Inactive Hepatitis B Surface Antigen Carriers Research Articles

Prevalence of hepatitis B virus infection among pregnant women in the mountainous regions of southern China: A retrospective single‐center study

Hepatitis B virus (HBV) infection remains a major public health issue worldwide. Moreover, its prevalence varies significantly in different geographic areas of China. The current study aimed to assess the prevalence of HBV infection among Hakka pregnant women in Meizhou, a remote mountainous region in southern China. This research was performed between January 2015 and December 2020. In total, 16,727 pregnant women receiving antenatal care at Meizhou People's Hospital were included in the analysis. All pregnant women were screened for serum HBV markers. The prevalence rates of hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody positivity among the participants were 11.74% (n=1964) and 48.00% (n=8029), respectively. The overall prevalence rates of susceptibility to infection, HBV immunity, previous/occult infection, inactive HBsAg carrier, and active infection were 36.16%, 33.61%, 16.94%, 8.11%, and 2.30%, respectively. According to age distribution, the prevalence rate of HBsAg positivity elevated concomitantly with increasing age (p < 0.001). From 2015 to 2020, the prevalence rate of HBsAg positivity decreased from 14.50% to 8.19% and that of hepatitis B pre-core antigen positivity from 4.42% to 2.31%. In addition, pregnant women with HBsAg-positive status were more likely to present with gestational diabetes, thrombocytopenia, and anemia than those with HBsAg-negative status. The HBV infection rate remains high among pregnant women in the indigenous Hakka population in southern China. To prevent vertical transmission, cautious surveillance of maternal HBV infection status should be considered in Hakka pregnant women in Meizhou.

Serum hepatitis B virus large and medium surface proteins as novel tools for predicting HBsAg clearance.

BackgroundThere is still lack of reliable predictors for hepatitis B surface antigen (HBsAg) clearance. Recent studies have shown that the levels of large (LHBs) and medium hepatitis B surface proteins (MHBs) are closely related to antiviral efficacy. This study aimed to investigate the possibility of LHB and MHB levels to predict HBsAg clearance.MethodsAn inactive HBsAg carriers (IHCs) cohort that had received pegylated interferon (Peg-IFN) treatment was divided into the HBsAg-cleared group (R group) and the HBsAg non-cleared group (NR group) based on whether HBsAg was cleared at 96 weeks. We detected the levels of LHBs and MHBs to evaluate the possibility of predicting HBsAg clearance.ResultsThere were 39 patients in the R group and 21 in the NR group. The total HBsAg, LHB, and MHB levels at baseline and at 12 weeks were significantly lower in the R group than in the NR group (all p< 0.05). Multivariate logistic regression indicated that LHB and MHB levels at baseline and 12 weeks were independent predictors of HBsAg clearance (OR = 0.435, p = 0.016; OR = 0.136, p = 0.003; OR = 0.137, p = 0.033; OR = 0.049, p = 0.043). The area under the curve (AUC) for the baseline and 12-week LHB and MHB levels was 0.827-0.896, which were greater than that of the total HBsAg level at baseline and 12-week (AUC: 0.654-0.755). Compared with the prediction results of a single indicator, the combination of LHB and MHB levels had better value in predicting HBsAg clearance. The AUCs of combination factor 1, constructed from baseline LHB and MHB, and combination factor 2, constructed from 12-week LHB and MHB, were 0.922 and 0.939, respectively, and the sensitivity (82.05%-100.00%) and specificity (85.71%-100.00%) were both high. The combined indicators based on baseline LHBs ≤ 13.99 ng/mL and MHBs ≤ 7.95 ng/mL predicted HBsAg clearance rate of more than 90%.ConclusionBaseline and 12-week LHB and MHB levels can predict HBsAg clearance obtained by Peg-IFN therapy in IHCs, and the predictive value is higher than that of the total HBsAg levels.

Pegylated Interferon Treatment for the Effective Clearance of Hepatitis B Surface Antigen in Inactive HBsAg Carriers: A Meta-Analysis.

