High Hepatitis B Surface Antigen Levels Research Articles

Persistently high HBsAg levels during HBeAg-seropositive stage predict lower risk of hepatocellular carcinoma in chronic hepatitis B patients.

High hepatitis B surface antigen (HBsAg) level predicts hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients with low viral load. The role of longitudinal HBsAg levels in predicting HCC in HBeAg-positive CHB patients remains unknown. HBeAg-positive CHB participants from the REVEAL-HBV cohort with ≥2 HBsAg measurements before HBeAg seroclearance were enrolled. Group-based trajectory modelling identified distinct HBsAg trajectory groups during a median of 11 years of HBeAg-positive status. Cox regression models were applied for investigating independent predictors of HCC and estimating adjusted hazard ratio (HRadj) with a 95% confidence interval (CI). A p-value less than 0.05 was considered statistically significant. A total of 319 patients were enrolled and classified by HBsAg trajectory patterns as (A) persistently high group (n = 72): HBsAg persistently ≥104 IU/mL, and (B) non-stationary group (n = 233): low HBsAg at baseline or declining to <104 IU/mL during the follow-up. Group B had higher proportions of abnormal ALT levels, HBV genotype C and basal core mutation than group A (p < 0.05); age at entry and gender were comparable. The annual incidence of HCC in group A and group B were 0.37% and 1.16%, respectively (p = 0.03). In multivariate analysis, age >40 years (HRadj [95% CI] = 4.11 [2.26-7.48]), genotype C (HRadj [95% CI] = 4.39 [1.96-9.81]) and the non-stationary group (HRadj [95% CI] = 3.50 [1.49-8.21]) were independent predictors of HCC. Basal core promoter mutation was the only risk factor of HCC in the persistently high HBsAg group (HRadj [95% CI] = 32.75 [5.41-198.42]). Patients with persistently high HBsAg levels during HBeAg-seropositive stage represent a unique population with low risk of HCC development.

Hepatitis B surface antigen reduction is associated with hepatitis B core-specific CD8+ T cell quality.

Despite treatment, hepatitis B surface antigen (HBsAg) persists in patients with chronic hepatitis B (CHB), suggesting the likely presence of the virus in the body. CD8+ T cell responses are essential for managing viral replication, but their effect on HBsAg levels remains unclear. We studied the traits of activated CD8+ T cells and HBV-specific CD8+ T cells in the blood of CHB patients undergoing nucleos(t)ide analog (NUC) therapy. For the transcriptome profiling of activated CD8+ T cells in peripheral blood mononuclear cells (PBMCs), CD69+ CD8+ T cells were sorted from six donors, and single-cell RNA sequencing (scRNA-seq) analysis was performed. To detect HBV-specific CD8+ T cells, we stimulated PBMCs from 26 donors with overlapping peptides covering the HBs, HBcore, and HBpol regions of genotype A/B/C viruses, cultured for 10 days, and analyzed via multicolor flow cytometry. scRNA-seq data revealed that CD8+ T cell clusters harboring the transcripts involved in the cytolytic functions were frequently observed in donors with high HBsAg levels. Polyfunctional analysis of HBV-specific CD8+ T cells utilized by IFN-γ/TNFα/CD107A/CD137 revealed that HBcore-specific cells exhibited greater polyfunctionality, suggesting that the quality of HBV-specific CD8+ T cells varies among antigens. Moreover, a subset of HBcore-specific CD8+ T cells with lower cytolytic potential was inversely correlated with HBsAg level. Our results revealed a stimulant-dependent qualitative difference in HBV-specific CD8+ T cells in patients with CHB undergoing NUC therapy. Hence, the induction of HBcore-specific CD8+ T cells with lower cytolytic potential could be a new target for reducing HBsAg levels.

