Phases Of HBV Infection Research Articles

Versatile performance edges of HBsAg Next assay in diagnosis and therapeutic monitoring of HBV infection.

HBsAg Next assay (HBsAgNx) claims improved detection of HBsAg. The aim was to investigate its performance in ascertaining HBsAg loss, ability to detect HBsAg in various phases of HBV infection, specificity and its amenability to in-house neutralization. Analytical sensitivity was investigated using NIBSC standard (3rd WHO-IS). For clinical performance, out of 91,962 samples tested for HBsAg (Qual-II), 512 samples consisting of 170 cases with evidence of HBsAg loss during treatment (n=116) and without treatment (n=54), acute-hepatitis B (n=90) and acute exacerbation of chronic-hepatitis B (n=41), acute-hepatitis A (n=24) and acute-hepatitis E (n=9) positive, HIV-1 positive (n=20), non-HBV, HAV and HEV related acute-hepatitis (n=81) and HBsAg prozone (n=14) as well as in-house neutralization (n=63) were included. The calculated limit of detection (LOD) was 0.004IU/mL. Of the 170 patients with apparent HBsAg loss, 18/116 (15.5%) among treated and 15/54 (27.7%) with spontaneous clearance were positive in HBsAgNx (p<0.0001). Additionally, it detected HBsAg in 12/95 (12.6%) and 6/34 (17.6%) patients who were HBV DNA negative in treatment experienced and spontaneous clearance groups respectively (p<0.001). The specificity of HBsAgNx was comparable to HBsAg Qual-II. The signal-intensity of HBsAgNx was significantly higher than HBsAg Qual-II across various phases of HBV infection and prozone samples. HBsAgNx significantly enhanced the accuracy of HBsAg detection without compromising the specificity in ascertaining HBsAg loss. The performance was superior in various phases of HBV infection including samples that exhibited prozone effect. Furthermore, it is amenable to cost-effective in-house neutralization to confirm low HBsAg levels.

Anti-HBc IgG Responses Occurring at the Early Phase of Infection Correlate Negatively with HBV Replication in a Mouse Model.

Anti-HBc IgG is usually recognized as a diagnostic marker of hepatitis B, while the functional role anti-HBc IgG in HBV infection has not been fully elucidated. In this study, we firstly investigated the relationship between the anti-HBc IgG responses and the replication of HBV using AAV8-1.3HBV infected C57BL/6N mice. Our data showed that the anti-HBc IgG responses at the early phase of infection correlated negatively with the concentrations of circulating HBsAg and HBV DNA at both the early and chronic phases of infection. This observation was confirmed by an independent experiment using AAV8-1.3HBV infected C57BL/6J mice. Furthermore, to comprehend the potential causal relationship between the anti-HBc IgG responses and HBV infection, mice were treated with an anti-HBc monoclonal antibody at three days post AAV8-1.3HBV infection. Our data showed that the anti-HBc mAb significantly suppressed the fold increase of circulating HBsAg level, and the protective effect was not affected by NK cell depletion. Collectively, our study demonstrated that anti-HBc antibodies occurring at the early phase of HBV infection may contribute to the constraint of the virus replication, which might be developed as an immunotherapy for hepatitis B.

Analysis of serum hepatitis B virus RNA levels among HBsAg and HBsAb copositive patients and its correlation with HBV DNA.

There are approximately 2 billion HBV-infected individuals worldwide, and approximately 1.87% to 7% of these individuals are copositive for HBsAg and HBsAb.Our study detected hepatitis B virus pgRNA (HBV RNA) levels in HBsAg and HBsAb copositive patients and then analyzed the correlation with HBV DNA, HBsAg, ALT, and AST levels. A total of 149 HBsAg and HBsAb copositive patients were identified from 66,617 outpatients.HBV RNA, HBV DNA, HBsAg, ALT, and AST serum levels were significantly different in different natural phases of HBV infection (immune tolerance phase, immune clearance phase, low replication phase, and reactivation phase) with statistical significance (P < .01). HBV RNA levels were positively correlated with HBV DNA, HBsAg, ALT, and AST levels. HBV RNA and HBV DNA levels were significantly increased in the HBeAg-positive group (66 patients) compared with the HBeAg-negative group (83 patients) (P < .01). In the HBeAg-positive group, HBV RNA levels were positively correlated with HBV DNA and HBsAg levels. In the HBeAg-negative group, HBV RNA levels were positively correlated with HBV DNA. Serum HBV RNA levels were positively correlated with HBV DNA, HBsAg, ALT, and AST levels.HBV RNA could be used as a virological indicator for antiviral therapy in HBsAg and HBsAb copositive hepatitis B patients.