BackgroundExpanding antiviral therapy to benefit more populations and optimizing treatment to improve prognoses are two main objectives in current guidelines on antiviral therapy. However, the guidelines do not recommend antiviral therapy for inactive hepatitis B surface antigen (HBsAg) carriers (IHCs). Recent studies have shown that antiviral therapy is effective with good treatment outcomes in IHC populations. We conducted a systematic review and meta-analysis of HBsAg clearance and conversion in IHCs.MethodsWe searched PubMed, Embase, Medline, and Web of Science to retrieve articles on HBsAg clearance in IHCs published between January 2000 and August 2021. Data were collected and analysed using the random-effects model for meta-analysis.ResultsA total of 1029 IHCs from 11 studies were included in this analysis. The overall HBsAg clearance rate was 47% (95% confidence interval (CI): 31% - 64%), with a conversion rate of 26% (95% CI: 15% - 38%) after 48 weeks of Pegylated interferon (Peg-IFN) treatment. In the control group (including nucleos(t)ide analogue (NA) treatment or no treatment), the overall HBsAg clearance rate was only 1.54% (95% CI: 0.56% - 3.00%), which was markedly lower than that in the Peg-IFN group. Further analysis showed that a low baseline HBsAg level and long treatment duration contributed to a higher HBsAg clearance rate.ConclusionThis study showed that treatment of IHCs can be considered to achieve a clinical cure for chronic hepatitis B virus (HBV) infection. After Peg-IFN treatment, the HBsAg clearance rate was 47%, and the conversion rate was 26%, which are markedly higher than those reported by previous studies on Peg-IFN treatment in patients with chronic hepatitis B (CHB). A low baseline HBsAg level and long treatment duration were associated with HBsAg clearance in IHCs. Therefore, antiviral therapy is applicable for IHCs, a population who may be clinically cured.Systematic Review Registration http://www.crd.york.ac.uk/PROSPERO, CRD): CRD42021259889.

Analysis of the Efficacy and Safety of PEGylated Interferon-α2b Treatment in Inactive HepatitisB Surface Antigen Carriers.

IntroductionHepatitis B virus (HBV) infection is associated with the onset of several major liver diseases. Inactive hepatitis B surface antigen (HBsAg) carriers (IHCs) may be successfully treated with PEGylated interferon-α2b (PEG-IFNα2b)-based antiviral therapy; however, studies on this treatment have been insufficient. In this study, we evaluated the efficacy and safety of PEG-IFNα2b treatment in IHCs.MethodsNineteen IHCs were treated with subcutaneous PEG-IFNα2b (180 μg/week) for 48 weeks (treatment group). Patients were followed up for 24 weeks after treatment discontinuation. Twenty untreated control patients were observed for 72 weeks (control group). HBsAg clearance (HBsAg < 0.05 IU/mL), HBsAg seroconversion, and alanine aminotransferase levels were monitored.ResultsOf the 19 patients treated with PEG-IFNα2b, 16 showed HBsAg loss (84.2%), and 13 showed HBsAg seroconversion (68.4%) at 72 weeks. All patients in the treatment group exhibited virological response (serum HBV DNA level < 10 IU/mL) at the time of drug withdrawal. In the control group, no patients experienced HBsAg loss during the observational period. There were no serious adverse events during treatment, and the therapy was well tolerated.ConclusionsShort PEG-IFNα2b therapy in IHCs produced a high functional cure rate and good safety profile, suggesting that PEG-IFNα2b treatment may be the best choice for clinical cure of some IHCs.

Need for Confirmatory Neutralization Tests for Hepatitis B Surface Antigen Tests in Populations with Intermediate Prevalence.

Hepatitis B surface antigen (HBsAg) is known as the hallmark of hepatitis B virus (HBV) infection. This study aimed to determine whether an HBsAg neutralization test is necessary to accurately interpret HBsAg test results. Initially reactive HBsAg specimens from a 5-year period, with cutoff index values between 1.0 and 2.0, were subjected to neutralization confirmatory testing using an Elecsys HBsAg Confirmatory test kit (Roche Diagnostics GmbH. Mannheim, Germany). The neutralization test showed 46.1% positive (confirmed positive group) and 53.9% negative (confirmed negative group) results from the total specimens. Among the confirmed negative group, 79.5% of patients were confirmed to be negative for the current infection, whereas 4 patients in the chronic hepatitis B subgroup showed a neutralization percentage close to 40%. More than half of patients in the confirmed positive group were considered to be in the hepatitis B e antigen-negative inactive HBsAg carrier phase. In populations with intermediate HBV prevalence, a neutralization test is necessary to confirm an HBsAg result and reduce the false positive and false negative rates of initial HBsAg tests.

