Quantitative hepatitis B core antibody and quantitative hepatitis B surface antigen:Novel viral biomarkers for chronic hepatitis B management

The management of hepatitis B virus(HBV)infection now involves regular and appropriate monitoring of viral activity,disease progression,and treatment response.Traditional HBV infection biomarkers are limited in their ability to predict clinical outcomes or therapeutic effectiveness.Quantitation of HBV core antibodies(qAnti-HBc)is a novel non-invasive biomarker that may help with a variety of diagnostic issues.It was shown to correlate strongly with infection stages,hepatic inflammation and fibrosis,chronic infection exacerbations,and the presence of occult infection.Furthermore,qAnti-HBc levels were shown to be predictive of spontaneous or treatment-induced HBeAg and HBsAg seroclearance,relapse after medication termination,re-infection following liver transplantation,and viral reactivation in the presence of immunosuppression.qAnti-HBc,on the other hand,cannot be relied on as a single diagnostic test to address all problems,and its diagnostic and prognostic potential may be greatly increased when paired with qHBsAg.Commercial qAnti-HBc diagnostic kits are currently not widely available.Because many methodologies are only semi-quantitative,comparing data from various studies and defining universal cut-off values remains difficult.This review focuses on the clinical utility of qAnti-HBc and qHBsAg in chronic hepatitis B management.

Clinical utility of hepatitis B surface antigen kinetics in treatment-na?ve chronic hepatitis B patients during longterm entecavir therapy

AIM To investigate the utility of hepatitis B surface antigen(HBsAg) kinetics in chronic hepatitis B patients during long-term entecavir treatment.METHODS This retrospective study included treatment-na?ve chronic hepatitis B patients who received at least 2 years of consecutive entecavir treatment. Patients were followed up at three to six month intervals with liver biochemistry, hepatitis B virus DNA, and abdominal sonography. In hepatitis B e antigen(HBeAg)-positive patients, HBeAg levels were assessed every three to six month until results became negative. Serum HBsAg levels were determined at the baseline, oneyear and five-year time points. Liver cirrhosis was diagnosed through liver biopsy, imaging examinations, or clinical findings of portal hypertension. Hepatocellular carcinoma was diagnosed by histological examination or dynamic image studies.RESULTS A total of 211 patients were enrolled. The median treatment time was 5.24(2.00-9.62) years. Multivariate analysis showed that lower baseline HBsAg levels were associated with an earlier virological response, earlier hepatitis B e antigen(HBeAg) seroconversion, and earlier biochemical response in HBeAg-positive patients(cut-off value: 4 log IU/mL) and an earlier virological response in HBeAg-negative non-cirrhotic patients(cut-off value: 2.4 log IU/mL). Although HBsAg levels decreased slowly during long-term entecavir treatment, higher HBsAg decrease rates were found in the first year for HBeAg-positive non-cirrhotic patients, and patients with higher baseline HBsAg levels. More favorable clinical outcomes were not observed by a rapid HBsAg decline per se, but depended on lower baseline HBsAg levels.CONCLUSION Baseline HBsAg can be used to predict treatment responses. HBsAg levels and decrease rates should be considered together according to disease status while interpreting HBsAg changes.

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

AIM: To examine the association between interferon(IFN) therapy and loss of hepatitis B surface antigen(HBs Ag) in inactive HBs Ag carriers. METHODS: This was a retrospective cohort study in inactive HBs Ag carriers, who were treatment-naive, with a serum HBs Ag level < 100 IU/m L and an undetectable hepatitis B virus(HBV) DNA level(< 100 IU/m L). 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 HBs Ag, HBV DNA, and alanine aminotransferases were monitored every 3 mo in the treatment group and every 3-6 mo in the control group. RESULTS: Thirteen(65.0%) of 20 treated patients achieved HBs Ag loss, 12 of whom achieved HBs Ag seroconversion. Mean HBs Ag level in treated patients decreased to 6.69 ± 13.04 IU/m L after 24 wk of treatment from a baseline level of 26.22 ± 33.00 IU/m L. Serum HBV DNA level remained undetectable(< 100 IU/m L) in all treated patients during the study. HBs Ag level of the control group decreased from 25.72 ± 25.58 IU/m L at baseline to 17.11 ± 21.62 IU/m L at week 96(P = 0.108). In the control group, no patient experienced HBs Ag loss/seroconversion, and two(5.0%) developed HBV reactivation.CONCLUSION: IFN treatment results in HBs Ag loss and seroconversion in a considerable proportion of inactive HBs Ag carriers with low HBs Ag concentrations.

