Baseline Hepatitis B Surface Antigen Levels Research Articles

A nation-wide medical record database study: Value of hepatitisB surface antigen loss in chronic hepatitisB patients in Japan.

HepatitisB surface antigen (HBsAg) seroclearance is considered to be one of the best surrogate endpoints of functional cure for hepatitisB virus (HBV) infection. However, evidence regarding the relationship between achieving HBsAg seroclearance or a low baseline HBsAg level, and long-term clinical outcomes in Japanese patients with chronic HBV infection remains to be confirmed in a real-world setting. A retrospective observational cohort study was performed with an electronic medical record database, including data from 230 hospitals across Japan. Chronic HBV infection was defined as two consecutive, positive HBsAg laboratory measurements for HBV infection. The date of the second positive was used as a baseline to identify subsequent HBsAg seroclearance and liver disease progression. In the database, 2523 patients with chronic HBV infection were identified as the chronic hepatitisB (CHB) cohort. Among the CHB cohort with an average observational period of 5.19±3.87years, 202 patients (8%) achieved HBsAg seroclearance after baseline. They had a lower risk of developing hepatocellular carcinoma (HCC) (adjusted hazard ratio [aHR] 0.206, p<0.01) and cirrhosis (aHR 0.361, p<0.01). When the CHB cohort was stratified into two groups based on baseline HBsAg levels (<100IU/mL and ≥100IU/mL), patients with a lower baseline level of HBsAg (<100IU/mL) had a lower risk of developing liver disease (HCC aHR 0.600, p<0.01; cirrhosis aHR 0.618, p<0.05). These results confirm the clinical significance of HBsAg seroclearance and low HBsAg level at baseline with respect to long-term outcomes of patients with CHB in the Japanese population.

Predictive Value of Baseline Serum Marker Levels for the Effect of Interferon Therapy in Patients With Chronic Hepatitis B

To study the changes in the serum markers in chronic hepatitis B patients who have had previous treatment with long-acting interferon therapy of nucleoside and those who have not and to assess the value of the serum markers for clinical prognosis evaluation. The clinical data of 411 cases of chronic hepatitis B were collected. All cases were given the additional treatment of long-acting interferon between October 2019 to April 2022. The cases were divided into two groups, a previously treated group consisting of patients who had been treated with nucleoside and nucleotide analogues (NAs) for more than 6 months after they became infected with hepatitis B virus (HBV) for over 6 months and an initial treatment group, or treatment naïve group, consisting of patients who had HBV infection for over 6 months and received no treatment or patients who have stopped NAs therapy for more than 6 months. The serum marker levels of the previously treated group and the initial treatment group, i.e., the previously treatment-naïve patients, were compared, and the receiver operating characteristics (ROC) curve was used to evaluate the value of the baseline levels of hepatitis B surface antigen (HBsAg) and HBV pregenomic RNA (pgRNA) for predicting the rate of cured cases in the two groups. There was no significant difference in the rate of cured cases between the previously treated group and the initial treatment group. The baseline HBV DNA, HBsAg, and hepatitis B e antigen (HBeAg) levels of the cured cases in both groups were significantly lower than those in the uncured cases (P<0.0001). After 48 weeks of treatment, the serum HBsAb levels (mIU/mL) of the cured cases in both the previously treated and initial treatment groups were significantly higher than those of the uncured cases in the two groups (previously treated group: 78.97±22.57 vs. 0.99±0.38, P<0.0001; initial treatment group: 235.50±175.00 vs. 1.32±0.88, P<0.0001). The serum HBsAb levels (mIU/mL) of the cured cases in the initial treatment groups were significantly higher than that of cured cases in the previously treated group (235.50±175.00 vs. 78.97±22.57, P<0.0001). Within 0 to 60 weeks of treatment, HBV pgRNA levels of cured cases in both groups were significantly lower than those of the the uncured cases in both groups (P<0.0001). Multivariate logistic regression and ROC curve analysis showed that baseline serum HBsAg was the influencing factor and predictor of interferon efficacy in both the previously treated cases and the initial treatment cases, with the area under the curve (AUC) being 0.80 (95% confidence interval [CI]: 0.7423-0.8615, P<0.0001) and 0.74 (95% CI: 0.6283-0.8604, P=0.0079), respectively, and the optimal cut-off values being 244.60 IU/mL and 934.40 IU/mL, respectively. However, the baseline serum HBV pgRNA level of under 1340.00 copies/mL in the initial treatment cases led to better sensitivity and better specificity in efficacy prediction, with the AUC of the baseline HBV pgRNA being 0.9649 (95% CI: 0.9042-1.0000, P<0.0001). Among the previously treated cases and the initial treatment cases, patients who achieve clinical cure have lower levels of HBV DNA, HBsAg, and HBeAg at baseline, lower level of HBV pgRNA over the course of their treatment, and higher level of HBsAb at week 48. Baseline HBsAg levels can be used to effectively predict the clinical cure outcomes in previously treated cases and initial treatment cases. Baseline HBV pgRNA levels also exhibit a high predictive value for treatment outcomes in initial treatment cases.

