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B Infection (b + infection)
Kinds of B Infection Selected AbstractsThe intrahepatic immune response during chronic hepatitis B infection can be monitored by the fine-needle aspiration biopsy techniqueFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 1 2003Thjon J Tang Abstract Frequent analysis of the intrahepatic cellular immune response during chronic hepatitis B infection is not feasible with the liver tissue biopsy technique, due to its risk profile and patient discomfort. We investigated whether the relatively safe and patient-friendly cytological fine-needle aspiration biopsy (FNAB) technique is suited for this purpose. FNABs taken during hepatitis flares in three chronic hepatitis B patients treated with interferon-,, showed significant increments of CD8+ -lymphocytes compared with the FNABs taken before and after the flares. No increments were observed in peripheral blood. The increments of intrahepatic CD8+ lymphocytes detected by the FNAB were related to anti-viral immune reactivity, since they coincided with significant serum hepatitis B virus DNA level reductions and in two of three patients with HBeAg seroconversion. In conclusion, the FNAB technique is suited to investigate the intrahepatic immune response during chronic hepatitis B infection on a frequent basis. [source] Hepatitis A and B immunization for individuals with inherited bleeding disordersHAEMOPHILIA, Issue 2 2009M. STEELE Summary., Hepatitis A and B vaccines are highly effective tools that can greatly reduce infection risk in the bleeding disorder population. Although hepatitis A and B immunization for individuals with bleeding disorders is universally recommended, various advisory bodies often differ with respect to many practical aspects of vaccination. To review the published literature and guidelines and form a practical, comprehensive and consistent approach to hepatitis A and B immunization for individuals with bleeding disorders. We reviewed published immunization guidelines from North American immunization advisory bodies and published statements from North American and international haemophilia advisory bodies. A search of the MEDLINE database was performed to find original published literature pertaining to hepatitis A or B immunization of patients with haemophilia or bleeding disorder patients that provided supporting or refuting evidence for advisory body guidelines. Various advisory bodies' immunization guidelines regarding individuals with bleeding disorders have contradictory statements and often did not clarify issues (e.g. post vaccination surveillance). Published literature addressing immunization in bleeding disorder patients is sparse and mostly examines route of vaccine administration, complications and corresponding antibody response. Although the risk of hepatitis A and B infection is low, the use of simple measures such as vaccination is reasonable and advocated by haemophilia advisory bodies. Following our review of the available literature and North American guidelines, we have developed comprehensive and practical recommendations addressing hepatitis A and B immunization for the bleeding disorder population that may be applicable in Bleeding Disorder clinics. [source] Virion half-life in chronic hepatitis B infection is strongly correlated with levels of viremia,HEPATOLOGY, Issue 4 2008Maura Dandri Analysis of hepatitis B virus (HBV) kinetics with mathematical models may disclose new aspects of HBV infection and host response mechanisms. To determine the kinetics of virion decay from the blood of patients in different phases of chronic infection, we applied mathematical modeling to real-time polymerase chain reaction assays, which enable quantification of viremia and intrahepatic HBV productivity by measuring both copy number and activity of covalently closed circular DNA (relaxed circular DNA/covalently closed circular DNA) in the liver of 80 untreated chronically active HBV carriers (38 hepatitis B e antigen [HBeAg]-positive and 42 HBeAg-negative individuals). We found that the half-life of circulating virions is very fast (median 46 and 2.5 minutes in HBeAg-positive and HBeAg-negative individuals, respectively) and strongly related to viremia, with clearance rates significantly accelerating as viral loads decrease. To investigate whether immune components can influence the kinetics of virion decay, we analyzed viral dynamics in immunodeficient urokinase-type plasminogen activator chimera mice. Virion half-life in mice (range, 44 minutes to >4 hours) was comparable to estimates determined in high viremic carriers, implying that clearance rates in these patients are mostly determined by common nonspecific mechanisms. Notably, the lack of correlation between virion half-life and viremia in mice indicated that immune components significantly accelerate virion clearance rates in individuals with low titers. Conclusion: Our analyses suggest that both host defense mechanisms and levels of circulating virions affect the kinetics of HBV decay assessed in the serum of chronic carriers. Identification of the factors affecting clearance rates will be important for future antiviral drug developments and it may give insights into the mechanisms involved in clearance of other chronic infections, such as human immunodeficiency virus and hepatitis C virus. (HEPATOLOGY 2008.) [source] Impact of the hepatitis B virus genotype and genotype mixtures on the course of liver disease in Vietnam,HEPATOLOGY, Issue 6 2006Nguyen L. Toan Eight genotypes (A-H) of