Performance of rapid diagnostic tests for hepatitis B surface antigen detection in serum or plasma

Hepatitis B surface antigen (HBsAg) is a key marker for screening and laboratory diagnosis of HBV infection. Rapid diagnostic tests (RDTs) represent promising alternatives to immunoassay-based methods because they are simple, fast and cheap. These tests, therefore, represent a powerful tool for large-scale screening and diagnosis of HBV infection in the clinical setting.Performance of 6 RDTs have been assessed in a large series of serum or plasma samples (n = 501) collected in France and in Cameroon.Specificity varied from 98.0% to 99.5%, while clinical sensitivity, compared to immunoassays as the reference, was excellent for all six RDTs (98.3%–99.3%). The VIKIA HBsAg and First Responseࣨ HBsAg Card Test reached sensitivity ≥99%. False-negative results were rare and mostly encompassed inactive HBsAg carriers or patients treated with nucleoside/nucleotide analogues.A number of RDTs may widely use to increase access to testing to all levels of the health care system.

Sequence analysis of persistently low level expression of hepatitis B surface antigen S gene in patients with hepatitis B virus infection

Objective To reveal the characteristics of S gene sequence of hepatitis B surface antigen (HBsAg) in hepatitis B virus (HBV)-infected patients with low HBsAg level. Methods From February 2016 to December 2017, 1 308 serum samples of inactive HBsAg carriers were collected from the 903rd Hospital of PLA and Hangzhou Jianggan District People′s Hospital.The cases were divided into high-level group and low-level group according to the level of serum HBsAg (10 IU/mL) expression. The HBV S gene was sequenced in patients with low-level HBsAg expression. In addition, in patients with high-level HBsAg, 100 patients were randomly selected (stratified sampling) for HBV S gene sequencing based on the matching of age and serological pattern (hepatitis B e antigen [HBeAg] negative) of low-level HBsAg group. A comparative analysis was conducted between HBV S gene sequences from inactive HBsAg carrier in low HBsAg expression group and the HBV reference S gene sequences from inactive HBsAg carrier in high HBsAg expression group.The results of normal distribution data were expressed as Mean±SD, and analyzed using t-test. The results of non-normal distribution data were expressed by M(QR), and analyzed using Mann-Whitney U test.Chi-square test or Fisher exact test was used to compare continuous variables and classification variables between the two groups. Results There were 276 serum samples from the low level group and 1 032 serum samples from the high level group, including 257 HBsAg/HBeAg/anti-HBc-positive cases, 753 HBsAg/anti-HBe/anti-HBc-positive cases, and 22 HBsAg/anti-HBc-positive cases. Successful HBV S gene sequencing was performed on 126 out of 276 patients in the low-level HBsAg group. According to the age inthe low-level HBsAg group, 100 samples with negative HBeAg in the high-level HBsAg group were randomly selected, among which 94 patients were genotyped and hemotyped. The results showed that there were statistically significant differences in HBV serological markers, HBV DNA level and HBV genotype distribution between the high level group (94 cases) and the low level group (126 cases) (all P 0.05). For genotype B, 12 single point mutations and 4 dual co-mutations were found in low level group. Among them, one single point mutation (S210R) and 3 dual co-mutations (G44E/V+ T45P/I, G44E/V+ L49P/R and N40S+ I208T) were not hot spot mutations, while 2 dual co-mutations and 2 single point mutations were found in high level group. The difference between two groups was statistical significant (χ2=7.533, P=0.006). For genotype C, 5 single point mutations (T5A, A45T, T47A/K, Q101R and I126S/T) were found in low level group and 1 single point mutation (N3S) in high level group. The difference in mutation frequency between two groups were statistical significant (χ2=47.914, P=0.000). Conclusions Significant mutations in multiple regions and at multiple sites (including co-mutations) on both sides of the MHR may be one of the causes of low HBsAg expression level in this population. Key words: Hepatitis B surface antigens; Genotype; HBV markers; HBV DNA; S gene; Mutation site

