Hepatitis B Surface Antigen Positive Individuals Research Articles

Opportunistic screening using point-of-care testing leads to successful linkage to care of HBV-infected migrant populations in a low endemic country

Background and aimsIn low endemic countries, screening for hepatitis B surface antigen (HBsAg) in migrants is cost-effective in reducing the disease burden of hepatitis B virus (HBV) infections, but linkage to care (LTC) remains a challenge. This study aims to guide future screening initiatives, with 3 objectives: 1. to compare LTC between different ethnic groups screened for HBsAg with point-of-care testing (POCT) in an outreach setting; 2. to estimate the proportion of HBsAg seropositivity for ethnic minorities; and 3. to investigate the association between seropositivity and HBV risk factors. MethodsOpportunistic outreach screenings using finger prick HBsAg tests were performed at civic integration programmes between 11/2017 and 09/2022. If an individual tested positive, an appointment was given immediately at the outpatient hepatology clinic for follow-up and confirmation of HBsAg positivity in blood. Dedicated personnel contacted these individuals to motivate them for further LTC, which was defined as being assessed by a hepatologist, a blood test and an abdominal ultrasound. ResultsA total of 677 people from different ethnicities (Asian, Middle Eastern and African) were serologically screened using POCT. The observed positivity for HBsAg was 3.4 % (95% CI 2.17-5.05, 23/677). Apart from ethnicity and male sex, none of the surveyed HBV risk factors were associated with HBsAg seropositivity. All HBsAg positive individuals were linked to care and assessed by a hepatologist, despite the COVID-19 pandemic increase in time to follow-up of 82 days (95% CI 51–112 days) vs. 24 days (95% CI 5–43 days, p = 0.008)).Among HBV-infected patients, 31.8% (7/22), 100 % (22/22) and 26.1% (6/23) met the criteria for treatment indication, intrafamilial transmission risk and need for hepatocellular carcinoma surveillance, respectively. ConclusionThe proportion of HBsAg seropositivity in ethnic minorities was 3.4%. POCT and commitment of dedicated personnel can overcome previously identified barriers resulting in a 100% LTC.

Hepatitis delta: Epidemiology to recent advances in therapeutic agents.

Hepatitis D virus (HDV) was first described in 1977 and is dependent on the presence of hepatitis B surface antigen (HBsAg) for its entry into cells and on the human host for replication. Due to the envelopment with the hepatitis B virus (HBV) envelope, early phases of HDV entry resemble HBV infection. Unlike HBV, HDV activates innate immune responses. The global prevalence of HDV is estimated to be about 5% of HBsAg positive individuals. However, recent studies have described a wide range of prevalence between 12 to 72 million individuals. Infection can occur as super-infection or co-infection. The diagnosis of active HDV infection involves screening with anti HDV antibodies followed by quantitative PCR testing for HDV RNA in those who are HBsAg positive. The diagnostic studies have evolved over the years improving the validity and reliability of the tests performed. HDV infection is considered the most severe form of viral hepatitis and the HDV genotype may influence the disease course. There are eight major HDV genotypes with prevalence varying by geographic region. HDV treatment has been challenging as HDV strongly depends on the host cell for replication and provides few, if any viral targets. Better understanding of HDV virology has led to the development of several therapeutic agents currently being studied in different phase II and III clinical trials. There is increasing promise of effective therapies that will ameliorate the course of this devastating disease.

Sensitivity and specificity of commercially available rapid diagnostic tests for viral hepatitis B and C screening in serum samples

Early diagnosis of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections is pivotal for optimal disease management. Sensitivity and specificity of 19 rapid diagnostic test (RDT) kits by different manufacturers (ABON, CTK Biotech, Cypress Diagnostics, Green Gross, Human Diagnostic, Humasis, InTec, OraSure, SD Bioline, Wondfo) were assessed on serum samples of 270 Mongolians (90 seropositive for hepatitis B surface antigen (HBsAg), 90 seropositive for hepatitis C antibody (HCV-Ab), 90 healthy subjects). All tested RDTs for detection of HBsAg performed with average sensitivities and specificities of 100% and 99%, respectively. Albeit, overall sensitivity and specificity of RDTs for detection of HCV-Ab was somewhat lower compared to that of HBsAg RDTs (average sensitivity 98.9%, average specificity 96.7%). Specificity of RDTs for detection of HCV-Ab was dramatically lower among HBsAg positive individuals, who were 10.2 times more likely to show false positive test results. The results of our prospective study demonstrate that inexpensive, easy to handle RDTs are a promising tool in effective HBV- and HCV-screening especially in resource-limited settings.

