Trajectories of serum HBsAg during treatment and association with HBsAg loss in children with HBeAg-positive chronic hepatitis B: a latent class trajectory analysis.

BACKGROUND: The change of serum hepatitis B surface antigen (HBsAg) during treatment are associated with HBsAg loss. However, little is known about the trajectory patterns of HBsAg in early treatment and their relationship with subsequent HBsAg loss. This study aimed to identify trajectories of HBsAg in children with HBeAg-positive chronic hepatitis B (CHB) and investigate the association between trajectory patterns and HBsAg loss. METHODS: A retrospective study was conducted on 166 treatment-naive children with HBeAg-positive CHB. Latent class trajectory analysis was used to identify trajectory groups of serum HBsAg. Cox proportional hazard model was used to assess the association between HBsAg trajectory groups and HBsAg loss. RESULTS: The median follow-up time was 20.70 (12.54, 34.17) months, and HBsAg loss occurred in 70(42.17%) of all study participants. Using latent class trajectory analysis, HBeAg-positive CHB patients were classified into three trajectory groups: trajectory 1 (sustained stability, 24.70%), trajectory 2 (slow decline, 38.55%), and trajectory 3 (rapid decline, 36.75%), respectively. The median decline levels of HBsAg at the 3-month and 6-month follow-ups were the highest in trajectory 3 (1.08 and 3.28 log10 IU/ml), followed by trajectory 2 (0.27 and 1.26 log10 IU/ml), and no change in trajectory 1. The risk of achieving HBsAg loss was higher in both trajectory 2 (HR, 3.65 [95% CI, 1.70-7.83]) and trajectory 3 (HR, 7.27 [95% CI, 3.01-17.61]), respectively. CONCLUSION: Serum HBsAg levels during early treatment can be classified into distinct trajectory groups, which may serve as an additional predictive indicator for HBsAg loss in HBeAg-positive CHB children.

PAGE-B incorporating moderate HBV DNA levels predicts risk of HCC among patients entering into HBeAg-positive chronic hepatitis B.

BACKGROUND & AIMS: Recent studies reported that moderate HBV DNA levels are significantly associated with hepatocellular carcinoma (HCC) risk in hepatitis B e antigen (HBeAg)-positive, non-cirrhotic patients with chronic hepatitis B (CHB). We aimed to develop and validate a new risk score to predict HCC development using baseline moderate HBV DNA levels in patients entering into HBeAg-positive CHB from chronic infection. METHODS: This multicenter cohort study recruited 3,585 HBeAg-positive, non-cirrhotic patients who started antiviral treatment with entecavir or tenofovir disoproxil fumarate at phase change into CHB from chronic infection in 23 tertiary university-affiliated hospitals of South Korea (2012-2020). A new HCC risk score (PAGED-B) was developed (training cohort, n = 2,367) based on multivariable Cox models. Internal validation using bootstrap sampling and external validation (validation cohort, n = 1,218) were performed. RESULTS: Sixty (1.7%) patients developed HCC (median follow-up, 5.4 years). In the training cohort, age, gender, platelets, diabetes and moderate HBV DNA levels (5.00-7.99 log10 IU/ml) were independently associated with HCC development; the PAGED-B score (based on these five predictors) showed a time-dependent AUROC of 0.81 for the prediction of HCC development at 5 years. In the validation cohort, the AUROC of PAGED-B was 0.85, significantly higher than for other risk scores (PAGE-B, mPAGE-B, CAMD, and REAL-B). When stratified by the PAGED-B score, the HCC risk was significantly higher in high-risk patients than in low-risk patients (sub-distribution hazard ratio = 8.43 in the training and 11.59 in the validation cohorts, all p <0.001). CONCLUSIONS: The newly established PAGED-B score may enable risk stratification for HCC at the time of transition into HBeAg-positive CHB. IMPACT AND IMPLICATIONS: In this study, we developed and validated a new risk score to predict hepatocellular carcinoma (HCC) development in patients entering into hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) from chronic infection. The newly established PAGED-B score, which included baseline moderate HBV DNA levels (5-8 log10 IU/ml), improved on the predictive performance of prior risk scores. Based on a patient's age, gender, diabetic status, platelet count, and moderate DNA levels (5-8 log10 IU/ml) at the phase change into CHB from chronic infection, the PAGED-B score represents a reliable and easily available risk score to predict HCC development during the first 5 years of antiviral treatment in HBeAg-positive patients entering into CHB. With a scoring range from 0 to 12 points, the PAGED-B score significantly differentiated the 5-year HCC risk: low <7 points and high ≥7 points.

