Quantitative Hepatitis Research Articles

Baseline quantitative hepatitis B core antibody titre alone strongly predicts HBeAg seroconversion across chronic hepatitis B patients treated with peginterferon or nucleos(t)ide analogues

ObjectiveThe investigation regarding the clinical significance of quantitative hepatitis B core antibody (anti-HBc) during chronic hepatitis B (CHB) treatment is limited. The aim of this study was to determine the...

Changing serum levels of quantitative hepatitis B surface antigen and hepatitis B virus DNA in hepatitis B virus surface antigen carriers: A follow-up study of an elderly cohort

This study was to elucidate longitudinally quantitative changes of hepatitis B virus (HBV) surface antigen (HBsAg) and HBV DNA in elder HBsAg carriers in a community. Among 1002 residents screened for HBsAg in 2005, 405 responded to this follow-up study in 2010. Fifty-nine (14.6%) were HBsAg carriers in 2005; HBsAg quantification and HBV DNA were measured. HBsAg quantification (cutoff 1600 IU/mL) and HBV DNA (cutoff 2000 IU/mL) were combined to stratify the participants between two screens. A total of 30 men and 29 women with a mean age of 63.9 ± 7.9 years were enrolled. Quantitative levels of HBsAg and HBV DNA were significantly correlated in 2005 (r = 0.509, p < 0.001) and 2010 (r = 0.777, p < 0.001). Concentrations of HBsAg (IU/mL) significantly decreased from 2.2 ± 1.0 log in 2005 to 1.7 ± 1.5 log in 2010 (p < 0.001). The level of HBsAg was decreased in 48 (81.4%) individuals and HBsAg was undetectable in eight (13.6%). The annual incidence of HBsAg clearance was 2.7%. These 59 HBsAg carriers in 2005 were divided into four groups: low HBsAg low HBV DNA (n = 32), high HBsAg low HBV DNA (n = 5), low HBsAg high HBV DNA (n = 12) and high HBsAg high HBV DNA (n = 10). All 32 individuals in the low HBsAg low HBV DNA group were still in that group in 2010, whereas only two of the high HBsAg high HBV DNA group became inactive. As with a younger cohort in hospital, HBsAg quantification was still well correlated with HBV DNA in elderly HBsAg carriers in the community. Lower levels of both HBsAg and HBV DNA might represent an inactive HBV infection.

Quantitative hepatitis B core antibody levels in the natural history of hepatitis B virus infection

We previously demonstrated that pretreatment quantitative anti–hepatitis B core protein (qAnti-HBc) levels can predict the treatment response for both interferon and nucleoside analogue therapy, but the characteristics of qAnti-HBc during chronic hepatitis B virus (HBV) infection remain poorly understood. To understand this issue, the qAnti-HBc levels were evaluated in individuals with past HBV infection, occult HBV infection and chronic HBV infection in the immune tolerance phase, immune clearance phase, low-replicative phase and hepatitis B e antigen (HBeAg)-negative hepatitis phase. Individuals with hepatitis B surface antigen (n = 598, 3.74 ± 0.90 log10 IU/mL) had significantly higher (p < 0.001, approximately 1000-fold) serum qAnti-HBc levels than those who had occult HBV, and serum qAnti-HBc levels were significantly higher in the occult HBV group than in the past HBV infection group (p < 0.001). qAnti-HBc levels were positively correlated with alanine aminotransferase levels (R = 0.663, p < 0.001), and subjects with an abnormal alanine aminotransferase level had a higher qAnti-HBc level (p < 0.001). Serum qAnti-HBc level varied in different phases of HBV infection, as determined by host immune status. Serum qAnti-HBc level is strongly associated with hepatitis activity in subjects with chronic HBV infection.

Viral hepatitis B: clinical and epidemiological characteristics.