Functional cure is associated with younger age in children undergoing antiviral treatment for active chronic hepatitis B

Background and AimsFunctional cure is difficult to achieve using current antiviral therapies; moreover, limited data are available regarding treatment outcomes in children. This retrospective study aimed to assess the frequency of functional cure among children undergoing antiviral treatment for active chronic hepatitis B (CHB).MethodsA total of 372 children aged 1–16 years, with active CHB were enrolled and underwent either nucleos(t)ide analog monotherapy or combination therapy with interferon-α (IFN-α) for 24–36 months. All children attended follow-up visits every 3 months. Functional cure was defined as evidence of hepatitis B virus (HBV) DNA loss, circulating hepatitis B e antigen (HBeAg) loss/seroconversion, and hepatitis B surface antigen (HBsAg) loss.ResultsAfter 36 months of antiviral treatment and/or follow-up visits, children with CHB aged 1– < 7 years exhibited higher rates of HBV DNA clearance, HBeAg seroconversion, and HBsAg loss than CHB children ≥ 7–16 years of age (93.75% versus [vs.] 86.21% [p < 0.0001]; 79.30% vs. 51.72% [p < 0.0001]; and 50.78% vs. 12.93% [p < 0.0001], respectively). Longitudinal investigation revealed more rapid dynamic reduction in HBV DNA, HBeAg, and HBsAg levels in children aged 1–7 years than in those aged ≥ 7–16 years with CHB. According to further age-stratified analysis, HBsAg loss rates were successively decreased in children with CHB who were 1– < 3, 3– < 7, 7– < 12, and 12–16 years of age (62.61% vs. 41.13% vs. 25.45% vs. 1.64%, respectively; p < 0.0001) at 36 months. In addition, baseline HBsAg level < 1,500 IU/mL was found to favor disease cure among these pediatric patients. No serious adverse events were observed throughout the study period.ConclusionResults of the present study demonstrated that children aged 1– < 7 years, with active CHB can achieve a high functional cure rate by undergoing antiviral therapy compared to those aged ≥ 7 years, who undergo antiviral therapy. These data support the use of antiviral treatment at an early age in children with CHB. However, future prospectively randomized controlled trials are necessary to validate the findings of this study.Graphical The younger age, the higher functional cure rate in children with chronic hepatitis B undergoing on-time antiviral treatment.

A high functional cure rate was induced by pegylated interferon alpha-2b treatment in postpartum hepatitis B e antigen-negative women with chronic hepatitis B virus infection: an exploratory study.

Limited data have been reported on achieving functional cure using pegylated interferon (Peg-IFN) alpha-2b treatment for postpartum hepatitis B e antigen (HBeAg)-negative women with chronic hepatitis B virus (HBV) infection. This study was to assess the effectiveness and safety of Peg-IFN alpha-2b in HBV postpartum women without HBeAg and identify factors linked to the functional cure. A total of 150 HBeAg-negative postpartum women were retrospectively recruited.47 patients received Peg-IFN alpha-2b [Peg-IFN(+) group] and 103 patients did not [Peg-IFN(-) group]. Propensity score matching (PSM) was used to adjust the baseline imbalance between the two groups. The patients were followed for at least 48 weeks. The primary endpoints were hepatitis B surface antigen(HBsAg) loss and HBsAg seroconversion at 48 weeks. Logistic regression analysis was used to assess factors associated with HBsAg loss at 48 weeks. At week 48,the HBsAg loss and seroconversion rate in Peg-IFN(+) group were 51.06%(24/47) and 40.43%(19/47), respectively. Even after PSM, Peg-IFN(+) group still showed higher HBsAg loss rate (50.00% vs 7.14%,p<0.001) and higher HBsAg seroconversion rate (38.10% vs 2.38%,p<0.001). Baseline HBsAg levels (Odds Ratio [OR]: 0.051, 95% Confidence Interval [CI]: 0.003-0.273, P=0.010), HBsAg at week 24 (OR:0.214, 95%CI:0.033-0.616, P=0.022), HBsAg decline at week 24 (OR:4.682, 95%CI: 1.624-30.198, P=0.022) and postpartum flare (OR:21.181, 95%CI:1.872-633.801, P=0.030) were significantly associated with HBsAg loss at week 48 after Peg-IFN alpha-2b therapy. Furthermore, the receiver operating characteristic curve (ROC) showed that the use of baseline HBsAg<182 IU/mL, HBsAg at week24 < 4 IU/mL and HBsAg decline at week24>12IU/mL were good predictors of HBsAg loss. No serious adverse events were reported. Peg-IFN alpha-2b treatment could achieve a high rate of HBsAg loss and seroconversion in HBeAg-negative postpartum women with reliable safety, particularly for patients experience postpartum flare and have low baseline HBsAg levels.