Predicting hepatitis B e Antigen seroconversion after pregnancy-The SydPregScore.

BACKGROUND AND AIMS: Achieving Hepatitis B e antigen seroconversion (HBeAg SC) at an earlier age confers a better prognosis. We examined baseline and post-partum factors associated with HBeAg SC after pregnancy. We developed a tool, the SydPregScore, to estimate the likelihood of HBeAg SC in the years after pregnancy. METHODS: A retrospective analysis of an HBeAg-positive pregnant cohort was conducted. Variables including baseline age, parity, alanine aminotransferase level, HBV viral load, quantitative HBsAg, use of antiviral therapy and post-partum flare were collected. Univariate and multivariate Cox regression analyses to determine predictors of HBeAg SC and develop a predictor score were performed. RESULTS: We analysed HBeAg SC rates in 220 pregnancies to 149 HBeAg-positive women from 2006 to 2019. At baseline, their median age was 33 (IQR 29-37), ALT 23 U/L (IQR 17-33) and viral load 8 log10 IU/mL (IQR 6.3-8.2 log10 IU/mL). The majority (133/198, 67.2%) received short-course antiviral therapy to prevent mother-to-child transmission, and 109/192 (56.8%) had a post-partum flare. HBeAg SC occurred in 74/220 (33.6%) after pregnancy (median follow-up 814 days, IQR 405-1531). Multivariate analysis identified baseline viral load <8 log10 IU/mL (HR 2.426 [1.224-4.809], p = .011), baseline ALT ≥2 ULN (HR 2.726 [1.299-5.721], p = .008) and age <35 (HR 2.859 [1.255-6.513], p = .012) to be positive predictors of HBeAg SC. The 'SydPreg Score' estimated the probability of HBeAg SC at 2000 days as 10%, 30%, 70% and 80% for 0, 1, 2, and 3 predictors respectively. CONCLUSION: The SydPreg Score allows the prediction of HBeAg SC in the years after pregnancy. Even in those without elevated ALT, age <35 and viral load <8 log10 IU/mL can identify women with a good chance of subsequent HBeAg SC. Those without a chance may benefit from viral suppression.

Application of hepatitis B immunoglobulin in prevention of mother-to-child transmission of chronic hepatitis B in HBsAg- and HBeAg-positive mother.

The aim of our study was to compare the efficacy of two dosages of hepatitis B immunoglobulin (HBIG) combined with HBV vaccine (HBVac) to prevent mother-to-child transmission (MTCT) of hepatitis B in HBsAg- and HBeAg-positive mother. We enrolled 331 mother-infant pairs with HBsAg- and HBeAg-positive maternal state from the Women's Hospital School of Medicine of Zhejiang University. Newborns were randomly distributed into two groups according to the dosages of HBIG injection: 100 IU and 200 IU. Newborns from both groups were injected with HBVac in the same doses. We compared the immune outcomes between the two groups and explore the influencing factors of immune outcomes through regression analysis. There was no statistically significant relationship between HBsAg serological transmission of newborns and dosages of HBIG in HBsAg- and HBeAg-positive mother (p > .05). The Logistic regression showed that high DNA load is a risk factor for passive-active immunoprophylaxis failure for both 100 IU and 200 IU group, but higher-dosage HBIG is not necessary for higher-viral-load pregnant women with HBsAg- and HBeAg-positive. In conclusion, combined application of HBVac and a single dose of 100 IU HBIG can achieve the ideal MTCT interruption results for HBsAg- and HBeAg-positive pregnant women.IMPACT STATEMENTWhat is already known on this subject? Passive-active immunoprophylaxis is proved to be effective in preventing mother-to-child transmission of hepatitis B. Hepatitis B vaccine combined with 100 IU or 200 IU immunoglobulin is mostly recommended in China.What do the results of this study add? At present, there is still a lack scientific basis for improving existing strategies and measures to prevent mother-to-child transmission of hepatitis B in China.What are the implications of these findings for clinical practice and/or further research? 100 IU and 200 IU immunoglobulin show equivalent blocking effect, and combined use of hepatitis B vaccine and 100 IU immunoglobulin is more cost-effective.