It is now 50 years since the discovery of the hepatitis B virus (HBV), and, despite the availability of a prophylactic vaccine for more than 20 years, HBV infection remains a disease of significant global health burden. It is estimated that more than 240 million people are chronically infected with HBV and, therefore, are at risk for the development of cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). The risk of clinical complications has traditionally been higher in older males with hepatitis B e antigen (HBeAg)-positive disease, high-grade liver necroinflammation, and progressive fibrosis. Recent advances in the understanding of the natural history of chronic HBV infection have identified an important role for plasma HBV DNA levels as a marker of risk for clinical outcomes. Among adults, persistent high-level HBV replication is associated with an increased risk of cirrhosis, as well as HCC development. This has led to the therapeutic focus on achieving sustained viral suppression. There is an emerging role for quantitative hepatitis B surface antigen (HBsAg) levels as a marker of natural history. Low levels of HBsAg have been associated with sustained immune control, HBsAg seroclearance, as well as lower risk of HCC. In this work, we review the natural history of HBV infection, with a focus on the determinants of clinical outcomes in patients with chronic hepatitis B (CHB) infection.

Historic and current hepatitis B viral DNA and quantitative HBsAg level are not associated with cirrhosis in non-Asian women with chronic hepatitis B

Some studies done in Asian patients have shown that serum levels of hepatitis B virus (HBV) DNA predict the development of cirrhosis. However, it is unclear whether this also applies for non-Asian patients. This study investigated historic and current HBV DNA and quantitative hepatitis B surface antigen (HBsAg) levels as predictors of cirrhosis in non-Asian women with chronic HBV. A retrospective cohort study of non-Asian women with chronic HBV was performed. Among other variables, HBV DNA and quantitative HBsAg levels were measured in stored historic serum samples obtained during pregnancy (period 1990-2004) and current serum samples (period 2011-2012) to determine any association with liver cirrhosis by liver stiffness measurement (LSM). One hundred and nineteen asymptomatic, treatment-naïve non-Asian women were included; the median number of years between the historic sample and the current sample was 17 (interquartile range (IQR) 13-20). The median historic log HBV DNA and quantitative log HBsAg levels were 2.5 (IQR 1.9-3.4) IU/ml and 4.2 (IQR 3.6-4.5) IU/ml, respectively. LSM diagnosed 14 patients (12%) with F3-F4 fibrosis, i.e. stiffness >8.1kPa. No association of cirrhosis was found with historic HBV DNA (relative risk (RR) 0.34, 95% confidence interval (CI) 0.05-2.44) or with the quantitative HBsAg level (HBsAg level >1000 IU/ml, RR 0.35, 95% CI 0.11-1.11). Multivariable analysis identified alcohol consumption (odds ratio (OR) 6.4, 95% CI 1.3-30.1), aspartate aminotransferase >0.5 times the upper limit of normal (OR 15.4, 95% CI 1.9-122.6), and prothrombin time (OR 12.0, 95% CI 1.2-120.4), but not HBV DNA or quantitative HBsAg level, to be independent predictors of the presence of cirrhosis. Neither historic nor current HBV DNA or the quantitative HBsAg level is associated with the development of HBV-related cirrhosis in non-Asian women.

HBsAg as an important predictor of HBeAg seroconversion following antiviral treatment for HBeAg-positive chronic hepatitis B patients.

BackgroundSerum quantitative hepatitis B surface antigen (HBsAg) levels may be an important predictor of hepatitis B e antigen (HBeAg) seroconversion (SC) in HBeAg-positive chronic hepatitis B (CHB) patients during antiviral treatment. The pattern of HBsAg variation in CHB patients either with or without SC following tenofovir disoproxil fumarate (TDF) treatment is not clearly understood.MethodsTwenty patients with full experimental data were enrolled, and liver biochemistry, serum HBV DNA, and circulating CD4+CD25+ regulatory T cell (Treg) levels were determined at baseline and every 12weeks after the initiation of TDF treatment (for a total of 96weeks). In addition, the relationship between HBsAg or HBeAg and alanine aminotransferase (ALT), HBV DNA and Treg levels in SC and non-SC patients was analyzed.ResultsIn all, 9 patients had undergone HBeAg seroconversion by week 72 of TDF treatment, and biochemical and virological indexes and Treg percentages declined to normal levels. Furthermore, the positive correlation between HBsAg and ALT, HBV DNA and Treg levels was significant for SC patients, but not for non-SC patients. However, for HBeAg, significant positive correlations were or not observed for both SC and non-SC patients.ConclusionsThe quantitation of HBsAg is a more useful indicator than HBeAg for distinguishing SC and non-SC patients during TDF treatment. Moreover, HBsAg may be related to immune regulatory property of CHB patients during antiviral treatment.

