Serum HBsAg Levels Research Articles

Do the circulating Pre-S/S quasispecies influence hepatitis B virus surface antigen levels in the HBeAg negative phase of HBV infection?

Virus, host factors and their interplay influence Hepatitis B surface Antigen serum levels during Hepatitis B Virus (HBV) infection course and treatment. To study the Pre-S/S circulating quasispecies in a cohort of untreated, HBeAg negative, genotype-D, HBsAg carriers. We studied 260 carriers: 71 with HBeAg negative infection (ENI; HBV-DNA ≤2000IU/mL); 42 Grey Zone (GZ; HBV-DNA ≤20000IU/mL); 82 chronic hepatitis (CH) and 65 cirrhosis (CI) (HBV-DNA>20000IU/mL). Population sequencing was applied to identify Pre-S/S gene mutations responsible for any amino acid substitution or potential biological/antigenic implications (M-muts) on HBsAg. HBsAg serum levels were lower in ENI+GZ than in CH+CI (2.61 [-1.10/4.06] vs 3.62 [2.41/4.92] log10 IU/mL, P<0.001) and in CI than CH (3.48 [2.41/4.38] vs 3.66 [2.57/4.92] log10 IU/mL, P<0.001). M-muts were found in 73 (28.1%) cases: 5 (7.0%) ENI, 3 (7.1%) GZ, 26 (31.7%) CH, 39 (60.0%) CI (P<0.001) and mostly in Pre-S2 (17.6%) than Pre-S1 (5.8%) and Small-S (10.8%; P<0.001). Overall HBsAg serum levels were higher in carriers with M-muts (3.56 [0.95/4.38] vs 3.17 [-1.10/4.92] log10 IU/mL, P<0.001), but comparable in carriers with or without M-mut when considering separately ENI+GZ (2.84 [0.95/3.89] vs 2.61 [-1.10/4.06] log10 IU/mL, P=0.330] and CH+CI (3.57 [2.67/4.38] vs 3.63 [2.41/4.92] log10 IU/mL, P=0.37). Infection phase (β: 0.422, P<0.001), age (β: -0.260, P<0.001), ALT (β: -0.103, P=0.045), liver stiffness (β: -0.118, P=0.039) and HBV-DNA (β: 0.384, P<0.001), but not M-mut were independently associated with HBsAg serum levels. In HBeAg negative, genotype-D, carriers Pre-S/S heterogeneity increases with severity of liver disease, but does not influence HBsAg serum levels, that in low viraemic carriers are associated with an effective control of HBV.

Significance of switching of the nucleos(t)ide analog used to treat Japanese patients with chronic hepatitis B virus infection from entecavir to tenofovir alafenamide fumarate.

The significance of switching of the nucleos(t)ide analog used to treat patients with hepatitis B virus (HBV) from entecavir (ETV) to tenofovir alafenamide fumarate (TAF) is uncertain. The subjects of this study were 159 patients with HBV who received treatment with ETV followed by TAF. Among these patients, serial changes in the HBV marker levels were monitored in 92 patients in whom the serum HBsAg levels were ≥100 IU/mL during the 48-week period immediately before and after the switching. A questionnaire survey for medication compliance was performed in 127 patients. The serum HBsAg levels (log IU/mL) decreased by 0.041 during the ETV treatment period and by 0.068 during the TAF administration period. The degree of reduction was higher during the TAF administration period than during the ETV administration period in patients without cirrhosis (P = .030), patients with genotype B HBV (P = .014), and patients with undetectable serum HBcrAg (P = .038). Multivariate analysis revealed the HBV genotype (B vs C; odds ratio, 3.400; P = .025) and serum aspartate aminotransferase level (every 1+; 1.111; P = .015) at the time of switching as factors influencing the treatment efficacy. Thirty-six patients (28%) responded that the number of days that they forgot to take the drug decreased after the drug switching, and 77 patients (61%) reported feeling satisfied with the drug switching. Switching of the nucleos(t)ide analog used from ETV to TAF may be useful in the treatment of patients with HBV infection, as it is associated with both a decrease in the serum HBsAg level and improvement of the medication compliance.

