HBeAg-positive CHB Patients Research Articles

STAT1 is associated with NK cell dysfunction by downregulating NKG2D transcription in chronic HBV-infected patients

PurposeNatural killer (NK) cells are key players in the immune system, however, the exact mechanism of NK cell dysfunction during HBV infection remains poorly defined. MethodsHepatitis B envelope antigen-negative (HBeAg-, n = 19) chronic hepatitis B infection (CHB) patients, HBeAg-positive (HBeAg+, n = 20) CHB patients, HBV-related hepatocellular carcinoma (HBV-HCC, n = 12) patients and healthy blood donors (HD, n = 20), were enrolled in our study. The phenotype and function of the corresponding NK cells of these subjects were then determined. NK cells were cocultured with HBV to assess whether HBV influences the activation of STAT1. Receptors, proliferation, apoptosis rate, and cytotoxicity of NK-92 cells were detected after STAT1 overexpression and knockdown. The relationship between STAT1 and NKG2D promoter was determined by luciferase assay. ResultsThe levels of NKG2D and STAT1 were the lowest in the HBV-HCC group compared with the HD group, followed by the HBeAg+ group and then the HBeAg- group, respectively. Interestingly, STAT1 levels were positively correlated with NKG2D expression and HBeAg status. Furthermore, STAT1 directly bound to the NKG2D promoter to regulate the transcription and expression of NKG2D. Finally, the results also suggested that knockdown of STAT1 can inhibit proliferation, increase apoptosis rate of NK-92 cells and impair cytotoxicity of NK-92 cells. ConclusionSTAT1 is correlated with NK cell dysfunction by downregulating NKG2D transcription in HBV-infected patients. Our findings demonstrate that STAT1 is an important and positive regulator of NK cells, which could provide a potential immunotherapy target for CHB.

Adenosine Triphosphate in Serum as a Promising Biomarker for Differential Diagnosis of Hepatitis B Disease Progression.

The need to be diagnosed with liver biopsy makes the clinical progression of chronic HBV infection diagnosis a challenge. Existing HBV serum biochemical assays are used throughout clinical but have limited effects. Studies have shown that mitochondrial function is tightly coupled to HBV infection. Here, we verified the diagnostic value of serum Adenosine Triphosphate (ATP) as a potential marker for differential HBV infection progress by detecting the level of ATP in the serum from a wide spectrum of HBV-infected populations, and confirmed the role of ATP in the deterioration of HBV infection-related diseases through HBV-infected cells and mouse models. The results showed that there were significantly lower serum ATP levels in HBeAg-positive CHB patients compared with healthy controls. And during the progression of CHB to liver cirrhosis and hepatocellular carcinoma, the ATP level was increased but not higher than healthy controls. The area under the curve (AUC) of serum ATP was 0.9063 to distinguish HBeAg-positive CHB from healthy, and another AUC was 0.8328 in the CHB against the HCC group. Preliminary exploration of the mechanism indicated that the decline of serum ATP was due to impaired mitochondria in CHB patients. Our data provide evidence that serum ATP distinguishes the various progress of HBV infection-related diseases and expands diagnostic biomarkers for HBeAg-positive CHB patients with healthy controls.

A study of the effectiveness of nucleos(t)ide analogues in the treatment of HBeAg- positive chronic hepatitis B with normal alanine aminotransferase and high level of HBV DNA

Objective: To investigate the effectiveness of nucleos(t)ide analogues in the treatment of HBeAg-positive chronic hepatitis B with normal alanine aminotransferase and high level of HBV DNA. Methods: Treatment-naïve chronic hepatitis B patients who were followed up at the Center of Infectious Diseases, West China Hospital of Sichuan University from January 2019 to January 2020 were selected as subjects. Demographic characteristics, the results of laboratory examination before treatment and one year after treatment were retrospectively collected. Patients were divided into tenofovir dipivoxil (TDF) and propofol fumurate tenofovir (TAF) treatment group according to different types of medication. The changes of serum HBV DNA level, HBeAg serological conversion and HBsAg quantitative level were analyzed and compared between the two groups. Results: A total of 38 cases were enrolled. Among them, there were 16 and 22 cases in the TDF and TAF group, respectively. There was no statistically significant difference in demographic characteristics, baseline HBV DNA levels and HBsAg quantitative levels between the two groups. Virological response was achieved in 60.5% (23/38) of patients after one year of antiviral therapy. Serum HBV DNA levels below the lower limit of detection [68.2% (15/22) vs. 50.0% (8/16), P=0.258] and higher HBeAg seroconversion rate [18.2%] (4/22) vs. 6.3% (1/16), P=0.374] was obtained in TAF than TDF group; however, there was no statistically significant differences between the two. Serum HBsAg quantitative level was significantly reduced with TDF and TAF treatment. In addition, alanine aminotransferase elevation was reduced in TAF than TDF treated group. Multivariate logistic regression analysis showed that patient age was an independent predictor of a virological response to antiviral therapy. Conclusion: HBeAg-positive CHB patients with normal alanine aminotransferase, and high HBV DNA level can obtain better curative effect after TDF and TAF treatment.

