver biopsies from patients with chronic HBV with varying degrees of inflammation (ALT values) were selected. Acute hepatitis and normal liver specimens served as controls. Immune effector cells, cytotoxic effector molecules and cytokine producing cells were quantified after immunohistochemical staining in lobular and portal areas of the biopsies. The intralobular number of CD8+ T-lymphocytes was significantly decreased in biopsies of patients with high ALT (r = ,0.54; P < 0.001). Higher ALT-values were correlated with increased numbers of granzyme+ cells in portal areas (r = 0.65; P < 0.001) and higher numbers of intralobular Fas-L+ cells (r = 0.32; P = 0.05). Fas-L was expressed on Kupffer and lymphoid cells. More intralobular CD8+ T-lymphocytes were found in HBeAg, than in HBeAg+ patients (P = 0.002). But IFN- , and TNF- , producing cells were observed sporadically in chronic HBV patients. Hence, in chronic HBV infection, low viral replication and HBeAg negativity is related to increased presence of intralobular CD8+ T-lymphocytes. Persistence of the virus may be caused by the absence of cells producing anti-viral cytokines in the liver. Inflammatory liver injury during chronic HBV infection is probably not the result of increased numbers of infiltrating CD8+ T-lymphocytes, but of Fas-L expression by Kupffer cells and increased cytolytic activity of cells in portal areas. [source] Comparing the safety, tolerability and quality of life in patients with chronic hepatitis B vs chronic hepatitis C treated with peginterferon alpha-2aLIVER INTERNATIONAL, Issue 4 2008Patrick Marcellin Abstract Background/Aims: Hepatitis B and C viruses (HBV and HCV) are two clinically distinct but related diseases. Pooled data from five studies of peginterferon alpha-2a in patients with chronic HCV infection (CHC) were compared with two studies of the drug in patients with chronic HBV infection (CHB). Method: The HBV studies included both hepatitis B e antigen (HBeAg)-positive (n=271) and HBeAg-negative (n=177) patients; 791 patients took part in the HCV trials. In all studies, patients were treated with 180 ,g peginterferon alpha-2a monotherapy once weekly for 48 weeks. The number of adverse events (AEs), discontinuations and dose modifications were documented. Health-related quality of life (HRQL) was assessed using the Short-Form 36 questionnaire. Safety was assessed throughout the treatment period. A 24-week treatment-free follow-up period was also included. Results: Differences (HBV vs HCV) were observed in the incidence of AEs (88,89 vs 96,100%), serious AEs (4,5 vs 7,16%) and treatment withdrawals (6,8 vs 17,33%). The frequency of depression-related events was lower in CHB patients (4 vs 22%, P<0.001), as was the impact of treatment on HRQL. Conclusions: The safety and tolerability of peginterferon alpha-2a in patients with CHB compares favourably with that observed in CHC patients, with a lower incidence of common interferon-related AEs and a significantly lower incidence of depression. [source] Clinical significance and evolution of core promoter and precore mutations in HBeAg-positive patients with HBV genotype B and C: a longitudinal studyLIVER INTERNATIONAL, Issue 6 2007Chien-Hung Chen Abstract Background/Aims: The aims of this longitudinal study were to investigate whether the clinical outcome and evolution of core promoter and precore mutations were different during hepatitis B e antigen (HBeAg) seroconversion between hepatitis B virus (HBV) genotypes B and C in HBeAg-positive patients with chronic hepatitis B. Patients and Methods: The core promoter and precore sequences were determined from serial sera of 156 HBeAg-positive patients with chronic HBV infection. Results: In HBV genotype C, the T1762/A1764 mutant was detected earlier than the A1896 mutant, and the frequency was significantly higher than in HBV genotype Ba over the entire follow-up period. In HBV genotype Ba, A1896 was found earlier than the T1762/A1764 mutant, and the frequency was significantly higher than in genotype C only before HBeAg seroconversion, and the A1896 mutant played an important role in HBeAg seroconversion in HBV genotype Ba. In addition, the T1846 variant was an independent factor associated with HBeAg seroconversion. Furthermore, HBV genotype C was associated with the development of G or C1753 and T1766/A1768 mutations, and the reactivation of hepatitis after HBeAg seroconversion. Based on Cox's regression analysis, the significant risk factors of liver cirrhosis were older age at entry [hazard ratio (HR)=1.085, 95% confidence interval (CI)=1.036,1.136, P=0.001], alanine transaminase (ALT) >80 U/l (HR=3.48, 95% CI=1.37,8.86, P=0.009), and the T1762/A1764 mutant (HR=5.54, 95% CI=2.18,14.08, P<0.001). Conclusions: Our study showed that different HBV genotypes were associated with various mutations in the core promoter and precore regions during HBeAg seroconversion. T1762/A1764 mutation could be useful in predicting clinical outcomes in HBeAg-positive patients with HBV infection. [source] Is leptin a predictive factor in the end of therapy