Effects of Hepatitis B Surface Antigen on Virus-Specific and Global T Cells in Patients With Chronic Hepatitis B Virus infection

Chronic hepatitis B virus (HBV) infection is characterized by the presence of defective viral envelope proteins (hepatitis B surface antigen [HBsAg]) and the duration of infection-most patients acquire the infection at birth or during the first years of life. We investigated the effects of these factors on patients' lymphocyte and HBV-specific T-cell populations. We collected blood samples and clinical data from 243 patients with HBV infection (3-75 years old) in the United Kingdom and China. We measured levels of HBV DNA, HBsAg, hepatitis B e antigen, and alanine aminotransferase; analyzed HBV genotypes; and isolated peripheral blood mononuclear cells (PBMCs). In PBMCs from 48 patients with varying levels of serum HBsAg, we measured 40 markers on nature killer and T cells by mass cytometry. PBMCs from 189 patients with chronic infection and 38 patients with resolved infections were incubated with HBV peptide libraries, and HBV-specific T cells were identified by interferon gamma enzyme-linked immune absorbent spot (ELISpot) assays or flow cytometry. We used multivariate linear regression and performed variable selection using the Akaike information criterion to identify covariates associated with HBV-specific responses of T cells. Although T- and natural killer cell phenotypes and functions did not change with level of serum HBsAg, numbers of HBs-specific T cells correlated with serum levels of HBsAg (r= 0.3367; P < .00001). After we performed the variable selection, the multivariate linear regression model identified patient age as the only factor significantly associated with numbers of HBs-specific T cells (P= .000115). In patients younger than 30 years, HBs-specific T cells constituted 28.26% of the total HBV-specific T cells; this value decreased to 7.14% in patients older than 30 years. In an analysis of immune cells from patients with chronic HBV infection, we found that the duration of HBsAg exposure, rather than the quantity of HBsAg, was associated with the level of anti-HBV immune response. Although the presence of HBs-specific T cells might not be required for the clearance of HBV infection in all patients, strategies to restore anti-HBV immune responses should be considered in patients younger than 30 years.

The Factors Affecting the Efficacy of ?-interferon in the Treatment of (CHB)

Objective: To analyze the factors affecting the efficacy of ?-interferon in the treatment of chronic hepatitis B (CHB). Methods: A total of 100 patients with CHB treated in our hospital from June 2018 to June 2019 were selected. All patients were treated with ?-interferon to evaluate the efficacy, and the factors affecting the effect of ?-interferon on CHB were analyzed. Results: After treatment, 54 patients fully responded and 46 patients did not; the levels of white blood cells, HBV DNA, and HBsAg in the complete response group were lower than those in the incompletely response group, and the differences were statistically significant (P &lt;0.05); Multivariate logistic regression analysis found that serum HBV DNA and HBsAg were independent factors affecting the efficacy of ?-interferon in the treatment of CHB (OR&gt; 1, P&lt;0.05). Conclusion: Serum HBV DNA and HBsAg are risk factors that affect the efficacy of ?-interferon in the treatment of CHB. Monitoring the changes of serum HBV DNA and HBsAg levels has important clinical significance for predicting the efficacy.

Rapidly decreased HBV RNA predicts responses of pegylated interferons in HBeAg-positive patients: a longitudinal cohort study

BackgroundAs an important anti-HBV drug, pegylated interferon α (PegIFNα) offers promising clinical efficacy, but biomarkers that accurately forecast treatment responses are yet to be elucidated. Here, we evaluated whether HBV RNA could act as an early monitor of pegylated interferon responses.MethodsWe analyzed a phase 3, multicenter, randomized cohort of 727 HBeAg-positive non-cirrhotic patients receiving a 48-week treatment of PegIFNα-2a or PegIFNα-2b and a 24-week treatment-free follow-up. Serum levels of HBV RNA, HBV DNA, HBeAg, and HBsAg were measured at weeks 0, 12, 24, 48, and 72.ResultsHBeAg seroconversion and HBsAg loss at week 72 were observed in 217 (29.8%) and 21 (2.9%) patients, respectively. During the 48-week treatment, HBV RNA decreased more rapidly than HBV DNA and HBsAg, but HBV RNA and HBeAg shared similar dynamics with positive correlations. Multivariate regression analyses consistently revealed the significance of HBV RNA at weeks 0, 12, 24, and 48 to monitor HBeAg seroconversion but not HBsAg loss. Although baseline HBV RNA only showed a modest AUC performance, HBV RNA with a significant increase of AUC at week 12 outperformed other HBV biomarkers to forecast HBeAg seroconversion (p value < 0.05). HBV RNA ≤ 1000 copies/mL was an optimized cutoff at week 12 that offered better prediction than other HBV biomarkers. This optimized cutoff plus patient age, HBV genotype B, and HBeAg offered a strong estimation of HBeAg seroconversion (accuracy 95.2%, true negative rate 99.8%).ConclusionHBV RNA at week 12 is an effective monitor of HBeAg seroconversion in HBeAg-positive patients treated with pegylated interferons.