Hepatitis B virus infection:defective surface antigen expression and pathogenesis

Hepatitis B virus(HBV) infection is a global public health concern. HBV causes chronic infection in patients and can lead to liver cirrhosis, hepatocellular carcinoma, and other severe liver diseases. Thus, understanding HBV-related pathogenesis is of particular importance for prevention and clinical intervention. HBV surface antigens are indispensable for HBV virion formation and are useful viral markers for diagnosis and clinical assessment. During chronic HBV infection, HBV genomes may acquire and accumulate mutations and deletions, leading to the expression of defective HBV surface antigens. These defective HBV surface antigens have been found to play important roles in the progression of HBV-associated liver diseases. In this review, we focus our discussion on the nature of defective HBV surface antigen mutations and their contribution to the pathogenesis of fulminant hepatitis B. The relationship between defective surface antigens and occult HBV infection are also discussed.

Hepatitis B surface antigen levels during natural history of chronic hepatitis B: A Chinese perspective study

AIM: To determine the baseline hepatitis B surface antigen(HBsAg) levels during the different phases of chronic hepatitis B(CHB) patients in China.METHODS: Six hundred and twenty-three hepatitis B virus or un-infected patients not receiving antiviral therapy were analyzed in a cross-sectional study. The CHB patients were classified into five phases: immunetolerant(IT, n = 108), immune-clearance(IC, n = 161), hepatitis B e antigen negative hepatitis(ENH, n = 149), low-replicative(LR, n = 135), and liver cirrhosis(LC, n = 70). HBsAg was quantified(Abbott ARCHITECT assay) and correlated with hepatitis B virus(HBV) DNA, and serum alanine aminotransferase/aspartate aminotransferase(ALT/AST) in each phase of CHB was also determined.RESULTS: Median HBsAg titers were different in each phase of CHB(P < 0.001): IT(4.85 log10 IU/mL), IC(4.36 log10 IU/mL), ENH(2.95 log10 IU/mL), LR(3.18 log10 IU/mL) and LC(2.69 log10 IU/mL). HBsAg titers were highest in the IT phase and lowest in the LC phase. Serum HBsAg titers showed a strong correlation with HBV viral load in the IC phase(r = 0.683, P < 0.001). No correlation between serum HBsAg level and ALT/AST was observed.CONCLUSION: The mean baseline HBsAg levels differ significantly during the five phases of CHB, providing evidence on the natural history of HBV infection. HBsAg quantification may predict the effects of immunemodulator or oral nucleos(t)ide analogue therapy.

Add-on pegylated interferon augments hepatitis B surface antigen clearance vs continuous nucleos(t)ide analog monotherapy in Chinese patients with chronic hepatitis B and hepatitis B surface antigen≤1500 IU/mL:An observational study