HBV DNA and HBsAg Levels at 24 Weeks Off-Treatment Predict Clinical Relapse and HBsAg Loss in HBeAg-Negative Patients Who Discontinued Antiviral Therapy

Patients who discontinue nucleo(s)tide analogue therapy are at risk of viral rebound and severe hepatitis flares, necessitating intensive off-treatment follow-up. We studied the association between hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA levels at off-treatment follow-up week 24 (FU W24), with subsequent clinical relapse, and HBsAg loss in a multicenter cohort of hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B who discontinued nucleo(s)tide analogue therapy. We studied 475 patients, 82% Asian, and 55% treated with entecavir. Patients with higher HBV DNA levels at FU W24 had a higher risk of clinical relapse (hazard ratio [HR], 1.576; P < .001) and a lower chance of HBsAg loss (HR, 0.454; P < .001). Similarly, patients with higher HBsAg levels at FU W24 had a higher risk of clinical relapse (HR, 1.579; P < .001) and a lower chance of HBsAg loss (HR, 0.263; P < .001). A combination of both HBsAg <100 IU/mL and HBV DNA <100 IU/mL at FU W24 identified patients with excellent outcomes (9.9% clinical relapse and 58% HBsAg loss at 216 weeks of follow-up). Conversely, relapse rates were high and HBsAg loss rates negligible among patients with both HBsAg>100 IU/mL and HBV DNA >100 IU/mL (P < .001). Among HBeAg-negative patients with chronic hepatitis B who discontinued antiviral therapy and who did not experience clinical relapse before FU W24, serum levels of HBV DNA and HBsAg at FU W24 can be used to predict subsequent clinical relapse and HBsAg clearance. A combination of HBsAg <100 IU/mL with HBV DNA <100 IU/mL identifies patients with a low risk of relapse and excellent chances of HBsAg loss and could potentially be used as an early surrogate end point for studies aiming at finite therapy in HBV.

Clinical features of chronic hepatitis B patients with lean nonalcoholic fatty liver disease.

The clinical features have been well described in obese chronic hepatitis B (CHB) patients with nonalcoholic fatty liver disease (NAFLD). However, little is known about the clinical features of lean CHB-NAFLD patients. The study retrospectively included treatment-naïve CHB patients who underwent ultrasound between 2015 and 2021. Liver fibrosis was assessed by aspartate aminotransferase (AST) to platelet ratio index (APRI), Fibrosis-4 score (FIB-4), NAFLD fibrosis score (NFS), and transient elastography. Among 1226 CHB-NAFLD patients, 25.0% patients were lean. The age, gender, and platelet, alanine aminotransferase, AST, and albumin levels were comparable between lean CHB-NAFLD and nonlean patients. The levels of plasma glucose, triglycerides, total cholesterol, and uric acid, as well as proportions of concurrent hypertension and diabetes, were lower in lean patients. Lean patients presented higher hepatitis B surface antigen (HBsAg) levels (3.4 log10 IU/ml vs. 3.2 log10 IU/ml, p=0.006), hepatitis B virus (HBV) DNA levels (4.1 log10 IU/ml vs. 3.2 log10 IU/ml, p<0.001), and hepatitis B e antigen (HBeAg) positive proportions (40.4% vs. 30.2%, p=0.002) than nonlean patients. The values of APRI, FIB-4, and liver stiffness were comparable between two groups. However, lean patients had lower NFS values (-3.0 vs. -2.6, p<0.001) and lower proportions (12.6% vs. 21.1%, p=0.003) of advanced fibrosis (NFS≥-1.5) than nonlean patients. Similar results were observed in HBeAg-positive and HBeAg-negative subgroups. Nearly a quarter of CHB-NAFLD patients were lean. Lean patients had lower proportions of metabolic abnormalities and advanced liver fibrosis than nonlean patients. However, lean CHB-NAFLD patients had higher HBsAg levels, HBV DNA levels, and HBeAg-positive proportions. Registry and registration no. of the study/trial: Clinicaltrials.gov, Identifier: NCT03097952.