Emerging Diagnostic Tools to Decide When to Discontinue Nucleos(t)ide Analogues in Chronic Hepatitis B.

The aim of this review is to outline emerging biomarkers that can serve as diagnostic tools to identify non-cirrhotic chronic hepatitis B (CHB) patients who could safely discontinue nucleos(t)ide analogues (NAs) before HBsAg loss. Regarding possible predictors of post-NAs outcomes, a number of studies have evaluated numerous factors, which can be categorised in markers of hepatitis B virus (HBV) activity, markers of host immune response and markers of other patient characteristics. In clinical practice, the most important question for patients who discontinue NAs is to differentiate those who will benefit by achieving HBsAg loss or at least by remaining in remission and those who will relapse requiring retreatment. Most of the discontinuation studies so far came from Asian and only few from European populations and examined the rates and predictors of post-NA virological and/or combined relapses or HBsAg loss. To date, there is still controversy about predictors of post-NA relapses, while only HBsAg serum levels at NA discontinuation seem to be the most robust predictive marker of the probability of subsequent off-treatment HBsAg seroclearance. Newer viral markers such as HBV RNA and hepatitis B core-related antigen seem promising, but further research is required.

Research progress of siRNA in reducing serum HBsAg levels in patients with chronic hepatitis B

Small interfering RNA (siRNA) is mainly involved in RNA interference for stopping gene translation by targeting and degrading HBV-transcribed mRNA. Targeting and stability in siRNA can be enhanced via chemical modification, combination use and improved delivery system. Clinical studies have identified JNJ-3989 (ARO-HBV) and ARB-1740 as well-tolerated siRNA drugs, which significantly reduce HBsAg levels. This article expounds the main mechanisms of siRNA in inhibiting HBsAg expression, improving target and stability as well as relevant preclinical and clinical studies.

Circulating serum HBsAg level is a biomarker for HBV-specific T and B cell responses in chronic hepatitis B patients

Chronic hepatitis B (CHB) infection functional cure is defined as sustained loss of HBsAg and several therapeutic strategies are in clinical development designed to pharmacologically reduce serum HBsAg, break immune tolerance, and increase functional cure rates. However, little is known about pre-treatment HBsAg levels as an indicator of HBV immune potential. Here, we compared the phenotypes and HBV-specific response of lymphocytes in CHB patients stratified by serum HBsAg levels <500 (HBslo) or >50,000 IU/ml (HBshi) using immunological assays (flow cytometry, ICS, ELISPOT). HBshi patients had significantly higher expression of inhibitory PD-1 on CD4+ T cells, particularly among TEMRA subset, and higher FcRL5 expression on B cells. Upon HBcAg(core) or HBsAg(env)-stimulation, 85% and 60% of HBslo patients had IFNγ+TNFα+ and IFNγ+ IL2+ CD4+ T cell responses respectively, in comparison to 33% and 13% of HBshi patients. Checkpoint blockade with αPD-1 improved HBV-specific CD4+ T cell function only in HBslo patients. HBsAg-specific antibody-secreting cells (ASCs) response was not different between these groups, yet αPD-1 treatment resulted in significantly higher fold change in ASCs among patients with HBsAg <100 IU/ml compared to patients with HBsAg >5,000 IU/ml. Thus, serum HBsAg correlates with inhibitory receptor expression, HBV-specific CD4+ T cell responses, and augmentation by checkpoint blockade.