A study of the clinical curative effect of nucleos(t)ide analogues treated to pegylated interferon-α add-on therapy in patients with chronic hepatitis B

Objective: To investigate the hepatitis B surface antigen (HBsAg) clearance condition and its predictive factors after treatment with nucleos(t)ide analogues to pegylated interferon-α add-on therapy in patients with chronic hepatitis B. Methods: Patients with chronic hepatitis B who visited the First Affiliated Hospital of Zhengzhou University from 2018~2019 were prospectively enrolled. HBsAg≤ 1500 IU/mL, hepatitis B e antigen-negative, HBV DNA undetectable, received antiviral treatment with nucleos(t)ide analogues for at least one year, and pegylated interferon-α add-on therapy for 48 weeks were included. The primary endpoint of study was to determine the proportion of HBsAg clearance at 72 weeks. Concurrently, the predictive factors for HBsAg clearance were analyzed. Quantitative and qualitative data were analyzed using a t-test or non-parametric test and a Fisher's exact test. Results: A total of 38 cases were included in this study, of which 13 cases obtained HBsAg clearance at 48 weeks of therapy and another six cases obtained HBsAg clearance throughout the extended treatment period of 72 weeks, accounting for 50.00% of all enrolled patients. There was a significant difference in HBsAg dynamics between the HBsAg clearance group and the non-clearance group (P < 0.05). Univariate logistic regression analysis showed that patients' age, baseline, 12-and 24-week HBsAg levels, and early HBsAg reduction were predictive factors for HBsAg clearance at 72 weeks of treatment. Multivariate logistic regression analysis showed that age (OR = 1.311; P = 0.016; 95% confidence interval: 1.051~1.635) and HBsAg levels at 24 weeks of treatment (OR = 4.481; P = 0.004; 95% confidence interval: 1.634~12.290) were independent predictors for HBsAg clearance. Conclusion: Hepatitis B e antigen-negative, nucleos(t)ide analogue treated, HBsAg ≤ 1500 IU/mL, and HBV DNA undetectable, peg-IFNα add-on treatment for 48 weeks could promote HBsAg clearance in patients with chronic hepatitis B. Six of the sixteen cases (37.50%) who did not obtain HBsAg clearance at week 48 did so with the course of therapy extended to week 72. Hence, the optimal individualized treatment strategy should be customized according to the predictors rather than the fixed 48-week course. Age (≤ 38), baseline HBsAg level (≤2.86 log(10)IU/ml), HBsAg level at 24 weeks (≤ 0.92 log(10)IU/ml), and 12-week HBsAg decrease from baseline (≥ 0.67 log(10)IU/ml) indicate that patients are highly likely to obtain HBsAg clearance at the 72 weeks of combination therapy, in which the combined indicator based on HBsAg level ≤0.92 log(10)IU/ml at 24 weeks will identify 85.0% to 100.0% of patients with HBsAg clearance.

A simple-to-use score system for predicting HBsAg clearance to peginterferon alfa-2b in nucleoside analogs-experienced chronic hepatitis B patients

ObjectivePatients with chronic hepatitis B (CHB) often fail to achieve clearance of the hepatitis B surface antigen (HBsAg) with peginterferon treatment. Our study aimed to develop a simple-to-use scoring system to predict the likelihood of HBsAg clearance following treatment with peginterferon alfa-2b(PEG-IFN-α2b) in patients with CHB.MethodsA total of 231 patients were enrolled and divided into HBsAg clearance (n = 37) and non-HBsAg clearance (n = 194) groups. Multifactor logistic models were constructed using univariate and multiple logistic regression analyses. The area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis were used to evaluate the discrimination, calibration, and clinical applicability of the predictive scoring system.ResultsFour clinical variables (age, baseline HBsAg level, HBsAg level decline at week 12, and alanine aminotransferase ratio at week 12) were independently associated with HBsAg clearance after PEG-IFN-α2b treatment and, therefore, were used to develop a predictive scoring system ranging from 0 to 13. The optimal cut-off value was &amp;gt;4, with a sensitivity of 86.49%, specificity of 72.16%, positive predictive value of 37.2%, negative predictive value of 96.6%, and an AUC of 0.872. This model exhibited good discrimination, calibration, and clinical applicability. Among patients with scores &amp;lt;4, 4, or &amp;gt; 4 HBsAg clearance was achieved in 0.85, 14.29, and 37.21% of the patients, respectively.ConclusionThe scoring system could effectively predict the predominance of HBsAg clearance after PEG-IFN-α2b treatment in the early stage. This may be helpful when making clinical decisions for the treatment of patients with CHB.

Incidence and factors associated with hepatitis B surface antigen seroclearance in patients co-infected with HBV/HIV during antiretroviral therapy in Guangdong, China.

