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Hepatitis B Virus Infection (hepatitis + b_virus_infection)
Kinds of Hepatitis B Virus Infection Selected AbstractsVirologic and Clinical Outcomes of Hepatitis B Virus Infection in HIV-HBV Coinfected Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2010C. S. Coffin Liver transplantation (LT) is the treatment of choice for end-stage liver disease, but is controversial in patients with human immunodeficiency virus (HIV) infection. Using a prospective cohort of HIV-hepatitis B virus (HBV) coinfected patients transplanted between 2001,2007; outcomes including survival and HBV clinical recurrence were determined. Twenty-two coinfected patients underwent LT; 45% had detectable HBV DNA pre-LT and 72% were receiving anti-HBV drugs with efficacy against lamivudine-resistant HBV. Post-LT, all patients received hepatitis B immune globulin (HBIG) plus nucleos(t)ide analogues and remained HBsAg negative without clinical evidence of HBV recurrence, with a median follow-up 3.5 years. Low-level HBV viremia (median 108 IU/mL, range 9,789) was intermittently detected in 7/13 but not associated with HBsAg detection or ALT elevation. Compared with 20 HBV monoinfected patients on similar HBV prophylaxis and median follow-up of 4.0 years, patient and graft survival were similar: 100% versus 85% in HBV mono- versus coinfected patients (p = 0.08, log rank test). LT is effective for HIV-HBV coinfected patients with complications of cirrhosis, including those who are HBV DNA positive at the time of LT. Combination HBIG and antivirals is effective as prophylaxis with no clinical evidence of HBV recurrence but low-level HBV DNA is detectable in ,50% of recipients. [source] Active Immunization to Prevent De Novo Hepatitis B Virus Infection in Pediatric Live Donor Liver RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2007C.-C. Lin This study aims to evaluate the efficacy of HBV vaccination as an alternative preventive measure against de novo HBV infection in pediatric living donor liver transplantation (LDLT). Sixty recipients were enrolled in this study. Thirty received grafts from anti-HBc(+) donors, and another 30 received grafts from anti-HBc(,) donors. HBV vaccine was given pretransplant to every candidate. Posttransplant, lamivudine was routinely given to recipients receiving anti-HBc(+) grafts for about 2 years. Forty-seven (78%) recipients achieved high levels of anti-HBs titer (>1000 IU/L). Two (3.3%) recipients developed de novo HBV infection where one received an anti-HBc(,) graft and another received an anti-HBc(+) graft. Both recipients were in the lower anti-HBs titer group (<1000 IU/L). The incidence of de novo HBV infection was significantly higher in the lower titer group (15.4% vs. 0%, p = 0.04). The median follow-up period was 51 months in recipients with anti-HBc(,) grafts and 57 months in those with anti-HBc(+) grafts. Active immunization is an effective method to prevent de novo HBV infection. It can result in high levels of anti-HBs titer (>1000 IU/L) which may prevent de novo HBV infection in pediatric patients with efficient primary vaccination undergoing LDLT. [source] Hepatitis B Virus Infection and B-Cell Non-Hodgkin's Lymphoma in a Hepatitis B Endemic Area: A Case-control StudyCANCER SCIENCE, Issue 5 2002Jee Hyun Kim Several studies have reported a higher prevalence of chronic hepatitis C virus (HCV) infection in patients with B-cell non-Hodgkin's lymphoma and suggested a pathogenic role for HCV, but studies on hepatitis B virus (HBV) infection and non-Hodgkin's lymphoma are limited. To determine the association between HBV infection and non-Hodgkin's lymphoma, we performed a case-control study in Korea, a hepatitis B endemic area. We recruited 222 patients newly diagnosed with non-Hodgkin's lymphoma at Seoul National University Hospital between January 1997 and December 1998 as cases. Four age- and sex-matched controls were selected for each case, and the control groups comprised of 439 patients with non-hematological malignancy (control group 1) and 444 subjects with non-malignant conditions (control group 2). Relative risk of developing non-Hodgkin's lymphoma among individuals tested positive for hepatitis B surface antigen was calculated after controlling for other potential risk factors of lymphoma, such as smoking, alcohol drinking, transfusion history and HCV infection. Hepatitis