Effect of nucleos(t)ide analogue on serum HBsAg level in chronic hepatitis B patients: A 3-years study

AimWe aim to explore the effects of nucleos(t)ide analogues (NUCs) on the changes of HBsAg in chronic hepatitis B (CHB) patients. MethodsA total of 264 CHB patients were enrolled in our study. All of them were treated with NUCs for at least three years. Quantification of HBsAg levels were measured by Elecsys HBsAg II. ResultsAlthough HBsAg levels were significantly higher in HBeAg seropositive CHB patients at baseline than in HBeAg seronegative CHB patients (3.84 ± 0.82 vs 3.21 ± 0.59 IU/mL), HBsAg levels declined more rapidly in the HBeAg seropositive group (P < 0.001). In HBeAg-positive CHB patients, HBsAg level in the telbivudine (LDT)-treated group was 3.68 ± 0.56 IU/mL after 52-week of treatment, which was significantly higher than that in lamivudine (LAM)-treated group (P = 0.009). Multivariable analyses showed that baseline HBV DNA viral load (OR = 0.75, P = 0.018), baseline ALT level (OR = 0.99, P = 0.015), and baseline HBsAg level (OR = 0.188, P < 0.001) were independent factors that affected HBsAg decline in HBeAg seropositive CHB patients. For HBeAg seronegative CHB patients, the average of serum HBsAg levels in LAM-, LdT-, adefovir (ADV)-, and entecavir (ETV)-treated groups at baseline, 52 weeks, 104 weeks, and 156 weeks were similar. Multivariable analyses showed that only baseline HBV DNA level (OR = 0.56, P = 0.020) and baseline HBsAg level (OR = 0.57, P = 0.012) were independent factors that affected HBsAg decline in HBeAg seronegative patients with CHB. Baseline HBV DNA level (OR = 0.72, P = 0.010) and baseline HBsAg level (OR = 0.19, P < 0.001) were independent factors that affected all CHB patients. ConclusionsCHB Patients who had received NUCs antiviral treatment showed a slow but significant decrease in serum HBsAg level. Long-term monitoring and continuous antiviral treatment are necessary, especially for those patients with risk factors associated with HBsAg decline.

48 weeks outcome after cessation of nucleos(t)ide analogue therapy in chronic hepatitis B patients

Introduction and objectiveThe aim of the present study was to investigate the significance of serum HBsAg levels in treatment cessation of nucleoside analogues (NAs) in patients with chronic hepatitis B (CHB) infection. MethodsIn 158 CHB patients with long-term NAs treatment, 74 patients were in HBeAg negative and had a HBsAg level <1500IU/mL, 36 of whom were informed and consented to cease NAs. HBsAg, HBV DNA and liver function were examined in the 1st, 3rd, 6th, 9th and 12th month after treatment cessation. ResultsThe sustained response rate was 88.89% (32/36) within one year after NAs cessation. Sub-group analysis was based on HBsAg levels of patients with NAs cessation, there was no relapse case in 11 patients whose HBsAg <50IU/mL, and the negative predictive value (NPV) was 100%. Seroconversion of HBsAg occurred in 3 patients. 2 patients from 21 cases whose HBsAg was between 50IU/mL and 1000IU/mL relapsed. 2 of 4 patients whose in HBsAg >1000IU/mL relapsed. HBsAg of patients with a sustained response decreased slowly. In contrast, HBsAg levels increased gradually in relapsed patients, and the increase of HBsAg was precedent to relapses of HBV DNA and ALT. Multivariate analysis suggested that only HBsAg level showed a close correlation with HBV DNA relapses. ROC curve analysis suggested that the increase of HBsAg level in the 3rd and 6th month after NAs cessation had a great predictive value for relapses. ConclusionMonitoring of base line HBsAg level can predict outcomes of NAs cessation in HBeAg-negative chronic hepatitis B. HBsAg <50IU/mL has higher predictive values of better sustained responses in HBeAg-negative CHB patients.

The Prevalence of HBV Infection: A Retrospective Study of 13 Years in a Public Hospital of Northeast China.