The relationship between hepatitis B virus S gene mutations and hepatitis B virus-related acute on chronic liver failure

Objective To investigate and analyze the relationship between hepatitis B virus (HBV) S gene mutations and the occurrence of HBV-related acute on chronic liver failure (HBV-ACLF). Methods A total of 377 patients were enrolled in this study, including 51 inactive hepatitis B surface antigen (HBsAg) carriers, 78 chronic hepatitis B (CHB) patients, 101 HBV-ACLF patients, 69 HBV-related liver cirrhosis (LC) patients and 78 HBV-related hepatocellular carcinoma (HCC) patients. Serum samples were collected from July 2012 to September 2017 in Guangzhou Eighth People′s Hospital. Nested polyoneras chain reaction (PCR) was performed for all the samples, the HBV whole genome and HBV S gene were amplified. PCR products were sequenced by Sanger sequencing method. HBV genotypes were determined by the phylogenetic tree based on HBV S gene constructed by Mega 7.0 software with the neighbor-joining method. Geneious R10.0.5 software was used to analyze the mutations of the HBV genome. The data in different groups were compared by χ2 test or Fisher′s exact test. The correlation analysis was done by logistic regression. Results Among the 377 patients enrolled in this study, the HBV-ACLF, CHB, inactive HBsAg carriers, and HCC patients infected with HBV genotype B were 83, 51, 34, 31, and 35 cases respectively, and the patients infected with HBV genotype C were 18, 27, 17, 38, and 43 cases respectively. The results of this study showed that 11 mutations were significantly higher in HBV-ACLF patients than CHB patients who were infected with HBV genotype B, including T216C, G285A and A529G in HBV S gene, A1317G in HBV enchanter I, A1762T/G1764A in basal core promoter (BCP) gene, A1846T, C1913A, G1896A, T2045A, C2078G, C2304A in HBV preC/C gene. However, no significant difference mutations were found in HBV-ACLF patients and CHB patients who were infected with HBV genotype C. In the patients infected with HBV genotype B, the prevalence of T216C (sL21S) mutation in HBV-ACLF was significantly higher than those in inactive HBsAg carriers, CHB and HCC patients (χ2=14.474, 10.982, and 5.440, respectively, all P 0.05). Logistic regression analysis showed that male (OR=6.90, 95% CI: 1.52-24.39, P=0.010), hepatitis B e antigen negative (OR=4.73, 95% CI: 1.60-13.94, P=0.005), HBV genotype B (OR=4.80, 95% CI: 1.82-12.16, P=0.006) and G285A mutation (OR=7.72, 95% CI: 5.64-16.37, P=0.006) were the independent risk factors associated with HBV-ACLF. Conclusions The HBV S gene mutation may be associated with HBV-ACLF. Key words: Hepatitis B virus; Mutation; Acute on chronic liver failure

Hepatitis B surface antigen clearance in inactive hepatitis B surface antigen carriers treated with peginterferon alfa-2a.

To examine the association between interferon (IFN) therapy and loss of hepatitis B surface antigen (HBsAg) in inactive HBsAg carriers. This was a retrospective cohort study in inactive HBsAg carriers, who were treatment-naive, with a serum HBsAg level < 100 IU/mL and an undetectable hepatitis B virus (HBV) DNA level (< 100 IU/mL). All the 20 treated patients received subcutaneous PEG-IFN alfa-2a 180 μg/wk for 72 wk and were then followed for 24 wk. There were 40 untreated controls matched with 96 wk of observation. Serum HBsAg, HBV DNA, and alanine aminotransferases were monitored every 3 mo in the treatment group and every 3-6 mo in the control group. Thirteen (65.0%) of 20 treated patients achieved HBsAg loss, 12 of whom achieved HBsAg seroconversion. Mean HBsAg level in treated patients decreased to 6.69 ± 13.04 IU/mL after 24 wk of treatment from a baseline level of 26.22 ± 33.00 IU/mL. Serum HBV DNA level remained undetectable (< 100 IU/mL) in all treated patients during the study. HBsAg level of the control group decreased from 25.72 ± 25.58 IU/mL at baseline to 17.11 ± 21.62 IU/mL at week 96 (P = 0.108). In the control group, no patient experienced HBsAg loss/seroconversion, and two (5.0%) developed HBV reactivation. IFN treatment results in HBsAg loss and seroconversion in a considerable proportion of inactive HBsAg carriers with low HBsAg concentrations.