HBeAg Levels Vary across the Different Stages of HBV Infection According to the Extent of Immunological Pressure and Are Associated with Therapeutic Outcome in the Setting of Immunosuppression-Driven HBV Reactivation.

HBeAg is a marker of HBV-activity, and HBeAg-loss predicts a favorable clinical outcome. Here, we characterize HBeAg-levels across different phases of HBV infection, their correlation with virological/biochemical markers and the virological response to anti-HBV therapy. Quantitative HBeAg (qHBeAg, DiaSorin) is assessed in 101 HBeAg+ patients: 20 with acute-infection, 20 with chronic infection, 32 with chronic hepatitis and 29 with immunosuppression-driven HBV-reactivation (HBV-R). A total of 15/29 patients with HBV-R are monitored for >12 months after starting TDF/ETV. qHBeAg is higher in immunosuppression-driven HBV-R (median[IQR]:930[206–1945]PEIU/mL) and declines in chronic hepatitis (481[28–1393]PEIU/mL, p = 0.03), suggesting HBeAg production, modulated by the extent of immunological pressure. This is reinforced by the negative correlation between qHBeAg and ALT in acute infection (Rho = −0.66, p = 0.006) and chronic hepatitis (Rho = −0.35; p = 0.05). Interestingly, qHBeAg strongly and positively correlates with qHBsAg across the study groups, suggesting cccDNA as a major source of both proteins in the setting of HBeAg positivity (with limited contribution of integrated HBV-DNA to HBsAg production). Focusing on 15 patients with HBV-R starting TDF/ETV, virological suppression and HBeAg-loss are achieved in 60% and 53.3%. Notably, the combination of qHBeAg > 2000 PEIU/mL + qHBsAg > 52,000 IU/mL at HBV-R is the only factor predicting no HBeAg loss (HBeAg loss: 0% with vs. 72.7% without qHBeAg > 2000 PEIU/mL + qHBsAg > 52,000 IU/mL, p = 0.03). In conclusion, qHBeAg varies over the natural course of HBV infection, according to the extent of immunological pressure. In the setting of HBV-R, qHBeAg could be useful in predicting the treatment response under immunosuppression.

Dynamic measurement of spleen size and liver stiffness helps to judge whether antiviral therapy is needed in the immune-tolerant phase of HBV infection

Dynamic measurement of spleen size and liver stiffness helps to judge whether antiviral therapy is needed in the immune-tolerant phase of HBV infection

Profile Quantitative Hepatitis B Surface Antigen (qHBsAg) of Chronic Nai?ve Hepatitis B Patients in Dr. Soetomo Hospital, Surabaya, Indonesia

This study aimed to evaluate the profile of qHBs Ag profile, and also to investigate the correlation betweenqHBs Ag and HBV DNA. Seventy samples of chronic-nai?ve hepatitis B patients in Dr. Soetomo Hospitalwere analyzed in a cross-sectional study. Patients were categorized according to the HBe Ag positive (n=30)and HBe Ag negative (n=18), also based on qHBs Ag 1000 IU/mL and qHBs Ag &gt;1000 IU/mL. qHBs Agwas correlated with HBV DNA. qHBs Ag by CLEIA method from Sysmex, KOBE HISCL, HBV DNAwas measured by real-time Polymerase Chain method from Gene Xpert, Cepheid. 70 patients nai?ve CHBtreatment showed a median of ALT level 60.21±70.76 U/L. 30 patients showed a positive-HBeAg, 18 patientsshowed negative-HBeAg, 22 patients were not evaluated (N/A). Positive-HBeAg patients had 70% qHBsAg&gt;2500 mg/dL and median HBV DNA 7.49×107IU/mL. Negative-HBeAg patients had 55.6% HBsAg ?1000mg/dL and median HBV DNA 9.66×102 IU/mL. qHBsAg correlated with HBV DNA (p &lt;0.001). This datademonstrated that quantitative HBsAg was associated with a phase of HBV-infection, quantitative HBsAgshowed a moderate correlation with DNA HBV, quantitative HBsAg levels might be a predictor of initiationtherapy for CHB patients.