The prevalence of hepatitis B virus (HBV) infection was an imbalance in different provinces of China. This study aimed to investigate the prevalence of HBV infection and evaluate the prophylactic measures in a public hospital of northeast China over the preceding 13 years. A total of 13,948 patients in 2004 and 15,256 patients in 2017 of Shengjing Hospital of China Medical University were tested of serum HBsAg, HBeAg, HBsAb, HBeAb, and HBcAb levels with Abbott MEIA Kits. In people born before 1992, HBsAg-positive rate was 5.45% and 6.47%; isolated HBsAb positive rate was 14.62% and 21.24%; HBV marker negative rate was 54.27% and 42.77% in 2004 and 2017 survey, respectively. The males had a significant higher HBsAg-positive rate than the females. In people born during 1992-2004, HBsAg positive rate was 0.58% and 0.57%, isolated HBsAb positive rate was 41.47% and 46.57%; and HBV marker negative rate was 51.97% and 46.86% in 2004 and 2017 survey, respectively. Males and females had no difference of HBsAg-positive rate. In children born after 2005, HBsAg positive rate was 0.11%, isolated HBsAb positive rate was 76.68%, and HBV marker negative rate was 18.51% in 2017 survey. No difference of HBsAg-positive rate was found between the genders. A dramatic decrease of HBsAg positive rate and a progressive increase of HBsAb-positive rate were found among people born after 1992 and progressed further in those born after 2005. Immunization of infants and timely birth dose was the key method for prevention of HBV infection. Expanded HB vaccination would be needed for people born before 2005, especially those born between 1992 and 2004.

Significance of switching of the nucleos(t)ide analog used to treat Japanese patients with chronic hepatitis B virus infection from entecavir to tenofovir alafenamide fumarate.

The significance of switching of the nucleos(t)ide analog used to treat patients with hepatitis B virus (HBV) from entecavir (ETV) to tenofovir alafenamide fumarate (TAF) is uncertain. The subjects of this study were 159 patients with HBV who received treatment with ETV followed by TAF. Among these patients, serial changes in the HBV marker levels were monitored in 92 patients in whom the serum HBsAg levels were ≥100 IU/mL during the 48-week period immediately before and after the switching. A questionnaire survey for medication compliance was performed in 127 patients. The serum HBsAg levels (log IU/mL) decreased by 0.041 during the ETV treatment period and by 0.068 during the TAF administration period. The degree of reduction was higher during the TAF administration period than during the ETV administration period in patients without cirrhosis (P = .030), patients with genotype B HBV (P = .014), and patients with undetectable serum HBcrAg (P = .038). Multivariate analysis revealed the HBV genotype (B vs C; odds ratio, 3.400; P = .025) and serum aspartate aminotransferase level (every 1+; 1.111; P = .015) at the time of switching as factors influencing the treatment efficacy. Thirty-six patients (28%) responded that the number of days that they forgot to take the drug decreased after the drug switching, and 77 patients (61%) reported feeling satisfied with the drug switching. Switching of the nucleos(t)ide analog used from ETV to TAF may be useful in the treatment of patients with HBV infection, as it is associated with both a decrease in the serum HBsAg level and improvement of the medication compliance.

The clinical significance of quantitative HBSAG in patients with HBEAG negative chronic hepatitis B

Background: The quantification of HBsAg provides different and complementary information that helps in determination of the different phases of chronic hepatitis B viral infection, evaluation and follow-up of liver disease progression as well as in treatment individualization.Aim: To evaluate the clinical significance of quantitative HBsAg (qHBsAg) in patients with HBeAg negative chronic hepatitis (CHB) and its correlation with the serum levels of alanine aminotransferase (ALT), quantitative HBV DNA and liver fibrosis.Subjects and Methods: The study included 53 treatment naïve patients with HBeAg negative chronic hepatitis B. All patients underwent complete laboratory and serology testing, quantification of HBV DNA and HBs antigen. The liver stiffness was measured with elastography. Patients’ demographic characteristics, viral and biochemical markers were recorded at one point of time.Results: Correlation analysis between the qHBsAg and ALT showed an significant, positive correlation between the parameters for R=0.42 and p&lt;0.05; there was statistically non-significant positive correlation for R=0.25 and p&gt;0.05 between qHBsAg and HBV DNA. There was a positive correlation between qHBsAg and liver fibrosis for R=0.08 and p&gt;0.05. The serum levels of HBsAg had greater impact on the serum levels of ALT compared to that of HBV DNA for R=0.15 and p&gt;0.05.Conclusion: Patients with higher ALT values and higher liver fibrosis score have higher qHBsAg; qHBsAg can reflect the serum HBV DNA levels.