Hepatitis B surface antigen (HBsAg) clearance is vital for a functional cure of hepatitis B virus (HBV) infection. However, the incidence and predictors of HBsAg seroclearance in patients co-infected with HBV and human immunodeficiency virus (HIV) remain largely unknown in Guangdong, China. Between 2009 and 2019, patients co-infected with HBV/HIV undergoing antiretroviral therapy (ART) in Guangzhou Eighth People's Hospital affiliated to Guangzhou Medical University were retrospectively reviewed with the endpoint on December 31, 2020. The incidence and risk factors for HBsAg seroclearance were evaluated using Kaplan-Meier and multivariate Cox regression analyses. A total of 1550 HBV/HIV co-infected patients were included in the study, with the median age of 42 years and 86.0% (1333/1550) males. Further, 98.3% (1524/1550) received ART containing tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC). HBV DNA was examined in 1283 cases at the last follow-up. Over the median 4.7 years of follow-up, 8.1% (126/1550) patients achieved HBsAg seroclearance, among whom 50.8% (64/126) obtained hepatitis B surface antibody, 28.1% (137/488) acquired hepatitis B e antigen seroconversion, and 95.9% (1231/1283) undetectable HBV DNA. Compared with patients who maintained HBsAg positive, cases achieving HBsAg seroclearance showed no differences in age, gender, CD4 + T cell count, alanine aminotransferase (ALT) level, or fibrosis status; however, they presented lower HBV DNA levels, lower HBsAg levels, and higher rates of HBV genotype B at the baseline. Multivariate analysis showed that baseline HBsAg <1500 cutoff index (COI) (adjusted hazard ratio [aHR], 2.74, 95% confidence interval [95% CI]: 1.48-5.09), ALT elevation >2 × upper limit of normal during the first six months after receiving ART (aHR, 2.96, 95% CI: 1.53-5.77), and HBV genotype B (aHR, 3.73, 95% CI: 1.46-9.59) were independent predictors for HBsAg seroclearance (all P <0.01). Long-term TDF-containing ART has high anti-HBV efficacy including relatively high overall HBsAg seroclearance in HBV/HIV co-infected patients. Lower baseline HBsAg levels, HBV genotype B, and elevated ALT levels during the first six months of ART are potential predictors of HBsAg seroclearance.

The Predictive Role of Hepatitis B Biomarkers on HBV Reactivation following Direct-Acting Antiviral Therapy in HBV/HCV Coinfected Patients.

Hepatitis B and C (HBV/HCV) coinfected patients have a potential risk of hepatitis B reactivation (HBVr) after direct-acting antivirals (DAAs) treatment. The study intends to investigate the predictive role of HBV biomarkers in HBVr. Forty-six HBV/HCV coinfected patients receiving DAAs were enrolled. All patients completed treatment and follow-up to the 12th-week post-DAA treatment (P12). Blood samples were measured for HBV biomarkers, including hepatitis B surface antigen (HBsAg), hepatitis B core-related antigen (HBcrAg), and HBV pregenomic RNA (HBV pgRNA). The predictive factors for HBVr after DAA treatment were analyzed. Among 31 patients without nucleot(s)ide analogue (NA) treatment, seven (22.5%, 7/31) developed HBVr without hepatitis flare-up. Patients with HBVr had higher HBsAg titers than those without HBVr from baseline to P12 (p = 0.008, 0.009, 0.004, and 0.006 at baseline, week 4, end of treatment, and P12, respectively). The baseline HBsAg level was the only predictive factor associated with HBVr (HR, 2.303; 95% CI, 1.086–4.882; p = 0.030). In predicting HBVr, a baseline HBsAg titer > 20 IU/mL had a sensitivity, specificity, positive predictive value, and negative predictive value of 85.7%, 75.0%, 50%, and 94.7%, respectively. No patient had HBVr if the baseline HBsAg titer was <8 IU/mL. Serum HBcrAg and HBV pgRNA levels had no role in predicting HBVr. In conclusion, HBV/HCV coinfected patients are at risk of HBVr after DAA treatment. The baseline HBsAg level was the predictive factor associated with HBVr. Patients with a baseline HBsAg titer < 8 IU/mL can be considered as not having HBVr.

Pegylated interferon-α-2b combined with tenofovir disoproxil fumarate, granulocyte-macrophage colony-stimulating factor, and hepatitis B vaccine treatment for naïve HBeAg-positive chronic hepatitis B patients: A prospective, multicenter, randomized controlled study.