A booster hepatitis B vaccine for children with maternal HBsAg positivity before 2 years of age could effectively prevent vaccine breakthrough infections

BackgroundThe long-term protective effect of hepatitis B vaccine (HepB), the incidence of hepatitis B virus (HBV) vaccine breakthrough infections (VBIs), and whether a booster HepB is necessary remain to be clarified in children born to mothers with chronic HBV infection.MethodsBased on a long-term follow-up prospective cohort of 1177 hepatitis B surface antigen (HBsAg)-positive mothers and their paired infants which was established from 2009 to 2011, total 454 children with immunoprophylaxis success as determined by postvaccination serologic testing (PVST) at 7 months old were included in this study. Among the 454 children, 246 never had a booster HepB, and 208 children received a booster HepB from 1 to 5 years of age. Multivariate logistic regression analysis was used to analyse the risk factors for HBV VBIs.ResultsThe hepatitis B surface antibody (anti-HBs) levels declined sharply from 7 months to 2 years old, and the anti-HBs seronegative rate in the children increased significantly from 2 years old. A total of 31 (6.83%) of the 454 children experienced VBIs, of which 7 had overt and 7 had occult HBV infections. Notably, 14 (45.16%) of the 31 children with VBIs were diagnosed at 2 years old, and all of them had anti-HBs positivity (> 10 mIU/mL) at 1 year old. Maternal hepatitis B e antigen (HBeAg) positivity, higher HBV DNA and HBsAg levels, lower initial infant anti-HBs levels and not receiving a booster HepB were independent risk factors for VBIs. The incidence of VBIs was significantly lower in children with a booster HepB than in nonboosted children (0.50 vs. 11.90%, P < 0.001), and none of the boosted children developed overt or occult HBV infection. The anti-HBs levels of 76.67% for the children with VBIs in the nonboosted group indicated positivity before VBIs was detected.ConclusionsAfter the primary full immunization with HepB, children born to mothers with chronic HBV infection, especially the children with maternal HBeAg positivity, high HBV DNA levels, high HBsAg levels and/or low initial infant anti-HBs levels, were at a high risk of VBIs, and a booster HepB for these children before 2 years old, instead of when their anti-HBs level is < 10 mIU/mL, could reduce the incidence of VBIs.

Clinical features of chronic hepatitis B patients with low hepatitis B surface antigen levels and determinants of hepatitis B surface antigen seroclearance.

Background and AimA low hepatitis B surface antigen (HBsAg) level is reported to be predictive of future HBsAg seroclearance. A hospital‐based cohort study was conducted to clarify the clinical features of patients with low HBsAg levels and to demonstrate the usefulness of low HBsAg levels for predicting HBsAg seroclearance.MethodsA total of 1459 patients with chronic hepatitis B were included in the study. Of these, 587 had repeated measurements for HBsAg levels and two or more records of HBsAg‐positive results. HBsAg levels were measured with a commercially available HBsAg assay. Based on a cut‐off index (COI) of 2000, a high HBsAg level was defined as HBsAg ≥2000 COI, and a low HBsAg level was defined as HBsAg <2000 COI.ResultsThe proportion of patients with low HBsAg levels at baseline tended to increase with age. Patients with low HBsAg levels at baseline had significantly older age, lower transaminase levels, and lower hepatitis B virus (HBV) DNA levels than those with high HBsAg levels. The annual HBsAg seroclearance rate was 1.30%/year. The cumulative incidences of HBsAg seroclearance differed significantly by HBsAg level at baseline (<2000 vs ≥2000 COI), age (≥50 vs <50 years), and HBV DNA level (<4.0 vs ≥4.0 log copies/mL). Cox proportional hazards regression analyses showed that low HBsAg level (<2000 COI) and low HBV DNA level (<4.0 log copies/mL) were significantly associated with HBsAg seroclearance.ConclusionAging was one of the factors affecting HBsAg level. HBsAg seroclearance was significantly associated with low HBsAg level and low HBV DNA level at baseline.

Risk Factors for Prognosis of Hepatocellular Carcinoma After Curative Resection In Patients with Low Hepatitis B Viral Load.