Hepatitis B surface antigen levels after hepatitis B e-antigen seroclearance: a longitudinal follow-up study.

The role of quantitative hepatitis B surface antigen (HBsAg) after hepatitis B e-antigen (HBeAg) seroclearance is not well defined. To determine the role of HBsAg levels in predicting significant viremia and hepatitis flares after HBeAg seroclearance. A total of 228 chronic hepatitis B patients with spontaneous HBeAg seroclearance were included. Patients were followed up regularly at 3-6 monthly intervals with routine liver biochemistry and hepatitis B serology. Levels of HBV DNA and HBsAg were measured at yearly intervals for up to 5 years after HBeAg seroclearance. The median log HBsAg and HBV DNA level after HBeAg seroclearance was 3.52 IU/ml and 4.13 IU/ ml respectively, with no significant correlation observed between them (P = 0.572). The HBV DNA at HBeAg seroclearance was 4.13 log IU/ml, compared with 3.12 log IU/ml after 5 years (P < 0.001). No significant change was observed for HBsAg levels (P = 0.991). Hepatitis B flares occurred in 76 (33.3%) patients. Patients who developed hepatitic flares compared with those without hepatitic flares were older (40 vs. 36 years, P = 0.001), had a higher HBV DNA at the time of HBeAg seroclearance (4.70 vs. 3.77 log IU/ml, P =< 0.001), and more likely to be males (42.7% vs. 23.4%, P = 0.002) respectively. There was no difference in HBsAg levels between those with and without hepatitis flare (3.54 vs. 3.52 log IU/ml respectively, P = 0.555). HBV DNA levels, but not HBsAg levels, after HBeAg seroclearance were associated with subsequent significant viremia and hepatitic flares. Male gender and older age was associated with significant viremia.

Hepatitis B surface antigen concertration in prediction of response to treatment-naive, hepatitis B e antigen-positive patients receiving entecavir

Objective To monitor the dynamic changes of quantitative hepatitis B surface antigen concentrations in HBeAg-positive treatment-naive CHB patients and to investigate its potential role in predicting virological response to entecavir therapy. Methods This was a retrospective study. 26 HBeAg-positive treatment-naive CHB patients receiving ETV (0.5 mg once a day) were consecutively recruited and followed up for 1 year from the Center of Liver diseases of the First Affiliated Hospital of Fujian Medical University between January 2011 and July 2013. Serums samples were collected at baseline and every 3 months (month 3, month 6, month 9 and month 12, respectively). HBsAg and HBeAg concentrations were measured using commercially available chemiluminescence assay. HBV DNA levels were determined by real-time polymerase chain reaction. ALT levels were measured by velocity method. A VR（virological response） was defined as HBV DNA levels decreased to less than 500 IU/ml through 1 year of ETV treatment. The statistical analyses including Student t-test, χ2-test, ROC curve analysis, etc. were performed using statistical analysis software SPSS version 16.0 and GraphPad Prism software version 5.0. Results After 1 year of treatment, 17 patients achieved VR, 9 patients didn't. Baseline characteristics of the patients were as follows: there was no significant difference of ALT levels between the VR+ group and VR- group (141.82±77.29 IU/ml and 134.2±49.76 IU/ml, respectively, t=0.27, P=0.793). HBV DNA levels of VR+ group was signi?cantly lower than that of the VR- group (6.76±1.00 lg IU/ml and 7.65±0.87 lg IU/ml, respectively, t=-2.27, P=0.033). HBsAg concentration of the VR+ group was lower than that of the VR- group, but showed no-statistically significant (3.79±0.61 lg IU/ml and 4.19±0.43 lg IU/ml, respectively, t=-1.75 P=0.094). A rapid decline in HBsAg concentration during the first 3 months of therapy followed by a much slower decline in the subsequent period was observed. From baseline to month 3, the reductions of HBsAg concentration were 0.32±0.29 and 0.14±0.10 lg IU/ml in VR+ and VR- groups (t=2.245, P=0.035), respectively. The lg HBsAg concentration at month 3 showed the biggest area under the curve (AUC) (AUC=0.840, P=0.005). The best cut-off value for the HBsAg concentration at month 3 for the prediction of VR was 3.8650 lg IU/ml, with a diagnostic sensitivity and specificity of 82.4% and 77.8%, respectively. Conclusions HBsAg level less than or equal to 3.8650 lg IU/ml at month 3 of ETV treatment may be a useful parameter in predicting virological response to ETV in HBeAg-positive CHB patients.（Chin J Lab Med，2014,37：96-99） Key words: Hepatitis B chronic; Hepatitis B surface antigen; Hepatitis B e antigen; Guanine