hepatitis B virus (HBV) have been identified. However, the impact of different genotypes on the clinical course of hepatitis B infection remains controversial. We investigated the frequency and clinical outcome of HBV genotypes and genotype mixtures in HBV-infected patients from Vietnam, Europe, and Africa. In addition, we analyzed the effects of genotype mixtures on alterations in in vitro viral replication. In Asian patients, seven genotypes (A-G) were detected, with A, C, and D predominating. In European and African patients, only genotypes A, C, D, and G were identified. Genotype mixtures were more frequently encountered in African than in Asian (P = .01) and European patients (P = .06). In Asian patients, the predominant genotype mixtures included A/C and C/D, compared to C/D in European and A/D in African patients. Genotype A was more frequent in asymptomatic compared with symptomatic patients (P < .0001). Genotype C was more frequent in patients with hepatocellular carcinoma (HCC; P = .02). Genotype mixtures were more frequently encountered in patients with chronic hepatitis in comparison to patients with acute hepatitis B (P = .015), liver cirrhosis (P = .013), and HCC (P = .002). Viral loads in patients infected with genotype mixtures were significantly higher in comparison to patients with a single genotype (P = .019). Genotype mixtures were also associated with increased in vitro HBV replication. In conclusion, infection with mixtures of HBV genotypes is frequent in Asia, Africa, and Europe. Differences in the replication-phenotype of single genotypes compared to genotype-mixtures suggest that co-infection with different HBV-genotypes is associated with altered pathogenesis and clinical outcome. (HEPATOLOGY 2006;43:1375,1384.) [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] Long-term follow-up of interferon alfa treatment in chinese patients with chronic hepatitis B infection: The effect on hepatitis B e antigen seroconversion and the development of cirrhosis-related complicationsHEPATOLOGY, Issue 1 2001Man-Fung Yuen The long-term effect of interferon alfa (IFN-,) in Chinese patients with chronic hepatitis B infection is unknown. A total of 411 chronic hepatitis B patients (208 treated with IFN-, and 203 as control) were followed up for hepatitis B serology and the development of hepatoma and other cirrhosis-related complications. The hepatitis B e antigen (HBeAg) seroconversion rate in the IFN-,,treated group, though significantly greater at 6 and 24 months, was comparable with the control group on subsequent follow-up, irrespective of pretreatment alanine transaminase (ALT) levels. HBeAg seroreversion rate was higher in the IFN-, group compared with the control group (21.1% vs. 2.2%; P = .001). Loss of hepatitis B surface antigen (HBsAg) occurred in 2.4% of the IFN-,,treated patients and 0.49% of the control patients (P = NS). Around 90% of the anti-HBe,positive patients in both groups were still hepatitis B virus (HBV)-DNA,positive by polymerase chain reaction (PCR) assay. Two patients suffered from hepatic reactivation during the course of treatment. Nine (4.3%) patients in the IFN-, group and 2 (1.0%) in the control group developed complications of cirrhosis and hepatoma (P = .062). In Chinese HBsAg carriers, IFN-, was of no long-term benefit in inducing HBeAg seroconversion or in the prevention of hepatoma and other cirrhosis-related complications. [source] Antituberculosis drug-related liver dysfunction in chronic hepatitis B infectionHEPATOLOGY, Issue 1 2000Wai-Man Wong Liver toxicity is a common side effect of antituberculosis (anti-TB) drugs. We studied the differences in liver dysfunction observed during anti-TB treatment between hepatitis B virus carriers (HBV) and noncarriers. Three hundred twenty-four patients on anti-TB drugs were recruited and followed up for 1 year. Forty-three patients with HBV and 276 non-HBV patients were included for analysis. Liver function tests and viral markers were monitored monthly. Liver biopsy was requested whenever the alanine transaminase (ALT) was persistently abnormal. Eighty-six HBV carriers who were not given anti-TB drugs were chosen as a second control and evaluated prospectively. The incidence of liver dysfunction was significantly higher in HBV carriers given anti-TB drugs (34.9%) when compared to noncarriers (9.4%, P < .001) and with HBV carriers not given anti-TB drugs (8.1%, P < .001). For patients given anti-TB drugs, HBV carriers who developed liver dysfunction were younger (P = .011) and had more severe liver injury compared with noncarriers (P = .008). By multiple logistic regression analysis, age (P = .002) and hepatitis B infection (P < .001) were the only 2 significant risk factors for hepatotoxicity related to anti-TB therapy. [source] Epidemiology and carcinogenesis of hepatocellular carcinomaHPB, Issue 1 2005TRISHE Y.