B surface antigen was positive in 28 of 222 patients (12.6%) with non-Hodgkin's lymphoma compared with 32 of 439 (7.3%) in control group 1, and 21 of 444 (4.7%) in control group 2 (P=0.001). The crude odds ratio for B-cell non-Hodgkin's lymphoma among the HBV carriers was 2.54 (1.46,4.45) and the adjusted odds ratio was 3.30 (1.69,6.45) by multivariate analysis. The present study suggests that the risk of B-cell non-Hodgkin's lymphoma is increased in HBV carriers and warrants further investigation of the possible role of hepatitis B virus in the pathogenesis of B-cell non-Hodgkin's lymphoma. [source] Production of Hepatitis B Surface Antigen in Recombinant Plant Systems: An UpdateBIOTECHNOLOGY PROGRESS, Issue 3 2007G. B. Sunil Kumar There is a growing interest to develop oral vaccines for infectious diseases, as it is the most convenient and effective way to attain mucosal immunity. Hepatitis B continues to be a major infectious disease in many developing countries despite the availability of recombinant vaccine. On a global scenario, Hepatitis B Virus infection is probably the single most prevalent cause of persistent viraemia in humans. There are about 350 million chronic carriers of HBV, which is about 5% of the total world population. It is estimated that 75,100 million of them will die of liver cirrhosis and/or hepatocellular carcinoma. Progress in plant genetic engineering has enabled the transfer of useful genes for desirable traits. The recent trend is to use this technique to exploit plants as biofactories for the production of therapeutic proteins including vaccines. Rapid progress has been made in this area to develop plant-based vaccines for hepatitis B. This review describes the expression, characterization, and immunogenicity studies of hepatitis B vaccines produced in recombinant plant systems and their implications for developing a plant-based vaccine. [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] Review article: hepatitis B and liver transplantationALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2006D. MUTIMER Summary Liver transplantation is an excellent treatment for hepatitis B virus infected patients who have acute or chronic liver failure and/or primary liver cancer. Advances in antiviral prophylaxis prevent clinically significant graft re-infection for the majority of patients. Graft and patient survival has improved significantly during the past decade, and results of transplantation for hepatitis B virus are now superior to those achieved for most other indications. In particular, the availability of lamivudine and adefovir have transformed outcome. The addition of lamivudine to passive immunoprophylaxis with hepatitis B virus immunoglobulin prevents re-infection in most cases. Adefovir should be added to this combination when the patient develops lamivudine resistance before transplantation. The significance of serum hepatitis B virus DNA positivity in the absence of circulating hepatitis B surface antigen is uncertain. Hepatitis B virus infection of the graft can be observed when prophylaxis is inadequate, when the donor liver contains latent hepatitis B virus infection (so-called de novo infection from the hepatitis B virus core antibody positive donor), and when the donor is exposed to third party infection (sexual or nosocomial transmission). Established hepatitis B virus graft infection is a good indication for combination nucleoside analogue therapy. Combination therapy can achieve sustained suppression of viral replication, and hepatitis B e antigen and hepatitis B surface antigen clearance can also be observed. [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] Serum hepatitis B virus-DNA cutoff levels in hepatitis B e antigen,negative chronic hepatitis B virus infection,HEPATOLOGY, Issue 2 2007George V. Papatheodoridis No abstract is available for this article. [source] Influence of genotypes and precore mutations on fulminant or chronic outcome of acute hepatitis B virus infection,,HEPATOLOGY, Issue 2 2006Atsushi Ozasa The outcome of acute hepatitis B virus (HBV) infection is variable, influenced by host and viral factors. From 1982 through 2004, 301 patients with acute HBV infection entered a multi-center cross-sectional study in Japan. Patients with fulminant hepatitis (n = 40) were older (44.7 ± 16.3 vs. 36.0 ± 14.3 years, P < .0017), less predominantly male (43% vs. 71%, P = .0005), less