Role of Levels of Mannose-Binding Lectin in Hepatitis B Virus Infection

Introduction : Hepatitis B virus (HBV) infection is an infectious disease that maintains its importance. Recovery, inactive HBsAg (hepatitis B surface antigen) carrier state, chronic hepatitis, cirrhosis, hepatocellular carcinoma and hepatic failure are the results which may occur during the clinical course of the disease. Immune system and host-related genetic factors play an important role in the prognosis. Mannose-Binding Lectin (MBL) is known to have a function in inflammatory response. In this study, it was aimed to investigate the role of serum MBL levels during the clinical course of HBV infection. Methodology-Result : A total of 147 patients were included in the study. Serum MBL levels of chronic HBV infection group, inactive HBsAg carrier group and healthy control group were determined to be 4504 ± 3185 ng/mL, 3301 ± 2631 ng/mL and 3329 ± 2484 ng/mL; respectively. Although serum MBL levels were determined to be higher in the patients with chronic HBV infection compared to the other groups, this was not statistically significant (p=0,148). Conclusions : The role of MBL in HBV infection is not clear as to reach a clear conclusion and it seems to be an insignificant factor compared to the more important factors contributing to the infection. Again in the studies performed in recent years, a strong correlation was determined between lower levels of serum MBL and codon variants and it has been suggested that codon variants could be used as genetic marker of lower levels of serum MBL. Based on the knowledge of there was a correlation between MBL gene mutations and lower levels of serum MBL, it has been thought that MBL gene study was not cost-efficient to determine the relationship of MBL gene mutations with infections.

Serum hepatitis B surface antigen level might predict cirrhosis and hepatocellular carcinoma in older patients with chronic hepatitis B

SummaryBackground and aimDistinguishing inactive hepatitis B surface antigen (HBsAg) carriers from hepatitis B e antigen‐negative hepatitis remains difficult but is important because patients with active hepatitis may develop severe complications. Long‐term follow‐up data with stringent criteria are required for the identification of inactive HBsAg carriers. A single serum HBsAg level may be used to solve this difficult diagnostic issue; however, very few studies on its application in older patients have been published. This study was designed to evaluate the clinical significance of a single serum HBsAg level in older patients with chronic hepatitis B (CHB).Materials and methodsFrom January 2012 to December 2012, the clinical manifestations of 1749 HBsAg‐positive patients were analyzed including 412 patients aged ≥ 60 years (mean age at enrollment, 68.6 ± 6.9 years; range, 60–90 years; 262 males and 150 females). We investigated the possibility of using a single serum HBsAg level to predict cirrhosis and hepatocellular carcinoma (HCC) in older patients with CHB.ResultsOf the 1749 HBsAg‐positive patients, those aged ≥ 60 years tended to have lower serum HBsAg levels than the younger patients. In fact, all patients aged ≥ 60 years had a serum HBsAg level ≤ 10,000 IU/mL. Of the 412 patients aged ≥ 60 years, 122 (29.6%) had cirrhosis and 59 (14.3%) developed HCC. When an HBsAg‐titer &lt; 100 IU/mL was used to examine severe clinical outcomes (cirrhosis or HCC), the sensitivity, specificity, positive predictive value, and negative predictive value for being free of liver cirrhosis and HCC were 49.3% and 95.2%, 19.7% and 28.8%, 85.6% and 95.2%, and 40.0% and 71.2%, respectively.ConclusionA single serum HBsAg level &lt; 100 IU/mL might predict favorable clinical results in older patients with late‐stage CHB virus infection.

Prevalence and severity of depression in chronic viral hepatitis in Iran.

