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Hepatitis B [keywords]
- Inhibitory receptor molecules in chronic hepatitis B and C infections: novel targets for immunotherapy? [Journal Article, Research Support, Non-U.S. Gov't]
- Rev Med Virol 2014 Mar; 24(2):125-38.
Chronic HBV and HCV infections are the leading cause of liver-related morbidity and mortality. For effective antiviral immunity, virus-specific T cells are required, but these cells have been shown to be weak or absent in chronic HBV and HCV patients. One of the mechanisms that underlies the impaired T-cell response is the result of the continuously high viral load that causes HBV-specific and HCV-specific T cells to become exhausted, which is characterized by impaired proliferation, cytokine production and cytotoxic activity of T cells as well as high susceptibility to apoptosis. In vitro studies from chronic HBV and HCV patients as well as in vivo studies in animal models demonstrated a reversible state of T-cell exhaustion, which can be manipulated to reinvigorate the specific antiviral immune responses. In chronic HCV infection, this concept has been explored in clinical trials by administration of specific antibody to block the inhibitory pathways. The manipulation of inhibitory receptors is a promising and potential strategy for immunotherapeutic interventions in chronic HBV and HCV patients to facilitate complete elimination of the viruses or sustained viral control.
- Inactıve hepatitis B surface antigen carriers and intrafamilial tramsmission: results of a 10-year study. [Journal Article]
- Clin Mol Hepatol 2014 Mar; 20(1):56-60.
The aims of the present study were to determine the outcomes of inactive hepatitis B virus (HBV) surface antigen (HBsAg) carriers over a 10-year study period and to elucidate the HBV serological profile of their family members.We retrospectively analyzed the medical files of inactive HBsAg carriers followed up at the Department of Infectious Diseases of Kocatepe University Medical Faculty Hospital between March 2001 and January 2011.In total, 438 inactive HBsAg carriers were enrolled in this trial. The follow-up period was 33.7±22.5 months (mean±SD). Anti-hepatitis-B surface antibody seroconversion occurred in 0.7% of cases, while chronic hepatitis B was found in 0.5%. The anti-hepatitis-D virus (HDV) status was evaluated in 400 patients and anti-hepatitis C virus (HCV) in 430. It was found that 1% and 0.2% were positive for anti-HDV and anti-HCV, respectively. HBV serology was investigated in at least 1 family member of 334/438 (76.3%) patients. The HBsAg positivity rate was 34.6% in 625 family members of 334 patients. A comparison of the HBsAg positivity rates in terms of HBV DNA levels in index cases revealed that HBsAg seropositivity rates were higher in family members of HBV DNA-negative patients than in family members of HBV DNA-positive cases (P=0.0001).The HBsAg positivity rate was higher in family members of inactive HBsAg carriers than in the general population; these family members therefore have a higher risk of HBV transmission. Furthermore, despite negative HBV DNA levels, transmission risk was not reduced in these patients, and horizontal transmission seems to be independent of the HBV DNA value.
- Hepatitis B and hepatitis C virus infections among antiretroviral-naive and -experienced HIV co-infected adults. [Journal Article]
- J Med Microbiol 2014 May; 63(Pt 5):742-7.