Hepatitis B surface antigen kinetics after discontinuation of and retreatment with oral antivirals in non-cirrhotic HBeAg-positive chronic hepatitis B.

The outcome of nucleos(t)ide analogues (NAs) discontinuation and retreatment is still uncertain. We evaluated hepatitis B surface antigen (HBsAg) kinetics after NAs discontinuation and during retreatment due to off-treatment clinical relapse among non-cirrhotic HBeAg-positive CHB patients. Four groups were studied: 129 HBeAg-positive patients from a prospective cohort who stopped NAs therapy after achieving sustained response (Group A), 39 patients who received retreatment after off-treatment clinical relapse in the discontinuation group (Group B), 214 patients who maintained treatment after achieving sustained response (Group C) and 291 patients who firstly initiated antiviral treatment (Group D). During a 5-year follow-up, the cumulative incidence of HBsAg loss was significantly higher in Group A than Group C (22.3% vs. 1.6%, p<.001). The quantitative HBsAg (qHBsAg) level at enrolment and NAs discontinuation were independently associated with HBsAg loss. Additionally, patients in Group B showed significantly greater HBsAg loss than those in the Groups C and D, with 5-year cumulative incidences of 9.0%, 1.6% (p=.040) and 0.6% (p<.001), respectively. Moreover, patients in the Group B exhibited better virologic response (100% vs. 98.8%, p<.001) and HBeAg seroconversion (92.6% vs. 69.8%, p<.001) than those in Group D at year 5. Propensity score-matched analysis also showed the similar trend of HBsAg decline. NAs discontinuation with or without subsequent retreatment resulted in a more profound reduction of HBsAg in non-cirrhotic HBeAg-positive patients, suggesting that discontinuation may be a potential cure strategy for those with sustained virological suppression.

Study on early predictive factors of an incomplete viral response with 48 week-entecavir therapy in HBeAg-positive chronic hepatitis B patients

Objective: To study the virological and serological indicators before treatment and 24 weeks after treatment to predict the partial virological response (PVR) of 48-week entecavir (ETV) treatment, and formulate early clinical adjustment treatment plans for HBeAg-positive CHB patients. Methods: HBeAg-positive CHB-naïve patients diagnosed in the Department of Infectious Diseases, Shengjing Hospital, China Medical University, who were treated with oral ETV monotherapy from January 2018 were enrolled. The groups were divided according to the test results of HBV DNA at 48 weeks. Among them, HBV DNA < 20 IU/ml was the complete viral response (CVR) group, and HBV DNA ≥ 20 IU/ml was the PVR group. The virological and serological indexes of the two groups before treatment and 24 weeks after treatment were compared. ROC curve univariate analysis and multivariate logistic regression were performed to find out the early predictors of PVR in HBeAg-positive CHB patients receiving ETV therapy for 48 weeks. Results: As of July 2020, a total of 90 cases had completed 48 weeks of treatment, including 50 cases of CVR (55.56%) and 40 cases of PVR (44.44%). Before treatment and at 24 weeks of treatment, HBsAg, HBeAg and HBV DNA in the PVR group were significantly higher than those in the CVR group (P < 0.001). Univariate analysis showed that HBV DNA quantification (AUC = 0.961, P < 0.001, PPV = 97.06%, NPV = 87.50%) and HBeAg quantification (AUC = 0.883, P < 0.001, PPV = 90.63%, NPV = 81.03%) had higher predictive value at 24 weeks of treatment. Multivariate analysis showed that HBeAg > 1.952 log(10) S/CO (OR = 3.177, 95% CI: 1.261 ~ 8.267, P = 0.018) and HBV DNA > 2.205 log(10) IU / ml (OR = 43.197, 95% CI: 6.858 ~ 272.069, P < 0.001) were independent predictors of PVR at 24 weeks of treatment, and their combination had the best predictive effect. Conclusion: In HBeAg-positive CHB patients receiving ETV treatment for 48 weeks, HBV DNA combined with HBeAg quantification can be an early predictor of PVR at 24 weeks. Additionally, patients with both HBV DNA and HBeAg > 2 log(10) at 24 weeks of treatment must wait 48 weeks to obtain CVR, so it is recommended that treatment strategies should be adjusted at this time.