-M. Abstract The incidence of hepatocellular carcinoma (HCC) shows marked variation worldwide but the magnitude of this tumor is reflected by the occurrence of at least 1 million new cases annually and the uniformly dismal outlook with median survivals of <25 months after resection and <6 months with symptomatic treatment. The strikingly uneven distribution of this tumor parallels the prevalence of hepatitis B infection with rising incidence in western countries attributed to hepatitis C infection. Chronic hepatitis and cirrhosis constitute the major preneoplastic conditions in the majority of HCCs and may be related to other etiologic agents such as environmental chemical carcinogens including nitrites, hydrocarbons, solvents, organochlorine pesticides, and the chemicals in processed foods, cleaning agents, cosmetics and pharmaceuticals, as well as plant toxins such as aflatoxins produced by fungi that cause spoilage of grain and food in the tropics. Genetic diseases such as genetic hematochromatosis, Wilson's disease, ,-1-antitrypsin deficiency, and the inborn errors of metabolism including hereditary tyrosinemia and hepatic porphyria, are known to be associated with HCC. Numerous genetic alterations and the modulation of DNA methylation are recognized in HCC and it is likely that these genetic and epigenetic changes combine with factors involved in chronic hepatocyte destruction and regeneration to result in neoplastic growth and multiple molecular pathways may be involved in the production of subsets of hepatocellular tumors. [source] Hepatocellular carcinoma in Sydney South West: late symptomatic presentation and poor outcome for mostINTERNAL MEDICINE JOURNAL, Issue 8 2007L. Gellert Abstract Background: Hepatocellular cancer (HCC) is a serious complication of cirrhosis and chronic hepatitis B infection. The aim of the study was to determine the characteristics of patients with HCC presenting within the South West Sydney area, including an analysis of the rates and benefits of hepatocellular surveillance. Methods: Data from patients with HCC presenting to Liverpool and Bankstown Hospitals from July 1993 to June 2003 were analysed retrospectively, predominantly from hospital records. Results: Of the 151 HCC patients, 41% were Asian born. Most of the patients required an interpreter. Chronic viral hepatitis infection was present in 91 patients, of whom only 7% had previously received antiviral therapy. Alcohol alone was considered responsible in 31 patients. Cirrhosis could be documented in 58% of patients. Most of the patients (75%) presented symptomatically. The median survival was 5.1 months. When HCC was detected by surveillance, the tumours were slightly but not significantly more likely to be operable and the patients tended to be offered some form of active treatment more frequently. Multivariate analysis identified detection by surveillance, lower Child,Pugh score, smaller tumour size and eligibility for some form of treatment to be associated with a more favourable outcome. Conclusion: We observed low rates of surveillance for HCC, low recognition of cirrhosis before development of HCC and low rates of prior treatment of viral hepatitis. The poor outcome of HCC in the small group who had some sort of community surveillance is also a concern requiring further investigation. [source] Elevated plasma osteopontin level is predictive of cirrhosis in patients with hepatitis B infectionINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 7 2008L. Zhao Summary Background:, Osteopontin (OPN) was shown to play an important role in the pathogenesis of various inflammatory and fibrotic processes and elevated in fibrotic liver of mouse model. However, the significance of OPN in hepatitis B virus (HBV)-induced liver cirrhosis (LC) remains unclear and is therefore evaluated in this study. Methods:, Thirty-nine patients with HBV-induced LC, 30 patients with HBV infection but without cirrhosis, 11 patients with HBV-related hepatocellular carcinoma (HCC) and 14 additional healthy controls were enrolled in this study. Plasma levels of OPN were measured with enzyme-linked immunosorbent assay and the relationship between OPN and clinical parameters was evaluated. Results:, When compared to HBV infection group (median 2.16 ng/ml), plasma levels of OPN were significantly increased in cirrhosis (4.52 ng/ml, p < 0.001) and cancer group (13.38 ng/ml, p < 0.001). The OPN level was correlated with the severity of liver damage according to Child,Pugh classification (p = 0.003). It showed at least comparable sensitivity and specificity to predict cirrhosis as aspartate aminotransferase to platelet ratio index, a previously established non-invasive serum marker of cirrhosis. Conclusions:, These data suggest that OPN could be used to evaluate the existence of LC, as OPN has previously been reported to be increased in the HCC; this unique feature makes OPN a promising candidate for prediction biomarker in the long-time surveillance of patients with HBV infection to evaluate the risk of cirrhosis and cancer. [source] Evaluation of IL10, IL19 and IL20 gene polymorphisms and chronic hepatitis B infection outcomeINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 3 2008Ann L. Truelove Summary Hepatitis B virus (HBV) infection remains a serious global health problem despite the availability of a highly effective vaccine. Approximately 5% of HBV-infected adults develop chronic hepatitis B, which may result in liver cirrhosis or hepatocellular carcinoma. Variants of interleukin-10 (IL10) have been previously associated with chronic hepatitis B infection and progression to hepatocellular carcinoma. Single nucleotide polymorphisms (SNP; n = 42) from the IL10, IL19 and IL20 gene regions were examined for an association with HBV infection outcome, either chronic or recovered, in a nested case,control study of African Americans and European Americans. Among African Americans, three nominally statistically significant SNP associations in IL10, two in IL20, and one haplotype association were observed with different HBV infection outcomes (P = 0.005,0.04). A SNP (rs1518108) in IL20 deviated significantly from Hardy,Weinberg equilibrium in African Americans, with a large excess of heterozygotes in chronic HBV-infected cases (P = 0.0006), which suggests a strong genetic effect. Among European Americans, a nominally statistically significant SNP association in IL20 and an IL20 haplotype were associated with HBV recovery (P = 0.01,0.04). These results suggest that IL10 and IL20 gene variants influence HBV infection outcome and encourage the pursuit of further studies of these cytokines in HBV pathogenesis. [source] Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese patients with chronic hepatitis B infectionJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 9 2008Jun-ping Shi Abstract Background and Aims:, The clinical significance of hepatic steatosis in chronic hepatitis B infection (CHB) is unclear. The aims of this study were thus to investigate the prevalence and risk factors for hepatic steatosis in patients with CHB and its relationship with liver injury. Methods:, Consecutive patients with biopsy-proven CHB at Hangzhou Sixth People's Hospital between January 2005 and June 2007 were included. Patients co-infected with other viruses or suffering from liver disease of any other cause were excluded. Liver steatosis, necroinflammation and fibrosis were assessed by both Brunt and Scheuer classifications. Results:, A total of 1915 patients (1497 men) with a mean age of 31 ± 9.5 years were analyzed. Hepatic steatosis was present in 260 (14%) patients. The steatosis involved < 33% of hepatocytes in 90% of cases, and was more frequent among men than women (15% vs 8%, P < 0.001). Two-thirds (178 of 260) of patients with steatosis were hepatitis B e antigen (HBeAg)-positive, but there was no correlation with either serum HBeAg status or hepatitis B virus DNA titer. Degree of inflammation and fibrosis were more mild among those with steatosis than those without. Multivariate analysis showed that steatosis was independently associated with body mass index, serum triglyceride, apolipoprotein B, uric acid, and fasting blood glucose. However, fibrosis was only independently associated with age and inflammatory grade, and the latter associated with viral load and fibrosis stage. Conclusions:, Hepatic steatosis is common in CHB, it is associated with metabolic factors not viral ones, and does not appear to affect the severity of liver disease. [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] Unusual case of hepatitic cholestasis resembling fibrosing cholestatic hepatitis in a dialysis patient with chronic hepatitis B infectionJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 10 2006Ping-Nam Wong [source] Current therapeutic approaches in childhood chronic hepatitis B infection: A multicenter studyJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2004BUNYAMIN DIKICI Abstract Background and Aim:, The aim of the present study was to compare the therapeutic efficacy of three different regimens in childhood chronic hepatitis B (CHB) infection. Methods:, A total of 182 children with CHB infection were prospectively allocated to three random groups. Sixty-two patients in the first group received high-dose interferon (IFN)-, 2b (10 MU/m2) thrice/weekly alone for 6 months. In the second (n = 60) and third groups (n = 60), IFN-, was used for 6 months (5 MU/m2) thrice/weekly in combination with lamivudine (LAM) (4 mg/kg, maximum 100 mg/day) for 12 months. Lamivudine was started simultaneously with IFN in the second group, while it was started 2 months prior to IFN injections in the third group. Results:, The initial mean alanine aminotransferase (ALT) values for the first, second and third groups were 109 ± 93 IU/L, 101 ± 64 IU/L and 92 ± 42 IU/L, respectively (P > 0.05). At the end of the therapy, ALT values decreased to 82 ± 111 IU/L, 38 ± 41 IU/L and 29 ± 16 IU/L in groups 1, 2 and 3, respectively. The mean ALT value of the first group was significantly different to the second and third groups (P = 0.046 and P = 0.002, respectively) at the end of the therapy and these differences were found to be sustained after 18 months. However, results in the second and third groups were similar (P > 0.05). There were no significant differences in HBeAg clearance and anti-HBe seroconversion at the initial stage, 12 months and 18 months between the three groups (P > 0.05). Hepatitis B virus (HBV) DNA clearance in the first group was different from the second and third groups, while the second and third groups had similar HBV DNA clearance ratios at 12 and 18 months. No significant difference was found in the complete response (normalization of ALT, clearance of HBV DNA and seroconversion of anti HBe) ratios of all groups (at 12 months: 28.8, 45.5, 35.8% and at 18 months 33.3, 49 and 34% in groups 1, 2 and 3, respectively, P > 0.05). Conclusions:, Although the ALT normalization and HBV DNA clearance ratios of IFN plus LAM combination groups were better than the high-dose IFN-, monotherapy group, no significant difference was found in the complete response ratios of all three groups. [source] Efficacy of granulocyte-macrophage colony-stimulating factor or lamivudine combination with recombinant interferon in non-responders to interferon in hepatitis B virus-related chronic liver disease patientsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2002RAJKUMAR C GUPTAN AbstractBackground and Aims : Non-response to interferon (IFN) monotherapy is a major therapeutic problem in the management of chronic hepatitis B infection. The efficacy of combination therapy to enhance the immunomodulatory effect of IFN by combining granulocyte-macrophage colony-stimulating factor (GMCSF) or decreasing viral load by adding an antiviral agent such