Hepatitis B surface antigen (HBsAg) loss or seroconversion is an ideal treatment endpoint for patients with chronic hepatitis B but is rarely achievable inhepatitis B e-antigen(HBeAg)-positive patients using existing treatment strategies. In this study, the effect of pegylated interferon (peg-IFN) alfa-2b plus tenofovir disoproxil fumarate (TDF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and hepatitis B vaccine was evaluated.This randomized controlled trial was conducted at nine liver centers in Chinese university hospitals from May 2018 to July 2020. Patients (n = 303) enrolled were randomly administered peg-IFN-α-2b combined with TDF, GM-CSF, and hepatitis B vaccine (experimental group); peg-IFN-α-2b plus TDF (control group 2); or interferon-α-2b alone (control group 1). The primary efficacy endpoint was HBsAg seroconversion at 48 weeks and the secondary endpoint included safety.No differences in baseline HBsAg levels were observed among the groups. The primary endpoint was achieved in three (3.0%), one (1.03%), and one (1.19%) patient in the experimental group, control group 2, and control group 1, respectively. The incidence of HBsAg seroconversion at week 48 was not significantly different among the three groups (p = 0.629). However, the decrease in serum levels of HBsAg at week 48 was significantly higher in the experimental and control group 2 compared with that in control group 1 (p = 0.008 and 0.006, respectively). No significant difference between the experimental and control group 2 was observed (p = 0.619). Adverse events were not significantly different among the groups except for the lower incidence of neutropenia in the experimental group.Peg-IFN-α-2b combined with TDF, GM-CSF, and hepatitis B vaccine is not superior to peg-IFN-α-2b combined with TDF in HBeAg-positive naïve patients. Clinical Trials Registration:ChiCTR1800016173.

Real-world study on HBsAg loss of combination therapy in HBeAg-negative chronic hepatitis B patients.

Combination therapy with pegylated interferon (PEG-IFN) and nucleos(t)ide analogues (NAs) can enhance hepatitis B surface antigen (HBsAg) clearance. However, the specific treatment strategy and the patients who would benefit the most are unclear. Therefore, we assessed the HBsAg loss rate of add-on PEG-IFN and explored the factors associated with HBsAg loss in chronic hepatitis B (CHB) patients. This was a real-world cohort study of adults with CHB. Hepatitis B e antigen (HBeAg)-negative NAs-treated patients with baseline HBsAg ≤1500 IU/ml and HBV DNA < the lower limit of detection, or 100 IU/ml, received 48 weeks of add-on PEG-IFN. The primary outcome of the study was the rate of HBsAg loss at 48 weeks of combination treatment. Using multivariable logistic regression analysis, we determined factors associated with HBsAg loss. HBsAg loss in 2579 patients (mean age: 41.2 years; 80.9% male) was 36.7% (947 patients) at 48 weeks. HBsAg loss was highest in patients from south-central and southwestern China (40.0%). Factors independently associated with HBsAg loss included: increasing age (odds ratio=0.961); being male (0.543); baseline HBsAg level (0.216); HBsAg decrease at 12 weeks (between 0.5 and 1.0 log10 IU/ml [2.405] and >1.0 log10 IU/ml [7.370]); alanine aminotransferase (ALT) increase at 12 weeks (1.365); haemoglobin (HGB) decrease at 12 weeks (1.558). There was no difference in the primary outcomes associated with the combination regimen. In conclusion, HBsAg loss by combination therapy was higher in patients from southern China than those from the north. An increased chance of HBsAg loss was associated with baseline characteristics and dynamic changes in clinical indicators.

Serum soluble programmed cell death 1 levels predict spontaneous functional cure in inactive carriers with chronic hepatitis B.

Hepatitis B surface antigen (HBsAg) seroclearance is the most important milestone indicating favourable clinical outcomes in patients with chronic hepatitis B (CHB). However, it is difficult to achieve due to the impaired HBV-specific immunity, such as programmed cell death 1 (PD-1)-associated T cell exhaustion. We assessed soluble PD-1 (sPD-1) as a novel seromarker for predicting spontaneous HBsAg loss. Serial serum levels of sPD-1 were evaluated in 1046 untreated hepatitis B e antigen (HBeAg)-seronegative individuals who had achieved undetectable serum HBV DNA. Multiple regression analyses were applied to assess associations among baseline and subsequent sPD-1 levels, HBsAg decline during follow-up, and spontaneous HBsAg seroclearance. A total of 390 individuals achieved spontaneous HBsAg seroclearance during 6464.4 person-years of follow-up. Baseline sPD-1 levels were inversely associated with baseline HBsAg levels (qHBsAg) as well as a greater decline in qHBsAg during follow-up. Incidence rates of HBsAg seroclearance were 11.5, 61.7, 96.7 and 151.0 per 1000 person-years for sPD-1 levels of ≥4000, 536-3999, 125-535 and <125pg/mL, respectively (Ptrend <0.0001). Compared with baseline sPD-1 levels ≥4000pg/mL, the rate ratio (95% CI) of HBsAg seroclearance was 2.1 (1.1-3.9), 3.0 (1.6-5.5) and 5.1 (2.8-9.5), for baseline sPD-1 levels of 536-3999, 125-535 and <125pg/mL, respectively, after adjustment for sex, age and serum alanine aminotransferase and HBsAg levels. sPD-1 level is a novel marker which independently predicts spontaneous HBsAg seroclearance of HBeAg-negative inactive CHB patients with undetectable HBV DNA. (word count: 234, <250).

