Core Antigen Positivity Research Articles

Development and characterization of a chronic hepatitis B murine model with a mutation in the START codon of an HBV polymerase.

Chronic hepatitis B (CHB) is caused by the Hepatitis B virus (HBV) and affects millions of people worldwide. Developing an effective CHB therapy requires using in vivo screening methods, such as mouse models reflecting CHB based on hydrodynamic delivery of plasmid vectors containing a replication-competent HBV genome. However, long-term expression of HBV proteins is accompanied by production of progeny virions, thereby requiring a Biosafety Level (BSL) 3 animal facility. In the present study, we introduced a point mutation in the START codon of the HBV polymerase to develop a mouse model reflecting chronic hepatitis B infection without formation of viral progeny. We induced the mouse model by hydrodynamic injection of adeno-associated virus plasmid vector (pAAV) and minicircle plasmid (pMC) constructs into C57Bl/6 and C3H/HeN mouse strains, monitoring HBV antigens and antibodies in blood by enzyme-linked immunosorbent assay and analyzing liver expression of HBV core antigen by immunohistology. Persisting expression of viral antigens over 140 days (study endpoint) was observed only in the C3H/HeN mouse strain when using pAAV/1.2HBV-A and pMC/1.0HBV-D with pre-C and pre-S recombination sites. In addition, pAAV/1.2HBV-A in C3H/HeN sustained HBV core antigen positivity up to the study endpoint in C3H/HeN mice. Moreover, introducing the point mutation in the START codon of polymerase effectively prevented the formation of viral progeny. Our study establishes an accessible and affordable experimental paradigm for developing a robust mouse model reflecting CHB suitable for preclinical testing of anti-HBV therapeutics in a BSL2 animal facility.

Antibody to hepatitis B virus core antigen positivity is a predictor of non-alcoholic fatty liver disease severity.

Insufficient information is available about co-factors favoring the progression of non-alcoholic fatty liver disease (NAFLD) toward cirrhosis. We aimed to evaluate the impact of a limited alcohol intake and of occult hepatitis B virus (HBV) infection (OBI) on the severity of NAFLD. Three-hundred-seventy-four alcohol non-abusers and HBV surface antigen negative NAFLD patients (223 males; mean age 55.4years), consecutively admitted to the outpatients clinic of a referral liver unit from January 1st, 2018 to December 31st, 2019, were studied. Anti-HBV core antigen antibody [(anti-HBc), a surrogate marker of OBI] was assessed in all patients. Patients were distinguished between teetotal and moderate alcohol consumers (intake of less than 30g and 20g if males or females, respectively). Liver fibrosis was non-invasively assessed by FIB-4 and transient elastography. Uni- and multivariate analyses were performed to identify predictors of advanced fibrosis. Patients had a mean BMI of 28.5kg/m2, and the majority presented metabolic and cardio-vascular comorbidities [258 patients (69%) had insulin resistance/diabetes, 249 (66.6%) dyslipidemia, 200 (53.5%) arterial hypertension]. Multivariate analysis showed that anti-HBc positivity (p = 0.046, OR 2.153) was a factor associated with advanced fibrosis at FIB-4 score testing, whereas moderate alcohol intake was not associated with severe NAFLD both at FIB-4 and transient elastography evaluations. The study showed that a moderate alcohol intake has no impact on NAFLD severity and suggested that OBI might negatively affect the NAFLD outcome.

Role of Hepatitis C Virus Core Antigen Assay in Blood Donors Screening at Zagazig University Hospitals

Background and study aim: Hepatitis C virus (HCV) infection is a major public health problem worldwide. Blood donations screening achieved mainly by serological identification of HCV-Antibody (Ab), has largely reduced HCV transmission. HCV Core Antigen (CAg) tests have been introduced to supplement anti-HCV tests and HCV PCR analyses. CAg may be a useful screening test for identifying window phase of HCV infected patients whom are candidate for blood donations. The study aimed to evaluate diagnostic performance of HCV core antigen in comparison to HCV-RNA quantification and anti-HCV-Ab analyses in attendances of blood bank of Zagazig University hospitals. Patients and Methods: The study was performed on 92 participants attending the blood banks of Zagazig University Hospitals for blood donation between May 2015 to November 2017. The participants were classified into two groups; group A, which included 46 donors (32 males and 14 females) with negative HCV antibody and group B, which Included 46 patients (30 males and 16 females) with positive HCV antibody. Clinical assessment, HCV AB detection by ELISA, Prototype ELISA for HCV core antigen for presence of HCV core antigen and HCV RNA Quantitative were done for all participants. Results: No significant differences between both studied regarding sex and age. A high significant relation between HCV AB positivity and negativity as regard HCV PCR was found in both groups. A high significant relation between HCV core antigen positivity and negativity as regard HCV PCR. There was high significant relation between HCV core antigen positivity and HCV PCR in group A patients. There was a high significant relation between HCV core antigen positivity and HCV PCR in positive HCV antibody patients and statistically a high significant relation between HCV core antigen negativity and HCV PCR in group B patients. Conclusion: HCV core Ag can be identified by serological ELISA. This assay is cheap, easily performed, and compatible with HCV PCR. Its application may prevent the vast majority of HCV transmissions caused by the transfusion of window phase donations.