as lamivudine was evaluated prospectively. Methods : Twenty-four patients with chronic hepatitis B who were non-responders to previous IFN therapy were randomized to receive an IFN and GMCSF (group A, n = 10) or IFN and lamivudine (group B, n = 14) combination for 6 months. The end-of-treatment response was assessed by hepatitis B virus (HBV)-DNA and hepatitis B e antigen (HBeAg) determination. Results : All patients successfully completed both the treatment schedules. The mean age, alanine aminotransferase (ALT) levels, liver histology, HBV-DNA levels and distribution of HBV genotypes were comparable between the two groups. At the end of treatment there was a significant decrease in mean ALT levels. The HBV-DNA and HBeAg loss was seen in six of 10 (60%) patients in group A and in seven of 14 (50%) patients in group B. During a mean follow-up of 15 ± 3 months, two of six (33%) patients in group A and three of seven (43%) patients in group B relapsed with HBV-DNA and HBeAg positivity, which meant an overall sustained response of 40% and 28%, respectively. None of the factors such as HBV viral load, ALT levels or liver histology could predict the non-response to combination therapy or occurrence of relapse. There was a trend in patients with genotype A compared with genotype D towards non-response to therapy, although the difference was not significant. Conclusions : The combination of IFN plus GMCSF or lamivudine was effective in non-responders to IFN monotherapy. Larger studies using such combination therapies would be helpful in improving treatment strategies for chronic hepatitis B. © 2002 Blackwell Publishing Asia Pty Ltd [source] Decline in hepatitis B infection observed after 11 years of regional vaccination among Danish drug usersJOURNAL OF MEDICAL VIROLOGY, Issue 10 2010B.K. Mössner Abstract The aims of this study were to determine the current prevalence of viral hepatitis and HIV among drug users, and to compare this prevalence with previous findings in the same geographical region. Cross-sectional surveys of drug users attending treatment centers on the island of Funen with approximately 500,000 inhabitants were administered in 1996 and 2007. The 2007 prevalence estimates were: anti-HBc 50.2%, HBsAg 0.9%, anti-HCV 66.8%, HCV-RNA 40%, and anti-HIV 1.1%. The corresponding 1996 prevalence values were: anti-HBc 70% (P,<,0.0001), HBsAg 9.8% (P,<,0.0001), anti-HCV 82.8% (P,<,0.0001), HCV-RNA 56.3% (P,=,0.002), and anti-HIV 1% (P,=,1). The 2007 prevalence of viral hepatitis decreased due to the increasing proportion of non-injectors. Among injectors, the prevalence remained unchanged except for a significant decrease in HBsAg. The 2007 prevalence of ongoing HBV infection among infected (HBsAg/anti-HBc proportion) was the lowest that to our knowledge has been reported among drug-users. Vaccination coverage among susceptible persons tested in 2007 was 24%, compared to 0.7% in 1996. Therefore, despite an unchanged prevalence of anti-HBc among injecting drug users, a highly significant drop in HBsAg prevalence was seen during the last decade. This observation may be linked causally to an increase in hepatitis B vaccination of the susceptible population. Our findings suggest that even incomplete vaccination, without persistent protective anti-HBs levels, may induce an immune memory sufficient to prevent chronic infection upon transmission. J. Med. Virol. 82:1635,1639, 2010. 2010 Wiley-Liss, Inc. [source] Prevalence and impact of occult hepatitis B infection in chronic hepatitis C patients treated with pegylated interferon and ribavirin,JOURNAL OF MEDICAL VIROLOGY, Issue 5 2010Marion Levast Abstract The prevalence of occult hepatitis B, defined by absence of HBsAg and HBV DNA, ranges widely in patients with hepatitis C. This may influence the treatment of hepatitis C and the severity of liver disease. Sensitive and specific real-time PCR techniques are available commercially and can detect more reliably low HBV DNA levels. The aim of this study was to determine the prevalence of occult hepatitis B virus infection using the COBAS Taqman assay (Roche Diagnostics, Meylan, France) in the serum and liver of HBsAg negative patients with chronic hepatitis C and to evaluate its clinical consequences on liver pathology and its impact on the response to treatment with peg-IFN, and Ribavirin. HBV DNA detection was assessed retrospectively on 140 sera and 113 liver biopsies of HCV positive/HBsAg negative patients before treatment. A 4.4% (5/113) prevalence of occult hepatitis B was recorded in liver samples and in none of the sera. Anti-HBc was not detected in one, three of whom were sustained virological responders to treatment, one was relapsed responder and one was non-responder. Furthermore, in this cohort composed of 12% anti-HBs negative/anti-HBc positive and 20% anti-HBs positive/anti-HBc positive patients, anti-HBc was not associated with pre-therapeutic viral load, ALT serum levels, and histological activity or fibrosis. Using a commercial real-time PCR assay, we observed a low prevalence of occult B hepatitis. This, just as anti-HBC status, had no clinical impact in a large cohort of hepatitis C patients. It therefore does not appear useful to screen for occult hepatitis B in these patients with this test before beginning HCV treatment. J. Med. Virol. 82: 000,000, 2010. © 2010 Wiley-Liss, Inc. J. Med. Virol. 