Pegylated Interferon Treatment for the Effective Clearance of Hepatitis B Surface Antigen in Inactive HBsAg Carriers: A Meta-Analysis.

BackgroundExpanding antiviral therapy to benefit more populations and optimizing treatment to improve prognoses are two main objectives in current guidelines on antiviral therapy. However, the guidelines do not recommend antiviral therapy for inactive hepatitis B surface antigen (HBsAg) carriers (IHCs). Recent studies have shown that antiviral therapy is effective with good treatment outcomes in IHC populations. We conducted a systematic review and meta-analysis of HBsAg clearance and conversion in IHCs.MethodsWe searched PubMed, Embase, Medline, and Web of Science to retrieve articles on HBsAg clearance in IHCs published between January 2000 and August 2021. Data were collected and analysed using the random-effects model for meta-analysis.ResultsA total of 1029 IHCs from 11 studies were included in this analysis. The overall HBsAg clearance rate was 47% (95% confidence interval (CI): 31% - 64%), with a conversion rate of 26% (95% CI: 15% - 38%) after 48 weeks of Pegylated interferon (Peg-IFN) treatment. In the control group (including nucleos(t)ide analogue (NA) treatment or no treatment), the overall HBsAg clearance rate was only 1.54% (95% CI: 0.56% - 3.00%), which was markedly lower than that in the Peg-IFN group. Further analysis showed that a low baseline HBsAg level and long treatment duration contributed to a higher HBsAg clearance rate.ConclusionThis study showed that treatment of IHCs can be considered to achieve a clinical cure for chronic hepatitis B virus (HBV) infection. After Peg-IFN treatment, the HBsAg clearance rate was 47%, and the conversion rate was 26%, which are markedly higher than those reported by previous studies on Peg-IFN treatment in patients with chronic hepatitis B (CHB). A low baseline HBsAg level and long treatment duration were associated with HBsAg clearance in IHCs. Therefore, antiviral therapy is applicable for IHCs, a population who may be clinically cured.Systematic Review Registration http://www.crd.york.ac.uk/PROSPERO, CRD): CRD42021259889.

Virological breakthrough after immune checkpoint inhibitor and nucleos(t)ide analog treatment in patients with hepatitis B surface antigen positive hepatocellular carcinoma: a real-world study

BackgroundImmune checkpoint inhibitors (ICIs) have been shown to be a promising and effective treatment for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, there is a lack of evidence-based data...

Usefulness of a Hepatitis B Surface Antigen-Based Model for the Prediction of Functional Cure in Patients with Chronic Hepatitis B Virus Infection Treated with Nucleos(t)ide Analogues: A Real-World Study.

In patients with chronic hepatitis B (CHB) under long-term treatment with nucleso(t)ide analogues (NAs), the loss of hepatitis B surface antigen (HBsAg) is a rare event. A growing body of evidence supports the use of quantitative HBsAg for the prediction of functional cure, although these results are mainly derived from studies performed on Asian patients with hepatitis B e antigen (HBeAg)-positive CHB. Here, we investigated the clinical role of quantitative HBsAg in a real-life cohort of CHB patients under treatment with NAs in a tertiary care center from North-West Italy. A total of 101 CHB patients (HBeAg-negative, n = 86) undergoing NAs treatment were retrospectively enrolled. HBsAg was measured at baseline (T0), 6 months (T1), 12 months (T2) and at the last follow-up (FU). Median FU was 5.5 (3.2–8.3) years; at the end of FU, 11 patients lost the HBsAg (annual incidence rate = 1.8%). Baseline HBsAg levels were significantly different between patients with no HBsAg loss and those achieving a functional cure (3.46, 2.91–3.97 vs. 1.11, 0.45–1.98 Log IU/mL, p < 0.001). Similarly, the HBsAg decline (Δ) from T0 to T2 was significantly different between the two groups of patients (0.05, −0.04–0.13, vs. 0.38, 0.11–0.80 Log IU/mL, p = 0.002). By stratified cross-validation analysis, the combination of baseline HBsAg and ΔHBsAg T0–T2 showed an excellent accuracy for the prediction of HBsAg loss (C statistic = 0.966). These results corroborate the usefulness of quantitative HBsAg in Caucasian CHB patients treated with antivirals for the prediction of HBsAg seroclearance.

Predictors of Virological Suppression After Clinical Relapse in Patients Who Discontinued Entecavir or Tenofovir.