positive for hepatitis B e antigen (HBeAg) (23% vs. 60%, P < .0001), less infected with subgenotype Ae (0% vs. 13%, P < .05), and more frequently with Bj (30% vs. 4%, P < .0001) than those with acute self-limited hepatitis (n = 261). Precore (G1896A) and core-promoter (A1762T/G1764A) mutations were more frequent in patients with fulminant than acute self-limited hepatitis (53% vs. 9% and 50% vs. 17%, P < .0001 for both). HBV infection persisted in only three (1%) patients, and they represented 2 of the 23 infected with Ae and 1 of the 187 with the other subgenotypes (9% vs. 0.5%, P = .032); none of them received antiviral therapy. In multivariate analysis, age 34 years or older, Bj, HBeAg-negative, total bilirubin 10.0 mg/dL or greater, and G1896A mutation were independently associated with the fulminant outcome. In in vitro transfection experiments, the replication of Bj clone was markedly enhanced by introducing either G1896A or A1762T/G1764A mutation. In conclusion, persistence of HBV was rare (1%) and associated with Ae, whereas fulminant hepatitis was frequent (13%) and associated with Bj and lack of HBeAg as well as high replication due to precore mutation in patients with acute HBV infection. (HEPATOLOGY 2006;44:326,334.) [source] Comparison of adefovir and tenofovir in the treatment of lamivudine-resistant hepatitis B virus infection,HEPATOLOGY, Issue 6 2004Florian van Bömmel Adefovir dipivoxil was recently approved for the treatment of wild-type and lamivudine-resistant hepatitis B virus (HBV) infection. Tenofovir disoproxil fumarate, a congender of adefovir that is used in the treatment of HIV infected patients, has recently been shown to also be effective in patients with lamivudine-resistant HBV infection. We therefore compared the two substances in a study of 53 patients defined by high HBV DNA (>6 log10 copies/mL) levels and genotypic evidence of lamivudine resistance. Thirty-five patients received tenofovir for 72 to 130 weeks, and 18 received adefovir for 60 to 80 weeks. Changes in HBV DNA levels were followed for the complete period of 48 weeks. Early viral kinetics were compared on matched subgroups of 5 patients each. Individually, all tenofovir-treated patients showed a strong and early suppression of HBV DNA within a few weeks whether they were coinfected with HIV or were without comorbidity. In contrast, considerable individual variations in HBV DNA decline were observed in the adefovir group. Thus at week 48, only 44% of these patients had HBV DNA levels below 105 copies/mL in contrast to 100% of the tenofovir-treated patients (P = .001). No severe side effects were noticed in either group. No evidence of phenotypic viral resistance could be demonstrated in the tenofovir-treated patients in the long term (up to 130 weeks). In conclusion, tenofovir may become an effective alternative for the treatment of patients with lamivudine-resistant HBV infection. (HEPATOLOGY 2004;40:1421,1425.) [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] Association of estrogen receptor , polymorphisms with susceptibility to chronic hepatitis B virus infectionHEPATOLOGY, Issue 2 2004Guohong Deng Several studies have demonstrated that estrogen receptor , (ESR1) participates in the pathogenesis of persistent hepatitis B virus (HBV) infection. To examine whether polymorphisms at the ESR1 gene locus are associated with persistent HBV infection, we resequenced ESR1 genomic region for single nucleotide polymorphisms (SNPs) in 27 unrelated Chinese. Two haplotype-tagged SNPs (htSNP), T29C and A252966G, were selected for genotyping in 1,277 persistent HBV-infected cases, 748 spontaneously recovered controls, and 293 nuclear families using polymerase chain reaction (PCR)-restriction fragment length polymorphism (PCR-RFLP) analysis. We observed that the subjects bearing ESR1 29T/T genotype had an increased susceptibility to persistent HBV infection compared to those bearing at least one 29C allele (odds ratio 1.41; 95% CI, 1.17-1.71, P < .001). Consistent with the results of population-based association study, a significantly greater than expected transmission of the 29T allele (56.4%) from heterozygous parents to offspring with persistent HBV infection was observed (,2 = 4.60, P = .033) using the transmission-disequilibrium test (TDT) in 293 nuclear families. Linkage disequilibrium (LD) mapping analysis indicated that the T29C polymorphism contained