Most HIV positive people have not been tested for viral hepatitis and their treatments have not been optimized for possible co-infections. The aim of this study was to investigate the serological pattern of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among antiretroviral (ARV)-naive and -experienced HIV co-infected adults in Addis Ababa, Ethiopia. A total of 500 frozen HIV positive serum and plasma samples collected from ARV-naive (n = 250) and -experienced (n = 250) adults were randomly selected and screened for HBsAg, anti-HBs, HBeAg and anti-HCV using rapid two-site sandwich immunochromatographic assay. The test was performed at Aklilu Lemma Institute of Pathobiology, Addis Ababa University. Positive specimens for HBsAg and anti-HCV markers were further confirmed using third generation ELISA. Of the 500 specimens tested, 15 (3 %), 58 (11.6 %), 3 (0.6 %), 18 (3.6 %), 3 (0.6 %) and 1 (0.2 %) were positive for HBsAg, anti-HBs, HBeAg, anti-HCV, HBsAg and HBeAg, and HBsAg and anti-HBs markers, respectively. No specimen tested positive for both HBeAg and anti-HBs, and 442 (88.4 %) individuals were non-immune to HBV. Of the 250 ARV-naive individuals, 8 (3.2 %), 33 (13.2 %), 2 (0.8 %), 10 (4 %), 2 (0.8 %), and 1 (0.4 %) were positive for HBsAg, anti-HBs, HBeAg, anti-HCV, HBsAg and HBeAg, and HBsAg and anti-HBs markers, respectively. Of the 250 ARV-experienced individuals, 7 (2.8 %), 25 (10 %), 1 (0.4 %), 8 (3.2 %), 1 (0.4 %), and 0 (0 %) were positive for HBsAg, Anti-HBs, HBeAg, anti-HCV, HBsAg and HBeAg, and HBsAg and anti-HBs markers, respectively. In summary, seroprevalence of HIV/HBV and HIV/HCV co-infections was lower in Addis Ababa, Ethiopia, than in Sub-Saharan Africa and globally. HBV and HCV infections were not significantly different between HIV positive subjects who were or who were not on ARV. This suggests that the two groups have equal chance of being infected with these two viruses; despite this, disease progression could be different.
- Efficacy and safety of long term entecavir in chronic hepatitis B treatment naïve patients in clinical practice. [Journal Article]
- Ann Hepatol 2014 May-Jun; 13(3):327-36.
Background and aims. Entecavir (ETV) is effective and safe in patients with chronic hepatitis B in the short term, but its long term efficacy and safety has not been established. Material and methods. We evaluated HBV DNA clearance, HBeAg/antiHBe and HBsAg/antiHBs seroconversion rates in HBeAg-positive and negative NUC naïve HBV patients treated with ETV for more than 6 months, and predictors of response.
Results.A hundred and sixty nine consecutive patients were treated with ETV for a median of 181 weeks. 61% were HBeAg positive, 23% were cirrhotics, and mean HBV-DNA levels were 6,88 ± 1,74 log10 IU/mL. Overall, 156 (92%) patients became HBV DNA undetectable, 92 (88%) HBeAg positive and 64 (98%) HBeAg negative patients. Seventy four (71%) patients cleared HBeAg after a median of 48 weeks of treatment, 23 (14%) patients cleared HBsAg (19 HBeAg positive and 4 HBeAg negative, p 0.025) after a median of 96 weeks of treatment, and 22 (13%) patients developed protective titers of anti-HBs. At the end of the study, 35 (20%) patients had discontinued therapy: 33 HBeAg positive and 2 HBeAg negative; 9 of them (26%) developed virological relapse after a median of 48 weeks of stopping treatment. None of the patients had primary non response and one patient developed breakthrough. Two patients developed HCC, three underwent liver transplantation and 3 deaths were attributable to liver-related events. No serious adverse events were reported.
Conclusion.Long term ETV treatment showed high virological response rates, and a favorable safety profile for NUC-naive HBeAg-positive and negative patients treated in clinical practice.
- Lymphoma Immune Reconstitution Inflammatory Syndrome in the Center for AIDS Research Network of Integrated Clinical Systems Cohort. [JOURNAL ARTICLE]
- Clin Infect Dis 2014 Apr 21.