Associations between antibody to hepatitis B core antigen positivity and outcomes in hepatocellular carcinoma patients undergoing hepatic resection.

We aimed to evaluate the effect of antibody to hepatitis B core antigen (HBcAb) positivity on clinical outcomes after hepatic resection in hepatocellular carcinoma (HCC) patients with negative hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (HCVAb), termed non-B, non-C HCC (NBNC-HCC), or with HCV-related HCC. Two hundred and sixty-three patients who underwent hepatic resection for HCC and measurements of HBsAg, HCVAb, and HBcAb were enrolled in this study. The percentages of HBcAb positivity were 52.3% (n = 57) and 56.9% (n = 66) in patients with NBNC- and HCV-related HCC, respectively. The proportion of multiple NBNC-HCCs was significantly greater in patients with HBcAb positivity compared to HBcAb negativity (P = 0.028). There were no significant differences in the recurrence-free and overall survival rates between NBNC-HCC patients with HBcAb positivity versus negativity (P = 0.461 and P = 0.190, respectively). Furthermore, for HCV-related HCC patients, there were no significant differences in the baseline factors between patients with positive versus negative HBcAb. The proportion of patients with HBcAb-positive HCV-related HCC who underwent anatomical resection of the liver was significantly greater than that of HBcAb-negative patients, whereas the recurrence-free and overall survival rates were not significantly different (P = 0.158 and P = 0.191, respectively). In our study, the presence of HBcAb had no impact on surgical outcomes after hepatic resection in patients with NBNB- and HCV-related HCC. Occult HBV infection might be associated with hepatocarcinogenesis in patients with NBNC-related HCC.

Transfusion Transmitted Hepatitis B Virus among Multitransfused Thalassaemic Children in a Tertiary Health Care Centre in Bangladesh

Background: Repeated blood transfusion is the main life line support for thalassaemic children and so they are more prone to be infected with HBV. In Bangladesh the main source of blood for transfusion is the professional donors and so the possibility of HBV infection is higher. Objective: To assess the frequency of HBV among children who received more than 3 blood transfusions. Materials and Methods: This cross sectional analytical study was conducted in Pediatrics ward of Bangabandhu Sheikh Mujib Medical University, Dhaka during the period of July 2003 to June 2004. Ninety five children aged less than 15 years, suffering from ? thalassaemia major and Hb E ? thalassaemia having blood transfusion more than three times and 20 controls of similar age and sex were included in this study. Seromarkers of HBV were tested and the results were analyzed using SPSS version Windows 11.0. Results: Out of 115 children 68 were ? thalassaemic (mean age 6.8 ± 2.84 yrs and male:female is 4.2:1), 27 were Hb E ? thalassaemic children (mean age 8.78 ± 2.99 yrs and M:F 1.4:1) and 20 were nontransfused, age and sex matched controls (mean age 6.23 ± 1.88 yrs and M:F 1:2.3). Out of 95 thalassaemic children 21 (22.1%) were positive for HBsAg. Among them 13 were ? thalassaemic and 8 were Hb E ? thalassaemic. None of the controls showed HBsAg positivity indicating a significant statistical difference (p=0.033). 28 (29.5%) children were positive for anti-HBc. Among them 23 were ? thalassaemic and 5 were Hb E ? thalassaemic and there was no core antigen positivity among the controls showing a significant statistical difference (p=0.022). Four (4.2%) patients showed HBeAg positivity, out of whom 3 were ? thalassaemic and 1 was Hb E ? thalassaemic. But this antigen was not found in any control and thereby, no statistical significant difference was observed (p=0.637). Among 20 controls, 2 were positive for anti-HBe antibody, but none of the thalassaemic children was positive for this antibody showing statistically significant difference (p=0.008). Conclusion: A significantly higher sero-prevalence of hepatitis B viral marker was observed among the multitransfused thalassaemic children. DOI: http://dx.doi.org/10.3329/jemc.v2i2.12838J Enam Med Col 2012; 2(2): 56-61