Hepatitis D virus infection among hepatitis B virus surface antigen positive individuals in Upper Egypt: Prevalence and clinical features

Background/PurposeAbout 248 million people are chronic HBV surface antigen carriers in the world. Hepatitis D virus (HDV) infection present in more than 15 million people worldwide. HDV needs hepatitis B surface antigen (HBsAg) to help its replication. We aimed to estimate the prevalence of HDV infection among HBsAg positive individuals and to determine the clinical, laboratory and virological characters of HDV infected patients. MethodsThis study was prospective cross-sectional analytic one including 186 HBsAg positive cases. Anti-HBc total, IgM and HBV PCR were done for all of these cases. Anti-HDV ELISA analysis was done for all cases. Positive samples for Anti-HDV by ELISA were then tested by HDV PCR. ResultsOf the 186 HBsAg positive cases, 80 were reactive for anti-HDV antibodies, resulting in an overall anti-HDV seropositivity of 43%. Higher prevalence of liver cirrhosis (43.8%), HCC on top of cirrhosis (8.8%) were found in anti-HDV positive compared to anti-HDV negative cases (17.9%) and (3.8%) respectively (p value<0.001). Portal hypertension and Child-Pugh grade B, C were significantly higher in anti-HDV-positive cases as compared to the anti-HDV-negative ones (47.5% versus 18.9%) and (11.3% versus 6.6%); (16.3% versus 3.8%) respectively (p value<0.001 for each). HDV RNA was positive in 25 out of 80 anti-HDV-positive cases (31.3%). ConclusionAnti-HDV was seropositive in 43% among HBsAg positive cases in Upper Egypt. HDV RNA was positive by PCR in 25 out of 80 anti-HDV-positive cases (31.3%). HDV prevalence using PCR was 25/186 (13.4%) in Upper Egypt.

Prevalence of elevated ALT values, HBsAg, and anti-HCV in the primary care setting and evaluation of guideline defined hepatitis risk scenarios

Prevalence data for hepatitis B and C and an evaluation of a guideline based screening in the primary care setting are not yet available. We therefore implemented a hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus (HCV) screening and developed guideline based screening strategies. HBsAg, anti-HCV, and alanine aminotransferase (ALT) were included in a routine check-up together with a questionnaire covering 16 guideline adapted risk scenarios. Significant risk factors were identified by stepwise logistic regression. 51 private practices screened 21,008 patients. The HBsAg, anti-HCV, and HCV-RNA prevalence was 0.52%, 0.95%, and 0.43%, respectively. Infections were previously unknown in 85% and 65% of HBsAg and anti-HCV positive individuals, respectively. Sexual risk factors were under-reported, while the following scenarios were significantly associated with viral infections (Odds ratio [95% confidence interval]). HBV: Immigration (4.4 [2.9, 6.7]), infection in household (2.5 [1.2, 4.5]), male gender (1.6 [1.1, 2.4]). Male immigrants had a 2.1% HBsAg prevalence and 80% were unaware of the infection. HCV: IV drug use (384 [233, 644]), blood transfusion before 1992 (5.3 [3.5, 7.9]), immigration (2.4 [1.5, 3.6]). Presence of either one of the HBV related guideline defined risk scenarios or elevated ALT identified 82% of previously undiagnosed patients. Presence of one of the three significant HCV risk factors or elevated ALT levels diagnosed 83% of unknown HCV-RNA positive cases by screening only 26% of the population. Undiagnosed hepatitis B and C infections frequently exist in the primary care setting. Easy to apply guideline defined risk scenarios help to diagnose previously unknown infections.

Hepatitis B Virus (HBV) Serological Patterns in Benue State, Nigeria

A total of 1535 randomly collected blood specimens from different groups of consenting subjects in Benue State, were screened by ELISA for Hepatitis B surface antigen (HBsAg), hepatitis B surface antibodies (HBsAb), hepatitis B core antibodies (HBcAb), hepatitis Be antigen (HBeAg) and Hepatitis B core IgM antibodies (HBcIgM). The pattern of occurrence of these HBV markers in each blood sample was used to determine individuals with current, acute or chronic infection histories. Of the 1535 sampled individuals, 1319 (85.9%) showed a serological evidence of exposure to HBV infection, some through natural infection (22.7%) and others (13.0%) through vaccination; 12% of the exposed were inferred to be currently infected and 91.2% chronically infected. Hepatitis delta virus (HDV) antigen was also detected in 2.7% of the HBsAg positive individuals; and was encountered more (6.7%) in those with acute hepatitis than those with chronic disease. Thus, there are apparently healthy persons with acute and chronic HBV and HDV infection who may serve as source of infection to others. This calls for a government organized Hepatitis Programme to treat cases of acute and chronic hepatitis and roll out strategy for preventing the spread of HBV infections.

