Quantitative HBeAg Research Articles

Investigating the Correlation between Semi quantitative HBeAg and HBV DNA Levels: Validating HBeAg Quantification as a Marker in Asymptomatic HBeAg-Positive Carriers

Investigating the Correlation between Semi quantitative HBeAg and HBV DNA Levels: Validating HBeAg Quantification as a Marker in Asymptomatic HBeAg-Positive Carriers

Quantitative HBeAg is a strong predictor of HBeAg loss among patients receiving pegylated interferon

BackgroundHBeAg loss is an important endpoint for antiviral therapy in chronic hepatitis B (CHB), however there are no reliable biomarkers to identify patients who will respond to the addition of pegylated interferon to nucleos(t)ide analogue (NA) therapy. AimTo evaluate the use of serum biomarkers to predict HBeAg loss. MethodsHBeAg positive CHB participants on NAs who switched-to or added-on 48 weeks pegylated interferon alpha2b (clinicaltrial.gov NCT01928511) were evaluated at week 72 for HBeAg loss. The predictive ability of qHBeAg, qHBsAg, HBV RNA and clinical variables for HBeAg loss were investigated. ResultsHBeAg loss occurred in 15/55 (27.3%) participants who completed 48 weeks of pegylated interferon. There was a lower baseline qHBeAg (1.18 IU/mL [2.27] versus 10.04 IU/mL [24.87], P = 0.007) among participants who lost HBeAg. Baseline qHBeAg (OR = 0.15, 95% CI 0.03–0.66, P = 0.01) and detectable HBV DNA at baseline (OR = 25.00, 95% CI 1.67–374.70, P = 0.02) were independent predictors of HBeAg loss. In addition, on-treatment qHBeAg was also a strong predictor of HBeAg loss (OR = 0.39, 95% CI 0.18–0.81, P = 0.012). The models combining detectable baseline HBV DNA with baseline (C-statistic 0.82) and on-treatment (C-statistic 0.83) had good accuracy for predicting HBeAg loss. A rise in qHBeAg ≥ 10 IU/ml was a predictor of flare (ALT ≥ 120 U/ml) on univariable analysis but not after adjustment for treatment arm. ConclusionsBaseline and on-treatment qHBeAg is a useful biomarker that can identify participants on NA therapy who may benefit from adding or switching to pegylated interferon.

Changes in serum hepatitis B surface and e antigen, interferon-inducible protein 10, and aminotransferase levels during combination therapy of immune-tolerant chronic hepatitis B.

Treatment of immune-tolerant (IT) children and adults with combined peginterferon alfa-2a and entecavir results in a decline in serum HBeAg and HBsAg concentrations but rarely results in loss of HBeAg or sustained off-treatment response. Factors associated with declines in these viral antigens during treatment remain unexplored. We investigated the pattern of virologic and biochemical response in 86 participants (59 children, 27 adults) by serial quantitative measurement of HBsAg (qHBsAg), quantitative HBeAg (qHBeAg), HBV RNA, interferon-inducible protein (IP-10), IL-18, and alanine aminotransferase (ALT). Each individual had previously been treated with 8 weeks of entecavir followed by 40 weeks of combined peginteferon and entecavir. We defined the interrelationships between these parameters and virologic response measured as nadir declines from baseline for HBeAg and HBsAg. The patterns of HBsAg and HBeAg decline were similar in pediatric and adult participants. Higher levels of IP-10 were observed during treatment in participants with greater ALT elevations and greater reductions of qHBsAg and qHBeAg. Individuals with peak ALT values exceeding three times the upper limit of normal were significantly more likely to have >1 log10 decline in both viral antigens. HBV DNA became undetectable in 21 of 86 (24%) and HBV RNA in 4 of 77 (5%) during therapy, but both markers remained negative only in those who became HBsAg negative, all of whom also had ALT elevations. Induction of IP-10 during peginterferon treatment in adults and children in the IT phase of chronic HBV infection is associated with ALT elevations and decline in viral antigens, suggesting a degree of interferon-inducible viral control.

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.

Clinical significance of quantitative e antigen in a cohort of hepatitis B virus-infected children and adults in North America.

In chronic hepatitis B (CHB) viral infection, e antigen positivity (HBeAg+) is associated with high levels of viral replication and infectivity. Furthermore, HBeAg-positive CHB is associated with a liver disease spectrum ranging from none to severe. To assess whether the level of circulating HBeAg is associated with different clinical presentations of HBeAg-positive CHB. A cross-sectional analysis was conducted among HBV mono-infected participants enrolled in Hepatitis B Research Network (HBRN) cohorts to explore clinical and virological associations with quantitative HBeAg (qHBeAg). Among 763 HBeAg+ participants (56% female; 85% Asian; median age 26years), multivariable median regression modelling significantly associated qHBeAg with liver injury (inverse qHBeAg association with ALT p<.001 and APRI p<.001), and with both race and age (p=0.01). Among Asians, qHBeAg was inversely related to age; a relationship less clear among Blacks and Whites. Among Asians also, median qHBeAg levels were higher among those infected with HBV genotype C versus B (p<0.001), suggesting causal virologic differences. Across all races, median qHBeAg was higher in women (p=.01). Independent of sex, age, race and HBV genotype, qHBeAg was higher in participants with predominant wild-type versus basal core promoter and/or precore 'stop' viral variants (p<0.001). Lower qHBeAg was observed among HBRN participants with the greatest degree of liver injury independent of demographics and HBV genotype. These data support longitudinal studies to examine the role of qHBeAg in modulating the host immune response and predicting the outcomes of chronic HBV infection.