A Rationalized Approach to the Treatment of Patients Infected with Hepatitis B

It is estimated that there are 350-400 million individuals with chronic hepatitis B virus infection (HBV) worldwide. The natural course of HBV infection is variable with a number of individuals developing no or only mild disease, while others will die from liver-associated complications if left untreated. It is estimated that 25% of individuals with HBV infection will eventually die from the complications of HBV-associated liver disease. Several viral and host variables including hepatitis B e antigen status, HBV genotype, viral load, hepatitis B surface antigen and transaminase levels, and viral mutations have been identified as determinants of disease outcomes. The personalized approach to the treatment of chronic hepatitis B might include mere monitoring of the disease in some patients but aggressive treatment in others. Individuals who require treatment should have close monitoring to help ensure maximum medication compliance, to watch for adverse events, and to monitor virologic and biochemical responses. Therefore, management of patients with chronic HBV infection requires a practical setting to demonstrate the relevance of personalized medicine, the roles and limitations of genetic and non-genetic factors, and the risks and benefits of individualized patient care. This article provides an overview of the viral and host genetics of chronic HBV and reviews the clinical utility of serum quantitative hepatitis B surface antigen in the management of patients with chronic HBV infection.

Quantitative Hepatitis B Surface Antigen Titres in Chinese Chronic Hepatitis B Patients over 4 Years of Entecavir Treatment

The clinical value of quantitative hepatitis B surface antigen (qHBsAg) titre in patients taking nucleotide/nucleoside analogues (NAs) is still controversial. This study aims to investigate the dynamic changes of qHBsAg titres and their significance for predicting virological response (VR) and serological response (SR) to long-term entecavir (ETV) treatment. A total of 48 ETV-naive patients were enrolled and followed prospectively for 4 years, 32 of whom were hepatitis B e antigen (HBeAg)-positive at baseline. Serum alanine aminotransferase (ALT), qualitative HBV serological markers and HBV DNA were detected; qHBsAg titres were measured using Elecsys(®) HBsAg II Quant Assay (Roche Diagnostics, Penzberg, Germany). The mean baseline HBV DNA and qHBsAg were 7.51 log10 copies/ml and 3.78 log10 IU/ml, respectively. After 48 months of ETV treatment, the rates of VR (<291 copies/ml), ALT normalization and SR (HBeAg/antibody to HBeAg [anti-HBe]) were 89.6% (43/48), 89.6% (43/48) and 34.4% (11/32), respectively. There was a decrease in qHBsAg titres from baseline to month 48, ranging from 3.78 to 3.10 log10 IU/ml. The greatest decrease of qHBsAg was observed in the first 3 months of treatment (0.47 log10 IU/ml), which was significantly correlated with corresponding HBV DNA decreases (3.89 log10 copies/ml; P=0.032). By using receiver operating characteristic (ROC) curve analysis, qHBsAg titres at baseline (area under the curve [AUROC]=0.647) and 3 months after treatment (AUROC=0.586) had poor power in predicting 48-month VR; qHBsAg titres at baseline (AUROC=0.779) and 3 months after ETV treatment (AUROC=0.658) had poor power in predicting 48-month SR in patients who were HBeAg-positive at baseline. Additionally, the decrease of qHBsAg in the first 3 months of treatment also had poor power in predicting either 48 month VR or SR. ETV is efficacious in NA-naive patients, and qHBsAg titres decreased significantly in the first 3 months of ETV treatment. However, qHBsAg titre was not a good predictor of 4-year VR and HBeAg/anti-HBe SR in this cohort.