response in chronic hepatitis B?PEDIATRICS INTERNATIONAL, Issue 4 2005Mukadder Ayle Selimo}lu Abstract, Background:,The purpose of this study was to determine the leptin levels in children with chronic hepatitis B virus (HBV) infection, and to evaluate the effect of serum leptin levels on the end of therapy response (ETR). It is known that leptin stimulates T-cell immunity and so T-cell mediated immune response is critical in the outcome of chronic HBV infection. Methods:,Leptin levels in children with chronic HBV infection were investigated and its effects on the ETR in 24 children who were treated with interferon-, and lamivudine combination therapy were evaluated. Results:,The mean leptin level of the patients was higher than that of healthy children (P = 0.034). Of the patients, seven (29.2%) had ETR. The mean hepatic activity index and portal inflammation score were higher, the HBV DNA was lower, and the leptin level was similar in children with ETR when compared to others (P = 0.017, P = 0.04, P = 0.007, P = 0.34, respectively). HBV DNA and the fibrosis score were positively correlated (P = 0.016). Conclusion:,Although the higher leptin value observed in children with ETR was not statistically significant, because of close interactions between leptin, cytokines and lymphocytes, it is thought that leptin should be investigated as a predictive factor of ETR in further studies. [source] Markers of hepatitis B virus infection and immunity in Victoria, Australia, 1995 to 2005AUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH, Issue 1 2010Benjamin Cowie Abstract Objective: Estimating the prevalence of chronic hepatitis B virus (HBV) infection in generally low-prevalence populations containing communities with a higher disease burden is difficult. This study was conducted to estimate the prevalence of serological markers of infection with, and immunity to, HBV in the Victorian population and to analyse trends in these estimates over time. Methods: A serological survey of 3,212 samples of convenience collected in the years 1995, 2000 and 2005 was conducted using a selection procedure designed to reduce selection bias. All samples were tested for hepatitis B surface and core antibodies; all core antibody positive samples (indicating previous infection) were then tested for the presence of hepatitis B surface antigen (HBsAg). Results: HBsAg prevalence was 1.1% (95%CI 0.8-1.6%) with significant differences observed by area of residence, age, gender and test year. Serological evidence of immunisation in infants and adolescents were lower than established estimates following the introduction of universal vaccination for these groups. Conclusions: This study emphasises the significant and growing problem of chronic HBV infection in Victoria and suggests lower than expected population immunity deriving from universal vaccination programs. Implications: Greater efforts are needed to formulate a comprehensive public health response to address this relatively neglected blood borne viral infection, the burden of which is very significant in some marginalised sections of our community. Increased attention to improving the universality of our immunisation programs is also needed. [source] Hepatitis B virus pre-S mutants, endoplasmic reticulum stress and hepatocarcinogenesisCANCER SCIENCE, Issue 8 2006Hui-Ching Wang Although hepatitis B virus (HBV) has been documented to cause hepatocellular carcinoma (HCC), the exact role of HBV in the development of HCC remains enigmatic. Several hypotheses have been proposed to explain the potential mechanism, including insertional mutagenesis of HBV genomes and transcriptional activators of HBV gene products such as hepatitis B x protein (HBx) and truncated middle S mutants. In the past few years, we have identified two types of large HBV surface antigens (LHBs) with deletions at the pre-S1 (,S1-LHBs) and pre-S2 (,S2-LHBs) regions in ground glass hepatocytes. The pre-S mutant LHBs are retained in the endoplasmic reticulum (ER) and escape from immune attack. The pre-S mutants, particularly ,S2-LHBs, are increasingly prevalent in patients with hepatitis B e antigen (HBeAg)-positive chronic HBV infection, ranging from 6% before the 3rd decade to 35% in the 6th decade. In HCC patients, the two pre-S mutants were detected in 60% of HCC patients, in the serum and in HCC tissues. Pre-S mutant LHBs can initiate ER stress to induce oxidative DNA damage and genomic instability. Furthermore, pre-S mutant LHBs can upregulate cyclooxygenase-2 and cyclin A to induce cell cycle progression and proliferation of hepatocytes. In transgenic mice, the pre-S mutants can induce dysplasia of hepatocytes and development of HCC. In a nested control study, the presence of pre-S mutants carried a high risk of developing HCC in HBV carriers. In summary, the findings we describe in this review suggest a potential role for HBV pre-S mutants in HBV-related hepatocarcinogenesis, providing a model of viral carcinogenesis associated with ER stress. (Cancer Sci 2006; 97: 683,688) [source] | |||||||||||||||||||||||||