A Predictive Model to Evaluate the HbeAg Positivity of Chronic Hepatitis B Virus Patients in Clinics: A Cross-Sectional Study.

Background and Objective: The study aims to investigate the correlation between Hepatitis B 'e' antigen (HBeAg) and HBV DNA levels, and to find a convenient tool to estimate the HBV DNA level for clinicians. Materials and Methods: We enrolled 1020 patients in this cross-sectional study and divided them into four groups: an HbeAg-positive and -negative group, and high and low HBV DNA levels groups. Results: Alanine aminotransferase (ALT), Albumin (ALB) and HBeAg are independent risk factors for CHB patients. When the level of HBeAg is higher than 16.15 S/CO, it is four times more likely that the patients will have high levels of HBV DNA than those who do not. The ALT and TB are independent risk factors in HBeAg-negative patients with a high HBV DNA level. We have drawn three predictive models to estimate the HBV DNA levels for those with the chronic hepatitis B virus (CHB), and those that are HBeAg-positive and HBeAg-negative (Y1 = 0.004 × ALT(IU/L) + 1.412 × HBeAg (S/CO) - 0.029 × ALB (g/L) + 0.779, the AUC is 0.672, and the cutoff value is -0.072, there the sensitivity is 0.615, the specificity is 0.648, PPV is 65.182% and NPV is 60.837%; Y2 = 0.007 × HBeAg (S/CO) - 0.016 × HGB (g/L) + 3.070, the AUC is 0.724, and the cutoff value is 1.216, where the sensitivity is 0.626, the specificity is 0.897, PPV is 94.118% and NPV is 34.437%; Y3 = -0.005 × ALT(IU/L) + 0.006 × TB (umol/L) + 0.385, the AUC is 0.661, and the cutoff value is 0.263, where the sensitivity is 0.677, the specificity is 0.587, PPV is 66.820% and NPV is 40.774%, respectively). We propose that HBeAg is the most important risk factor for the patient with a high HBV DNA level, however, it is not as important in the HBeAg-positive group. Conclusions: HBeAg is an independent risk factor that reflects the level of HBV DNA with a strong correlation. Patient with HBeAg (-) should combine TB and ALT to estimate the level of HBV DNA.

Switching from entecavir to tenofovir disoproxil fumarate for HBeAg-positive chronic hepatitis B patients: a phase 4, prospective study.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is widely used and recommended as first-line treatment for patients infected with the hepatitis B virus (HBV). However, current data are limited regarding the efficacy and safety of switching to TDF for the treatment of chronic hepatitis B in hepatitis B e-antigen (HBeAg)-positive patients who are virologically suppressed with another nucleos(t)ide analogue. The primary objective of this study was to evaluate the hepatitis B surface antigen (HBsAg) reduction potential of switching from entecavir (ETV) to TDF at week 48 in HBeAg-positive chronic hepatitis B patients with undetectable serum HBV-DNA. METHODS: In this multicenter, single-arm, open-label, phase 4 clinical study, 75 participants currently treated with ETV 0.5 mg once daily were switched to TDF 300 mg once daily for 96 weeks. RESULTS: At week 48, 3/74 participants (4%) achieved 0.25 log10 reduction of HBsAg levels from baseline (the primary endpoint). Mean HBsAg reduction was -0.14 log10 IU/mL and 12% (9/74) achieved 0.25 log10 reduction by 96 weeks. No participants achieved HBsAg seroclearance. HBsAg reduction at weeks 48 and 96 was numerically greater in participants with higher alanine aminotransferase levels (≥ 60 U/L). Seventeen participants (25%) achieved HBeAg seroclearance up to week 96. No participants experienced viral breakthrough. All drug-related adverse events (18 participants [24%]) were mild in intensity, including an increase in urine beta-2-microglobulin (15 participants [20%]). CONCLUSIONS: In conclusion, HBsAg reduction was limited after switching from ETV to TDF in this study population. Further investigation is warranted to better understand the clinical impact of switching from ETV to TDF. ClinicalTrials.gov: NCT03258710 registered August 21, 2017. https://clinicaltrials.gov/ct2/show/NCT03258710?term=NCT03258710&draw=2&rank=1.