A retrospective cohort study was conducted to investigate the effect of hepatitis B surface antigen (HBsAg) level on prognosis in low viral load (< 2000 IU/mL) patients with hepatitis B-related hepatocellular carcinoma (HCC) after curative resection. A total of 192 patients with low viral load who had received curative resection of pathologically confirmed HCC were analyzed to determine the factors affecting prognosis. The risk factors for survival, early and late recurrence (2 years as a cut-off) were studied. The median follow-up time was 38.5 months. The overall survival rates at 1-, 3-, and 5-year after curative resection were 94.2%, 64.0%, and 45.2%, respectively. The cumulative recurrence rates at 1-, 3, and 5-year after curative resection were 22.4%, 46.5%, and 67.0%, respectively. Patients with high serum HBsAg levels (> 250 IU/mL) had significantly lower survival rates than those with low HBsAg levels (HR: 1.517, 95% CI: 1.005-2.292, P = 0.047). Stratified analysis showed that patients with high HBsAg levels had a significantly higher late recurrence incidence than those with low HBsAg levels (HR: 2.155, 95% CI: 1.094-4.248, P = 0.026), but did not have a significantly higher risk of early recurrence postoperatively (HR: 1.320, 95% CI: 0.837-2.082, P = 0.233). Multivariate analysis revealed that HBsAg > 250 IU/mL was an independent risk factor associated with late recurrence (HR: 2.109, 95% CI: 1.068-4.165, P = 0.032). HBsAg > 250 IU/mL at the time of tumor resection was an independent risk factor for late recurrence in low viral load HCC patients.

Hepatitis B surface antigen predicts recurrence after radiofrequency ablation in patients with low hepatitis B virus loads.

Radiofrequency ablation (RFA) is a first-line option for the treatment of small liver cancers, but the recurrence remains a problem affecting long-term survival. Hepatitis B virus (HBV) activity is associated with the prognosis of hepatocellular carcinoma (HCC). We investigated the significance of hepatitis B surface antigen (HBsAg) in HCC recurrence after curative RFA treatment in HBV-related small HCC.We enrolled 404 HBV-related patients with small HCC (≤3 cm) who underwent curative RFA. We used univariate and multivariate analyses to investigate the baseline levels of HBsAg, in addition to other known risk factors for HCC recurrence, for association with HCC tumor recurrence after curative RFA.The overall 1-, 2-, and 3-year recurrence-free survival (RFS) rates were 75%, 50%, and 34%, respectively. The median recurrence-free time was 25 months. The level of HBsAg was an independent risk factor for recurrence in patients with lower HBV-DNA levels. In hepatitis Be antigen (HBeAg)-negative patients, the 1-, 2-, and 3-year RFS rates were 79%, 64%, and 44%, respectively, for that with low HBsAg levels, compared with 73%, 50%, and 37%, respectively, for that with high HBsAg levels (P = .039).HBsAg might serve as a valuable marker to evaluate the risk of HCC recurrence in HBeAg-negative patients with low HBV viral load.

Risk Factors for Prognosis of Hepatocellular Carcinoma After Curative Resection In Patients with Low Hepatitis B Viral Load

BackgroundA retrospective cohort study was conducted to investigate the effect of hepatitis B surface antigen (HBsAg) level on prognosis in low viral load (< 2000 IU/mL) patients with hepatitis B-related hepatocellular carcinoma (HCC) after curative resection. Material and MethodsA total of 192 patients with low viral load who had received curative resection of pathologically confirmed HCC were analyzed to determine the factors affecting prognosis. The risk factors for survival, early and late recurrence (2 years as a cut-off) were studied. ResultsThe median follow-up time was 38.5 months. The overall survival rates at 1-, 3-, and 5-year after curative resection were 94.2%, 64.0%, and 45.2%, respectively. The cumulative recurrence rates at 1-, 3-, and 5-year after curative resection were 22.4%, 46.5%, and 67.0%, respectively. Patients with high serum HBsAg levels (> 250 IU/mL) had significantly lower survival rates than those with low HBsAg levels (HR: 1.517, 95% CI: 1.005-2.292, P = 0.047). Stratified analysis showed that patients with high HBsAg levels had a significantly higher late recurrence incidence than those with low HBsAg levels (HR: 2.155, 95% CI: 1.094-4.248, P = 0.026), but did not have a significantly higher risk of early recurrence postoperatively (HR: 1.320, 95% CI: 0.837-2.082, P = 0.233). Multivariate analysis revealed that HBsAg > 250 IU/mL was an independent risk factor associated with late recurrence (HR: 2.109, 95% CI: 1.068-4.165, P = 0.032). ConclusionsHBsAg > 250 IU/mL at the time of tumor resection was an independent risk factor for late recurrence in low viral load HCC patients.