Adefovir Dipivoxil plus Chinese Medicine in HBeAg-Positive Chronic Hepatitis B Patients: A Randomized Controlled 48-Week Trial.

To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients. A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented. The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns. Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).

THU-103-HBEAG negative CHB patients is associated with more severe liver fibrosis than hbeag positive CHB patients: A propensity score matching analysis

THU-103-HBEAG negative CHB patients is associated with more severe liver fibrosis than hbeag positive CHB patients: A propensity score matching analysis

Serum HBcrAg is better than HBV RNA and HBsAg in reflecting intrahepatic covalently closed circular DNA.

The correlation between serum HBcrAg and HBV RNA is unclear, and correlations of intrahepatic cccDNA with HBcrAg, HBV RNA and HBsAg are rarely reported in the same cohort. This study aimed to assess the correlation of HBcrAg with HBVRNA and HBsAg, and investigate whether serum HBcrAg is superior to serum HBV RNA and HBsAg in reflecting intrahepatic HBV cccDNA in HBeAg-positive and HBeAg-negative CHB patients. In this study, 85 HBeAg-positive and 25 HBeAg-negative patients who have never received antiviraltherapy were included. Among HBeAg-positive patients, HBcrAg was correlated positively with HBsAg (r=0.564, P<0.001) and HBV RNA (r=0.445, P<0.001), and HBV RNA was also correlated positively with HBsAg (r=0.323, P=0.003). Among HBeAg-negative patients, no significant correlation was observed between HBcrAg, HBsAg and HBV RNA. By multivariable linear regression, HBcrAg (β=-0.563, P<0.001), HBsAg (β=-0.328, P<0.001) and HBV RNA (β=0.180, P=0.003) were all associated with cccDNA levels among HBeAg-positive patients, but only serum HBcrAg was associated with cccDNA level (β=0.774, P=0.000) among HBeAg-negative patients. HBcrAg was better correlated with cccDNA as compared to HBsAg and HBV RNA, irrespective of HBeAg status. Among HBeAg-positive patients, though HBcrAg level was influenced by hepatic inflammatory activity and HBV DNA levels, the good correlations of HBcrAg with cccDNA persisted after stratification by inflammatory activity and HBV DNA levels. In conclusion, correlations ofserum HBcrAg, HBV RNA and HBsAg levels differ significantly between HBeAg-positive and HBeAg-negative patients, but serum HbcrAg correlates with cccDNA levels better than HBV RNA and HBsAg, irrespective of HBeAg status.

Association between KIR Genes and Efficacy of Treatment of HBeAg-Positive Chronic Hepatitis B Patients with Entecavir.

To investigate whether the killer immunoglobulin-like receptor (KIR) genes were associated with seroconversion in HBeAg positive CHB responder patients treated with ETV. Polymerase chain reaction with sequence-specific primers (PCR-SSP) method was performed to genotype KIR genes in 200 healthy controls and 198 HBeAg-positive CHB patients which 59 were defined as the complete response group (CRG) to the treatment with ETV and 139 were defined as null or partial response group (NPRG). The frequencies of KIR2DS2 and KIR2DS3 were significantly higher (P=0.030, OR=1.57，95%CI=2.36-1.05 and P=0.018, OR=1.773，95%CI=2.77-1.13, respectively), while, the frequencies of KIR2DL3, KIR2DS1 and KIR3DS1 were significantly lower (P=0.038, OR=0.525, 95%CI=0.96-0.29,and P=0.031, OR=0.640, 95%CI =0.95-0.43, and P=0.035, OR=0.641, 95%CI=0.96-0.43, respectively) in HBeAg-positive CHB patients than those in healthy controls. The frequency of KIR2DS3 gene was significantly higher in NPRG than that in CRG (P=0.018, OR=0.402, 95%CI=0.83-0.20). The frequencies of KIR2DL3 and KIR3DS1 genes were significantly higher in CRG than those in NPRG (P=0.019, OR=3.625, 95%CI=10.83-1.21 and P=0.041, OR=1.949, 95%CI=3.65-1.04, respectively). Patients with KIR2DS3 might have negative responses to anti-HBV therapy with ETV and patients with KIR2DL3 and KIR3DS1 might have advantage in the therapy with ETV.