Aim: The aim of this study was to compare the prevalence and severity of depression in chronic hepatitis B (CHB) patients, chronic hepatitis C (CHC) patients, and healthy participants.Methods: Two hundred and fifty-three persons participated in this cross-sectional study between 2011 and 2012 in Imam Khomeini Hospital. The prevalence and severity of depression were assessed using the Hamilton Scale.Results: There was significantly higher prevalence of depression in CHC patients (35.9%) than in healthy participants (11.3%) and CHB patients (19.8%) (both P < 0.01). However, CHB and CHC patients did not differ significantly in their depression prevalence after excluding inactive hepatitis B surface antigen (HBsAg) carriers (29.3% vs. 35.9%; P > 0.05). Inactive HBsAg carriers differed significantly from CHB patients—excluding inactive HBsAg carriers—in depression prevalence (10.0% vs. 29.3%; P < 0.05). No statistically significant difference was found in depression severity between all groups (P > 0.05).Conclusion: Depression screening in chronic hepatitis B and chronic hepatitis C patients may be beneficial in disease management.

Changes in lymphocyte surface expression of CD8 and CD38 molecules in peripheral blood of inactive HBsAg carriers following pegylated interferon a-2a therapy

To investigate the effects of pegylated interferon a-2a (Peg-INFa-2a) treatment on expression of CD8 and CD38 surface molecules on lymphocytes from peripheral blood of inactive hepatitis B surface antigen (HBsAg) carriers. Forty-four patients with hepatitis B virus (HBV) chronic infection (CHB) received a 48-week course of Peg-INFa-2a treatment, with 30 administered 135 mug/week and 14 administered 180 mug/week. Every 12 weeks of treatment, the subjects were assessed for HBsAg titer, presence of anti-hepatitis B e (HBe) antibody, serum alanine amino transaminase (ALT) levels, and lymphocyte surface expression of CD8 and CD38 molecules. Patients were classified as responders and non-responders according to standard parameters. Dynamic differences between the two groups over time were assessed by multivariate repeated measures ANOVA with Greenhouse-Geisser correction and differences at single time points were assessed by univariate ANOVA. Linear regression analysis was performed to evaluate the relationship of two variables. The responders showed a significantly higher increase in ALT at week 12 (60.75+/-24.95 U/L vs. non-responders: 37.03+/-18.45 U/L; t = 2.905, P less than 0.01) and significantly higher proportion of CD8+CD38+ cells at week 24 (71.20+/-11.70% vs. non-responders: 56.79+/-7.72%; F = 23.941, P less than 0.01). The decline in level of HBsAg at week 24 was positively correlated with the increase in ALT level at week 12 (r = 0.386, P less than 0.01) and with expression levels of CD8 and CD38 molecules on lymphocytes at week 24 (r = 0.397, P less than 0.01). Lower baseline levels of HBsAg correlated to better Peg-INFa-2a-related HBsAg clearance. Increased expression of CD8 and CD38 on lymphocytes is suggestive of intensive cellular immunity in CHB patients and may be related to HBV-induced hepatocyte damage and may promote the HBsAg clearance.

Performance of rapid tests for detection of HBsAg and anti-HBsAb in a large cohort, France

The systematic use of rapid tests performed at points-of-care may facilitate hepatitis B virus (HBV) screening and substantially increase HBV infection awareness. The aim of this study was to evaluate the effectiveness of such tests for HBsAg and anti-HBsAb detection among individuals visiting a variety of healthcare centers located in a low HBV-prevalent area. Three rapid tests for hepatitis B surface antigen (HBsAg) detection (VIKIA, Determine and Quick Profile) and one test for anti-hepatitis B surface antibody (anti-HBsAb) detection (Quick Profile) were evaluated in comparison to ELISA serology. Sensitivity (Se), specificity (Sp), positive and negative predictive values (PPV and NPV, respectively) and area under the ROC curve were used to estimate test performance. Non-inferiority criteria of the joint Se, Sp were set at 0.80, 0.95. Among the 3956 subjects screened, 85 (2.1%) were HBsAg-positive and 2225 (56.5%) had a protective anti-HBsAb titer. Test Se and Sp (lower bound of 97.5% CI) were as follows: 96.5% (89.0%), 99.9% (99.8%) for Vikia; 93.6% (80.7%), 100.0% (99.8%) for Determine; and 90.5% (80.8%), 99.7% (99.5%) for Quick Profile; with all three tests achieving minimal non-inferiority criteria. False negatives were typically observed in inactive HBsAg carriers. The anti-HBsAb Quick Profile test had excellent specificity (97.8%) and PPV (97.8%) albeit low sensitivity (58.3%), thus failing to establish non-inferiority. All three HBsAg rapid tests could be considered ideal for HBV screening in low HBV-prevalent countries, given the ease of use, rapidity, and high classification probabilities. The anti-HBsAb Quick Profile could be considered reliable only for positive tests.