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

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. 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). 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. Serum qHBsAg-based simple tests, especially GqHBsR, can accurately and specifically identify significant fibrosis in treatment-naïve HBeAg-positive HBV carriers.

Quantification of serum hepatitis B surface antigen in predicting the response of pegylated interferon alfa-2a in HBeAg-positive chronic hepatitis B with prior lamivudine exposure

AimsMajority of previous studies of pegylated interferon α-2a (PegIFNα-2a) forced on naïve chronic hepatitis B (CHB) patients, and the data of PegIFNα-2a in therapy of patients with prior exposure to nucleos(t)ide analogues is rare. This study aimed to investigate the predictive role of serum quantitative hepatitis B surface antigen (HBsAg) in predicting sustained response of PegIFNα-2a in HBeAg-positive CHB patients with prior lamivudine exposure.MethodsForty-six patients with prior lamivudine exposure received PegIFNα-2a for 12 months and followed-up for 6 months. The clinical features of responders and non-responders were compared, and the predictive role of quantitative HBsAg in predicting responders at the end of follow-up was evaluated. Responders were defined as an ALT normalization, HBeAg seroconversion and sustained virological response at the end of follow-up.ResultsIn this cohort, only 26.1% (12/46) patients were responders. The baseline characteristics of the responders and non-responders were similar; however, the rates of ALT normalization, HBV DNA undetectability and HBeAg seroconversion were all significantly higher in responders than that in non-responders. During the treatment and follow-up, the HBsAg levels were all significantly lower in responders than that in non-responders. In predicting reponders, the serum HBsAg cutoff of 6000 IU/mL at months 6 had a positive predictive value of 73.3 and a negative predictive value of 96.8%, and with an area under the receiver operating characteristic curve of 0.869.ConclusionThe responders toward PegIFNα-2a in CHB patients with prior lamivudine exposure is not high, and serum HBsAg <6000 IU/Ml at months 6 of on-treatment had a high value to predict long-term outcomes of treatment.

The Change of Quantitative of HBeAg Can Predict the Efficacy of Peg-IFN-α 2a in HBeAgpositive CHB Patients

Abstract Objective To investigate the quantitation of hepatitis B e antigen (HBeAg) at week 24 in predicting the efficacy of pegylated-interferon alfa-2a (Peg-IFN-α 2a) in HBeAg-positive chronic hepatitis B (CHB) patients at week 48 and to find a useful predictor for treatment efficacy and investigate individualized treatment of antiviral therapy. Methods Ninety-six HBeAg-positive CHB patients with detectable HBeAg who were treated with Peg-IFN-α 2a were enrolled in this trial. They were categorized into 3 groups according to the changes of HBeAg in week 24: HBeAg decline &gt; 2 log10 group (group A), HBeAg decline between 1 1og10 - 2 log10 (group B), HBeAg decline &lt; 1 log10 group (group C), and group C was randomly distributed into C1 and C2. The patients in group A, group B, and group C1 continued the original therapy and the patients in group C2 were given lamivudine plus Peg-IFN-α 2a for 24 weeks. At week 48, the treatment efficacy and hepatitis B virus covalently closed circular DNA (HBV cccDNA) in liver biopsies were analyzed. Results At week 48, mean reduction of serum HBV DNA: group A: 5.8 log10 copies/ml, group B: 3.8 log10 copies/ml, group C1: 2.8 log10 copies/ml, group C2: 5.7 log10 copies/ml, the reduction of HBV DNA in group A was greater than groups B and C1 (P &lt; 0.01), that in group C1 was greater than group C2 (P &lt; 0.01), the difference between groups B and C1 had no statistical significance (P = 0.19). Mean reduction of HBeAg: group A: 2.7 log10S/CO, group B: 1.9 log10S/CO, group C1: 0.9 log10S/CO, group C2: 1.5 log10S/CO, the difference among groups A, B and C1 and between groups C1 and C2 were statistically significant (P &lt; 0.01). At week 48, HBV DNA undetectable rate in group A, group B, group C1 and group C2 were 87.5%, 34.5%, 17.4% and 81.9%, respectively, the rate in group A was greater than groups B and C1 (P &lt; 0.01)，that in group C1 was greater than group C2 (P &lt; 0.01). HBeAg seroconversion rate were 75.0%, 24.1%, 13.0% and 22.7%, respectively, that in group A was greater than groups B and C1 (P &lt; 0.01). Group A had lower cccDNA in liver tissue than group B and group C1 (P &lt; 0.01). The difference of HBV cccDNA between groups B and C1 and that between groups C1 and C2 had no statistical significance. Conclusions HBeAg decline &gt; 2 log10 at week 24 in Peg-IFN-α 2a-treated hepatitis B patients suggested a better efficacy at week 48; HBeAg decline &lt; 2 log10 at week 24 suggests a worse efficacy at week 48, the combined therapy of Peg-IFN-α and lamivudine could improve the clinical responses. The change of quantitative of HBeAg at week 24 may be used as a predictor of treatment effects at week 48.