Adherence to hepatitis B screening and prophylactic lamivudine for prevention of rituximab-associated hepatitis B reactivation

Treatment with rituximab can be associated with hepatitis B reactivation leading to fulminant hepatitis and sometimes fatal hepatitis. The manufacturer has recommended screening the high-risk patients and monitoring hepatitis B virus carriers during and several months after the therapy. Prophylaxis with lamivudine has been recommended to prevent reactivation in hepatitis B virus carriers receiving rituximab. An institutional guideline was developed and implemented. This study evaluated the adherence to these clinical guidelines of hepatitis B screening in patients receiving rituximab-based treatment, the use of lamivudine prophylaxis, and the prevalence of positive hepatitis B virus surface antigen in this patient population in southeast Michigan. A retrospective chart review of patients begun on rituximab therapy from January 2009 through June 2010 was conducted. Two hundred and eighty patients who received rituximab were identified. Approximately 70% of patients had hepatitis B virus surface antigen screening test prior to rituximab therapy. Antibody to hepatitis B virus core antigen was detected in 11.1% of patients, although the hepatitis B virus surface antigen positive rate was only 0.6%. One patient had hepatitis B virus reactivation despite lamivudine prophylaxis, but fully recovered after antiviral therapy was changed to tenofovir. The prevalence of hepatitis B virus surface antigen positivity is low in this study; however, antibody to hepatitis B virus core antigen positivity is high. Education to clinicians is warranted to increase awareness and further improve adherence to the clinical guidelines.

Prevalence of Antibodies against Hepatitis C Virus in the Elderly: A Seroepidemiological Study in a Nursing Home and in an Open Population

Background: The prevalence of antibodies against hepatitis C virus (anti-HCV) increases in the general population with advancing age. Several discrepancies exist in the epidemiology of HCV, however, when selected elderly population groups are tested. Objective: To evaluate the HCV prevalence in two groups of elderly people living in the same geopgraphical area of northeast Italy, i.e., one including residents of a nursing home, the other including subjects living at home. Methods: The overall sample included 496 subjects (mean age 79.31 ± 8.9 years); 288 were in a nursing home, and 208 were living at home. Enrollment in the latter group was based on all subjects over 65 years old listed under the public health service in the same district. The overall rate of adhesion to the study was 90%. Each subject was administered an anonymous questionnaire testing sociodemographic data and risk factors for HCV infection. Serological tests included: anti-HCV and hepatitis B virus serum markers. Multiple logistic regression analysis was performed to evaluate risk factors for anti-HCV positivity. Results: Anti-HCV positivity was found in 34 of 288 (11.8%) elderly in the nursing home and in 23 of 208 (11.1%) in the open population. When the total population was considered, females exhibited a significantly a higher prevalence of anti-HCV than males (13.4 vs. 7.5%, p < 0.05). In both males and females, the highers rate of anti-HCV prevalence was found among the 75- to 79-year-old subjects. A decline in anti-HCV prevalence was observed in the very old subjects (over 80 years of age). None of the anti-HCV-positive subjects was found to be coinfected with hepatitis B surface antigen. However, multiple logistic regression analysis identified the age group between 70 and 79 years, female gender, and positivity for antihepatitis B surface antigen and/or antihepatitis B core antigen as independent variables significantly associated with HCV prevalence. Conclusions: The prevalence of anti-HCV proved identical among elderly people living in the nursing home or at home, suggesting that nursing homes do not represent a risk factor for HCV infections; the significant association between HCV prevalence and antihepatitis B surface antigen and/or antihepatitis B core antigen positivity supports a common route of transmission of the two viruses; these findings would suggest that there was an epidemic of HCV infection during the Second World War and in the years immediately afterwards.

Risk factors for cirrhosis in patients with chronic hepatitis C virus infection: Results of a case-control study