Evaluation of Hepatitis B Viraemia Levels in Patients with HBeAg-negative Chronic Hepatitis B Virus Infection

To evaluate patients with chronic hepatitis B virus (HBV) infection and low-level viraemia in terms of determining HBV DNA cut-off values and levels of alanine aminotransferase (ALT) and other possible markers for discriminating between chronic hepatitis B e-antigen (HBeAg)-negative patients and hepatitis B surface antigen (HBsAg) inactive carriers. HBV-infected patients who were HBeAg-negative with undetectable HBV DNA by standard hybridization assay and high (HBeAg-negative group, n = 81) or normal (HBsAg inactive carrier group, n = 77) ALT levels were enrolled. Quantitative polymerase chain reaction assay using a COBAS Amplicor HBV monitor test was performed to detect low HBV DNA levels. The HBV DNA level was found to be significantly higher in the HBeAg-negative chronic HBV group (mean ± SD 94,477 ± 167,528 copies/ml) compared with the HBsAg inactive carrier group (mean ± SD 19,215 ± 57,970 copies/ml). A low level of viral replication may persist in chronic HBV-infected patients who are HBeAg-negative, and the level of HBV DNA was higher in the HBeAg-negative group than in the inactive HBsAg carrier group. Necroinflammation also persisted in the HBeAg-negative group and these patients had a higher level of ALT than the inactive HBsAg carriers.

Assessment of hepatic fibrosis and necroinflammation among inactive HBsAg carriers in Egypt

Introduction. The inactive hepatitis B surface antigen (HBsAg) carrier state is usually characterized by minimal or absent liver pathology. However, in developing countries, owing to the very early age of infection with hepatitis B virus (HBV), this state is reached after a very prolonged immune tolerant and immune reactive phase, during which considerable liver damage may have occurred. The extent of liver damage in inactive HBsAg carriers has not been thoroughly assessed in developing countries. We thus sought to characterize liver pathology among Egyptian inactive HBsAg carriers.Material and methods. Liver biopsy was conducted on 30 inactive HBsAg carriers [positive for HBsAg; negative for HBeAg; positive for antibody to HBeAg (anti-HBe); HBV-DNA levels < 2,000 IU/mL; persistently normal serum alanine aminotransferase (ALT)]. Liver histopathology was assessed according to the Ishak scoring system.Results. Among the studied carriers, 6.7% had no hepatic fibrosis, 73.3% had stage 1 fibrosis, and 20% had stage 2 fibrosis. The majority (80%) of carriers had minimal hepatic necroinflammation (grades 2-4), while 20% had mild hepatic necroinflammation (grade 5). All patients with stage 2 fibrosis were males, while no gender predilection was observed for necroinflammation. Age, ALT and HBV-DNA levels did not differ significantly according to fibrosis or ne-croinflammatory scores. Conclusion. Our study findings do not support the presence of significant hepatic fibrosis or necroinflammation among Egyptian inactive HBsAg carriers. However, follow-up studies on these carriers may be required to monitor any further pathological progress of the disease.