Quantitative HBeAg varies in the different phases of HBV infection, and can predict therapeutic outcome in the setting of immunosuppression driven HBV reactivation

Quantitative HBeAg varies in the different phases of HBV infection, and can predict therapeutic outcome in the setting of immunosuppression driven HBV reactivation

Quantitative HBeAg varies across the different phases of HBV infection, and can predict treatment outcome in the setting of HBV-reactivation driven by iatrogenic immunosuppression

Introduction and aim: Qualitative HBeAg is a marker of active HBV-replication and HBeAg-loss is an important clinical/therapeutic end-point. Here, we quantify HBeAg-levels in different phases of HBV-infection, their correlation with virological/biochemical markers and their role in predicting virological-response to anti-HBV therapy.

Antiviral activity of PLK1-targeting siRNA delivered by lipid nanoparticles in HBV-infected hepatocytes.

A link between HBV and PLK1 was clearly evidenced in HBV-driven carcinogenesis, and we have also recently shown that PLK1 is a proviral factor in the early phases of HBV infection. Moreover, we have shown that BI-2536, a small molecule PLK1 inhibitor, was very efficient at inhibiting HBV DNA neosynthesis, notably by affecting nucleocapsid assembly as a result of the modulation of HBc phosphorylation. Yet, as small molecule kinase inhibitors often feature poor selectivity, a more specific and safer strategy to target PLK1 would be needed for a potential development against chronic HBV infections. Here, we analysed using both freshly isolated primary human hepatocytes and differentiated HepaRG, the anti-HBV properties of an LNP-encapsulated PLK1-targeting siRNA. Standard assays were used to monitor the effect of LNP siPLK1, or controls (LNP siHBV and LNP siNon-targeting), on HBV replication and cell viability. A dose as low as 100 ng/ml of LNP-siPLK1 resulted in a >75% decrease in secreted HBV DNA (viral particles), which was comparable to that obtained with LNP siHBV or 10 µM of tenofovir (TFV), without affecting cell viability. Interestingly, and in contrast to that obtained with TFV, a strong inhibition of viral RNA and HBe/HBsAg secretions was also observed under LNP siPLK1 treatment. This correlated with a significant intracellular decrease of vRNA accumulation, which was independent of any change in cccDNA levels, thus suggesting a transcriptional or post-transcriptional modulation. Such an effect was not obtained with a biochemical approach of PLK1 inhibition, suggesting an enzymatic-independent role of PLK1. This study emphasizes that a specific PLK1 inhibition could help in achieving an improved HBsAg loss in CHB patients, likely in combination with other HBsAg-targeting strategies.

Chronic hepatitis B virus infection is associated with decreased serum 25(OH)D concentration in non-cirrhotic patients.

Aim of the studyRecent reports provide evidence for the immunomodulatory properties of vitamin D. Decreased vitamin D levels may contribute to the progression of liver disease in hepatitis B virus (HBV) infection. This study aims to assess serum 25(OH)D in patients with chronic HBeAg-negative HBV (CHB) infection at different phases of disease.Material and methodsFifty-eighty patients with CHB, 10 with a history of HBsAg/anti-HBs seroconversion, were enrolled. The control group consisted of 9 healthy volunteers. Serum 25(OH)D concentration was assessed by ELISA.ResultsSerum 25(OH)D concentration was significantly lower in the CHB group in comparison to the HC group. It did not differ across the consecutive phases of the HBeAg-negative HBV infection. Negative correlations between serum 25(OH)D and alanine aminotransferase (ALT) as well as frequency of peripheral blood monocytes were observed. Serum 25(OH)D in samples collected in winter was significantly lower in comparison to the pool of samples collected in the summer. Serum 25(OH)D concentration was not associated with the phases of HBV-infection, HBV viral load, APRI or liver histology.ConclusionsSerum 25(OH)D is significantly decreased in HBV infection irrespectively of the phase of the infection and negatively correlates with serum ALT level, which may reflect the deterioration of liver function. Based on our results, we can conclude that the role of vitamin D in the immune control of HBV infection is probably irrelevant.