Detection of cytokines (IL-1α and IL-2) and oxidative stress markers in hepatitis B envelope antigen-positive and -negative chronic hepatitis B patients: Molecular and biochemical study

This study aimed to detect hepatitis B virus (HBV)-DNA in patients using quantitative real-time polymerase chain reaction (qRT-PCR). Cytokines (interleukins 1-α [IL-1α] and 2 [IL-2]), enzymatic and non-enzymatic antioxidants, and lipid peroxidation markers were also measured. Patients infected with HBV were assessed using serological markers (rapid immunochromatographic assays) and HBV-DNA levels (qRT-PCR). Cytokines, lipid peroxidation markers, and antioxidants were detected using enzyme-linked immunosorbent assays (ELISAs). Preliminary screening identified 80 patients who were HBsAg-positive. Serum levels of HBsAg were significantly higher in hepatitis B envelope antigen (HBeAg)-positive patients (7779.9 ± 3898 IU/mL) than in HBeAg-negative individuals (3233.8 ± 2474 IU/mL), as was the HBV-DNA load (P < .001). IL-2 levels were significantly higher in HBeAg-negative patients (P = .001) than in HBeAg-positive patients or healthy individuals. Vitamin C levels in HBeAg-positive patients were significantly lower (P = .001) than those in HBeAg-negative patients and healthy individuals. The levels of superoxide dismutase in both HBeAg-positive and -negative patients were less than in healthy subjects (both, P < .001) as were the mean malondialdehyde levels. The qRT-PCR test provides a clinical advantage for the diagnosis and follow-up treatment of HBV infections. Further, vitamin C and superoxide dismutase levels are useful for monitoring hepatocellular damage in patients infected with HPB; both parameters are significantly reduced in HBeAg-positive patients. Analysing levels of IL-1α and IL-2 revealed information about the HBV infection status and are essential parameters of hepatic inflammatory activity.

The cyclophilin inhibitor CRV431 inhibits liver HBV DNA and HBsAg in transgenic mice.

Hepatitis B virus (HBV) infection is a major health burden worldwide with 240 million chronically infected individuals. Nucleos(t)ide analogs and interferons are the current standards of care due to their suppression of HBV replication, but the treatments rarely eradicate HBV from individuals. Similar to current treatments for human immunodeficiency virus type-1 (HIV-1) and hepatitis C virus (HCV) patients, improved HBV therapies will require the combination of multiple drugs which target distinct steps of the HBV life cycle. In this study, we tested the potential of a cyclophilin inhibitor, CRV431, to affect HBV replication in transgenic mice. We found that oral treatment with CRV431 (50 mg/kg/day) for a period of 16 days significantly reduced liver HBV DNA levels and moderately decreased serum HBsAg levels. We observed an additive inhibitory effect on liver HBV DNA levels in mice treated with a combination of low doses of CRV431 (10 mg/kg/day) and the nucleotide prodrug, tenofovir exalidex (TXL), (5 mg/kg/day). No toxicity was observed in CRV431-treated mice. Although it is well known that CRV431 neutralizes the peptidyl-prolyl isomerase activity of cyclophilins, its anti-HBV mechanism(s) of action remains unknown. Nevertheless, this study provides the first demonstration of a beneficial effect of a cyclophilin inhibitor in vivo in an HBV transgenic mouse model. Altogether our data reveal the potential of CRV431 to be part of improved new therapies for HBV patients.

Serum HBV RNA quantification: useful for monitoring natural history of chronic hepatitis B infection