82: 747,754, 2010. © 2010 Wiley-Liss, Inc. [source] Molecular evolutionary analysis and mutational pattern of full-length genomes of hepatitis B virus isolated from Belgian patients with different clinical manifestationsJOURNAL OF MEDICAL VIROLOGY, Issue 3 2010Mahmoud Reza Pourkarim Abstract Molecular evolutionary patterns of 62 HBV full-length genomes obtained from Belgian patients were characterized. Phylogenetic analysis revealed diverse HBV subgenotypes including A2 and A6 (46.8%), D1,D4 (38.8%), E (9.7%), C1 (1.6%), and B2 (1.6%). The study population consisted of patients with different ethnic origin (Caucasian, Turkish, Asian, Arab, and African). One HBV D/C recombinant isolate was identified, which encoded subtype adw2. An HBV subgenotype D4 with an aberrant subtype ayw4 was detected. Although none of the genotypes was associated with a specific disease outcome, several nucleotide substitutions, deletions and insertions were observed within the HBV preS1/S and X genes, particularly among patients with active chronic hepatitis B infection and patients with cirrhosis. Within the immunological domain of the HBsAg gene, the most frequent substitutions were sT125M and sT118A. High rates of precore and basal core promoter mutations were detected in patients infected with genotype D of HBV. Almost half of the patients who received lamivudine therapy for at least 1 year had HBV variants associated with lamivudine drug resistance. In conclusion, the most common HBV genotypes in West Europe (A and D) also prevail in Belgium. The highest degree of genetic diversity was detected in HBV genotype D. In addition, this study reveals the circulation of exotic HBV genotypes B, C, and E in Belgium. J. Med. Virol. 82:379,389, 2010. © 2010 Wiley-Liss, Inc. [source] Occult hepatitis B infection in patients infected with HIV: Report of two cases of hepatitis B reactivation and prevalence in a hospital cohortJOURNAL OF MEDICAL VIROLOGY, Issue 2 2010B. Bloquel Abstract Patients co-infected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are particularly at risk of hepatitis B reactivation. Two cases of patients infected with HIV with isolated anti-HBc antibodies who had experienced an HBV reactivation are described. In the two cases HBV reactivation occurred after withdrawal of anti-retroviral treatment with anti-HBV activity from the patients' highly active antiretroviral therapy (HAART), in accordance with HIV genotypic resistance profiles. Consequently, plasma samples from 383 patients infected with HIV were tested to assess the prevalence of occult HBV infection in the Infectious Diseases Department Unit of Nancy Hospital by investigating serological patterns and HBV replication. Forty-five percent (172/383) of patients had had previous contact with HBV. Isolated anti-HBc antibodies were observed in 48 patients (48/383, 12%) and, among these, 2 were HBV-DNA positive. Since 75% (288/383) of the patients were treated with HAART, including at least one drug active against HBV, occult HBV infection was perhaps unrecognized. In cases of HIV infection, all patients should be screened for HBV infection and the knowledge of HBV status as well as the monitoring of HBV viral load are essential in preventing HBV reactivation. Consideration should be given to the continuation of drugs with anti-HBV activity in co-infected patients receiving HAART, as cessation of therapy is associated with a risk of HBV reactivation. At least, close monitoring of the HBV viral load is warranted in such situations. J. Med. Virol. 82:206,212, 2010. © 2009 Wiley-Liss, Inc. [source] Long-term immunogenicity of preservative-free hepatitis B vaccine formulations in adults,JOURNAL OF MEDICAL VIROLOGY, Issue 10 2009Pierre Van Damme Abstract Vaccination with recombinant hepatitis B vaccines is highly effective in preventing hepatitis B infection. Recently, a preservative-free (PF) formulation of hepatitis B vaccine [GlaxoSmithKline (GSK) Biologicals, Rixensart, Belgium] has been licensed. The immunogenicity of the PF hepatitis B vaccine and antibody persistence 6 years later was assessed in this study. This formulation was compared with the preservative- containing (PC) formulation of the vaccine and a low-preservative (LP) content formulation. Five hundred forty-one healthy adult subjects were evaluated in the primary study. Over 94% of the subjects in the three study groups had seroprotective anti-HBs antibody concentrations (,10,mIU/ml) 1 month after completing primary vaccination. Antibody measurements in 242 healthy adults who returned for the follow-up study and who had received primary vaccination 6 years earlier showed that over 81% of subjects in the three study groups still had anti-HBs antibody concentrations ,10,mIU/ml. No apparent differences in antibody decline or distribution between the study groups were observed. These results indicate that the removal of preservatives from the hepatitis B vaccine does not affect adversely its immunogenicity both in the short and in the longer term. J. Med. Virol. 