Occult HBV infection in Chinese blood donors: role of N-glycosylation mutations and amino acid substitutions in S protein transmembrane domains

ABSTRACT Occult hepatitis B virus infection (OBI) is a low-level asymptomatic phase of HBV infection. Evidence of OBI clinical relevance is emerging but the mechanisms of its occurrence remain unclear. In this study, the molecular characteristics of 97 confirmed OBI from Chinese blood donors were analyzed and relevant mutations were identified. Recombinant HBsAg bearing these mutations were expressed in vitro and the antigenicity and HBsAg secretion properties were analyzed. Results showed that 45 (46.4%) genotype B, 50 (51.5%) genotype C, and 2 (2.1%) genotype D sequences were identified. Two groups of mutations in the S gene were significantly associated with OBI. The first group included mutations creating new N-linked glycosylation sites at positions s116, s123, s130, and s131 + s133 or removing the existing one at s146. Mutations TCT123-125NCT/NFT were associated with reduced antigenicity, while TST116-118NST, GTS130-132NTS, and TSM131-133NSS/NYT/NST were associated with varying levels of impaired HBsAg secretion. N146 mutations had no effect on HBsAg production pattern. The second group included substitutions within the S transmembrane domains TMD1-3. Only mutations C85R, L87R, L88R, and C90R within TMD2 were associated with defective HBsAg production. These mutations appear to be rare and mostly strain specific but they may contribute to the multifactorial occurrence of OBI.

The dynamics of integration, viral suppression and cell-cell transmission in the development of occult Hepatitis B virus infection

BackgroundOut of several phases of HBV infection, the least understood phase is occult hepatitis B virus infection. The paucity of data due to non-availability of biological tissues and the prerequisite of ultra-sensitive assays for the detection of occult hepatitis B virus infection prompted us to utilize mathematical modeling in determining mechanisms that lead to occult hepatitis B virus infection and characteristics of HBV infection during occult hepatitis B virus infection. MethodsWe proposed two mathematical models (M1 and M2), considering two different phenomenon for episomal maintenance and accumulation of covalently closed circular DNA (cccDNA) in infected hepatocytes: (i) M1 – recirculation of the relaxed circular DNA/double-stranded linear DNA from cytoplasm to the nucleus, and (ii) M2 – reinfection of infected hepatocytes with virions. We further incorporated the dynamics of integrated Hepatitis B virus DNA (iHBV) to investigate its role in the development of occult hepatitis B virus infection. ResultsThe analysis showed that the main mechanism for the spread of infection during occult hepatitis B virus infection is cell-to-cell transmission and not cell-free virus transmission. A significant viral suppression (of at least 99% from its peak production values) was essential but not sufficient in the development of occult hepatitis B virus infection under M1; however under M2, the viral suppression was neither sufficient nor essential as the inhibition of the production of HBsAg without viral suppression can also explain the development of occult hepatitis B virus infection. Our analysis also revealed that occult hepatitis B virus infection seropositive cases are more likely to progress into liver cirrhosis compared to occult hepatitis B virus infection seronegative cases. The iHBV was found to be mostly silent (by either being absent or non-productive for HBsAg) during occult hepatitis B virus infection. ConclusionThe viral suppression is neither essential nor sufficient to explain the development of occult hepatitis B virus infection on its own. Not only the viral suppression but the inhibition -of the production and the export of HBsAg from cccDNA and iHBV also plays an important role in the development of occult hepatitis B virus infection. This is the first study, which incorporates the dynamics of iHBV and shows that HBV primarily spreads via cell-cell transmission during occult hepatitis B virus infection.

Prediction value of serum HBV large surface protein in different phases of HBV infection and virological response of chronic hepatitis B patients