Real-World Application of the Roadmap Model in Chronic Hepatitis B Patients with Telbivudine Therapy

BackgroundThe roadmap concept provides a strategy to maximize hepatitis B virus suppression and minimize drug resistance by add-on or switching therapy in patients with a suboptimal response at Week 24. The efficacy of this strategy in routine clinical practice remains to be validated. ObjectiveThe aim of our study was to validate the roadmap concept in the treatment of chronic hepatitis B, and to investigate the virologic efficacy and kinetics of quantitative hepatitis B surface antigen (qHBsAg) during telbivudine therapy in a real-world setting. MethodsA prospective, cohort study enrolled 96 consecutive, treatment-naïve patients with chronic hepatitis B receiving telbivudine therapy. At Week 24, only 17 of 42 (40%) partial or inadequate responders (hepatitis B virus DNA 60–2000 and >2000 IU/mL, respectively) followed the roadmap model and consented to adefovir add-on therapy. The remaining patients continued to receive telbivudine monotherapy. ResultsAt Week 96, none of the patients receiving adefovir add-on therapy, and 28% of patients receiving telbivudine monotherapy, either partial or inadequate responders, developed genotypic resistance (P = 0.03). Poor early qHBsAg kinetics (an increase in qHBsAg >0.4 log IU/mL at Week 12) was the only significant predictor of genotypic resistance (adjusted hazard ratio = 13.83; 95% CI, 1.79–106.76; P = 0.01). Telbivudine monotherapy was efficacious in 94% of partial responders who did not have poor early qHBsAg kinetics, remaining free of drug resistance after 2 years. ConclusionsThe application of the roadmap model with add-on adefovir therapy prevented genotypic resistance. However, telbivudine monotherapy achieved a good response in the majority of partial responders who did not have poor early qHBsAg kinetics. Poor early qHBsAg kinetics was an early predictor of genotypic resistance at Week 96. Modification of the roadmap model to incorporate early qHBsAg kinetics may further optimize the efficacy of the treatment strategy of hepatitis B virus.

Relevance of hepatitis B surface antigen levels in patients with chronic hepatitis B during 5 year of tenofovir treatment.

The role of quantitative hepatitis B surface antigen (HBsAg) levels in patients receiving highly potent oral antiviral therapy is controversial, and here, we determined the HBsAg response in 121 chronic hepatitis B patients treated with tenofovir 300 mg daily. During tenofovir treatment, HBsAg decline of ≥ 1.0 log from baseline was seen in 16.1%, 16.3%, 18.4%, 34.6%, 36.4% and 11.8%, 15.2%, 14.8%, 28.6%, 20% at years 1, 2, 3, 4, 5 for HBeAg-positive and HBeAg-negative patients, respectively. Early decline in HBsAg levels at week 4 was predictive of subsequent significant HBsAg level decline. HBeAg seroconversion occurred in 29.9% of HBeAg-positive patients. On multinomial logistic regression, HBsAg level decline from baseline at week 4 and week 12 or any time subsequently did not correlate with HBeAg seroconversion and HBV DNA level decline from baseline at week 4 and week 12 (OR = 3.704; 95% CI = 1.511-9.076; P = 0.006 and OR = 1.732; 95% CI = 1.032-2.867; P = 0.037, respectively) was significantly predictive of seroconversion. A small proportion of chronic HBV-infected patients treated with tenofovir exhibit a significant (≥ 1.0 log) decline in HBsAg levels. Early decline in HBsAg levels at week 4 was predictive of subsequent and significant HBsAg level decline. The HBsAg decline did not correlate with HBeAg seroconversion in HBeAg-positive patients. Reduction in HBV DNA levels at week 4 and 12 correlated with seroconversion.