The predictors of persistent virological suppression after clinical relapse remain unclear. To investigate the predictors of retreatment or persistent virological suppression after clinical relapse in chronic hepatitis B (CHB) patients who discontinued entecavir or tenofovir disoproxil fumarate (TDF). A total of 243 hepatitis B e antigen-negative CHB patients without cirrhosis who experienced clinical relapse after entecavir or TDF cessation were enrolled. Of the 243 CHB patients, 192 received retreatment and 51 did not receive retreatment after clinical relapse. Of the 51 patients without retreatment, 23 achieved persistent virological suppression (persistent HBV DNA < 2000IU/mL at least 2years) and 10 experienced hepatitis B surface antigen (HBsAg) loss. The Cox regression analysis showed that short consolidation duration, short duration of the first clinical relapse from the end of treatment (EOT), and high bilirubin and HBV DNA levels at the first clinical relapse were independent predictors of retreatment. Long duration of the first clinical relapse from the EOT and low HBsAg levels at the first clinical relapse were independent factors of patients with persistent virological suppression. The rates of persistent virological suppression at the first clinical relapse among patients with HBsAg < 100 and ≥ 100IU/mL were 44.4% (12/27) and 5.1% (11/216) (P < 0.001), respectively. Baseline HBsAg levels and no retreatment requirement were independent factors associated with HBsAg loss. The HBsAg of 100IU/mL at the first clinical relapse could predict persistent virological suppression after clinical relapse in patients who discontinued entecavir or TDF therapy.

Factors Associated with Hepatitis B Surface Antigen Kinetics and Responses in Pegylated Interferon Alpha-2a Monotherapy for Patients with Chronic Hepatitis B.

Objective Pegylated-interferon monotherapy is the standard treatment for patients with chronic hepatitis B; however, the factors associated with its therapeutic effects remain unclear. Methods Patients with chronic hepatitis B were treated with pegylated interferon α-2a for 48 weeks. We evaluated the kinetics of hepatitis B surface antigen (HBsAg) during treatment and follow-up periods and the factors associated with an HBsAg response (defined as a change in HBsAg of ≥-1 log IU/mL from baseline). Results The study population comprised 50 patients. The median baseline levels of hepatitis B virus DNA and HBsAg were 5.00 and 3.40 log IU/mL. The median values of HBsAg reduction from baseline were -0.44 (n=48), -0.41 (n=40), and -0.68 (n=11) log IU/mL at the end of treatment and at 48 and 144 weeks post-treatment, respectively. The rates of HBsAg response were 24.0% and 22.5% at the end of treatment and at 48 weeks post-treatment, respectively. A multivariate analysis identified HBsAg <3.00 log IU/mL as an independent baseline factor contributing to the HBsAg response at the end of treatment and 48 weeks post-treatment (p=1.07×10-2 and 4.42×10-2, respectively). There were significant differences in the reduction of the HBsAg levels at 12 weeks of treatment and in the incidence of serum ALT increase during treatment between patients with and without an HBsAg response. Conclusion These findings suggest that the baseline HBsAg level, HBsAg kinetics at 12 weeks of treatment, and ALT increase during treatment are important factors contributing to the HBsAg response in pegylated interferon α-2a monotherapy for patients with chronic hepatitis B.

Short-term Peginterferon-Induced High Functional Cure Rate in Inactive Chronic Hepatitis B Virus Carriers With Low Surface Antigen Levels.

BackgroundNone of the current guidelines recommend antiviral therapy for inactive hepatitis B virus (HBV) carriers (IHCs).MethodsIn this real-world, multicenter, nonrandomized study, 32 participants meeting the inclusion criteria were enrolled 1:1 for treatment with peginterferon α-2b or monitoring without treatment based on participant preference. The expected treatment duration was 48 weeks. The primary end point was hepatitis B surface antigen (HBsAg) loss. The HBV vaccine could be injected after HBsAg loss.ResultsAll patients had HBsAg levels of <20 IU/mL. The mean baseline HBsAg levels were 6.6 IU/mL and 5.8 IU/mL in the treated and untreated groups, respectively. Fifteen (93.8%) participants achieved HBsAg loss, 5 obtained HBsAg seroconversion after undergoing a mean of 19.7 weeks of therapy in the treated group, and no one in the follow-up group achieved HBsAg loss during a mean follow-up time of 12.6 months (P < .0001). Generally, the therapy was well tolerated. Nine of 11 individuals who exhibited HBsAg loss benefited from receiving the HBV vaccine.ConclusionsThis study provides justification for further studies of short-course peginterferon α-2b for the functional cure of IHCs with low HBsAg levels. Additionally, HBV vaccine injection is beneficial after interferon-induced HBsAg loss.