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.

Comparative study of HBV DNA levels in HBeAg positive and negative female patients suffering from chronic hepatitis b in child bearing age.

To compare HBV DNA values in HBeAg positive and negative female patients suffering from chronic hepatitis B of child bearing age. Study Design: Cross sectional study. Setting: Hospitals attached to Peshawar Medical College, Peshawar after taking ethical approval from the institution’s ethical board. Period: October 2014 to March 2015. Materials and Methods: Blood samples were collected from 100 chronic hepatitis B females of child bearing age. Quantitative HBeAg was done by ELISA and HBV DNA values were estimated by PCR. The data obtained was statistically analyzed by using the Statistical Package for the Social Sciences (SPSS) version 17 and statistical significance between the variables was calculated using Fisher’s exact test. Results: The mean age of the sample was 28.69±6.83 years. A positive correlation (p=0.000) was found in HBeAg positive status and younger age group females (17-30). 84 cases were HBeAg negative but 42/84 had high levels of circulating Hepatitis B virus (2000 IU/ml). Conclusion: The present study established a positive association between HBeAg positive status and high HBV DNA values. However a statistically positive association was observed between HBeAg negative patients and high HBV DNA values (HBV DNA ≥2000IU/ml).&#x0D; &#x0D; Objective: To compare HBV DNA values in HBeAg positive and negative female patients suffering from chronic hepatitis B of child bearing age.&#x0D; &#x0D; Methodology: This cross sectional study was conducted from October 2014 to March 2015 in Hospitals attached to Peshawar Medical College, Peshawar after taking ethical approval from the institution’s ethical board. Blood samples were collected from 100 chronic hepatitis B females of child bearing age. Quantitative HBeAg was done by ELISA and HBV DNA values were estimated by PCR.&#x0D; The data obtained was statistically analyzed by using the Statistical Package for the Social Sciences (SPSS) version 17 and statistical significance between the variables was calculated using Fisher’s exact test.&#x0D; &#x0D; Results: The mean age of the sample was 28.69±6.83 years. A positive correlation (p=0.000) was found in HBeAg positive status and younger age group females (17-30). 84 cases were HBeAg negative but 42/84 had high levels of circulating Hepatitis B virus (2000 IU/ml).&#x0D; &#x0D; Conclusion: The present study established a positive association between HBeAg positive status and high HBV DNA values. However a statistically positive association was observed between HBeAg negative patients and high HBV DNA values (HBV DNA ≥2000IU/ml).&#x0D; &#x0D; Key Words: Hepatitis B virus, HBeAg, HBV DNA

Different methods detecting low quantitative HBeAg in serum

Objective To evaluate the performance of ELISA and time-resolved immunofluorometric assay (IFMA) detecting low quantitative HBeAg in serum.Methods The positive results of HBeAg were retrospectively analyzed from Janurary to June 2014 at our hospital.81 serum samples with the HBeAg concentration ranging from 1.00 to 29.99 S/CO were collected and then detected by ELISA and IFMA.Results The quantitation of HBeAg significantly correlated with the quantitation of HBsAg (r=-0.680,P ＜ 0.01).32.69％ patients positive in HBsAg were positive in HBeAg.39.35％ patients positive in HBeAg had low quantitative HBeAg and all were in young or middle age.The positive rate of HBeAg decreased as the age of patients positive in HBsAg increased (x 2=386.041,P ＜ 0.01).The detection rate of low quantitative HBeAg was 60.49％.by ELISA and 45.68％ by IFMA,without statistical difference (x 2=3.569,P ＞ 0.05).At levels of 1.00-4.99 S/CO and 5.00-29.99 S/CO,the detection rate were 25.64％ and 92.86％ by ELISA and 10.26％ and 78.57％ by IFMA.All the results of low quantitative HBeAg detected by ELISA and IFMA positively correlated with the results detected by CMIA (r=0.868 and 0.858,P ＜ 0.01).Conclusions Because of the methods' sensitive digree,ELISA and IFMA would fail in detecting low quantitation of HBeAg high proportionally.Therefore,it' s not suitable for evaluating the situation of the patients infected by HBV detecting low quantitation of HBeAg by these two methods. Key words: ELISA; Time-resolved immunofluorometric assay; Chemiluminescent immunoassay; Hepatitis B e antigen; Low quantitation

444 Clinical importance of quantitative HBEAG levels during lamivudine therapy: As a predictive factor for HBEAG seroconversion and viral breakthrough

444 Clinical importance of quantitative HBEAG levels during lamivudine therapy: As a predictive factor for HBEAG seroconversion and viral breakthrough