Serum hepatitis B surface antigen titer and transient elastography in screening for insignificant fibrosis in HBeAg-positive chronic hepatitis B patients.

ObjectiveTo explore the predictive value of serum hepatitis B surface antigen (HBsAg) titer and transient elastography in screening for insignificant fibrosis in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients.MethodsWe conducted a cross-sectional study of eligible patients treated from March 2012 to May 2013 at the West China Hospital of Sichuan University. Eligible patients underwent liver transient elastography and liver biopsy. We assessed the serum HBsAg level, serum hepatitis B virus (HBV) deoxyribonucleic acid (DNA) level, HBV genotypes, liver stiffness measurement (LSM) values by transient elastography, and histological fibrosis staging by METAVIR classification.ResultsA total of 129 consecutive patients were recruited. The LSM value (P<0.001, odds ratio 14.67, 95% CI 0.158–0.551) and log10HBsAg (P=0.045, odds ratio 4.03, 95% CI 0.136–0.976) correlated with a liver fibrosis score <F2, independently. Inverse correlations were found between log10HBsAg and the LSM value (r=−576, P<0.001) and fibrosis staging (r=−374, P<0.001). Patients with a fibrosis score <F2 had a significantly higher log10HBsAg than patients with a fibrosis score ≥F2 among those with an LSM value under 9.4 kPa (4.6±0.7 vs 4.3±0.5, P=0.006). The HBsAg titer achieved an area under the receiver operating characteristic curve of 0.758 (P<0.001, 95% CI 0.631–0.884) in predicting a fibrosis score <F2, with a cut-off value of 10,400 IU/mL, a positive predictive value of 73%, and a negative predictive value of 79%.ConclusionIn HBeAg-positive patients with an alanine aminotransferase level <2× the upper limit of normal, high serum HBsAg levels can predict a fibrosis score <F2, and a lower HBsAg titer could be supportive of early fibrosis in patients with an LSM value under 9.4 kPa.

Effect of serum hepatitis B surface antigen levels on predicting the clinical outcomes of chronic hepatitis B infection: A meta‐analysis

The impact of serum hepatitis B surface antigen (HBsAg) levels on the prognosis of chronic hepatitis B virus (HBV) infection remains unclear. This meta-analysis aimed to determine whether serum HBsAg levels influenced the risk of cirrhosis and hepatocellular carcinoma (HCC) development. Furthermore, we explored the role played by serum HBsAg levels in prediction of spontaneous HBsAg seroclearance. We performed this meta-analysis including 11 studies to assess the effect of HBsAg levels on predicting clinical outcomes in chronic HBV carriers. The pooled odds ratios (OR) were calculated using a random or fixed effects model. PUBMED, EMBASE, MEDLINE and the Cochrane Database were searched for articles published from 1990 to May 2014. Our results showed that high HBsAg levels significantly increased the risk of developing cirrhosis (OR, 2.51; 95% confidence interval [CI], 2.00-3.14; P < 0.01). Pooled data from two studies revealed that high HBsAg levels increased the risk of HCC occurrence (OR, 2.21; 95% CI, 1.52-3.22; P < 0.01). High HBsAg levels were associated with a significant increased risk of late HCC recurrence after curative resection (OR, 2.02; 95% CI, 1.48-2.77; P < 0.01), but not early recurrence (OR, 1.06; 95% CI, 0.89-1.27; P = 0.53). The pooled data indicated that low HBsAg levels were significantly in favor of spontaneous HBsAg seroclearance (OR, 7.89; 95% CI, 4.74-13.13; P < 0.01). High HBsAg levels were associated with development of cirrhosis and HCC comparatively. Therefore, lower serum HBsAg levels were associated with a higher rate of spontaneous HBsAg seroclearance.