Changes of serum sPD-1 levels in HBeAg-positive chronic hepatitis B patients with entecavir treatment and correlation with curative effect

Background/aim: This study aimed to assess expression changes of serum sPD-1 levels in HBeAg-positive chronic hepatitis B patients with entecavir treatment and explore the correlation with the curative effect. Materials and methods: A total of 220 HBeAg-positive CHB patients and 207 healthy individuals were included. sPD-1 levels and virological and biochemical responses were assessed at baseline and at 12, 24, and 48 weeks in CHB patients after antiviral therapy. Results: sPD-1 levels in HBeAg-positive CHB patients before treatment were significantly lower than those of healthy controls. After entecavir treatment, sPD-1 levels increased gradually over time. At 48 weeks after entecavir treatment, sPD-1 amounts in the HBeAg seroconversion group were significantly higher than the values of the HBeAg-negative and HBeAg-positive groups. sPD-1 levels in patients with alanine aminotransferase (ALT) returning to normal were significantly higher than in those with ALT not returning to normal. sPD-1 levels in treated patients with no HBV-DNA were significantly higher than in those with HBV-DNA remaining positive. sPD-1 was negatively correlated with ALT and HBV-DNA at 12, 24, and 48 weeks after entecavir treatment. Conclusion: sPD-1 may play a certain role in chronic hepatitis B and has a close relationship with the curative effect of entecavir.

Polymorphisms of CYP27B1 are associated with IFN efficacy in HBeAg-positive patients.

Host single nucleotide polymorphisms were associated with antiviral therapy in CHB patients. The CYP27B1 gene, encoding 25(OH)D3 -1α hydroxylase, might activate 25(OH)D3 to 1,25(OH)2 D3 in kidney resulted in influencing the efficacy of interferon (IFN). The aim of the study was to investigate the association between CYP27B1 polymorphisms and the response to IFN in HBeAg-positive patients. Eighty-seven HBeAg-positive CHB patients infected with HBV genotype B or C were included in the study. All patients were treated with IFN at least 1year. According to the response to PEG-IFN therapy, they were divided into three groups: 16 complete responses (CR), 42 partial responses (PR), and 29 nonresponses (NR). Sanger-sequencing was utilized to genotype the CYP27B1 SNPs(rs4646536 and rs10877012). In logistic regression analysis, the frequency of rs4646536 CC genotype was observed to be higher in the NR group. Besides, the GG genotype of rs10877012 differed significantly among the three groups. The GG genotype was prevalent in patients with CR, and patients with TT genotype result in NR at the end of IFN treatment. The most common haplotype TG was independently associated with CR, after adjustment, and haplotype CT appeared to be associated with NR and PR, rather than CR. The data also showed that patients with baseline 1,25(OH)2 D3 > 39.39pg/mL had higher CR rates at the end of IFN therapy. These results suggested CYP28B1 gene polymorphisms may be independently associated with the efficacy of IFN in HBeAg-positive patients.

Clinical effect of 156-week telbivudine sequential therapy in HBeAg-positive chronic hepatitis B patients with suboptimal response to pegylated interferon-α-2a therapy

Objective: To investigate the clinical effect of 156-week telbivudine sequential therapy in HBeAg-positive chronic hepatitis B patients with suboptimal response to pegylated interferon-α-2a (Peg-IFN-α-2a) therapy. Methods: A total of 35 HBeAg-positive CHB patients with HBV DNA < 500 IU/ml who were treated with Peg-IFN-α-2a for 48 weeks and did not experience seroconversion of HBeAg were given telbivudine sequential therapy for 156 weeks. HBeAg clearance rate, HBeAg seroconversion rate, HBV DNA clearance rate, safety, and drug resistance rate were analyzed. The t-test was used for the analysis of continuous data and the chi-square test was used for the analysis of categorical data. A multivariate Cox regression analysis was used to identify the influencing factors for HBeAg seroconversion. Results: Telbivudine sequential therapy achieved an ideal HBeAg seroconversion rate of 87.88% with good tolerability and low drug resistance. The HBeAg clearance rate and HBeAg seroconversion rate increased over the time of treatment and were 45.45% and 45.45%, respectively, at 24 weeks and 93.94% and 87.88%, respectively, at 156 weeks. No patient had virologic breakthrough or HBsAg clearance during treatment. The multivariate Cox regression analysis showed that baseline HBsAg level (hazard ratio [HR] = 0.404, P = 0.003) and > 0.5 lg IU/ml reduction in HBeAg at 24 weeks (HR = 2.196, P = 0.048) were predictive factors for HBeAg seroconversion at 156 weeks. Conclusions: In HBeAg-positive CHB patients with suboptimal response to Peg-IFN-α-2a therapy, 156-week telbivudine sequential therapy has a good clinical effect and can be used as an optimal regimen for such patients.