BACKGROUND Nucleos(t)ide analog(NA)has shown limited effectiveness against hepatitis B surface antigen(HBsAg)clearance in chronic hepatitis B(CHB)patients.AIM To evaluate the efficacy and safety of add-on peginterferonα-2a(peg-IFNα-2a)to an ongoing NA regimen in CHB patients.METHODS In this observational study,195 CHB patients with HBsAg≤1500 IU/m L,hepatitis B e antigen(HBeAg)-negative(including HBeAg-negative patients or HBeAg-positive patients who achieved HBeAg-negative after antiviral treatment with NA)and hepatitis B virus-deoxyribonucleic acid<1.0×10^2 IU/mL after over 1 year of NA therapy were enrolled between November 2015 and December2018 at the Second Affiliated Hospital of Xi'an Jiaotong University,China.Patients were given the choice between receiving either peg-IFNα-2a add-on therapy to an ongoing NA regimen(add-on group,n=91)or continuous NA monotherapy(monotherapy group,n=104)after being informed of the benefits and risks of the peg-IFNα-2a therapy.Total therapy duration of peg-IFNα-2a was 48 wk.All patients were followed-up to week 72(24 wk after discontinuation of peg-IFNα-2a).The primary endpoint was the proportion of patients with HBsAg clearance at week 72.RESULTS Demographic and baseline characteristics were comparable between the two groups.Intention-to-treatment analysis showed that the HBsAg clearance rate in the add-on group and monotherapy group was 37.4%(34/91)and 1.9%(2/104)at week 72,respectively.The HBsAg seroconversion rate in the add-on group was 29.7%(27/91)at week 72,and no patient in the monotherapy group achieved HBsAg seroconversion at week 72.The HBsAg clearance and seroconversion rates in the add-on group were significantly higher than in the monotherapy group at week 72(P<0.001).Younger patients,lower baseline HBsAg concentration,lower HBsAg concentrations at weeks 12 and 24,greater HBsAg decline from baseline to weeks 12 and 24 and the alanine aminotransferase≥2×upper limit of normal during the first 12 wk of therapy were strong predictors of HBsAg clearance in patients with peg-IFNα-2a add-on treatment.Regarding the safety of the treatment,4.4%(4/91)of patients in the add-on group discontinued peg-IFNα-2a due to adverse events.No severe adverse events were noted.CONCLUSION Peg-IFNα-2a as an add-on therapy augments HBsAg clearance in HBeAg-negative CHB patients with HBsAg≤1500 IU/m L after over 1 year of NA therapy.

Screening and evaluation of human single-chain fragment variable antibody against hepatitis B virus surface antigen

BACKGROUND: Phage display technology has become a vital tool in studies aimed at identifying molecules binding to a specific target. It enables the rapid generation and selection of high affinity, fully human antibody product candidates to essentially any disease target appropriate for antibody therapy. In this study, we prepared the recombinant single-chain fragment variable ( ScFv) antibody to hepatitis B virus surface antigen (HBsAg) by the phage display technology for obtaining a virus-targeting mediator. METHODS: mRNA was isolated from B-lymphocytes from a healthy volunteer and converted into cDNA. The fragment variables of heavy and light chain were amplified separately and assembled into ScFv DNA with a specially constructed DNA linker by polymerase chain reaction. The ScFv DNA was ligated into the phagmid vector pCANT-AB5E and the ligated sample was transformed into competent E. coli TG1. The transformed cells were infected with M13K07 helper phage to form a human recombinant phage antibody library. The volume and recombinant rate of the library were evaluated by bacterial colony count and restriction analysis. After two rounds of panning with HBsAg. the phage clones displaying ScFv of the antibody were selected by enzyme-linked immunosorbant assay ( ELISA) from the enriched phage clones. The antigen binding affinity of the positive clone was detected by competition ELISA. HB2151 E. coli was transfected with the positive phage clone demonstrated by competition ELISA for production of a soluble form of the anti-HBsAg ScFv. ELISA assay was used to detect the antigen binding affinity of the soluble anti-HBsAg ScFv. Finally, the relative molecular mass of soluble anti-HBsAg ScFv was measured by SDS-PAGE. RESULTS: The variable heavy ( VH ) and variable light (VL) and ScFv DNAs were about 340bp, 320bp and 750bp, respectively. The volume of the library was up to 2 × 106 and 8 of 10 random clones were recombinants. Two phage clones could strongly compete with the original HBsAb for binding to HBsAg. Within 2 strong positive phage clones, the soluble anti-HBsAg ScFv from one clone was found to have the binding activity with HBsAg. SDS-PAGE showed that the relative molecular weight of soluble anti-HBsAg ScFv was 32 kDa. CONCLUSION: The anti-HBsAg ScFv successfully produced by phage antibody technology may be useful for broadening the scope of application of the antibody.