81:1710,1715, 2009. © 2009 Wiley-Liss, Inc. [source] Role of surface promoter mutations in hepatitis B surface antigen production and secretion in occult hepatitis B virus infection,JOURNAL OF MEDICAL VIROLOGY, Issue 3 2007Sonali Sengupta Abstract The production, secretion, and localization of surface proteins of hepatitis B virus (HBV) and the ratio of large to small surface protein S was studied in HepG2 cells transfected with the wild-type and mutant pre-S1 and pre-S2/S promoters of HBV molecular clones 313.1 (GenBank accession no. AY161147) and 761.1 (GenBank accession no. AY161159) from two patients with occult HBV infection. Fusion constructs were made by in frame fusion of the wild-type surface gene to the mutant pre-S1 and pre-S2/S promoters and wild-type promoter so that the structural part of the small surface protein remains identical. HepG2 cells transfected transiently were used for analysis. HBV surface proteins production and secretion was determined by enzyme linked immuno assay (ELISA) and localization by immunofluorescence. Immunoprecipitation of the large, middle, and small surface protein was carried out in transient transfected and metabolically labeled cells to determine the ratio of the large to small surface protein. The results indicate that HepG2 cells transfected with mutant HBV promoters had reduced HBV surface proteins secretion compared to wild-type HBV. HepG2 cells transfected with mutant HBV pre-S1 and pre-S2/S promoters showed cytoplasmic aggregation of HBV surface proteins compared to wild-type HBV promoters, which showed diffuse cytoplasmic localization. In all cases, the HBV surface proteins localized to the endoplasmic reticulum. The ratio between the large and small surface protein was 1.89 and 0.56 with mutant HBV 313.1 and 761.1 pre-S1 and pre-S2/S promoters, respectively, compared to 0.17 in wild-type. Thus, the aggregation of surface proteins, altered ratio and secretion of surface proteins were possibly the causes of occult hepatitis B infection. J. Med. Virol. 79:220,228, 2007. © 2007 Wiley-Liss, Inc. [source] Dichotomy in cross-clade reactivity and neutralization by HIV-1 sera: Implications for active and passive immunotherapy,JOURNAL OF MEDICAL VIROLOGY, Issue 2 2005Lisa A. Cavacini Abstract The identification of broadly reactive and cross-clade neutralizing antibodies will facilitate the development of a more universally effective vaccine for human immunodeficiency virus (HIV). Antibodies in sera from individuals infected with Clade B HIV bind native primary viral isolates, and virus binding correlates with neutralization and stable clinical disease. In this study, we quantified cross-clade antibody reactivity and neutralization by Clades B and C sera. Primary viral isolates were captured by serum IgG bound to anti-human IgG and quantitated as p24 released by lysis of captured virus. Neutralization was determined using PHA-stimulated PBMC. Clade B antibodies reacted more frequently with Clade B R5 virus, but positive sera captured quantitatively more X4 virus than R5 and R5X4 virus. Clade B sera reacted less frequently and captured less Clade C virus than Clade B virus. Antibodies in Clade C sera captured Clades B and C isolates with equal frequency and quantity. There was no difference in neutralization of Clade B virus by either group of sera; however, Clade C sera neutralized Clade C virus, whereas Clade B sera were ineffective against Clade C virus. Thus, there are distinct differences in cross-clade reactivity of and neutralization by antibodies induced in response to Clade C infection compared to Clade B infection. Understanding antibody responses to native virions after Clade C infection and cross clade antibody behavior has implications for understanding pathogenesis and vaccine development. J. Med. Virol. 76:146,152, 2005. © 2005 Wiley-Liss, Inc. [source] Molecular epidemiology of hepatitis B virus in Amsterdam 1992,1997,JOURNAL OF MEDICAL VIROLOGY, Issue 2 2002J.E. van Steenbergen Abstract To gain insight into the spread of hepatitis B among various risk groups in Amsterdam a 6-year (1992,1997) retrospective DNA sequencing study was carried out on isolates from stored sera from reported primary cases of acute hepatitis B infection. Cases were classified according to risk behavior, as determined in interviews. Of the available serum, a selected region of hepatitis B-virus-DNA was amplified and sequenced. The nucleotide alignments were subjected to phylogenetic tree analysis. When nucleotide alignments were subjected to phylogenetic analysis, the strains of 54 isolates, 26% of the 204 reported primary cases, clustered in five genotypes: A, C, D, E, and F. In genotype A, a cluster related to men having sex with men was identified. In genotype D, two subclusters could be identified: one was related to injecting drug use and another was related to the Moroccan population in Amsterdam. The remaining strains showed a high genetic variability within three different genotypes: F, E, and C. Of the 14 identical isolates in the "homosexual men cluster," one was isolated from a female heterosexual. Of the 14 identical strains in the "drug users strain," six were from non-drug using heterosexual active individuals. In the cluster of twelve isolates related to hepatitis B-endemic areas, probable modes of transmission were varied. Sequence analysis provides important insight into the spread of hepatitis B among various high-risk groups. The analysis indicates that the prevention strategy in The Netherlands fails to stop transmission of hepatitis B from persistently infected individuals originating from hepatitis Bendemic countries. J. Med. Virol. 