HBcrAg and pg RNA and the therapeutic effect in HBeAg-positive patients receiving anti-viral therapy, baseline serum HBV-RNA is a powerful predictor of response.

We used HBV core antigen (HbcrAg), pre-genomic RNA (pg RNA) and other biomarkers to evaluate the therapeutic effect in HBV infected patients receiving anti-viral therapy. 127HBeAg-positive patients were enrolled: 35 patients received nucleotide therapy, 14 patients received interferon and 78 patients received combination therapy with both. HBcrAg, pg RNA and other biomarkers were detected at different time points, we defined the decreased titre of HBcrAg and HBeAg from baseline to 6 and baseline to 12 months as ∆HBcrAg and ∆HBeAg, which were used to predict HBeAg seroconversion. Furthermore, we used the time-dependent receiver operator curve of different markers to analyse HBeAg seroconversion. For HBeAg seroconversion: at 6 months, 0.75 log10 U/mL of ∆HBcrAg and 1.47 log10 PEI U/mL of ∆HBeAg showed maximum predictive value in receiver operator curve analysis (Youden's index values for area under the curve of 0.687 and 0.646, respectively). At 12 months, 2.05 log10 U/mL of ∆HBcrAg and 1.92 log10 PEI U/mL of ∆HBeAg showed improved prediction (maximum Youden's index values, with areas under the curve of 0.688 and 0.698, respectively).pg RNA was a better predictor of outcome due and the concentrations of 6.20 log10 I U/mL of pg RNA and 8.0 log10 U/mL of HBcrAg were cut-off values for response in a Kaplan-Meier curve analysis. Our results may be used to identify the pg RNA concentration in patients at baseline and ∆HBcrAg during therapy who are likely to achieve HBeAg seroconversion according to the cut-off value at different time points, thus helping to evaluate the therapeutic effect.

Long-term efficacy of Peg-Interferon/Ribavirin with and without Lamivudine therapy for HBeAg-positive hepatitis B and C dual infection.

BACKGROUND: The optimal therapeutic strategy for hepatitis B virus (HBV) e antigen (HBeAg)-seropositive and hepatitis C virus (HCV) dually infected patients remains unknown. We aimed to elucidate the effectiveness of peginterferon (Peg-IFN)/ribavirin (RBV) with and without lamivudine (LAM) combination therapy in the clinical settings. PATIENTS AND METHODS: Nine patients seropositive for HBV surface antigen, HBeAg, antibodies to HCV and HCV RNA for >6 months were treated with Peg-IFN/RBV with (n = 5) and without (n = 4) a 12-month LAM add-on therapy at treatment week 12. The treatment duration of Peg-IFN/RBV was 24 weeks (HCV genotype 1 [HCV-1] with rapid virological response [RVR] or HCV-2) or 48 weeks (HCV-1 without RVR). Primary endpoints included HBeAg loss and HCV-sustained virological response (SVR). RESULTS: All of the nine patients had undetectable HCV RNA at treatment weeks 4 and 12 and end-of-Peg-IFN/RBV therapy. However, SVR was achieved in 100% of patients treated with triple therapy, compared with only 50% in those with Peg-IFN/RBV therapy (P = 0.167). The 3-year durability of HCV SVR was 100%. HBeAg loss and HBV DNA <2000 IU/mL at 6 months post-LAM treatment were found in 100% and 40% of patients treated with triple therapy, compared with none of the four patients with Peg-IFN/RBV therapy achieved any HBV responses. Of the five patients with triple therapy, four had persistent HBeAg loss during 3-year follow-up period; one developed HBeAg seroreversion 15 months after treatment. CONCLUSION: For HBeAg-positive HBV/HCV dually infected patients, Peg-IFN/RBV was effective for HCV eradication. Add-on LAM might promote HBeAg loss in the clinical setting.

[Spleen, liver and kidney-strengthening formula combined with polyethylene glycol interferon in treatment of chronic hepatitis B].