Background. Lymphoma incidence is increased among HIV-infected individuals soon after antiretroviral therapy (ART), perhaps due to unmasking immune reconstitution inflammatory syndrome (IRIS). Clinical characteristics and survival for unmasking lymphoma IRIS have not been described. Methods. We studied lymphoma patients in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) from 1996 until 2011. Unmasking lymphoma IRIS was defined as lymphoma within 6 months after ART accompanied by a ≥0.5 log10copies/mL HIV RNA reduction. Differences in presentation and survival were examined between IRIS and non-IRIS cases. Results. Of 482 lymphoma patients, 56 (12%) met criteria for unmasking lymphoma IRIS. Of these, 12 (21%) had Hodgkin lymphoma (HL), 22 (39%) diffuse large B-cell lymphoma (DLBCL), 5 (9%) Burkitt lymphoma (BL), 10 (18%) primary central nervous system lymphoma (PCNSL), and 7 (13%) other NHL. Median CD4 cell count at lymphoma diagnosis among IRIS cases was 173 cells/µL (IQR 73-302), and 48% had suppressed HIV RNA <400 copies/mL. IRIS cases were similar overall to non-IRIS in histologic distribution and clinical characteristics, excepting more frequent hepatitis B/C (30% versus 19%, p=0.05), and lower HIV RNA at lymphoma diagnosis resulting from the IRIS case definition. Overall survival at five years was similar for IRIS (49%, 95% CI 37-64%) and non-IRIS (44%, 95% CI 39-50%), although increased early mortality was suggested among IRIS cases. Conclusions. In a large HIV-associated lymphoma cohort, 12% of patients met a uniformly applied unmasking lymphoma IRIS case definition. Detailed studies of lymphoma IRIS might identify immunologic mechanisms of lymphoma control.
- Liver stiffness by transient elastography predicts liver-related complications and mortality in patients with chronic liver disease. [Journal Article]
- PLoS One 2014; 9(4):e95776.
Liver stiffness measurement (LSM) by transient elastography (TE, FibroScan) is a validated method for noninvasively staging liver fibrosis. Most hepatic complications occur in patients with advanced fibrosis. Our objective was to determine the ability of LSM by TE to predict hepatic complications and mortality in a large cohort of patients with chronic liver disease.In consecutive adults who underwent LSM by TE between July 2008 and June 2011, we used Cox regression to determine the independent association between liver stiffness and death or hepatic complications (decompensation, hepatocellular carcinoma, and liver transplantation). The performance of LSM to predict complications was determined using the c-statistic.Among 2,052 patients (median age 51 years, 65% with hepatitis B or C), 87 patients (4.2%) died or developed a hepatic complication during a median follow-up period of 15.6 months (interquartile range, 11.0-23.5 months). Patients with complications had higher median liver stiffness than those without complications (13.5 vs. 6.0 kPa; P<0.00005). The 2-year incidence rates of death or hepatic complications were 2.6%, 9%, 19%, and 34% in patients with liver stiffness <10, 10-19.9, 20-39.9, and ≥40 kPa, respectively (P<0.00005). After adjustment for potential confounders, liver stiffness by TE was an independent predictor of complications (hazard ratio [HR] 1.05 per kPa; 95% confidence interval [CI] 1.03-1.06). The c-statistic of liver-stiffness for predicting complications was 0.80 (95% CI 0.75-0.85). A liver stiffness below 20 kPa effectively excluded complications (specificity 93%, negative predictive value 97%); however, the positive predictive value of higher results was sub-optimal (20%).Liver stiffness by TE accurately predicts the risk of death or hepatic complications in patients with chronic liver disease. TE may facilitate the estimation of prognosis and guide management of these patients.
- Correction: analysis of hepatitis B virus intrahepatic covalently closed circular DNA and serum viral markers in treatment-naive patients with acute and chronic HBV infection. [Journal Article]
- PLoS One 2014; 9(4):e96382.
[This corrects the article DOI: 10.1371/journal.pone.0089046.].
- Prevalence and trends of markers of hepatitis B virus, hepatitis C virus and human Immunodeficiency virus in Argentine blood donors. [JOURNAL ARTICLE]
- BMC Infect Dis 2014 Apr 23; 14(1):218.