Evaluation of the performance of four methods for detection of hepatitis B surface antigen and their application for testing 116,455 specimens

Hepatitis B surface antigen (HBsAg) is a crucial serum marker for the diagnosis of hepatitis B virus (HBV) infection. It is imperative to compare test results from different detection methods based on different principles. Four methods, chemiluminescent microparticle immunoassay (CMIA), electrochemiluminescent immunoassay (ECLIA), enzyme-linked immunosorbent assay (ELISA) and golden immunochromato-graphic assay (GICA) were applied to test the HBsAg level in 250 specimens. According to the EP12-A2 and EP15-A2 documents from Clinical and Laboratory Standards Institute (CLSI), the concentration at which repeated results are 50% positive (C50) of HBsAg detected by CMIA, ECLIA, ELISA and GICA was 0.05, 0.08, 0.15 and 15.0IU/ml, respectively. When the detection concentration of HBsAg was 0.5IU/ml, the imprecision degree of CMIA, ECLIA and ELISA was 8.1%, 5.9% and 14.9% respectively. When detecting high HBsAg level (≥20.0IU/ml) and HBsAg negative specimens, the consistency of the four methods was high, while for the low level (0.05–20.0IU/ml), the consistency was poor (except for the CMIA and ECLIA, P<0.05). When evaluation of the four methods in qualitative diagnosis of HBsAg level in the 116,455 specimens, there was no significant discrepancy among CMIA, CMIA and ECLIA, however, GICA was significantly different from the other 3 methods. Compared with CMIA, the false negative rate of ECLIA, ELISA and GICA was 0.2%, 1.3% and 12.3% respectively. In conclusion, GICA was only suitable for the preliminary screening of HBsAg positive individuals and ELISA can be applied to the qualitative diagnosis of HBsAg. Both CMIA and ECLIA were suitable for the quantitative determination of HBsAg.

Prevalence and risk factors of hepatitis B and C virus infections in an impoverished urban community in Dhaka, Bangladesh

BackgroundViral hepatitis is a serious global public health problem affecting billions of people globally, and both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are rapidly spreading in the developing countries including Bangladesh due to the lack of health education, poverty, illiteracy and lack of hepatitis B vaccination. Also there is lack of information on their prevalence among the general population. So, a population-based serological survey was conducted in Dhaka to determine the prevalence and risk factors of HBV and HCV infections.MethodsHealthy individuals were selected for demographic and behavioural characteristics by stratified cluster sampling and blood tested for hepatitis B surface antigen (HBsAg), antibody to HBV core antigen (anti-HBc), and anti-HCV antibodies (anti-HCV).ResultsFrom June 2005-November 2006, 1997 participants were screened for HBsAg, anti-HBc and anti-HCV, 738 (37%) were males with mean (SD) age of 24 (14) years. HBV-seropositivity was documented in 582 (29%) participants: 14 (0.7%) were positive for HBsAg, 452 (22.6%) for anti-HBc and 116 (5.8%) for both HBsAg and anti-HBc. Four (0.2%) participants were positive for anti-HCV, and another five (0.3%) for both anti-HBc and anti-HCV. Ninety-six/246 (39%) family members residing at same households with HBsAg positive participants were also HBV-seropositive [74 (30.1%) for anti-HBc and 22 (8.9%) for both HBsAg and anti-HBc], which was significantly higher among family members (39%) than that of study participants (29%) (OR 1.56; p < 0.001). In bivariate analysis, HBV-seropositivity was significantly associated with married status (OR 2.27; p < 0.001), history of jaundice (OR 1.35; p = 0.009), surgical operations (OR 1.26; p = 0.04), needle-stick injuries (OR 2.09; p = 0.002), visiting unregistered health-care providers (OR 1.40; p = 0.008), receiving treatment for sexually transmitted diseases (STD) (OR 1.79; p = 0.001), animal bites (OR 1.73; p < 0.001); ear-nose-body piercing in females (OR 4.97; p < 0.001); circumcision (OR 3.21; p < 0.001), and visiting community barber for shaving in males (OR 3.77; p < 0.001). In logistic regression analysis, married status (OR 1.32; p = 0.04), surgical operations (OR 1.39; p = 0.02), animal bites (OR 1.43; p = 0.02), visiting unregistered health-care providers (OR 1.40; p = 0.01); and ear-nose-body piercing in females (OR 4.97; p < 0.001) were significantly associated with HBV-seropositivity.ConclusionsThe results indicate intermediate level of endemicity of HBV infection in Dhaka community, with much higher prevalence among family members of HBsAg positive individuals but low prevalence of HCV infections, clearly indicating need for universal hepatitis B vaccination. The use of disposable needles for ear-nose-body piercing need to be promoted through public awareness programmes as a preventive strategy.