To observe the clinical efficacy of spleen, liver and kidney-strengthening formula combined with polyethylene glycol interferon in the treatment of HBeAg positive chronic hepatitis B(HP-HBV).One hundred and twenty-six patients with HP-HBV, who were treated in the hospital from June 2012 to December 2014, were selected and injected with polyethylene glycol interferon α-2a(or α-2b). The treatment course for the patients lasted for 24 weeks. Base on the level of HBV-DNA, patients are divided into response group and poor response group. According to random number table, the poor response group were randomized into control group and test group. Patients in the control group were injected with polyethylene glycol interferon α-2a(or α-2b), and patients in the test group were treated with spleen, liver and kidney-strengthening formula combined with polyethylene glycol interferon. Clinical efficacies of the 2 groups were observed, and changes in the level of HBeAg, ALT and HBV-DNA were observed before treatment and at the 24th week after treatment, and virological and serological response, biochemical responses, integral clinical symptoms and signs, adverse reactions were observed after 48 weeks of treatment.After 24 weeks of treatment, the response group was significantly better than the poor response group in HBeAg, ALT and the level of HBV-DNA(P<0.05). After 48 weeks of treatment, there was statistical significance in HBV-DNA negative conversion rate, HBeAg negative conversion rate between the 2 groups(P<0.05), and the test group was better in the two indicators. And the test group was significantly lower than the control group in clinical symptoms and signs score at the 48th week after treatment(P<0.05), with a significantly lower adverse reaction rate than the control group(P<0.05).Combination of spleen, liver and kidney-strengthening formula and polyethylene glycol interferon α-2a was effective and safe in the treatment of chronic hepatitis B, and so worth promoting in clinic.

IFNL3 (IL28B) polymorphism does not predict long-term response to interferon therapy in HBeAg-positive chronic hepatitis B patients.

UNLABELLED: The impact of IFNL3 (IL28B) polymorphism on response to interferon (IFN) treatment in patients infected with hepatitis B virus (HBV) is controversial. We aimed to investigate whether IFNL3 polymorphism (rs12979860) influences the long-term response of chronic hepatitis B (CHB) treatment to conventional IFN. DESIGN: Ninety-seven HBeAg-positive patients treated with IFN were evaluated in this study. Associations were investigated between IFNL3 genotypes and (i) HBeAg seroconversion at the end of treatment (EOT), (ii) sustained virological response (SVR) and (iii) HBsAg seroconversion through long-term follow-up (LTFU). Patients were followed for a median of 14 years. The majority of patients were infected with HBV genotype A (69.6%) and were Caucasian (77.9%). Ninety-five patients were genotyped at rs12979860. Similar IFNL3 distribution was observed among the different ethnicities (P = 0.62) or across HBV genotypes A through G (P = 0.70). Thirty-six patients experienced HBeAg seroconversion at EOT; HBeAg seroconversion rates were 37.0 and 35.5% in patients with CC and CT/TT genotypes, respectively (P = 0.82). Among the 44 patients (45%) who achieved a SVR, SVR rates were 48.9 and 39.6% in patients with CC and CT/TT IL28B genotypes, respectively (P = 0.80). HBsAg seroconversion occurred through LTFU in 28 patients. HBsAg seroconversion rates were 25.5 and 31.2% in patients with CC and CT/TT genotypes, respectively (P = 0.51). No significant relationship between IFNL3 rs12979860 and fibrosis stage was observed (P = 0.85). IFNL3 genotype was neither associated with SVR, nor with HBeAg seroconversion and long-term HBsAg seroconversion in HBeAg-positive CHB patients responding to IFN therapy.

HBeAg-positive chronic hepatitis B: why do i treat my patients with Nucleos(t)ide analogs?