Identifying Hepatitis B Carriers at Low Risk for Hepatocellular Carcinoma

Identifying Hepatitis B Carriers at Low Risk for Hepatocellular Carcinoma

Prevalence and clinical significance of hepatitis D virus co‐infection in patients with chronic hepatitis B in Korea

Hepatitis D virus (HDV) infection can cause severe acute and chronic liver disease in patients infected with hepatitis B virus (HBV). Despite the significant decline in the global HDV infection, it remains a major health concern in some countries. This study aimed to investigate the prevalence and clinical features of HDV co-infection in patients with chronic HBV infection in Korea, where HBV infection is endemic. Nine hundred forty patients [median age, 48 (18-94) years; men, 64.5%] infected chronically with HBV were enrolled consecutively. All patients who were positive for hepatitis B surface antigen (HBsAg) for at least 6 months and were tested for anti-HDV. A portion of the HDV delta antigen was amplified, sequenced, and subjected to molecular and phylogenetic analysis using sera from the patients who were anti-HDV positive. Clinical features and virologic markers were evaluated. Inactive HBsAg carriers, chronic hepatitis B, cirrhosis and hepatocellular carcinoma accounted for 29.5%, 44.7%, 17.9%, and 8.0%, respectively. Only three patients were positive for anti-HDV, corresponding to a 0.32% positive rate. All patients who were positive for anti-HDV were inactive HBsAg carriers. HDV RNA could be amplified by PCR from the sera of two patients. Phylogenetic analysis showed that both carried HDV genotype 1. In conclusion, the prevalence of HDV infection is very low (0.32%) in Korea. All HDVs were genotype 1 and detected in inactive HBsAg carriers. Therefore, HDV co-infection may not have a significant clinical impact in Korean patients with chronic HBV infection.

Cellular immune responses in patients with hepatitis B surface antigen seroclearance induced by antiviral therapy

BackgroundThe mechanisms by which chronic hepatitis B is completely resolved through antiviral therapy are unknown, and the contribution of acquired T cell immunity to hepatitis B surface antigen (HBsAg) seroclearance has not been investigated. Therefore, we measured the T-cell responses to core and envelope antigens in patients with HBsAg seroclearance.MethodsFourteen subjects with HBsAg seroclearance following antiviral treatment for chronic hepatitis B, 7 HBeAg-positive immunotolerant HBV carriers and 9 HBeAg-negative inactive HBsAg carriers were recruited. HBV-specific T-cell responses to recombinant HBV core (rHBcAg) and envelope (rHBsAg) proteins and pools of core and envelope peptides were measured using an ELISPOT assay detecting interferon-gamma and intracellular cytokine staining (ICS) assays detecting interferon-gamma or interleukin 2.ResultsInterferon-gamma ELISPOT assays showed a low frequency of weak responses to the rHBsAg and S peptide pool in the HBsAg seroclearance group, and the response frequency to the rHBcAg and the C peptide pool was higher than to the rHBsAg (P < 0.001) and S peptide pool (P = 0.001) respectively. A higher response frequency to C than S peptide pools was confirmed in the interferon-gamma ICS assays for both CD4+ (P = 0.033) and CD8+ (P = 0.040) T cells in the HBsAg seroclearance group. The responses to C and S antigens in the inactive carriers were similar.ConclusionsThere was a low frequency of CD4+ and CD8+ T cell immune responses to envelope antigens in Chinese subjects with HBsAg seroclearance following antiviral therapy. It is unlikely that these immune responses are responsible for HBsAg seroclearance in these subjects.

Diagnostic Markers of Chronic Hepatitis B Infection and Disease

Recent advances in therapy for patients with chronic hepatitis B (CHB) infection offer the potential for a more successful treatment outcome, but also raise a number of questions in clinical practice regarding diagnosis and staging of CHB to ensure such potential is realized. In patients without cirrhosis, some forms of antiviral therapy can switch patients from an active disease phase into an inactive hepatitis B surface antigen (HBsAg) carrier state, and eventually lead to HBsAg clearance and HBsAg antibody seroconversion, the closest to a cure in CHB; thus, one of the most important diagnostic questions that clinicians face is the identification of patients with early forms of CHB within a large cohort of asymptomatic HBsAg-positive individuals, most of whom are inactive HBsAg carriers. Two major categories of diagnostic markers are currently available: virus-specific markers and liver disease markers. Most markers involve the use of non-invasive serological testing, but invasive diagnostic procedures, such as liver biopsy, are also an option. In this article, we review current opinions on the appropriate use of diagnostic procedures, answering some important questions for the clinician, such as why, how, when and in whom they might best be used.