HBsAg quantification predicts off-treatment response to interferon in chronic hepatitis B patients: a retrospective study of 250 cases

BackgroundFor chronic hepatitis B (CHB) patients without willingness to extend the routine duration of interferon (IFN) therapy, it is important to identify patients who will benefit from treatment cessation. Hepatitis B surface antigen (HBsAg) quantification is recommended for management of IFN therapy. At present, the understanding on end-of-treatment (EOT) HBsAg level predicting post-treatment response to IFN is still finite.MethodsA total of 2451 non-cirrhosis, HBsAg-postive patients treated with IFN-based therapy during the period from December 2010 to December 2017 at Nanfang Hospital were enrolled in this study. Serum HBsAg levels at EOT were measured to evaluate the associations between EOT HBsAg levels (Group 1, HBsAg > 0.05 and ≤ 10 IU/mL; Group 2, HBsAg > 10 and ≤ 200 IU/mL; Group 3, HBsAg > 200 IU/mL) with post-treatment HBsAg loss. Chi-squared, t-test,,Kaplan-Meier analysis, Cox regression analysis, and Multivariate Logistic regression analysis were used to analyse and evaluate differences between the there groups.ResultsThe cumulative HBsAg loss rates 5 years after treatment in Group 1–3 were 30.4% (17/56), 9.8%(4/41) and 0%(0/153) (p < 0.001). An EOT HBsAg level of > 10 IU/mL showed relatively high negative predictive value (NPV) of up to 97.9% for HBsAg loss. Low baseline HBsAg level < 25,000 IU/mL, on-treatment HBsAg decline > 1 log10IU/mL at week 24 and EOT HBsAg level ≤ 10 IU/mL were found significantly associated with HBsAg loss. A total of 6 patients have achieved HBsAg loss at EOT and 17 patients with EOT HBsAg level ≤ 10 IU/mL have achieved post-treatment HBsAg loss. Baseline characteristics, dynamic changes of on-treatment HBsAg and duration of IFN therapy were balanced across patients with EOT or post-treatment HBsAg loss.ConclusionEOT HBsAg level can serve as a monitoring indicator for IFN therapy. EOT HBsAg level ≤ 10 IU/mL was found to lead to high rate of post-treatment HBsAg loss. For patients without willingness to extend IFN treatment, off-treatment follow-up could be considered when HBsAg level decreased to ≤10 IU/mL.

Quantification of Hepatitis B Surface Antigen: Is there a Role in HIV-Hepatitis B Virus Coinfection?

Hepatitis B surface antigen (HBsAg) level plays an important role in conjunction with other markers such as hepatitis B envelope antigen (HBeAg) and hepatitis B virus (HBV) deoxyribonucleic acid levels to predict disease activity in chronic Hepatitis B (CHB). Quantification of HBsAg is useful in differentiating carriers from active hepatitis in HBeAg negative patients, and current guidelines recommend monitoring of pegylated interferon alpha treatment in CHB infection. However, there are only few studies about the role of quantitative HBsAg (qHBsAg) monitoring in HIV-HBV coinfected patients. Studies have shown that tenofovir based antiretroviral therapy regimen leads to a very slow decline in HBsAg levels and a predicted time of 10-42 years to lose the HBsAg, in majority of patients. Rapid drop in HBsAg levels and gain in CD4 within the 1st year of treatment and low baseline HBsAg level are associated with faster seroconversion. The reported rate of HBsAg loss in this population is < 15%. In this review, we discuss utility of qHBsAg in monitoring disease activity and treatment in HIV-HBV coinfected population.

Predictors of hepatitis B surface antigen loss, relapse and retreatment after discontinuation of effective oral antiviral therapy in noncirrhotic HBeAg-negative chronic hepatitis B.

Reliable predictors of outcomes after treatment discontinuation in HBeAg-negative chronic hepatitis B (CHB) patients have not been established. We investigated the role of hepatitis B surface antigen (HBsAg), interferon-inducible protein-10 (IP10) and hepatitis B core-related antigen (HBcrAg) serum levels as predictors of HBsAg loss, relapse and retreatment in noncirrhotic HBeAg-negative CHB patients who discontinued long-term antiviral therapy. All HBsAg-positive (n=57) patients of the prospective DARING-B study were included and followed monthly for 3months, every 2/3months until month-12 and every 3/6months thereafter. HBsAg, IP10 and HBcrAg levels were measured by enzyme immunoassays, and SCALE-B score was calculated. Twelve patients achieved HBsAg loss before retreatment with 18-month cumulative incidence of 25%. Independent predictors of HBsAg loss were baseline HBsAg and month-1 IP10 levels. Of 10 patients with baseline HBsAg ≤100IU/mL, 70% cleared HBsAg and 10% required retreatment. Of 23 patients with baseline HBsAg >1000IU/mL, 4% cleared HBsAg and 43% required retreatment. Of 24 patients with intermediate baseline HBsAg (100-1000IU/mL), 17% cleared HBsAg and 21% required retreatment; in this subgroup, month-1 IP10 was significantly associated with HBsAg loss, which occurred in 30% and 7% of cases with IP10 >150 and ≤150pg/mL, respectively. Baseline HBcrAg was undetectable in all patients who cleared HBsAg and was associated with retreatment. SCALE-B was associated with HBsAg loss but not with relapse or retreatment. In conclusion, HBsAg, IP10 and HBcrAg serum levels can be useful for the decisions and management of treatment discontinuation in noncirrhotic Caucasian patients with HBeAg-negative CHB.