within a LD block located from promoter region to intron 3 of ESR1, suggesting that the strong association detected with T29C in ESR1 originated from ESR1 itself. In conclusion, our results suggest that the genetic variation at the ESR1 locus influences susceptibility to persistent HBV infection in a Chinese population. (HEPATOLOGY 2004;40:318,326.) [source] Safety and efficacy of oral entecavir given for 28 days in patients with chronic hepatitis B virus infectionHEPATOLOGY, Issue 3 2001Ph.D., Robert A. de Man M.D. Entecavir is an oral antiviral drug with selective activity against hepatitis B virus (HBV). We conducted a randomized, placebo-controlled, dose-escalating study in patients with chronic hepatitis B infection in which we evaluated the efficacy and safety of entecavir given for 28 days. Follow-up was 24 weeks. All doses of entecavir (0.05 mg, 0.1 mg, 0.5 mg, and 1.0 mg) showed a pronounced suppression of replication of the HBV with a 2.21, 2.29, 2.81, and 2.55 mean log10 reduction of viral load, respectively. Approximately 25% of patients on entecavir showed a decline of HBV DNA below the limit of detection of the Chiron HBV-DNA assay (<0.7 MEq/mL). In the postdosing follow-up period patients who were treated with 0.5 and 1.0 mg of entecavir showed a considerably slower return in their HBV DNA levels to baseline compared with those patients treated with lower dosages (P < .05). All doses of entecavir were well tolerated with no significant difference between treated patients and those receiving placebo. No significant changes in alanine transaminase (ALT) levels within the dose groups and the placebo group between baseline and the end of treatment were observed. Three patients (9%) (1 each in the 0.05-, 0.1-, and 0.5-mg groups) experienced asymptomatic hepatitis flares 16 weeks (2 patients) and 24 weeks (1 patient) after withdrawal of entecavir. In conclusion, in this 28-day study of entecavir a pronounced decrease of HBV DNA was observed and there were no significant side effects in entecavir patients in comparison with placebo-treated patients. (HEPATOLOGY 2001;34:578-582.) [source] Usefulness of transient elastography for assessment of liver fibrosis in chronic hepatitis B: Regression of liver stiffness during entecavir therapyHEPATOLOGY RESEARCH, Issue 9 2010Masaru Enomoto Aim:, The usefulness of transient elastography remains to be validated in chronic hepatitis B, particularly as a tool for monitoring the degree of liver fibrosis during treatment. Methods:, The subjects were 50 patients with chronic hepatitis B virus infection. Liver biopsy was performed in 38 patients, and in 12 patients with platelet counts of 50 × 109/L or less, cirrhosis was clinically diagnosed on the basis of specific signs of portal hypertension. Liver stiffness was measured by transient elastography at baseline and after 12 months of treatment in 20 nucleos(t)ide-naïve patients who started entecavir within 3 months after study entry. Results:, Twenty (40%) patients were classified as F1, 10 (20%) as F2, 5 (10%) as F3, and 15 (30%) as F4 (cirrhosis). Median liver stiffness (interquartile range) was 7.0 kPa (5.6,9.4), 9.8 kPa (5.6,14.7), 9.8 kPa (7.6,12.9), and 17.3 kPa (8.2,27.6) in fibrosis stages F1 to F4, respectively. Liver stiffness significantly correlated with fibrosis stage (r = 0.46; P = 0.0014). Of the patients who started entecavir, median liver stiffness significantly decreased from 11.2 kPa (7.0,15.2) to 7.8 kPa (5.1,11.9; P = 0.0090) during 12 months of treatment. Median levels of amino-terminal peptide of type III procollagen and type IV collagen 7S domain in serum significantly decreased from 0.9 (0.6,1.3) to 0.6 (0.5,0.7) U/mL (P = 0.0010) and from 5.0 (4.4,6.7) to 3.9 (3.2,4.4) ng/mL (P = 0.015), respectively. Conclusion:, Liver stiffness measurement can be useful for monitoring regression of liver fibrosis during entecavir treatment in patients with chronic hepatitis B virus infection. [source] Guidelines for the treatment of chronic hepatitis and cirrhosis due to hepatitis B virus infection for the fiscal year 2008 in JapanHEPATOLOGY RESEARCH, Issue 1 2010Hiromitsu Kumada In the 2008 guidelines for the treatment of patients with cirrhosis, who are infected with hepatitis B virus (HBV), the main goal is to normalize levels of alanine and aspartate aminotransferases by eliminating HBV or reducing viral loads. In patients with compensated