Prediction of Hepatocellular Carcinoma Recurrence in Patients With Low Hepatitis B Virus DNA Levels and High Preoperative Hepatitis B Surface Antigen Levels

In patients with low viral loads, high levels of hepatitis B surface antigen (HBsAg) have been shown to predict development of hepatocellular carcinoma (HCC). Whether high levels of HBsAg increase the risk for HCC recurrence after hepatic resection remains unknown. To investigate the association between levels of HBsAg and the risk for tumor recurrence after curative resection in HCC patients with low levels of hepatitis B virus (HBV) DNA. We performed a retrospective analysis of the clinical data of 1062 patients with low HBV DNA levels (<200 IU/mL) who underwent partial hepatectomy for HCC. In particular, we investigated the association between levels of HBsAg and recurrence of HCC. Partial hepatectomy for HCC. The risk for first tumor recurrence between patients with high and low HBsAg levels. We calculated cumulative incidences and hazard ratios after adjusting for competing mortality. The risk for tumor recurrence increased with HBsAg levels of 1000 IU/mL or greater. When we compared the groups with low (<1000 IU/mL) and high (≥1000 IU/mL) HBsAg levels, the 5-year disease-free survival rate (46.1% vs 34.1% [P = .002]) and the overall survival rate (57.5% vs 48.8% [P = .004]) were better in the group with low HBsAg levels. On multivariate analysis, hepatitis B e antigen seropositivity, HBsAg level of 1000 IU/mL or greater, tumor size of greater than 5 cm, blood transfusion, surgical margin of less than 1.0 cm, the presence of satellite nodules, and the presence of portal vein tumor thrombus were independent risk factors for HCC recurrence. When compared with hepatitis B e antigen status, HBsAg level better predicted recurrence of HCC. A preoperative HBsAg level of 1000 IU/mL or greater is an independent risk factor for HCC recurrence in patients with low HBV DNA levels.

Changes of HBsAg and HBV DNA levels in Chinese chronic hepatitis B patients after 5 years of entecavir treatment

Hepatitis B surface antigen (HBsAg) kinetics during long-term entecavir therapy has not been well investigated. We described the cumulative serologic, virologic, and biochemical outcomes and the occurrence of signature entecavir mutations among 222 Chinese treatment-naïve chronic hepatitis B (CHB) patients receiving entecavir for up to 5 years. The median rate of HBsAg reduction over 5 years was 0.125 log IU/mL/year. Patients with high baseline HBV DNA levels (≥ 8 log copies/mL or ≥ 7.3 log IU/mL), when compared with those with baseline hepatitis B virus (HBV) DNA < 7.3 log IU/mL, had a significantly greater median rate of HBsAg reduction (0.178 and 0.102 log IU/mL/year, respectively, P < 0.001). The difference in HBsAg decline was most prominent in the first year (0.324 and 0.062 log IU/mL/year, respectively, P < 0.001). Greater median rates of HBsAg reduction were also found in hepatitis B e antigen (HBeAg)-positive patients when compared with HBeAg-negative patients (0.144 and 0.098 log IU/mL/year, P = 0.015), and in patients with high baseline HBsAg levels (≥ 3 log IU/mL), when compared with patients with low baseline HBsAg < 3 log IU/mL (0.131 and 0.045 log IU/mL/year, respectively, P = 0.001). The 5-year cumulative rate of HBV DNA undetectability (< 20 IU/mL) was 97.1%. There were two cases of entecavir resistance, resulting in a 5-year cumulative resistance rate of 1.2%. In contrast to the profound HBV DNA suppression, long-term entecavir treatment achieved only a slow decline in serum HBsAg. Although certain patient subgroups exhibit a more rapid HBsAg reduction, additional therapeutic agents are needed to increase the chance of HBsAg seroclearance in CHB.