The role of the viral genotype, especially genotype 1b, in the severity of liver injury induced by chronic hepatitis C virus (HCV) infection is unclear, probably because of confounding factors such as the date and mode of contamination. Host genetic or environmental factors such as heterozygous MZ alpha1-antitrypsin deficiency or alcoholism, could also be potential risk factors for the development of cirrhosis. The aim of this study was to compare the prevalence of genotypes, alpha1-antitrypsin phenotype, past hepatitis B virus infection, and alcohol consumption in cirrhotic and noncirrhotic patients with chronic hepatitis C. We conducted a case-control study comparing 84 consecutive cirrhotic patients with chronic hepatitis C (cases) with 84 noncirrhotic patients with chronic hepatitis C (controls) selected from a cohort of 464 patients hospitalized during the same period. Controls were paired with cases according to age, sex, risk factors, and date of infection. HCV genotypes were determined using the InnoLiPA technique (Innogenetics, Zwijnaarde, Belgium) and classified according to the method of Simmonds. Patients were divided in three groups according to alcohol consumption: <30 g/d (light), 30 to 80 g/d (moderate), and >80 g/d (heavy). Cirrhotic and noncirrhotic patients were not significantly different in terms of genotype distribution (1a/1b/2a/3a/others/undetermined: 10/48/7/17/0/2 versus 11/43/10/10/5/5), alpha1-antitrypsin phenotype distribution (MM/MS/MZ: 84%/14%/2% vs. 87%/11%/2%, respectively), and prevalence of antibody to hepatitis B core antigen positivity (29% vs. 23%). Alcohol consumption was significantly different between cases and controls (L/M/H: 58%/27%/16% vs. 76%/15%/9%, respectively; P < .05). Two conclusions regarding patients with chronic hepatitis C virus infection can be drawn from this study: 1) viral genotype, especially 1b, past hepatitis B virus infection, and heterozygous MZ alpha1-antitrypsin deficiency are not risk factors for cirrhosis; and 2) alcohol consumption, even moderate, is a risk factor for cirrhosis. (Hepatology 1997 Sep;26(3):776-9)

Risk factors for cirrhosis in patients with chronic hepatitis C virus infection: results of a case-control study.

The role of the viral genotype, especially genotype 1b, in the severity of liver injury induced by chronic hepatitis C virus (HCV) infection is unclear, probably because of confounding factors such as the date and mode of contamination. Host genetic or environmental factors such as heterozygous MZ alpha1-antitrypsin deficiency or alcoholism, could also be potential risk factors for the development of cirrhosis. The aim of this study was to compare the prevalence of genotypes, alpha1-antitrypsin phenotype, past hepatitis B virus infection, and alcohol consumption in cirrhotic and noncirrhotic patients with chronic hepatitis C. We conducted a case-control study comparing 84 consecutive cirrhotic patients with chronic hepatitis C (cases) with 84 noncirrhotic patients with chronic hepatitis C (controls) selected from a cohort of 464 patients hospitalized during the same period. Controls were paired with cases according to age, sex, risk factors, and date of infection. HCV genotypes were determined using the InnoLiPA technique (Innogenetics, Zwijnaarde, Belgium) and classified according to the method of Simmonds. Patients were divided in three groups according to alcohol consumption: <30 g/d (light), 30 to 80 g/d (moderate), and >80 g/d (heavy). Cirrhotic and noncirrhotic patients were not significantly different in terms of genotype distribution (1a/1b/2a/3a/others/undetermined: 10/48/7/17/0/2 versus 11/43/10/10/5/5), alpha1-antitrypsin phenotype distribution (MM/MS/MZ: 84%/14%/2% vs. 87%/11%/2%, respectively), and prevalence of antibody to hepatitis B core antigen positivity (29% vs. 23%). Alcohol consumption was significantly different between cases and controls (L/M/H: 58%/27%/16% vs. 76%/15%/9%, respectively; P < .05). Two conclusions regarding patients with chronic hepatitis C virus infection can be drawn from this study: 1) viral genotype, especially 1b, past hepatitis B virus infection, and heterozygous MZ alpha1-antitrypsin deficiency are not risk factors for cirrhosis; and 2) alcohol consumption, even moderate, is a risk factor for cirrhosis.

Antibody Reactivity to Deletion Mutants of the HIV-1 SF2 Envelope

In human immunodeficiency virus type 1 (HIV-1) infected individuals, the antibody response to the external envelope (gp120) is associated with in vitro neutralization. To further characterize the anti-gp120 response, we examined the IgG reactivity of 75 HIV-1-seroconverted and 200 HIV-1-seropositive individuals to deletion mutants of gp120 in an enzyme immunoassay. We used yeast-derived, non-glycosylated recombinant HIV-1 SF2 gp120 equivalent and-variants deleted in variable regions. We observed two distinctive response patterns: IgG non-responders (SF2-V3-restricted responders) and IgG responders to conserved regions of gp120. This divergence in response pattern occurred soon after gag/env HIV-1 antibody seroconversion and persisted in time within an individual. In addition, the SF2-V3-restricted responders had a higher frequency of HIV-1 core antigen positivity and HIV-1 core antibody negativity than the non-restricted responders. These results suggest that specific and persistent host antibody response patterns to gp120 develop early in HIV-1 infection and that these patterns are associated with differences in HIV-1 expression.