Frequency of diagnostically significant hepatitis B surface antigen mutants

Mutations in the hepatitis B surface antigen (HBsAg) gene can result in amino acid changes in the HBsAg immunodominant determinant that affect the binding of antibodies used in immunoassays. The effects of mutations on immunoassay detection of HBsAg can range from little or no change in reactivity, to significantly reduced reactivity, to complete loss of detection. The frequency of mutations affecting HBsAg detection among hepatitis B virus (HBV) infected individuals in the United States is largely unknown. We investigated the frequency and nature of diagnostically significant HBsAg variants in the United States by evaluating 186 chronically infected, HBsAg positive individuals. As a first level differential screening strategy to serologically identify variants with potential diagnostic importance, HBsAg levels were estimated using two different immunoassays that employ antibodies recognizing different epitopes and that are known to differ in their detection of frequently reported mutations. Six individuals (3.2%) had results that were qualitatively or quantitatively discordant by at least ten-fold between the two immunoassays. All of the discordant samples were HBV DNA positive. Results of epitope mapping showed that one sample had no detectable wild-type HBsAg but contained an altered HBsAg consistent with a mutation in the second loop of the determinant. Another specimen was shown to have a mutation in the HBsAg gene resulting in an asparagine substitution at amino acid 134 within the first loop of the determinant. Results of this study indicate that at least 1.1% of HBsAg positive individuals may carry HBV mutations that affect detection by HBsAg immunoassays.

High prevalence of occult hepatitis B in Baltimore injection drug users

Occult hepatitis B is defined by the presence of hepatitis B virus (HBV) DNA in a serum or liver in the absence of hepatitis B surface antigen (HBsAg). The prevalence and clinical correlates of occult hepatitis B remain incompletely defined. A cross-sectional study was performed to determine the prevalence of occult hepatitis B in a high-risk cohort composed of 188 injection drug users in Baltimore, Maryland. All individuals had chronic hepatitis C viral infections confirmed by RNA detection and liver biopsy. Serologic assays for HBsAg and core antibody (HBcAb) were performed. Serum HBV DNA was detected using the COBAS HBV AMPLICOR monitor assay (lower limit of detection, 200 HBV copies per milliliter) and a semi-nested polymerase chain reaction (PCR) assay (lower limit of detection, 15 HBV copies per milliliter). Although almost all individuals (96%) were anti-HBC positive, only 8 of 188 (4%) were HBsAg positive. Occult hepatitis B was not identified using the COBAS assay, but was found in 81 of 180 (45%) of individuals using semi-nested PCR. Of the 8 HBsAg positive individuals, HBV DNA was found in 1/8 using the COBAS assay and 6/8 using the nested PCR assay. Overall, liver disease was mild, with a median serum alanine aminotransferase (ALT) of 38 IU/L, median activity grade of 3/18, and median fibrosis stage of 1/6. No association was found between the serum AST (aspartate aminotransferase), activity grade, or stage of liver disease and the presence of occult hepatitis B. Serum ALT levels were slightly higher in patients without occult hepatitis B (46 vs. 35 IU/L), and the median years since first injection drug use was somewhat longer in those without occult hepatitis B (24 vs. 20 years). In conclusion, although further research is needed to assess its clinical significance, there is a high prevalence of occult HBV infection in this cohort of HCV-infected injection drug users.

Virological profiles in patients with chronic hepatitis C and overt or occult HBV infection.