BackgroundSerum HBV large surface protein (HBV-LP) is an envelope protein that has a close relationship with HBV DNA level. This study is to explore the prediction value of HBV-LP in different phase of HBV infection and during antiviral therapy in chronic hepatitis B (CHB) patients. MethodsA retrospective study was conducted in 2033 individuals, which included 1677 HBV infected patients in different phases and 356 healthy controls. HBV-LP, HBV serum markers and HBV DNA were detected by ELISA, CMIA and qRT-PCR, respectively. 85 CHB patients receiving PegIFNα or ETV were divided into virological response (VR) and partial virological response (PVR). The dynamic changes of HBV DNA and HBV-LP were observed. ResultsThe level of HBV-LP in 2033 individuals was shown as: HBeAg-positive hepatitis > HBeAg-positive infection > HBeAg-negative hepatitis > HBeAg-negative infection > healthy controls. HBV-LP was positive in all patients whose HBV DNA > 1.0E + 06 IU/ml. When HBsAg was <0.05 IU/ml or >1000 IU/ml, HBV DNAs were all negative if HBV-LP < 1.0 S/CO. When HBsAg was between 0.05 IU/ml and 1000 IU/ml, the consistency of HBV-LP with HBV DNA was 100% in case of HBV-LP > 4.0 S/CO in HBeAg-positive patients and HBV-LP > 2.0 S/CO in HBeAg-negative ones. During antiviral therapy, baseline HBV-LP was lower in VR patients than that in PVR patients. The optimal cut-off points to predict VR by baseline HBV-LP were 32.4 and 28.6 S/CO for HBeAg-positive and HBeAg-negative hepatitis patients, respectively. ConclusionsHBV-LP may be a useful marker for distinguishing the different phases of HBV infection. Moreover, baseline HBV-LP level can be used for predicting VR of CHB patients.

Characterization of the "a" determinant region of the hepatitis B virus genome in Iranian patients at different clinical phases of chronic infection.

To determine the distribution of important mutations of the "a" determinant region in the HBV genome among patients in different clinical phases of HBV infection. Variations in Hepatitis B infection not only change the outcome of the disease but also the symptoms from which the chronic HBV patients are suffering. We have meticulously selected a total of 40 chronic HBV patients from four different subclasses of chronic HBV clinical phases including immune tolerant (IT), immune active (IA), inactive carrier (IC) and hepatitis B e antigen (HBeAg)-negative (ENEG); 10 samples per each phase. Mutations of the "a" determinant region were identified using PCR-Direct sequencing method. 17 amino-acid substitutions at 12 positions inside the "a" determinant were identified in all forty samples; 3 mutations in the IT group, 6 mutations in the IA phase, 3 mutations in the IC patients and 5 mutations in the ENEG phase. Different substitutions were observed in all four clinical phases. The IA phase was the most variant group with the highest number of amino-acid substitutions. These results did not reveal a strong pattern to distinguish different clinical phases of Chronic HBV infection, but there are some obvious differences regarding the number and position of mutations between these four clinical phases.

Serum Cytokeratin 18 M30 Levels in Chronic Hepatitis B Reflect Both Phase and Histological Activities of Disease.

Chronic hepatitis B has highly a dynamic course with significant fluctuations of HBV-DNA and ALT impeding assessment of disease activity. New biomarkers of inflammatory versus noninflammatory stages of HBV infection are urgently needed. Cytokeratin 18 epitope M30 (M30 CK-18) is a sensitive marker of cell death. We aimed to investigate an association between serum M30 CK-18 and histological activity and phase of HBV infection. 150 Caucasian patients with HBV-infection were included in the study. Serum M30 CK-18 levels reflected phase of disease, being significantly higher in both HBeAg(+) and HBeAg(−) hepatitis B in comparison to HBsAg(+) carrier groups. The highest serum M30 CK-18 levels were observed in subjects with the most advanced stages of HBV. Moreover, its serum concentrations correlated with both inflammatory activity and fibrosis advancement (ANOVA P < 0.001). Importantly, serum M30 CK-18 levels were able to discriminate patients with mild versus moderate-advanced fibrosis (AUC: 0.86) and mild versus active liver inflammation (AUC: 0.79). M30 CK-18 serum concentration has good sensitivity and specificity in discriminating mild versus moderate/severe fibrosis and inflammation even in patients with normal ALT activity. This study suggests M30 CK-18 as a potential noninvasive marker of disease activity and also a marker of phase of persistent HBV infection.

Expression Profiling of Cellular MicroRNA in Asymptomatic HBsAg Carriers and Chronic Hepatitis B Patients.