cirrhosis, the clearance of HBV from serum is aimed for by entecavir, as the main resort, for histological improvement toward the prevention of hepatocellular carcinoma (HCC). In patients with decompensated cirrhosis, by contrast, meticulous therapeutic strategies are adopted for the reversal to compensation, toward the eventual goal of decreasing the risk of HCC. For maintaining liver function and preventing HCC, branched chain amino acids and nutrient supplements are applied, in addition to conventional liver supportive therapies. For patients with chronic hepatitis B, separate guidelines are applied to those younger than 35 years and those aged 35 years or older. Even for patients with chronic hepatitis who are negative for hepatitis e antigen (HBeAg), but who harbor HBV DNA in titers of 7 log copies/mL or more, a "drug-free state" is aimed for by sequential treatment with interferon (IFN) plus entecavir as the first line. For patients with chronic hepatitis B aged 35 years or older, who are HBeAg-negative and carry HBV DNA in titers of less than 7 log copies/mL, long-term IFN for 24,48 weeks is adopted anew. To HBeAg-negative patients who have either or both platelet counts of less than 150 × 103/mm3 and less than 7 log copies of HBV DNA, also, long-term IFN for 24,48 weeks is indicated. [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] Prevention of hepatitis B virus infection by vaccination: Progress and problemsHEPATOLOGY RESEARCH, Issue 9 2007Kojiro Michitaka Sk Md No abstract is available for this article. [source] Physiological hepatic nuclear vacuolation,how long does it persist?HISTOPATHOLOGY, Issue 4 2010Adam P Levene Levene A P & Goldin R D (2010) Histopathology56, 426,429 Physiological hepatic nuclear vacuolation,how long does it persist? Aims:, Nuclear vacuolation\glycogenation is a characteristic histological feature of non-alcoholic fatty liver disease (NAFLD) that can help distinguish it from alcohol-induced liver disease. There are, however, other associations of nuclear vacuolation of which the commonest is as a normal feature of childhood. The aim of this study was to identify how long this physiological nuclear vacuolation persists. Methods and results:, Liver biopsy specimens from 872 patients with chronic hepatitis B virus infection (a condition known not to be associated with nuclear vacuolation) were studied to assess the frequency of nuclear vacuolation at different ages. All the patients studied had a body mass index of <25 kg/m2 and an alcohol intake of <15 units/week, as well as no other risk factors for liver disease. It was found that the frequency of nuclear vacuolation, in the absence of NAFLD, fell from 13% at age 20,24 years to 4% in the early 30s and to 0% at age 60,64 years. Conclusions:, Physiological hepatic nuclear vacuolation is common in the 20s and persists into the 30s. This knowledge can help in the assessment of liver biopsy specimens in which nuclear vacuolation is a feature. [source] Infliximab therapy in a patient with Crohn's disease and chronic hepatitis B virus infectionINFLAMMATORY BOWEL DISEASES, Issue 5 2004María del Valle García-Sánchez MD No abstract is available for this article. [source] Differential DNA methylation associated with hepatitis B virus infection in hepatocellular carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 6 2007Pei-Fen Su Abstract Gene inactivation through DNA hypermethylation plays a pivotal role in carcinogenesis. This study aimed to profile aberrant DNA methylation in different stages of liver disease, namely noncirrhosis, cirrhosis and hepatocellular carcinoma (HCC), and also to clarify the influence of hepatitis B virus (HBV) infection on the aberrant DNA methylation in HCCs. Promoter methylation in p14ARF, p16INK4a, O6 -methylguanine-DNA methyltransferase (MGMT), glutathione S -transferase pi (GSTP1) and E-cadherin (E-Cad) genes of 58 HCCs paired with adjacent nontumorous tissues was assayed by methylation-specific PCR. HBV infection was determined using a hepatitis B virus surface antigen (HBsAg) serological assay. The frequency of p16INK4a promoter methylation increased from noncirrhotic, cirrhotic, to HCC tissues (noncirrhotic vs. HCC, p < 0.001), while that of GSTP1 promoter methylation increased in cirrhotic tissues compared to noncirrhotic ones (p = 0.029). The frequency of GSTP1 promoter hypermethylation is significantly higher in HCC than