The virological profiles of hepatitis B and C viruses (HBV and HCV) and their interplay in cases of coinfection are undefined. A suppressed and occult HBV infection may occur in hepatitis B surface antigen (HBsAg) negative patients with chronic hepatitis C. The HCV core protein is able to inhibit HBV "in vitro," and serines at positions 99 and 116 are essential for such inhibition. We aimed to assess the HBV and HCV virological profiles in cases of coinfection and to evaluate the relationship between HCV core gene variability and HBV activity. Eighty-two anti-HCV positive patients were examined: 35 cases were HBsAg positive, 24 were HBsAg negative with "occult" HBV infection, and 23 were HBV negative. HBV and HCV viremia levels were evaluated in all cases. HCV genomic region coding for the aminoacid sequence 99-116 of core protein was amplified and sequenced in all HCV RNA positive cases. The entire core gene was amplified and sequenced in three randomly selected cases. Serum HCV RNA was detected in all cases but 13, all HBsAg positive individuals; HCV viremia levels of the other 22 HBsAg positive subjects were similar to those detected in HBsAg negative patients with or without occult HBV infection. Among the 35 HBsAg positive patients both HBV DNA and HCV RNA were detected in five cases, HCV RNA alone in 17, and HBV DNA alone in six, whereas seven cases had undetectable levels of both viruses. Sequencing analyses showed that the HCV core gene was highly preserved in all patients. A wide spectrum of HCV and HBV virological patterns may occur in a case of coinfection. HCV core variability is not related to HBV activity "in vivo."

Virological profiles in patients with chronic hepatitis C and overt or occult HBV infection

OBJECTIVES: The virological profiles of hepatitis B and C viruses (HBV and HCV) and their interplay in cases of coinfection are undefined. A suppressed and occult HBV infection may occur in hepatitis B surface antigen (HBsAg) negative patients with chronic hepatitis C. The HCV core protein is able to inhibit HBV “in vitro,” and serines at positions 99 and 116 are essential for such inhibition. We aimed to assess the HBV and HCV virological profiles in cases of coinfection and to evaluate the relationship between HCV core gene variability and HBV activity. METHODS: Eighty-two anti-HCV positive patients were examined: 35 cases were HBsAg positive, 24 were HBsAg negative with “occult” HBV infection, and 23 were HBV negative. HBV and HCV viremia levels were evaluated in all cases. HCV genomic region coding for the aminoacid sequence 99–116 of core protein was amplified and sequenced in all HCV RNA positive cases. The entire core gene was amplified and sequenced in three randomly selected cases. RESULTS: Serum HCV RNA was detected in all cases but 13, all HBsAg positive individuals; HCV viremia levels of the other 22 HBsAg positive subjects were similar to those detected in HBsAg negative patients with or without occult HBV infection. Among the 35 HBsAg positive patients both HBV DNA and HCV RNA were detected in five cases, HCV RNA alone in 17, and HBV DNA alone in six, whereas seven cases had undetectable levels of both viruses. Sequencing analyses showed that the HCV core gene was highly preserved in all patients. CONCLUSION: A wide spectrum of HCV and HBV virological patterns may occur in a case of coinfection. HCV core variability is not related to HBV activity “in vivo.”

A survey of liver pathology in needle biopsies from HBsAg and anti-HBe positive individuals

Aims—To use laboratory data and liver biopsies, prospectively obtained from hepatitis B surface antigen (HBsAg) and anti hepatitis B e antigen (anti-HBe) positive patients, for the assessment of: (1) the...

Evidence for clustering of hepatitis B virus infection in families of patients with primary hepatocellular carcinoma

Family member of 13 patients with hepatitis B surface antigen (HBsAg) positive primary hepatocellular carcinoma (PHC) were tested for the presence of hepatitis B virus-associated antigens and antibodies. Of the 122 members examined, circulating HGsAg was detected in 47 (39%), antibody to HBsAg (anti-HBs) was found in 37 (30%), and antibody to hepatitis B core antigen (anti-HBc) alone was present in 13 (11%). The relatives with the highest frequency of HBsAg positivity were the offspring of the propositus, followed by the nieces and nephews and the grandchildren. Anti-HBs and anti-HBc were detected most often in the spouses and non-blood relatives. Evidence for past and present hepatitis B virus (HBV) infection was more frequently found in the Asian family members when compared to the non-Asians. The e antigen (HBeAg) was present in 38% of the HBsAg positive individuals, including four with PHC; antibody to HBcAg (anti-HBe) was rarely detected. These results indicate that clustering of HBV infection was commonly present in family members of patients with PHC. The HBsAg positive individuals may be major contributors to the endemic pool of the virus, and may themselves be potential cases of chronic active type B hepatitis, cirrhosis, and PHC.