BackgroundAs an alternative biomarker of intrahepatic covalently closed circular DNA (cccDNA) transcriptional activity, hepatitis B virus (HBV) RNA may evolve during long-lasting virus-host interactions during chronic hepatitis B viral infection. The distribution pattern of serum HBV RNA levels in the natural course of chronic HBV infection remains unclear. The aim of this study was to evaluate the levels of HBV RNA during the natural course of CHB and the role in distinguishing the natural history of HBV infection.MethodsA total of 291 treatment-naïve chronic HBV carriers were enrolled. Based on the clinical, biochemical, serological, and histological data as well as HBV DNA levels, patients were classified into the following four categories: the immune-tolerant phase (IT,n = 35), HBeAg-positive immune-active phase (EPIA,n = 121), inactive chronic hepatitis B(ICH,n = 77) and HBeAg-negative immune reactive hepatitis (ENH,n = 58). The parameters and distribution patterns of serum HBV RNA were evaluated in relation to viral replication status, immune phase, disease category and Child-Pugh class. The relationships between serum HBV RNA and other serum hepatitis B viral markers were also analyzed.ResultsSerum HBV RNA levels were significantly lower in the HBeAg-negative patients compared to those in the HBeAg-positive patients, with the lowest levels seen in inactive carriers. In HBeAg-negative patients, serum HBV RNA levels increased if there is reactivation to active hepatitis and showed obvious superiority for the combination of serum HBV DNA (cutoff>3.39 Log copies/mL) and HBsAg (cutoff>2.74 Log IU/mL) in discriminating between ‘HBeAg-negative immune reactive’ phase and inactive chronic hepatitis B phases of HBeAg-negative chronic HBV infection. Serum HBV RNA levels were positively correlated with serum HBV DNA and HBsAg levels in all chronic HBV-infected patients. A stratified analysis revealed that a correlation between serum HBV RNA and HBV DNA or HBsAg was present in HBeAg-positive patients; however, in HBeAg-negative patients, serum HBV RNA was positively correlated with HBV DNA only.ConclusionDuring the natural course of chronic HBV infection, serum HBV RNA levels vary. Serum HBV RNA can act as a biomarker to predict the natural history of disease in chronic hepatitis B patients. In treatment-naïve HBeAg-negative chronic HBV-infected individuals, serum HBV RNA shows superiority in differentiating the ‘HBeAg-negative reactive’ phase.

Hepatitis B and Hepatitis C in prisons: a prevalence study.

Prisons, which are hazardous places for various contagious diseases, carry additional risks for HBV and HCV because of the communal lifestyle (common use of tools like razor blades, tattoo applications, intravenous drug use and homosexual intercourse). The purpose of this paper is to determine the prevalence of HBV and HCV, and also provide information for prisoners in this respect. This study included 180 prisoners from the Buca F-Type Closed Prison, and 180 prisoners from the Foça Open Prison in Turkey. After the training seminars, serum levels of HBsAg, anti HBs, anti HBc total and anti HCV in the prisoners were assessed using the MICROELISA method. All the prisoners were male. The mean age was 40(21-73) years. According to the results of 360 prisoners from both prisons, 17 (4.7 percent) prisoners were HBsAg positive and were diagnosed as HBV. Isolated anti HBs was positive in 33 (9.1 percent) prisoners who had been previously vaccinated. In 25 (6.9 percent) prisoners isolated Anti HBc total was positive, and in 61 (16.9 percent) prisoners both Anti HBs and Anti HBc total was positive in those who were considered to be recovered from the HBV. Anti HCV was positive in 2 (0.5 percent) prisoners; the process was repeated twice, and found to be repeatedly positive. Coinfection of HBV and HCV was not detected. In this study, the prevalence of HBV and HCV was determined to be similar to those in the normal population. However, it is not expedient to generalize this result and apply it to all prisons. For the sake of public health, prisons should be scanned for infectious diseases, and vaccinations must be applied as necessary, in order to provide protection. It is a study to determine the prevalence of HBV and HCV in the prisoner population, which constitute one of the risk groups because of the communal lifestyle (common use of some tools such as the razor blade, tattoo applications, intravenous drug use and homosexual intercourse), and to compare the results with other groups in Turkey and globally.

Relationship between the suppressor of cytokine signaling 3 expression and antiviral efficacy of nucleos(t)ide and interferon alpha therapy for chronic hepatitis B