in nontumorous tissues (p = 0.022) from HBsAg-positive patients, but not the HBsAg-negative controls (p = 0.289). While the frequency of E-Cad promoter hypermethylation remained high in both nontumorous tissues and HCCs from HBsAg-positive patients (p = 0.438), it was lower in HCCs than in nontumorous tissues from HBsAg-negative patients (p = 0.002). In contrast, the frequency of p16INK4a, MGMT and p14ARF promoter hypermethylation in HCCs was unrelated to HBsAg status. In conclusion, aberrant DNA methylation may begin at different stages of liver disease in a gene-dependent manner. Moreover, HBV infection may enhance or maintain GSTP1 and E-Cad promoter methylation and thereby affect hepatocarcinogenesis. © 2007 Wiley-Liss, Inc. [source] Occult hepatitis B virus infection and lamivudine-resistant mutations in isolates from renal patients undergoing hemodialysisJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 1 2010Jorge S. Motta Abstract Background and Aims:, Patients undergoing hemodialysis are at risk of infection with both hepatitis B virus (HBV) and hepatitis C virus (HCV). Occult HBV infection is usually associated with low levels of HBV and is frequently detected in HCV-infected patients. The aims of the present study were to compare the prevalence of occult HBV infection among anti-HCV-positive and anti-HCV-negative patients undergoing hemodialysis, and characterize the molecular patterns of HBV isolates from patients with occult infection. Methods:, Serum samples from 100 patients negative for hepatitis B surface antigen undergoing hemodialysis, half of whom were positive for anti-HCV antibodies, were tested for the presence of HBV-DNA using semi-nested polymerase chain reaction (PCR). PCR products of the S gene were directly sequenced. Results:, HBV-DNA was detected in 15 samples. There were no significant differences in HCV status, sex, age, time of dialysis, alanine aminotransferase levels or HBV serological markers between patients with or without occult HBV infection, with the exception of antibody to hepatitis B core antigen (anti-HBc)-only serological marker (P = 0.003). All six HBV isolates that could be sequenced were of genotype A/subgenotype A1. Four of these six HBV isolates contained mutations associated with lamivudine resistance in the DNA polymerase (two with L180M/M204V and two with rt173V/180M/204V) and a specific substitution (Y100C) in the HBV small surface protein. Conclusions:, HBV isolates with the identified substitutions have the potential to spread silently by nosocomial transmission within the hemodialysis unit. These results have potential implications for the management of patients with occult HBV infection undergoing hemodialysis. [source] Occult hepatitis B virus infection in Southern African blacks with hepatocellular carcinomaJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 9 2008Michael C Kew Abstract Background and Aim:, To ascertain the prevalence of occult hepatitis B virus (HBV) infection in southern African blacks with hepatocellular carcinoma. Methods:, Sera from 118 patients negative for HBV surface antigen but positive for HBV antibodies were studied. HBV-DNA was detected using a nested polymerase chain reaction (PCR) assay and confirmed by nucleotide sequencing of the surface and precore/core genes. Results:, Surface gene HBV-DNA was detected in a single PCR assay in 48.4% of the patients. Positive results increased to 57.7% after two PCR assays (not significant) and 75.7% after four assays (P < 0.001). No false positive results were obtained in these assays or in the 15 control samples for which PCR assays were performed four times. Significant differences in positivity rates were not observed between patients positive for HBV core antibody alone and those positive for core and surface antibodies. The sensitivity of the PCR amplification of the precore/core gene was significantly less than that of the surface open reading frame: the yield of positive results was 23.7% after one assay, 32.2% after two assays (not significant), and 52% after four assays (P < 0.001). Combining the results of the assays of the two genes increased the yield of positive results for the first assay (by 11.9%, P = 0.015), but not the second (6.1%) or fourth assays (4.6%). Conclusion:, Occult HBV infection is present in the serum of the majority of hepatocellular carcinomas in southern African blacks whose serum