Hepatitis B surface antigen seroconversion after HBV reactivation in non-Hodgkin's lymphoma

Reactivation of hepatitis B virus(HBV)can occur in lymphoma patients infected with HBV when they receive chemotherapy or immunotherapy.Prophylactic administration of lamivudine(LAM)reduces the morbidity and mortality associated with HBV reactivation.However,what defines HBV reactivation and the optimal duration of treatment with LAM have not yet been clearly established.HBV reactivation may occur due to the cessation of prophylactic LAM,although re-treatment with nucleoside analogs may sometimes result in hepatitis B surface antigen(HBsAg)seroconversion,which is a satisfactory endpoint for the management of HBV infection.We report a case of HBV reactivation in a 68-year-old HBsAg-positive patient who received rituximab-based immunochemotherapy for follicular lymphoma.HBV reactivation developed following cessation of prophylactic LAM therapy.The patient subsequently received treatment with entecavir(ETV),which led to a rapid and sustained suppression of HBV replication and HBsAg seroconversion.We also appraised the literature concerning HBV reactivation and the role of ETV in the management of HBV reactivation in lymphoma patients.A total of 28 cases of HBV reactivation have been reported as having been treated with ETV during or after immunosuppressive chemotherapy in lymphoma patients.We conclude that ETV is an efficacious and safe treatment for HBV reactivation following LAM cessation in lymphoma patients treated with rituximab-based immunochemotherapy.

Transformation of hepatitis B serologic markers in babies born to hepatitis B surface antigen positive mothers

AIM: To better understand the clinical significance of hepatitis B serologic markers in babies born to hepatitis B surface antigen (HBsAg) positive mothers, the incidence of maternal serologic markers of hepatitis B via placenta and its transformation in these babies were investigated.METHODS: Mothers with positive HBsAg were selected in the third trimester of pregnancy. Their babies received immunoprophylaxis with hepatitis B immunoglobulin and hepatitis B vaccine after birth, and were consecutively followed up for hepatitis B serologic markers and HBV DNA at birth, mo 1, 4, 7, 12, and 24. RESULTS: Forty-two babies entered the study, including 16 born to hepatitis B e antigen (HBeAg)-positive HBsAg carrier mothers and 26 to HBeAg-negative HBsAg carrier mothers. Apart from four babies born to HBeAg-positive carrier mothers and demonstrated persistent positive HBeAg eventually became HBV carriers, all other babies developed anti-HBs before 12 mo of age. Among the other 12 babies born to HBeAg-positive carrier mothers,HBeAg was detected in 7 at birth, in 4 at mo 1, and in none of them thereafter. No antibody response to the transplacental HBeAg was detected. Among the babies born to HBeAg-negative carrier mothers, anti-HBe was detected 100% at birth and mo 1, in 88.5% at mo 4, in 46.2% at mo 7, in 4.2% at mo 12 and none in mo 24. Among all the immunoprophylaxis-protected babies born to either HBeAg-positive or HBeAg-negative carrier mothers, anti-HBc was detected in 100% at birth, mo 1 and mo 4, in 78.9% at mo 7, in 36.1% at mo 12 and in none at mo 24.CONCLUSION: HBeAg can pass through human placenta from mother to fetus and become undetectable before 4 mo of age, but no antibodies response to the transplacental HBeAg can be detected till mo 24 in the immunoprophylaxisprotected babies. The sole existence of anti-HBe before 1 year of age or anti-HBc before 2 years of age in babies born to HBsAg carrier mothers may simply represent the transplacental maternal antibodies, instead of indicators of HBV infection status.