Baseline hepatitis B surface antigen quantitation can predict virologic response in entecavir-treated chronic hepatitis B patients

Several anti-viral drugs are approved for the treatment of hepatitis B virus (HBV) infection. However, whether quantitative hepatitis B surface antigen (qHBsAg) can predict the therapeutic response during long-term entecavir treatment remains unclear. Fifty-five chronic hepatitis B (CHB) patients who received entecavir for more than 2 years were enrolled. The serum qHBsAg level was measured by HBsAg II quant immunoassay. A significant decline in the qHBsAg level was defined as > 1 log reduction from baseline to 6 months of entecavir treatment. Of the 55 patients (41 males and 14 females with a mean age of 48.3 ± 11.4 years), 23 patients were positive for hepatitis B e antigen (HBeAg). The median treatment period was 34 months, and ranged from 26 months to 43 months. A total of 288 serum samples were used to determine the qHBsAg levels. At year 3 of entecavir therapy, one (1.8%) patient had HBsAg seroclearance. A high qHBsAg level was defined as greater than 10,000 IU/mL. Patients with a high baseline qHBsAg level had a lower rate of virologic response at year 1 (37.5% vs. 89.7%, p < 0.001) and year 2 (56.2% vs. 94.9%, p = 0.001). In this study population, 14.5% had a significant decline of the qHBsAg level. A significant decline could not predict HBeAg loss in HBeAg-positive or virologic response in all patients. The baseline serum qHBsAg level can predict virologic response in entecavir-treated CHB patients. However, a significant decline in the qHBsAg level cannot predict serologic or virologic response of entecavir treatment.

One-step real-time PCR assay for detection and quantitation of hepatitis D virus RNA

Hepatitis D virus (HDV) is a defective virus which requires hepatitis B virus (HBV) surface antigen (HBsAg) for its assembly. Hepatitis B infected individuals co-infected or superinfected with HDV often present with more severe hepatitis, progress faster to liver disease, and have a higher mortality rate than individuals infected with HBV alone. Currently, there are no commercially available clinical tests for the detection and quantitation of HDV RNA in the United States. A one-step TaqMan quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay was developed for detection of HDV RNA, designing primers located in the region just downstream from the HDV antigen gene. The assay has the potential to detect all eight HDV genotypes. A quantifiable synthetic RNA control was also developed for use in the determination of HDV RNA titers in clinical samples. The limit of detection of this assay is 7.5×102 HDV RNA copies/ml with a dynamic range of six logs. Most clinical specimens tested (40/41) fell within the linear range of the assay. The median HDV RNA titer of the tested specimens was 6.24×106copies/ml, with a range of 8.52×103–1.79×109copies/ml. Out of 132 anti-HDV-positive specimens 41 (31.1%) were positive for HDV RNA.