Background MicroRNAs (miRNAs) may serve as potential molecular markers to predict liver injury resulting from chronic hepatitis B (CHB). In the present study, we want to study the expression profile and clinical significance of miRNAs at different stages of CHB virus infection. Methods Using miRNA microarray, we investigated the global expression profiles of cellular miRNA in asymptomatic hepatitis B antigen carriers (ASCs) and CHB patients, compared with healthy controls (HCs). Results We identified 79 and 203 differentially expressed miRNAs in the peripheral blood mononuclear cells of ASCs and CHB patients compared to HCs, respectively. Some of these miRNAs were common to ASCs and CHB patients, but another set of miRNAs that showed differential expression between ASCs and CHB patients was also identified. Gene ontology and pathway enrichment analysis showed that the target genes of the identified miRNAs played a role in important biological functions, such as learning or memory, cell-cell adherens junction, ion channel inhibitor activity, TGF-beta signaling pathway, and p53 signaling pathway. Conclusion We identified some significant differentially expressed miRNA in different phases of HBV infection, which might serve as biomarkers or therapeutic targets in the future.

Predictive Value of Hepatitis B Core-Related Antigen (HBcrAg) During the Natural History of Hepatitis B Virus Infection.

The natural history of HBV infection includes immune tolerance (IT), immune clearance (IC), HBeAg-negative inactive/quiescent carrier (ENQ), and HBeAg-negative hepatitis (ENH) phases. As the current biomarkers for discriminating the four phases still have some weaknesses, additional serological indicators are needed. Hepatitis B core-related antigen (HBcrAg) encoded with the precore/core gene contains denatured HBeAg, HBV core antigen (HBcAg), and a 22-KDa precore protein (p22cr) and has been demonstrated to have a close association with the natural history of hepatitis B infection. However, no specific cutoff values and diagnostic parameters have been identified to evaluate the diagnostic efficacy. This study aimed to clarify the distribution of HBcrAg levels and evaluate the diagnostic performance during the natural history of HBV infection in a Western Chinese population. In this study, 294 samples were collected from treatment-naive HBV infection patients in different phases (IT = 64; IC = 72; ENQ = 100, and ENH = 58). We detected the HBcrAg values and analyzed the relationship between HBcrAg and HBV DNA. HBsAg and other clinical parameters were quantitatively detected. The HBcrAg levels of IT, IC, ENQ, and ENH were 9.30 log U/mL, 8.80 log U/mL, 3.00 log U/mL, and 5.10 log U/mL, respectively (p < 0.0001). Receiver operating characteristic curve analysis demonstrated that the areas under the curves (AUCs) for HBcrAg and quantitative HBsAg at cutoff values of 9.25 log U/mL and 4.355 log IU/mL for distinguishing the IT phase from the IC phase were 0.704 and 0.694, with a sensitivity of 53.13% and 79.69% and specificity of 76.39% and 59.72%, respectively. AUCs of HBcrAg and quantitative HBsAg at cutoff values of 4.15 log U/mL and 2.395 log IU/mL for discriminating between the ENQ and ENH phases were 0.931 and 0.653, with a sensitivity of 87.93% and 91.38% and specificity of 84.00% and 39.00%, respectively. HBcrAg levels varied significantly among the four natural phases of HBV infection and had higher predictive performance than quantitative HBsAg for distinguishing between ENQ-patients and ENH-patients and a similar performance as HBsAg for the discrimination between IT and IC phases, which indicated that HBcrAg could be a potential serological marker for HBV infection.

Role of serum hepatitis B virus marker quantitation to differentiate natural history phases of HBV infection

The purpose of this study was to characterize roles of serum hepatitis B virus marker quantitation in differentiation of natural phases of HBV infection. A total of 184 chronic hepatitis B (CHB) patients were analyzed retrospectively. Patients were classified into four categories: immune tolerant phase (IT, n=36), immune clearance phase (IC, n=81), low-replicative phase (LR, n=31), and HBeAg-negative hepatitis phase (ENH, n=36), based on clinical, biochemical, serological, HBV DNA level and histological data. Hepatitis B surface antigen (HBsAg) quantitation in four phases were 4.7±0.2, 3.8±0.5, 2.5±1.2 and 3.4±0.4log10IU/mL, respectively. There were significant differences between IT and IC (p<0.001) and between LR and ENH phases (p<0.001). Quantitation of hepatitis B e antigen (HBeAg) in IT and IC phases are 1317.9±332.9 and 673.4±562.1S/CO, respectively (p<0.001). Hepatitis B core antibody (HBcAb) quantitation in the four groups were 9.48±3.3, 11.7±2.8, 11.2±2.6 and 13.2±2.9 S/CO, respectively. Area under receiver operating characteristic curve (AUCs) of HBsAg and HBeAg at cutoff values of 4.41log10IU/mL and 1118.96S/CO for differentiation of IT and IC phases are 0.984 and 0.828, with sensitivity 94.4 and 85.2%, specificity 98.7 and 75%, respectively. AUCs of HBsAg and HBcAb at cutoff values of 3.4log10IU/mL and 10.5S/CO for differentiation of LR and ENT phases are 0.796 and 0.705, with sensitivity 58.1 and 85.7%, and specificity 94.4 and 46.2%, respectively. HBsAg quantitation has high predictive value and HBeAg quantitation has moderate predictive value for discriminating IT and IC phase. HBsAg and HBcAb quantitations have moderate predictive values for differentiation of LR and ENH phase.