Quantitative Levels of Hepatitis B Virus DNA and Surface Antigen and the Risk of Hepatocellular Carcinoma in Patients with Hepatitis B Receiving Long-Term Nucleos(t)ide Analogue Therapy

Background: Serum levels of hepatitis B virus (HBV) DNA are an important predictor of the risk of hepatocellular carcinoma (HCC) in patients with chronic HBV infection. However, little is known about whether high levels of hepatitis B surface antigen (HBsAg) increase the risk for HCC. Methods: We investigated 167 patients who were treated with nucleos(t)ide analogues (NA) for at least 2 years (median: 5.8 years, range: 2-13.1 years). Relationships between reduced levels of HBsAg and various factors were evaluated. In addition, we evaluated the usefulness of quantitative serum levels of HBV DNA and HBsAg as predictors of HCC development in patients receiving long-term NA therapy. Results: HCC developed in 9 of the 167 NA-treated patients. In the 9 patients with HCC, HBV DNA was undetectable (<2.1 log copies/mL), but HBsAg levels were ≥2000 C.O.I. in 7 patients. No maternal transmission, long NA treatment period, HBV DNA levels <3.0 log copies/mL, and reduced hepatitis B e antigen levels during the first 24 weeks of treatment were a significant factor of HBsAg levels <2000 C.O.I.. Conclusions: Hepatocarcinogenesis was observed in patients with high HBsAg levels, despite the negative conversion of HBV DNA as a result of long-term NA therapy. Therefore, to suppress hepatocarcinogenesis, it is important to control not only HBV DNA levels but also HBsAg levels.

Role of immunohistochemistry for hepatitis D and hepatitis B virus in hepatitis delta

Immunohistochemical assessment of liver tissue in chronic delta hepatitis (CDH) is underinvestigated. Aim of the study was (i) to assess variables associated with hepatitis D antigen (HDAg), hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) staining in the liver. Demographic, biochemical and virologic data collected from the HIDIT 1 study were used. HBsAg, HBcAg and HDAg immunohistochemical (IHC) staining was semiquantitatively assessed. Hepatitis D antigen immunohistochemical staining displayed positive correlations with age and alanine aminotransferase (ALT) and negative correlations with serum HBsAg (P = 0.01 for all). HBsAg IHC displayed a negative correlation with gamma glutamyl transferase and positive correlations with serum HBV DNA, serum HBsAg levels and HBeAg serology (P < 0.001, P = 0.02 and P = 0.007 respectively). HBcAg staining was mainly nuclear and displayed negative correlations with serum HBsAg and histologic activity (P = 0.002 and P = 0.02 respectively). Pegylated IFN based treatment led to a decline of all IHC markers, however, these markers had no impact on treatment outcome. These data suggest an association of liver injury with HDAg expression in CDH whereas the negative correlation between HBcAg expression and liver injury and the overall nuclear localization of HBcAg suggest that HBcAg does not contribute to liver injury in CDH. HDV cases with high level of HBV replication, high serum HBsAg levels, HBeAg positivity, that are probably in the earlier stages of disease (low gamma-glutamyl transferase), had a more intense HBsAg staining profile. Overall, the data enforce the importance of HDAg and HBsAg in different phases of CDH infection.

Serum Hepatitis B Surface Antigen Levels Help Predict Disease Progression in Patients With Low Hepatitis B Virus Loads

Chronic hepatitis B patients with high viral loads are at increased risk of cirrhosis and hepatocellular carcinoma (HCC). In patients with low viral loads, higher hepatitis B surface antigen (HBsAg) levels have been shown to predict HCC development. However, little is known about the difference in risk for other hepatitis B virus (HBV)-related adverse outcomes with varying HBsAg levels. A total of 1,068 Taiwanese hepatitis B e antigen (HBeAg)-negative HBV carriers with serum HBV DNA level <2,000 IU/mL at baseline were followed for a mean duration of 13.0 years. Patients were categorized based on their HBsAg levels, and the relationships between HBsAg level and development of HBeAg-negative hepatitis, hepatitis flare, and cirrhosis were investigated. Of the 1068 patients with low viral loads, 280 developed HBeAg-negative hepatitis, with an annual incidence rate of 2.0%. HBsAg level, but not HBV DNA level, was found to be a risk factor for HBeAg-negative hepatitis. Multivariate analysis showed that the adjusted hazard ratio in patients with an HBsAg level ≥ 1,000 versus <1000 IU/mL was 1.5 (95% confidence interval, 1.2-1.9). The positive correlation was present when evaluating other endpoints, including hepatitis flare and cirrhosis, and remained consistent when the study population was restricted to those with normal alanine aminotransferase (ALT) level at baseline. The annual incidence rate of HBeAg-negative hepatitis was lowered to 1.1% in patients with low levels of HBV DNA, HBsAg, and ALT. In HBeAg-negative patients with low viral loads and genotype B or C virus infection, a higher HBsAg level can predict disease progression. HBsAg <1,000 IU/mL in combination with low levels of HBV DNA and ALT help define minimal-risk HBV carriers.