Transfusion-transmitted infections are a major problem associated with blood transfusion. The aim of this study was to determine prevalence and trends of HBV, HCV and HIV in blood donors in Argentina.A retrospective study was carried out in blood donors of 27 transfusion centers covering the whole country over a period of eight years (2004-2011). Serologic screening assays for HBsAg, anti-HBc, anti-HCV, and anti-HIV were performed in all centers and nucleic acid amplification testing (NAT) was performed in 2 out of the 27 centers.The 2,595,852 samples tested nationwide from 2004 to 2011 showed that the prevalence of HBsAg decreased from 0.336% to 0.198% (p < 0.0001), that of anti-HBc from 2.391% to 2.007% (p < 0.0001), that of anti-HCV from 0.721% to 0.460%, (p < 0.0001) and that of anti-HIV from 0.208% to 0.200 (p = 0.075). The prevalence of HBV, HCV and HIV was unevenly distributed among the different regions of the country. Two out of 74,838 screening- negative samples were positive in NAT assays (1 HIV-RNA and 1 HCV-RNA); moreover, HBV-DNA, HCV-RNA and HIV-RNA were detected in 60.29, 24.54 and 66.67% of screening-positive samples of the corresponding assays. As regards donors age, positive HBV-DNA and HCV-RNA donors were significantly older than healthy donors (46.6, 50.5 and 39.5 y respectively, p < 0.001).Argentina has a low prevalence of HBsAg, anti-HCV and anti-HIV in blood donors, with a decreasing trend for HBsAg, anti-HBc and anti-HCV but not for anti-HIV over the last 8 years. The uneven distribution of transfusion-transmitted infections prevalence among the different regions of the country highlights the need to implement regional awareness campaigns and prevention. The discrepancy between samples testing positive for screening assays and negative for NAT assays highlights the problem of blood donors who test repeatedly reactive in screening assays but are not confirmed as positive upon further testing. The uneven distribution of age between healthy donors and NAT-positive donors could be related to changes in risks of these pathogens in the general population and might be attributed to a longer exposure to transmission risk factors in elderly people.
- Seroprevalence of occult hepatitis B among Egyptian paediatric hepatitis C cancer patients. [JOURNAL ARTICLE]
- J Viral Hepat 2014 Apr 23.
Occult hepatitis B infection is characterized by the presence of hepatitis B virus (HBV) DNA in the serum in the absence of hepatitis B surface antigen (HBsAg). Prevalence of hepatitis C virus (HCV) infections in Egypt is among the highest in the world. In this study, we aim at analysing the rates of occult HBV infections among HCV paediatric cancer patients in Egypt. The prevalence of occult HBV was assessed in two groups of paediatric cancer patients (HCV positive and HCV negative), in addition to a third group of paediatric noncancer patients, which was used as a general control. All groups were negative for HBsAg and positive for HCV antibody. HBV DNA was detected by nested PCR and real-time PCR. HCV was detected by real-time PCR. Sequencing was carried out in order to determine HBV genotypes to all HBV patients as well as to detect any mutation that might be responsible for the occult phenotype. Occult hepatitis B infection was observed in neither the non-HCV paediatric cancer patients nor the paediatric noncancer patients but was found in 31% of the HCV-positive paediatric cancer patients. All the detected HBV patients belonged to HBV genotype D, and mutations were found in the surface genome of HBV leading to occult HBV. Occult HBV infection seems to be relatively frequent in HCV-positive paediatric cancer patients, indicating that HBsAg negativity is not sufficient to completely exclude HBV infection. These findings emphasize the importance of considering occult HBV infection in HCV-positive paediatric cancer patients especially in endemic areas as Egypt.
- N,N,N-Trimethyl chitosan nanoparticles for controlled intranasal delivery of HBV surface antigen. [Journal Article]
- Carbohydr Polym 2012 Aug 1; 89(4):1289-97.
Hepatitis B virus surface antigen (HBsAg) loaded N,N,N-trimethyl chitosan nanoparticles (N-TMC NPs) were formulated and studied for controlled intranasal delivery. The size and surface properties of the NPs can be tuned by modifying the concentration of N-TMC and found to be 66±13, 76±9nm for 0.25 and 0.5wt.% respectively. Loading of 380 and 760μl of HBsAg yielded 143±33, 259±47nm sized spherical N-TMC NPs with highest loading efficiency and capacity of 90-93%, and 96-97% respectively. In vitro drug release analysis ensured 93% cumulative release of HBsAg antigen over prolonged period (43days). In vivo immunological study was performed using 6-8weeks old female BALB mice and reveals adjuvants efficiency of NPs for antigen is highly stable and better than standard. Obtained results show that N-TMC NPs can be extensively used in controlled intra nasal delivery to treat various diseases including hepatitis B and allergic rhinitis.