Objective: To investigate the molecular mechanism of poor response of nucleoside and interferon therapy in some patients with chronic hepatitis B (CHB) and the negative regulatory factor of suppressor of cytokine signaling 3 (SOCS3) expression in the interferon-signaling pathway. Also, study the clinical relationship between SOCS3 and antiviral efficacy of nucleoside and interferon. Methods: Peripheral blood and matched liver tissue samples from 54 CHB patients who participated in the OSST study were selected. HBsAg was measured at different time points (baseline and weeks 12, 24, 36, and 48) to observe the antiviral efficacy. Meanwhile, quantitative real-time PCR, and immunohistochemistry were used to detect the expression levels of SOCS3 mRNA in peripheral blood mononuclear cells (PBMCs) and matched liver tissues (baseline and 48 weeks). At the end of the 48-week treatment, patients with HBsAg negative or HBeAg seroconversion were defined as response group, and vice versa. Paired t-tests were used to compare normal distribution variables and the Mann-Whitney U test was used to compare the median differences between groups of non-normally distributed variables. Results: After 48 weeks of treatment, serum HBsAg levels in the Peg-IFN group continued to decline (average decrease of 1.14 log(10) IU / ml at week 48; P = 0.001 compared with baseline), while the entecavir group remained almost unchanged during treatment (average decrease was 0.05 log(10) IU / ml at week 48; compared with baseline P = 0.12). The expression of SOCS3 mRNA (Messenger RNA, mRNA) in peripheral blood and liver tissues of non-responder group was significantly higher than the response group in the course of Peg-IFNα2a treatment. The immunohistochemical results of liver tissue showed that the expression of SOCS3 in the non-responder group was significantly higher than that in the response group at baseline (P = 0.027). After 48 weeks of treatment with Peg-IFNα2a, the expression of SOCS3 in the non-responder group was significantly higher than that in the baseline and response groups (P = 0.003, P = 0.012, respectively). Conclusion: The expression of SOCS3 in peripheral blood mononuclear cells and liver tissues of non-responding CHB patients was significantly higher than that of responding CHB patients during interferon and nucleoside antiviral therapy. We speculated that SOCS3 might affect the antiviral efficacy through negative regulation of JAK-STAT signaling pathway, and partly expose the mechanism of interferon resistance.

Correlation between serum HBV DNA and HBsAg levels in non-cirrhotic HBeAg positive and negative chronic hepatitis B patients

Correlation between serum HBV DNA and HBsAg levels in non-cirrhotic HBeAg positive and negative chronic hepatitis B patients

Relationship between liver steatosis and serum virological markers during immune clearance phase of chronic hepatitis B

Objective To investigate the relationship between hepatic steatosis and virological markers in patients with chronic hepatitis B (CHB) during immune clearance (IC) phase. Methods Pathology proven CHB patients in IC phase were collected from the Liver Center of the First Affiliated Hospital of Fujian Medical University from January 2009 to October 2016. Patients were divided into non-to mild fatty liver (F0-F1) group and moderate to severe fatty liver (F2-F4) group according to the liver steatosis degree. The relationship between liver steatosis and virological markers in serum was compared. The measurement data were analyzed using independent sample t test, and the count data were analyzed by chi-square test. Results A total of 298 patients were included, including 237 males (79.5%) and 61(20.5%) females, and the average age was (32.4±10.3) years old. The 23.5% (70/298) of these patients had liver steatosis. A total of 273 (91.6%) cases were in F0-F1 group, and the remaining 25 (8.4%) cases were in F2-F4 group. The patients in F2-F4 group had higher body mass index ([25.90±2.70] vs [21.68±2.90] kg/m2), serum triglyceride ([1.52±0.77] vs [1.11±0.55] mmol/L) and cholesterol ([4.88±1.15] vs [4.33±0.92] mmol/L) than F0-F1 group, and the differences were all statistically significant (t=-7.007, -2.667, and -2.751, respectively, all P<0.05). In addition, the serum levels of HBsAg and HBV DNA in F2-F4 group were also significantly higher than F0-F1 group (t=-3.291 and -2.831, respectivelt, both P<0.01). According to the grading of inflammation and fibrosis, the differences of HBsAg and HBV DNA levels between F0-F1 group and F2-F4 group were statistically significant only in patients with more severe inflammation (t=-2.738 and -2.135, respectively, both P<0.05) or less severe fibrosis (t=-2.258 and -2.333, respectively, both P<0.05). Conclusion Among CHB patients experiencing immune clearance, serum HBsAg and HBV DNA levels are positively correlated with the severity of hepatic steatosis, and this phenomenon is closely related to the degree of liver inflammation. Key words: Hepatitis B, chronic; Hepatitis B surface antigens; Fatty liver; Immune clearance