High Hepatitis B Surface Antigen Levels Predict Insignificant Fibrosis in Hepatitis B e Antigen Positive Chronic Hepatitis B

IntroductionThere is no data on the relationship between hepatitis B surface antigen (HBsAg) levels and liver fibrosis in hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B (CHB).MethodsSerum HBsAg and HBV DNA levels in HBeAg-positive CHB patients with liver biopsies were analyzed. The upper limit of normal (ULN) of alanine aminotransferase (ALT) was 30 and 19 U/L for men and women respectively. Histologic assessment was based on Ishak fibrosis staging for fibrosis and Knodell histologic activity index (HAI) for necroinflammation.Results140 patients (65% male, median age 32.7 years) were recruited. 56 (40%) had ALT ≤2×ULN. 72 (51.4%) and 42 (30%) had fibrosis score ≤1 and necroinflammation grading ≤4 respectively. Patients with fibrosis score ≤1, when compared to patients with fibrosis score >1, had significantly higher median HBsAg levels (50,320 and 7,820 IU/mL respectively, p<0.001). Among patients with ALT ≤2×ULN, serum HBsAg levels achieved an area under receiver operating characteristic curve of 0.869 in predicting fibrosis score ≤1. HBsAg levels did not accurately predict necroinflammation score. HBsAg ≥25,000 IU/mL was independently associated with fibrosis score ≤1 (p = 0.025, odds ratio 9.042).Using this cut-off HBsAg level in patients with ALT ≤2×ULN, positive and negative predictive values for predicting fibrosis score ≤1 were 92.7% and 60.0% respectively. HBV DNA levels had no association with liver histology.ConclusionAmong HBeAg-positive patients with ALT ≤2×ULN, high serum HBsAg levels can accurately predict fibrosis score ≤1, and could potentially influence decisions concerning treatment commencement and reduce the need for liver biopsy.

Factors Associated with Serum Hepatitis B Surface Antigen Levels and Its On-Treatment Changes in Patients under Lamivudine Therapy

We aimed to investigate factors associated with serum hepatitis B surface antigen (HBsAg) levels and its kinetics under lamivudine treatment in chronic hepatitis B patients. HBsAg levels were measured with the Architect HBsAg assay (Abbott laboratories, Abbott Park, IL, USA) in genotype B (HBV/B) or C (HBV/C) patients (n=218). Early HBsAg kinetics in 86 hepatitis B e antigen (HBeAg)-positive patients and long-term HBsAg changes in 45 patients with rapid and sustained viral suppression were further analysed. Mean HBsAg levels were higher in male (n=181) than in female (n=37) patients (3.59 versus 3.23 log(10) IU/ml; P=0.036), and higher in 121 HBV/B than in 97 HBV/C patients (3.68 versus 3.34 log(10) IU/ml; P=0.006). In addition to HBV DNA loads (P<0.001), male gender (P=0.012) and HBV/B infection (P=0.035) were independently associated with higher HBsAg levels in antiviral-naive patients. HBsAg increases (0.00-0.87 log(10)) were found in 28/86 patients who obtained viral suppression under 12 weeks of lamivudine therapy. Higher baseline HBsAg levels (P=0.046), HBV/B infection (P=0.007) and faster HBV DNA declines (P=0.006) independently contributed to greater HBsAg decreases under 12 weeks treatment. An apparent dissociation between HBsAg and HBV DNA changes were found in 14/45 patients with rapid and sustained viral suppression, who had low baseline HBsAg levels and predominant HBV/C infection. HBV/B and male gender were associated with higher HBsAg levels in antiviral-naive patients. Higher baseline HBsAg levels and HBV/B infection contributed to greater early HBsAg declines in HBeAg-positive patients, and might correlate with discordance between HBsAg and HBeAg or HBV DNA under long-term lamivudine treatment.