HBsAg Level as Predictor of Liver Fibrosis in HBeAg Positive Patients With Chronic Hepatitis B Virus Infection

Preliminary data suggests lower serum hepatitis B surface antigen level is associated with more severe liver fibrosis in HBeAg positive patients. We evaluated the association of HBsAg level with biochemical, virological, and histological features in asymptomatic patients with chronic HBV infection. HBsAg levels were measured at baseline in 481 asymptomatic, treatment naive patients with chronic HBV infection. Subjects were followed-up prospectively (median, 12; range, 8-36 months). Phases of HBV infection were defined after regular monitoring of HBV-DNA and transaminases. Liver histology was scored using the METAVIR system. HBeAg positive (n, 126) patients were significantly younger than HBeAg negative (n, 355), median age 26 vs 30 years; P<0.01. HBV genotype could be determined in 350 patients, 240 (68.57%) had genotype D and 100 (28.57%) had genotype A. HBsAg level had modest correlation with serum HBV DNA(r=0.6 vs 0.4 in eAg positive & negative respectively). HBeAg+ve patients with fibrosis score≥F2 showed significantly lower median serum HBsAg levels and serum HBV DNA levels compared with patients with F0-F1 score (median, range; 4.51, 2.99-6.10 vs 5.06, 4.13-5.89, P<0.01) and (8.39, 3.85-10.60, P<0.01) respectively. Significant inverse correlation of HBsAg level was found with liver fibrosis in eAg positive group (r=-0.76; P<0.001). HBsAg level cut off value 4.7log10IU/ml predicted moderate to advance fibrosis (F≥2) with 92% sensitivity, 85% specificity & 91% negative predictive value. Lower HBsAg level might reflect the status of advanced liver fibrosis in HBeAg positive chronic hepatitis B subjects.

Clinical utility of hepatitis B surface antigen levels during the natural history and treatment of chronic hepatitis B infection.

IntroductionHepatitis B surface antigen (HBsAg) level quantitation may be helpful for understanding the natural history of the disease and its response to treatment.AimTo determine the serum HBsAg levels during the different phases of chronic hepatitis B (CHB) infection and HBsAg levels of patients who are on treatment with oral antiviral drugs.Material and methodsPatients were categorized in four groups: 9 patients in the immune clearance (IC) phase, 46 patients in the inactive carrier (INC) phase, 25 patients in the reactivated HBeAg negative disease (END) phase and 60 HBeAg negative patients who were on treatment with oral antiviral drugs. HBsAg levels were compared between all groups. HBsAg and HBV DNA levels were compared in three phases of HBV infection. Patients on treatment were divided into two groups, taking lamivudine (L) and taking tenofovir (T). HBsAg levels were compared between END, L and T groups.ResultsThe HBsAg levels were different between each phase of CHB (p < 0.0001). HBsAg levels were highest in the IC phase and lowest in the INC phase. The HBsAg/HBV DNA ratio was significantly higher in the INC phase than the END and IC phases (p < 0.0001). HBsAg levels were higher in the END phase than the INC phase (p < 0.0001) and higher than the treatment group (p = 0.007). The HBsAg levels had a good correlation with HBV DNA in the natural course of CHB (r = 0.72, p < 0.0001). HBsAg levels were higher in the END group than the L and T groups (p < 0.05). HBsAg levels were higher in the L than the T group (p < 0.05).ConclusionsThis study demonstrates that HBsAg levels vary during the natural history of chronic hepatitis B infection. Also, the monitoring of HBsAg levels may help us to determine the best management strategy and to decide future treatment algorithms.