Quantitative Hepatitis B Surface Antigen Analysis in Hepatitis B E Antigen-Positive Nucleoside-Naive Patients Treated with Entecavir

Entecavir is a potent nucleoside analogue for treating chronic hepatitis B (CHB). Quantitative hepatitis B surface antigen (qHBsAg) levels are predictive of response to interferon-α in CHB treatment; however, the clinical utility of qHBsAg in nucleoside/nucleotide analogue-based CHB therapy is not fully characterized. This study assessed changes in qHBsAg in patients treated with entecavir in the Phase III study ETV-022. This retrospective post hoc analysis included nucleoside/nucleotide-naive, hepatitis B e antigen (HBeAg)-positive patients receiving entecavir (0.5 mg daily) in ETV-022 who had samples available for qHBsAg analysis through week 48. qHBsAg, HBV DNA and alanine aminotransferase levels were assessed for the overall patient cohort, for cohorts with or without HBeAg loss or HBsAg loss by week 48, and by HBV genotype. Overall, 95 patients from ETV-022 had available samples for qHBsAg analysis through week 48. In all cohorts, 48 weeks of entecavir therapy resulted in effective HBV DNA suppression. In the overall cohort, qHBsAg declined by -0.92 log10 IU/ml through week 48. The decline in qHBsAg was more pronounced in patients with subsequent HBeAg loss or HBsAg loss, and in patients infected with HBV genotype D or A. On-treatment qHBsAg changes did not correlate with changes in HBV DNA; no on-treatment or baseline factor was found to be predictive of HBeAg loss or HBsAg loss. Through 48 weeks of entecavir therapy, qHBsAg declined predominantly in those patients who achieved seroclearance of HBeAg or HBsAg. However, unlike with interferon-α-based therapy, early qHBsAg decline was not predictive of serological response at year 1 of entecavir treatment.

Dynamic interplay between CXCL levels in chronic hepatitis C patients treated by interferon.

BackgroundCombined pegylated interferon-α and ribavirin therapy has sustained virological response (SVR) rates of 54% to 61%. Pretreatment predictors of SVR to interferon therapy have not been fully investigated yet. The current study assesses a group of chemokines that may predict treatment response in Egyptian patients with chronic HCV infection.Patients and methodsCXCL5, CXCL9, CXCL11, CXCL12, CXCL 13, CXCL 16 chemokines and E-Cadherin were assayed in 57 chronic HCV patients’ sera using quantitative ELISA plate method. All studied patients were scheduled for combined pegylated interferon alpha and ribavirin therapy (32 patients received pegylated interferon α 2b, and 25 patients received pegylated interferon α 2a). Quantitative hepatitis C virus RNA was done by real time RT-PCR and HCV genotyping by INNOLIPAII.ResultsThere was no significant difference (p > 0.05) in baseline HCV RNA levels between responders and non-responders to interferon. A statistically significant difference in CXCL13 (p = 0.017) and E-Cadherin levels (P = 0.041) was reported between responders and nonresponders at week 12. Significant correlations were found between changes in the CXCL13 levels and CXCL9, CXCL16, E-cadherin levels as well as between changes in E-cadherin levels and both CXCL16 and ALT levels that were maintained during follow up. Also, significant changes have been found in the serum levels of CXCL5, CXCL13, and CXCL16 with time (before pegylated interferon α 2 a and α 2 b therapy, and at weeks 12 and 24) with no significant difference in relation to interferon type and response to treatment.ConclusionSerum levels of CXCL13 and E-Cadherin could be used as surrogate markers to predict response of combined PEG IFN-α/RBV therapy, especially at week 12. However, an extended study including larger number of patients is needed for validation of these findings.Clinical trial NoNCT01758939

Successful treatment of chronic hepatitis B and D with pegylated-interferon plus entecavir

Interferon-based regimen has been used to treat hepatitis D virus (HDV) super-infection on top of hepatitis B virus (HBV) carriers; however, viral relapse is frequent after stopping therapy. Recently, quantitative hepatitis B surface antigen (qHBsAg) was introduced to help the management of chronic hepatitis B (CHB). Little is known about its role in the treatment of HBV and HDV dual infection. Herein, we reported a 45-year-old male HBV carrier with HDV co-infection who received combination therapy of pegylated-interferon α-2a plus entecavir. The qHBsAg level was adopted as the treatment guidance and a consolidation therapy of 12 months was continued after HBsAg loss. The patient achieved HBsAg seroconversion with HDV RNA undetectable after 35 months of combination therapy and sustained therapeutic response 12 months post-therapy. Therefore, personalized response-guided therapy by using qHBsAg may be an option for the treatment for HBV and HDV dual infection.