Long term follow-up and outcome of liver transplantation from hepatitis B surface antigen positive donors

Liver transplant for hepatitis B virus(HBV) currently yields excellent outcomes: it allows to rescue patients with an HBV-related advanced liver disease, resulting in a demographical modification of the waiting list for liver transplant. In an age of patient-tailored treatments, in liver transplantation as well the aim is to offer the best suitable graft to the patient who can benefit from it, also expanding the criteria for organ acceptance and allocation. With the intent of developing strategies to increase the donor pool, we set-up a multicenter study involving 3 Liver Transplant Centers in Italy: patients undergoing liver transplantation between March 03, 2004, and May 21, 2010, were retrospectively evaluated. 1408 patients underwent liver transplantation during the study period, 28(2%) received the graft from hepatitis B surface antigen positive(HBs Ag)-positive deceased donors. The average follow-up after liver transplantation was 63.7 mo [range: 0.1-119.4; SD ± 35.8]. None Primary nonfunction, re-liver transplantation, early or late hepatic artery thrombosis occurred. The 1-, 3-and 5-year graft and patient survival resulted of 85.7%, 82.1%, 78.4%. Our results suggest that the use of HBs Agpositive donors liver grafts is feasible, since HBV can be controlled without affecting graft stability. However, the selection of grafts and the postoperative antiviral therapy should be managed appropriately.

Evaluation of changes of serum hepatitis B surface antigen from a different perspective

AIM:To investigate the dynamic changes of serum hepatitis B surface antigen(HBs Ag) levels apportioned by the same hepatic parenchyma cell volume(HPCV),namely,hepatic cell quantities.METHODS:Serum HBs Ag levels were detected by electrochemiluminescence and serum HBs Ag levels apportioned by the same HPCV were figured out according to the theory of sphere geometry.HBs Ag levels were compared among different liver inflammation grades,as well as different hepatic fibrosis stages.RESULTS:In hepatitis B e antigen-negative chronic hepatitis B,serum HBs Ag levels in liver histological inflammation grades 1-4 were 3.66 ± 0.40,3.74 ± 0.35,3.74 ± 0.26 and 3.71 ± 0.34 log10 COI(cut off index),respectively,and there were no differences before apportion(P =0.640).Serum HBs Ag levels apportioned by the same HPCV were 5.57 ± 0.62,5.98 ± 0.65,6.59 ± 0.50 and 6.81 ± 0.84 log10 COI,respectively,and there were significant differences after apportion(P < 0.001).Serum HBs Ag levels in hepatic fibrosis stagesⅠ-Ⅳ were 3.66 ± 0.43,3.75 ± 0.33,3.71 ± 0.28 and 3.75 ± 0.26 log10 COI,respectively,and there were no differences before apportion(P =0.513).Serum HBs Ag levels apportioned by the same HPCV were 5.53 ± 0.66,5.98 ± 0.53,6.29 ± 0.46 and 7.06 ± 0.48 log10 COI,respectively,and there were significant differences after apportion(P < 0.001).CONCLUSION:Serum HBs Ag levels apportioned by the same HPCV(hepatic cell quantities),rather than serum HBs Ag levels,increase with liver inflammation grades and hepatic fibrosis stages.

Negative impact of hepatitis B surface seroclearance on prognosis of hepatitis B-related primary liver cancer

AIM To assess the impact of hepatitis B surface(HBs Ag) seroclearance on survival outcomes in hepatitis B-related primary liver cancer.METHODS Information from patients with hepatitis B-related liver cancer admitted in our hospital from 2008-2017 was retrieved. Cases diagnosed with HBs Ag(-) and HBc Ab(+) liver cancer were included in the HBs Ag seroclearance(SC) group. HBs Ag(+) liver cancer patients strictly matched for liver cancer stage(AJCC staging system, 8 th edition), Child-Pugh score, and first diagnosis/treatment method(surgery, ablation and TACE) were assigned to the HBsA g non-seroclearance(NSC) group. Then, clinical, pathological and survival data in both groups were assessed.RESULTS The SC and NSC groups comprised of 72 and 216 patients, respectively. Patient age(P < 0.001) and platelet count(P = 0.001) in the SC group were significantly higher than those of the NSC group. SC group patients who underwent surgery had more intrahepatic cholangiocarcinoma(ICC) and combined HCC-CC(CHC) cases than the NSC group, but no significant differences in tumor cell differentiation and history of liver cirrhosis were found between the two groups. The numbers of interventional treatments were similar in both groups(4.57 vs 5.07, P > 0.05). Overall survival was lower in the SC group than the NSC group(P = 0.019), with 1-,3-, and 5-year survival rates of 82.1% vs 85.1%, 43.2%vs 56.8%, and 27.0% vs 45.2%, respectively. Survival of patients with AJCC stage Ⅰ disease in the SC group was lower than that of the NSC group(P = 0.029).CONCLUSION Seroclearance in patients with hepatitis B-related primary liver cancer has protective effects with respect to tumorigenesis, cirrhosis, and portal hypertension but confers worse prognosis, which may be due to the frequent occurrence of highly malignant ICC and CHC.