is negative for hepatitis B surface antigen but positive for anti-HBV core antigen. The yield of positive results increases if more than one PCR assay is performed. [source] Adefovir dipivoxil therapy in liver transplant recipients for recurrence of hepatitis B virus infection despite lamivudine plus hepatitis B immunoglobulin prophylaxisJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 12 2007Murat Akyildiz Abstract Background:, Treatment of post-transplantation recurrence of hepatitis B virus (HBV) infection despite prophylaxis with hepatitis B immunoglobulin (HBIG) and lamivudine combination therapy is not easy. Because HBV reinfection has a severe course and could result in graft failure in liver transplant recipients, prompt medication is essential. Herein is reported the authors' experience with adefovir dipivoxil (AD) therapy in 11 liver transplant recipients who had HBV reinfection despite the administration of lamivudine and HBIG. Method:, Two-hundred and nine patients underwent liver transplantation (100 deceased donor liver transplantations [DDLT], 109 living donor liver transplantation [LDLT]) due to chronic hepatitis B infection between April 1997 and May 2005 in Ege University Medical School, Liver Transplantation Unit. Patients had prophylaxis with lamivudine and low-dose HBIG combination after liver transplantation. Treatment of recurrence consisted of AD 10 mg once a day and lamivudine 300 mg/daily and HBIG was discontinued in those patients. Results:, In total there were 11 HBV recurrences: five occurred in DDLT recipients and six in LDLT recipients, at a median follow up of 18 months (range, 6,48 months). In one of 11 patients, pretransplant HBV-DNA and HBeAg were positive. Three patients had a severe course and one patient had fibrosing cholestatic hepatitis. After AD treatment, HBV-DNA level decreased in all patients and became negative in seven patients. Two patients died due to hepatocellular carcinoma recurrence after 12 and 14 months of follow up. Serum creatinine level increased mildly in one patient and no other side-effect was observed, and all patients continued therapy. Conclusion:, Adefovir dipivoxil is a safe, effective treatment option for post-transplant HBV recurrence even among patients with fibrosing cholestatic hepatitis caused by lamivudine-resistant HBV. [source] A great deal of learning from the natural course of chronic hepatitis B virus infectionJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2007Rong-Nan Chien [source] How do naturally occurring YMDD-motif mutants influence the clinical course of lamivudine-naïve patients with chronic hepatitis B virus infection?JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 12 2006Akihito Tsubota [source] Genetic and epigenetic alterations of the KLF6 gene in hepatocellular carcinomaJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2006Jaehwi Song Abstract Background and Aim:, Kruppel-like factor 6 (KLF6) is a zinc finger tumor suppressor gene that is frequently mutated in several human cancers and is broadly involved in differentiation and development, growth-related signal transduction, cell proliferation, apoptosis, and angiogenesis. The aim of this study was to elucidate the potential etiological role of KLF6 in the development of hepatocellular carcinoma (HCC) in Korea. Methods:, The gene mutation, allelic loss, and methylation status of the KLF6 gene was analyzed in a series of 85 Korean patients: 21 with dysplastic nodules and 85 with HCC. Results:, No somatic mutations were observed in the patients with dysplastic nodules or with HCC. Allelic loss was found in five (6.8%) of 73 informative HCC tissues. Three of the five patients with allelic loss had HCC with hepatitis B virus infection and cirrhosis, and the remaining two had no viral infection and a non-specific background. In methylation analysis, unmethylated and methylated DNAs of the KLF6 gene were amplified in all corresponding non-neoplastic liver tissues. Only one HCC tissue showed methylated DNA without unmethylated DNA. Conclusions:, The results suggest that genetic and epigenetic alteration of KLF6 may play a minor role in the development of HCC. [source] Genetic susceptibility to chronic hepatitis B virus infectionJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2006Ian R Mackay [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] | ||||||||||||||||||||||||||||||||||