The ultimate goal of therapy for hepatitis B virus (HBV) infection is to obtain a clinical benefit for the patient by reducing infection-related complications, including hepatocellular carcinoma (HCC). Two main types of antiviral agents have been approved to treat patients in the immune clearance phase: interferon (IFN) and nucleos(t)ide analogues (NAs). NAs are used in most HBeAg-positive chronic hepatitis B patients for several reasons. They are oral drugs that are taken once a day and can be prescribed to all chronic hepatitis B patients, even those with contraindications for IFN. The current first-line NA options, entecavir (ETV) and tenofovir (TDF), have minimal or no risk of long-term resistance, and the sustained virological response is achieved in almost 100% of adherent HBeAg-positive patients. Tolerance is excellent and the safety profile is good, whereas IFN can be associated with adverse events that affect the patients' quality of life. There is considerable evidence to show that NAs modify the natural history of chronic hepatitis B, and increasing evidence that they reduce the risk of developing HCC. The need for long-term, perhaps indefinite treatment in patients who do not achieve anti-HBe seroconversion is the main limitation of NAs, but this is offset by their excellent tolerance and safety profile.

Relationship between hepatitis B virus genotype B and C and response to interferon therapy in HBeAg positive chronic hepatitis B patients: A meta-analysis.

BACKGROUND AND AIMS: Previous studies examining the relationship between hepatitis B virus (HBV) genotype B and C and response to interferon therapy in Hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients have yielded conflicting results. We aim to summarize data to reach firm conclusions on the role of HBV genotype B and C in response to interferon therapy. METHODS: PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched for relevant articles published up to March 2013. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated by fixed- or random-effects models. Heterogeneity, sensitivity analysis, and publication bias were also assessed. RESULTS: Fifteen studies were identified. All studies except for those evaluating the rate of end-of-treatment HBeAg seroconversion exhibited significant heterogeneity. There were significant differences in rates of end-of-treatment alanine aminotransferase (ALT) normalization, HBV DNA negative, and HBeAg seroconversion between the genotype B and genotype C groups, but not in HBeAg clearance. The pooled results showed higher rates of sustained ALT normalization (OR = 2.24, 95%CI 1.53-3.27), HBV DNA negative (OR = 2.60, 95%CI 1.65-4.12), HBeAg clearance (OR = 2.13, 95%CI 1.29-3.52) and HBeAg seroconversion (OR = 1.95, 95%CI 1.27-2.98) in patients with genotype B than those with genotype C. The sensitivity analysis did not alter the effects observed in the primary analysis. There was no evidence of publication bias except for HBeAg clearance rate. CONCLUSIONS: The results of the current meta-analysis indicate that HBV genotype B patients receiving interferon therapy respond better to treatment compared with genotype C patients, but this needs to be further examined.

Prevalence and clinical course of hepatitis delta infection in Greece: a 13-year prospective study.

BACKGROUND & AIMS: Hepatitis D virus (HDV) has decreased in Europe, but recent reports indicate a rising trend. We report the epidemiological changes, clinical progress, and effect of treatment on the natural course of HDV infection in Greece during the last 13 years. METHODS: Prospective data were extracted from the HepNet.Greece Cohort-Study. RESULTS: Since 1997, 4673 chronic HBV (CHB) cases (4527 adults, 146 children) have been followed prospectively. Two thousand one hundred thirty-seven patients were tested for anti-HDV [101 (4.7%) positive]. Anti-HDV testing in Greece decreased significantly (57.0% before 2003, 35.3% thereafter; p<0.001). Anti-HDV prevalence among HBsAg-positives was 4.2%; lower in native Greeks (2.8%) than in immigrants (7.5%) or in children (15.3%; p<0.001). Within 2.3 years of follow-up, HDV occurred in 11/2047 HBsAg-positive patients (2.2 new delta-infected adults and 8.7 children per 1000 HBsAg-positive annually). HDV-positive compared to CHB adults were younger (p=0.035) and had more active and advanced disease at baseline, as indicated by laboratory indices and the higher prevalence of cirrhosis at younger age. During a 4.2-year median observation, significantly more anti-HDV-positive than CHB adults developed a liver-related first event (20.0% vs. 8.5%, p Log-rank=0.014).Treatment was received by 46/90 (51.1%) patients, 40 of them interferon-based. In multivariable analysis, interferon significantly decreased disease progression in HDV-positive patients [HR=0.14 (95% CI: 0.02-0.86; p=0.033)]. CONCLUSIONS: In Greece, HDV serology is currently tested in only one-third of HBsAg-positive patients. HDV prevalence is lower in native Greeks compared to immigrants, who may contribute >50% of the HDV infection burden in Greece. Data show that HDV infection is a rapidly progressive disease, but interferon-based treatment may alter its course.