Hepatitis B surface antigen levels of cessation of nucleos(t)ide analogs associated with virological relapse in hepatitis B surface antigen-negative chronic hepatitis B patients

AIM:To investigate the virological relapse rate in hepatitis B e antigen(HBeAg)-negative patients after antiviral therapy discontinuation and analyze the factors associated with virological relapse.METHODS:Among patients diagnosed with chronic hepatitis B infection between May 2005 and July2010,204 were eligible for analysis.The Kaplan-Meier method and log-rank test were used to calculate the cumulative rate of relapse and compare cumulative relapse rates between groups.The Cox proportional hazards regression model was used to evaluate the predictive factor of virological relapse.RESULTS:The 2 and 1 year cumulative risks of virological relapse after antiviral therapy discontinuation were 79.41%(162/204) and 43.82%(71/162),respectively.Multivariate analysis revealed that only post treatment hepatitis B surface antigen(HBsAg)level was associated with virological relapse {P= 0.011).The cumulative risk of virological relapse was higher in the patients with HBsAg levels ≥1500 IU/L than in those with HBsAg levels < 1500 IU/L(P= 0.0013).The area under the curve was 0.603(P= 0.033).The cutoff HBsAg value for predicting virological relapse was 1443IU/L CONCLUSION:We found that the virological relapse rate remained high after antiviral therapy discontinuation in the HBeAg-negative patients and that the post treatment HBsAg levels predicted virological relapse.

Hepatitis B surface antigen escape mutations: Indications for initiation of antiviral therapy revisited

Approximately 240 million people are chronically infected with hepatitis B. The implementation of rigorous vaccination programs has led to an overall decrease in the prevalence of this disease worldwide but this may also have led to emergence of viral mutations that can escape the protection of hepatitis B surface antibody. As this phenomenon is increasingly recognized, concern for transmission to vaccinated individuals has also been raised. Herein, we describe two cases where the suspected presence of a hepatitis B surface antigen escape mutation impacted the decision to initiate early antiviral therapy, as well as provide a brief review of these mutations. Our findings described here suggest that a lower threshold for initiating therapy in these individuals should be considered in order to reduce the risk of transmission, as vaccination does not provide protection.

Expression of hepatitis B virus surface antigen in 120 Hodgkin's lymphoma patients

Background and Objective: Little is known about the incidence of hepatitis B virus (HBV) infection in Hodgkin's lymphoma patients. This study was to evaluate the impact of HBV infection on the survival of Hodgkin's lymphoma patient. Methods: Clinical data of 120 Hodgkin's lymphoma patients treated at the Sun Yat-sen University Cancer Center between January 2004 and October 2007 were collected. The impact of prognostic factors including HBV infection on survival was examined by univariate and multivariate analyses. A log-rank test was used for univariate analysis and the Cox proportional hazards regression model was used for multivariate analysis. Results: Of the 120 patients, 18 (15.0%) were hepatitis B virus surface antigen (HBsAg)-positive. The HBsAg-positive patients had lower 5-year survival rate than did the HBsAg-negative ones (66.9% vs. 91.3%, P = 0.006). When the patients were divided into early-stage (Ⅰ+Ⅱ) and advanced-stage (Ⅲ+Ⅳ) groups, the 5-year survival rate was significantly different between the HBsAg-positive and -negative patients in early-stage group (64.8% vs. 96.0%, P < 0.001), while not significantly different in advanced-stage group (75.0% vs. 84.8%, P=0.667). Both univariate and multivariate analyses showed that radiotherapy and HBV infection were independent prognosis factors for the patients with early-stage Hodgkin's lymphoma (P=0.006 and 0.014, respectively). Conclusions: The incidence of HBV infection is similar between Hodgkin's lymphoma patients and normal population. HBV infection is an independent prognosis factor for survival in the patients with early-stage Hodgkin's lymphoma.