66:159,165, 2002. © 2002 Wiley-Liss, Inc. [source] Review article: chronic viral infection in the anti-tumour necrosis factor therapy era in inflammatory bowel diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2010M. J. SHALE Summary Background, Anti-Tumour necrosis factor (TNF) therapy is now well established in the treatment of inflammatory bowel disease and the risk of opportunistic infection is recognized. However, specific considerations regarding screening, detection, prevention and treatment of chronic viral infections in the context of anti-TNF therapy in inflammatory bowel disease are not widely adopted in practice. Aim, To provide a detailed and comprehensive review of the relevance of chronic viral infections in the context of anti-TNF therapy in inflammatory bowel disease. Methods, Literature search was conducted using Medline, Pubmed and Embase using the terms viral infection, hepatitis, herpes, CMV, EBV, HPV, anti-TNF, infliximab, adalimumab, certolizumab pegol and etanercept. Hepatitis B and C and HIV had the largest literature associated and these have been summarized in Tables. Results, Particular risks are associated with the use of anti-TNF drugs in patients with hepatitis B infection, in whom reactivation is common unless anti-viral prophylaxis is used. Reactivation of herpes zoster is the most common viral problem associated with anti-TNF treatment, and may be particularly severe. Primary varicella infection may present with atypical features in patients on anti-TNF. Conclusion, Appreciation of risks of chronic viral disease associated with anti-TNF therapy may permit early recognition, prophylaxis and treatment. [source] Achieving ultimate control of hepatitis B infection in China: progress and challengesJOURNAL OF VIRAL HEPATITIS, Issue 2010J.D. Jia No abstract is available for this article. [source] The natural history of chronic hepatitis BJOURNAL OF VIRAL HEPATITIS, Issue 2007C.-L. Lai Summary., The natural history of chronic hepatitis B is dependent on the age of acquiring the hepatitis B infection. Those who are infected at adolescence or adulthood (including most of the Caucasians) tend to have stable disease after hepatitis B e antigen seroconversion with normal serum alanine aminotransaminase (ALT) and hepatitis B virus (HBV) DNA levels <105 copies/mL (20 000 IU/mL). In contrast, those who are infected at birth or early childhood (including the majority of the world's hepatitis B carriers, i.e. Asians) have a prolonged immune tolerance phase followed by a prolonged immune clearance phase. A proportion of these patients have progressive disease after HBeAg seroconversion with HBV DNA <104 copies/mL (<2000 IU/mL) and ALT between 0.5 and 2× upper limit of normal. Core promoter mutations may play a part in the development of cirrhosis-related complications. However, continuing viral replication, even at a relatively low level of <104 copies/mL (<2000 IU/mL), is probably the most important factor for the development of complications. [source] Lower serum viral loads in young patients with hepatitis-B-virus-related hepatocellular carcinomaJOURNAL OF VIRAL HEPATITIS, Issue 3 2007F.-C. Tsai Summary., Advanced age and high hepatitis B virus (HBV) DNA level are risk factors associated with the development of HBV-related hepatocellular carcinoma (HCC). However, little is known about the role of viral load in the carcinogenesis of HCC in young people. A total of 183 HBV-related HCC patients and 202 HBV carriers were therefore enrolled to compare serum viral loads in young (,40 years of age) and old (>40 years of age) age groups. Other factors associated with the development of HCC were also analysed. The results showed that serum alanine aminotransferase (38.7 ± 24.1 vs 58.4 ± 65.4 IU/L, P = 0.006) and HBV DNA levels (log10 titre: 4.20 ± 1.33 vs 4.80 ± 1.39, P = 0.053) were lower in young HCC patients than in old HCC patients. There was a positive correlation between age and serum HBV DNA level in HCC patients but a negative correlation in HBV carriers. Young HCC patients with HBV genotype B infection had higher viral loads than those with genotype C infection (log10 titre: 4.79 ± 1.34 vs 3.27 ± 0.60, P = 0.001). By multivariate logistic regression analyses, high serum HBV DNA level was associated with the development of HCC in old patients [odds ratio (OR) 1.584, 95% confidence interval (CI) 1.075,2.333] rather than in young patients (OR 0.848, 95% CI 0.645,1.116). In conclusion, viral factors in association with the development of HBV-related HCC in young patients may be different from their old counterparts. The complicated interplay between host and virus could be responsible for the emergence and aggressive outcome of early-onset HCC. [source] Occult hepatitis B viral DNA in liver carcinomas from a region with a low prevalence of chronic hepatitis B infectionJOURNAL OF VIRAL HEPATITIS, Issue 4 2004R. Kannangai Summary., Occult hepatitis B is defined by the presence of hepatitis B viral (HBV) DNA in the serum or liver in persons lacking hepatitis B surface antigen (HBsAg) in the serum. A high prevalence of occult HBV has been reported in hepatocellular carcinoma (HCC) from Asia, but little information is available on the prevalence of occult HBV in HCC from regions with a low prevalence of typical chronic hepatitis B infection. In a retrospective study, 19 cases of primary liver cancer were investigated for the presence of occult HBV DNA by amplification of the surface, core, and X gene. In addition, HBV copy numbers were quantitated by real time polymerase chain reaction, genotyped, and samples tested for covalently closed circular HBV DNA, which is a marker of active viral replication. Occult HBV was found in three of 19 cases (16%). Genotyping was successful in two cases, both of which were genotype A. HBV DNA copy numbers were low, all less than 10 copies/,g liver DNA. No closed circular HBV DNA was detected. Thus, in this study occult HBV was of genotype A and was found in a low percentage of cases of HCC and was associated with low tissue HBV DNA copy numbers and no detectable evidence for viral replication. [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] | ||||||||||||||||||||||||||||||||||