Serum hepatitis B surface antigen quantification as a useful assessment for significant fibrosis in hepatitis B e antigen-positive hepatitis B virus carriers.

BACKGROUND AND AIMS: The role of serum quantitative hepatitis B surface antigen (qHBsAg) in identifying hepatitis B virus (HBV) carriers with significant fibrosis is unknown. This study aims to evaluate the diagnostic value of qHBsAg for hepatic fibrosis in hepatitis B e antigen (HBeAg)-positive HBV carriers. METHODS: Consecutive biopsy-proven HBeAg-positive HBV carriers were prospectively recruited in our center from 2009 to 2011 and were randomly divided into training and validation set. Area under receiver-operator curve (AUC) was used to determine the diagnostic accuracy of simple tests for significant fibrosis (Scheuer stage, F ≥ 2). RESULTS: Overall, a total of 197 eligible patients (median age 31 years; 149 males) were enrolled. The median qHBsAg was 4.20 (log10 IU/mL). Significant fibrosis was confirmed in 112 (56.9%) patients. By logistical regression analysis, qHBsAg and γ-glutamyl transpeptidase were identified as predictors for significant fibrosis in training set (n = 124). Thus, qHBsAg index and γ-glutamyl transpeptidase to qHBsAg ratio (GqHBsR) were selected for the subsequent analysis. In the training set, an AUC of 0.762, 0.826, 0.749, and 0.771 was observed for qHBsAg index, GqHBsR, FIB-4, and aspartate aminotransferase to platelet ratio index, respectively (all P < 0.05). GqHBsR yielded a higher AUC than aspartate aminotransferase to platelet ratio index and FIB-4 (both P < 0.05). Using the optimal cut-off of 7.78, GqHBsR showed a sensitivity of 78.9% and a specificity of 73.6%. About 80% of liver biopsy could be avoided in the entire cohort. CONCLUSIONS: Serum qHBsAg-based simple tests, especially GqHBsR, can accurately and specifically identify significant fibrosis in treatment-naïve HBeAg-positive HBV carriers.

Early Treatment Consideration in Patients with Hepatitis B 'e' Antigen-Positive Chronic Infection: Is It Time for a Paradigm Shift?

Chronic hepatitis B (CHB) is associated with significant morbidity and mortality, due to the adverse sequelae of cirrhosis and hepatocellular carcinoma (HCC). To date, antiviral therapy has been reserved for patients with ostensibly active liver disease, fibrosis or cirrhosis, and/or increased risk of HCC. Historically, patients with hepatitis B 'e' antigen (HBeAg)-positive chronic infection, were not offered antiviral therapy. Nevertheless, there has been compelling evidence emerging in recent years, demonstrating that this disease phase is in fact not characterized by immunological tolerance. HBV integration into the human genome is a frequent event found in these patients. Additionally, it may well be associated with active inflammation and fibrosis, even in the presence of persistently normal liver enzymes. Likewise, it appears that the mechanisms of hepatocarcinogenesis are already present during this early stage of the disease. This was reflected in the European Association for the Study of the Liver (EASL) guidelines, where treating patients above the age of 30 years with HBeAg-positive chronic infection was proposed. Lowering the treatment threshold to broaden treatment eligibility is likely to slow disease progression and reduce the risk of developing HCC. The current review discusses the reasons to consider early antiviral therapy in HBeAg-positive chronic infection.

Change of Cytokines in Chronic Hepatitis B Patients and HBeAg are Positively Correlated with HBV RNA, Based on Real-world Study.