Inhibition of hepatitis B virus surface antigen expression by small hairpin RNA in vitro

AIM: To explore the anti-hepatitis B virus effect of RNA interference (RNAi) using small hairpin RNA (shRNA)expression vector.METHODS: Hepatitis B virus surface antigen green fluorescent protein (HBs-GFP) fusion vector and shRNA expression vectors were constructed and cotransfected transiently into HepG2 cells. mRNAs extracted from HepG2 cells were detected by real-time PCR. Fluorescence of HBs-GFP protein was detected by fluorescence-activated cell sorting (FACS). The effective shRNA expression vector was transfected into HepG2.2.15 cells. HBsAg and HBeAg in HepG2.2.15 cells were analyzed by radioimmunoassay (RIA) method.RESULTS: FACS revealed that shRNA targeting at HBsAg reduced the GFP signal by 56% compared to the control.Real-time PCR showed that HBs-GFP mRNA extracted from HepG2 cells cotransfected with pAVU6+27 and HBs-GFP expression plasmids decreased by 90% compared to the empty vector control. The expressions of HBsAg and HBeAg were also inhibited by 43% and 64%, respectively.CONCLUSION: RNAi using shRNA expression vector can inhibit the expression of HBsAg, providing a fresh approach to screening the efficient small interfering RNAs (siRNAs).

Serum hepatitis B surface antigen levels predict treatment response to nucleos(t)ide analogues

Quantification of hepatitis B surface antigen(HBsAg)has been suggested to be helpful in the management of chronic hepatitis B(CHB)patients.Nucleos(t)ide analogs(NAs)are the therapy of choice for CHB and are used in the majority of CHB patients.NAs are able to induce hepatitis B virus(HBV)viral suppression,normalization of alanine aminotransferase(ALT)levels,and improvement in liver histology.Automated quantitative assays for serum HBsAg have recently become available,facilitating standardized quantification of serum HBsAg.This has led to increased interest in the clinical application of quantitative serum HBsAg for predicting therapeutic response to NAs.Recent studies have shown that a decline in serum HBsAg levels in patients receiving peginterferon may signal successful induction of immune control over HBV,and can therefore be used to predict therapeutic response.NA treatment typically induces a less rapid decline in HBsAg than interferon treatment;it has been estimated that full HBsAg clearance can require decades of NA treatment.However,a rapid HBsAg decline during NA therapy may identify patients who will show clearance of HBsAg.Currently,there is no consensus on the clinical utility of serum HBsAg monitoring for evaluating patient responses to NA therapy.This review focuses on recent findings regarding the potential application of HBsAg quantification in the management of CHB patients receiving NA therapy.

Liver grafts from hepatitis B surface antigen-positive donors: A review of the literature

The scarcity of available organs and the gap between supply and demand continue to be the main limitations of liver transplantation. To relieve the organ shortage, current transplant strategies have implemented extended criteria, which include the use of liver from patients with signs of past or present hepatitis B virus(HBV) infection. While the use of liver grafts from donors with evidence of past HBV infection is quite limited, some data have been collected regarding the feasibility of transplanting a liver graft from a hepatitis B surface antigen(HBs Ag) positive donor. The aim of the present work was to review the literature regarding liver transplants from HBs Ag-positive donors. A total of 17 studies were identified by a search in Medline. To date, HBs Ag positive grafts have preferentially been allocated to HBs Ag positive recipients. The large majority of these patients continue to be HBs Ag positive despite the use of immunoglobulin, and infection prevention can only be guaranteed by using antiviral prophylaxis. Although serological persistence is evident, no significant HBV-related disease has been observed, except in patients coinfected with delta virus. Consistently less data are available for HBs Ag negative recipients, although they are mostly promising. HBs Agpositive grafts could be an additional organ source for liver transplantation, provided that the risk of reinfection/reactivation is properly prevented.