Background and Aims: The natural course of chronic hepatitis B virus (HBV) infection is widely studied; however, follow-up studies of the same patients are scanty. Here, we studied the dynamic changes of serum HBV RNA and cytokines in hepatitis B virus e antigen (HBeAg)-positive patients treated with entecavir (ETV) to explore the relationship between the HBV serum viral nucleic acids and host immunity. Methods: Thirty-three chronic hepatitis B patients who are HBeAg-positive, with high virus load (HBV DNA >20,000 IU/mL), and received standard nucleos(t)ide analogue (NA) antiviral therapy (ETV) for more than 48 weeks were included. The serum levels of HBV nucleic acids and selected cytokines were measured at 0, 12, 24, and 48 weeks respectively. Results: Serum HBV RNA could still be detected while serum HBV DNA had fallen below the detection limit in patients treated with ETV. There was a strong positive correlation between HBV RNA and HBeAg, with a concomitant decrease in the secretion of cytokines from type 1 helper T (Th1)/type 2 helper T (Th2)/interleukin (IL)-17 producing T (Th17) cells. IL-4 and IL-10 were the main cytokines negatively associated with serum HBV RNA. Conclusions: HBeAg can be used to reflect the load of HBV RNA indirectly, because serum HBV RNA has not been widely used in clinical practice. Meanwhile, serum IL-4 and IL-10 might be explored in combination with HBV RNA in guiding future clinical antiviral therapy.

Consolidation treatment needed for sustained HBsAg-negative response induced by interferon-alpha in HBeAg positive chronic hepatitis B patients.

Hepatitis B surface antigen (HBsAg) clearance is considered as functional cure in patients with chronic hepatitis B (CHB). This study aimed to assess the durability of HBsAg clearance achieved by interferon-based therapies in patients with CHB who were originally positive for hepatitis B envelope antigen (HBeAg). In this prospective study, HBeAg-positive CHB patients with confirmed HBsAg loss under interferon-based therapies were enrolled within 12 weeks from end of treatment and followed up for 48 weeks. Virological markers, biochemical indicators, and liver imaging examinations were observed every 3-6 months. Sustained functional cure was analysed as primary outcome. Factor associated with sustained HBsAg loss or reversion was also investigated. The rate of HBsAg loss sustainability was 91.8% (212/231). Patients receiving consolidation treatment for 12-24 weeks or ≥ 24 weeks had higher rates of sustained HBsAg negativity than those receiving consolidation treatment for < 12 weeks (98.3% and 91.2% vs. 86.7%, P â€‹= â€‹0.068), and the former groups had significantly higher anti-HBs levels than the later (P â€‹< â€‹0.05). The cumulative incidence of HBsAg reversion and HBV DNA reversion was 8.2% and 3.9%, respectively. Consolidation treatment of ≥ 12 weeks [odd ratio (OR) 3.318, 95% confidence interval (CI) 1.077-10.224, P â€‹= â€‹0.037) was a predictor of sustained functional cure, and HBeAg-positivity at cessation of treatment (OR 12.271, 95% CI 1.076-139.919, P â€‹= â€‹0.043) was a predictor of HBsAg reversion. Interferon-alpha induced functional cure was durable and a consolidation treatment of ≥ 12-24 weeks was needed after HBsAg loss in HBeAg-positive CHB patients.

Interpretation of HBV Serologies.

Hepatitis B was discovered by researchers who were investigating jaundice associated with blood transfusions as well as parenterally administered medications. Through trial and error, the HBV was identified. There are specific tests that detect HBV infection, whether it is a previous exposure or active infection. The various HBV serologies are reviewed in this work as well. Hepatitis B surface antigen has emerged as a tool in defining treatment endpoint and its significance is reviewed. HBV genotypes are distributed uniquely throughout the world, in particular, genotype C is associated with higher rates of hepatocellular carcinoma. Various HBV genotypes and their impact on the clinical course are discussed. The relationship of HBV serologies and HBV DNA to disease progression is outlined. There are specific recommendations on monitoring those infected with HBV and this is reviewed here. HBV mutations have an impact on the disease course and those of significance are also discussed.

Suboptimal Response to Tenofovir Alafenamide in Two Patients With HBeAg-Positive Hepatitis B: A Case Report.

Tenofovir alafenamide (TAF) is one of the most potent first-line nucleot(s)ide analogs for treating chronic hepatitis B virus (HBV) infections. To date, no cases of TAF drug resistance and/or suboptimal response have been reported. To our knowledge, this is the first report of two adult male patients presenting a suboptimal response response to TAF monotherapy. Our study indicates long-term observations and extensive data are needed to further evaluate the efficacy and safety of TAF, and highlights the need for the development of robust novel direct-acting antivirals and immune therapies for HBV.