Hepatitis B surface antigen and hepatitis B core-related antigen kinetics after adding pegylated-interferon to nucleos(t)ids analogues in hepatitis B e antigen-negative patients

BACKGROUND Hepatitis B e antigen-negative chronic hepatitis B patients under nucleos(t)ids analogues(NAs)rarely achieve hepatitis B surface antigen(HBsAg)loss.AIM To evaluate if the addition of pegylated interferon(Peg-IFN)could decrease HBsAg and hepatitis B core-related antigen(HBcrAg)levels and increase HBsAg loss rate in patients under NAs therapy.METHODS Prospective,non-randomized,open-label trial evaluating the combination of Peg-IFN 180μg/week plus NAs during forty-eight weeks vs NAs in monotherapy.Hepatitis B e antigen-negative non-cirrhotic chronic hepatitis B patients of a tertiary hospital,under NAs therapy for at least 2 years and with undetectable viral load,were eligible.Patients with hepatitis C virus,hepatitis D virus or human immunodeficiency virus co-infection and liver transplanted patients were excluded.HBsAg and HBcrAg levels(log10 U/mL)were measured at baseline and during ninety-six weeks.HBsAg loss rate was evaluated in both groups.Adverse events were recorded in both groups.The kinetic of HBsAg for each treatment group was evaluated from baseline to weeks 24 and 48 by the slope of the HBsAg decline(log10 IU/mL/week)using a linear regression model.RESULTS Sixty-five patients were enrolled,61%receiving tenofovir and 33%entecavir.Thirty-six(55%)were included in Peg-IFN-NA group and 29(44%)in NA group.After matching by age and treatment duration,baseline HBsAg levels were comparable between groups(3.1 vs 3.2)(P=0.25).HBsAg levels at weeks 24,48 and 96 declined in Peg-IFN-NA group(-0.26,-0.40 and-0.44)and remained stable in NA group(-0.10,-0.10 and-0.10)(P<0.05).The slope of HBsAg decline in Peg-IFN-NA group(-0.02)was higher than in NA group(-0.00)(P=0.015).HBcrAg levels did not change.Eight(22%)patients discontinued Peg-IFN due to adverse events.The HBsAg loss was achieved in 3(8.3%)patients of the Peg-IFN-NA group and 0(0%)of the NA group.CONCLUSION The addition of Peg-IFN to NAs caused a greater and faster decrease of HBsAg levels compared to NA therapy.Side effects of Peg-IFN can limit its use in clinical practice.

Seroprevalence of hepatitis B surface antigen in pregnant women attending antenatal clinic in Honiara Solomon Islands,2015

AIM To determine the seroprevalence of hepatitis B surface antigen(HBsAg) among pregnant women attending antenatal clinic in Honiara, Solomon Islands. METHODS This descriptive cross-sectional study was carried out in seven area health centers in Honiara. From March to June 2015, identification of eligible pregnant women in each site was conducted using systematic random sampling technique. A total of 243 pregnant women who gave written informed consent were enrolled. Standardized tool was used to record demographics, obstetric history and serology results. HBsAg and hepatitis B e antigen(HBeAg) were tested using point-of-care rapid diagnostic test. All HBsAg positive samples were verified using enzyme-linked immunosorbent assay. RESULTS The mean age of participants was 26 ± 6 years. The overall hepatitis HBsAg prevalence was 13.8% with higher rate(22%) reported in women between 30-34 years of age. Majority of HBsAg positive participants were Melanesians(29 out for 33). None of the pregnant women in the 15-19 years and ≥ 40 years tested positive for HBsAg. There was no statistically significant difference in HBsAg prevalence by age, ethnicity, education and residential location. The overall HBeAg seroprevalence was 36.7%. Women between 20-24 years of age had the highest rate of 54.5%. Low level of knowledge about hepatitis B vaccination was reputed. Overall, 54.6% of participants were not aware of their hepatitis B vaccination status and only 65.2% of mothers reported their child had been vaccinated. CONCLUSION Hepatitis B is a disease of public health importance in Solomon Islands and emphasize the need for integrated preventative interventions for its control.