Low Ratio of Treg to Th17 Cells After 36 Weeks of Telbivudine Therapy Predict HBeAg Seroconversion.

Changes of Treg/Th17 cells ratio and their associated cytokines have some correlations with an immune modulatory effect of Telbivudine treatment. The aim of our study was to investigate the role of the dynamic ratio of Treg/Th17 cells in the mechanism of LdT therapy and their relationships with the clinical responses. We detected the frequency and cytokines production of Treg and Th17 cells in 28 hepatitis B envelope antigen (HBeAg)-positive CHB patients at 0, 12, 24, 36, 48, and 96 weeks after initial LdT therapy. LdT could upregulate the frequency of Th17 cells and Th17 cells associated cytokines, downregulated the frequency of Treg cells and level of TGF-β, which leads to the decrease of Treg/Th17 ratio in HBeAg-positive CHB patients. Treg/Th17 ratio at treatment week 36 could independently predict HBeAg seroconversion in the first 2 years of Telbivudine treatment. Telbivudine therapy can decrease Treg/Th17 ratio, which may predict HBeAg seroconversion during treatment.

HLA-C and KIR combined genotype as new response marker for HBeAg-positive chronic hepatitis B patients treated with interferon-based combination therapy.

Current treatment for chronic hepatitis B infection (CHB) consists of interferon-based therapy. However, for unknown reasons, a large proportion of patients with CHB do not respond to this treatment. Hence, there is a pressing need to establish response markers to select patients who will benefit from therapy and to spare potential nonresponders from unnecessary side effects of antiviral therapy. Here, we assessed whether HLA-C and KIR genotypes were associated with treatment outcome for CHB. Twelve SNPs in or near the HLA-C gene were genotyped in 86 CHB patients (41 HBeAg positive; 45 HBeAg negative) treated with peginterferon alfa-2a + adefovir. Genotyping of killer immunoglobin-like receptors (KIRs) was performed by SSP-PCR. One SNP in HLA-C (rs2308557) was significantly associated with combined response in HBeAg-positive CHB patients (P = 0.003). This SNP is linked to the HLA-C group C1 or C2 classification, which controls KIR binding. The combination of KIR2DL1 with its ligand HLA-C2 was observed significantly more often in HBeAg-positive patients with a combined response (13/14) than in nonresponders (11/27, P = 0.001). Patients with the KIR2DL1/C2 genotype had significantly higher baseline ALT levels (136 vs 50 U/L, P = 0.002) than patients without this combination. Furthermore, KIR2DL1-C2 predicted response independent of HBV genotype and ALT at baseline. HLA-C and KIR genotype is strongly associated with response in HBeAg-positive CHB patients treated with interferon-based therapy. In combination with other known response markers, HLA-C/KIR genotype could enable the selection of patients more likely to respond to interferon-based therapy.

FRI-103 - The Presence of BCP/PC Variants Reduces the Rate of HBsAg Loss among HBeAg-Positive CHB Patients Treated with Long-Term Tenofovir DF Therapy

FRI-103 - The Presence of BCP/PC Variants Reduces the Rate of HBsAg Loss among HBeAg-Positive CHB Patients Treated with Long-Term Tenofovir DF Therapy

O116 : Predictive value of baseline and on-treatment qHBsAg level in HBeAg positive CHB patients who switched from NUCs to pegylated interferon A-2A: A further analysis from new switch study

O116 : Predictive value of baseline and on-treatment qHBsAg level in HBeAg positive CHB patients who switched from NUCs to pegylated interferon A-2A: A further analysis from new switch study

Expansion of circulating TFH cells and their associated molecules: involvement in the immune landscape in patients with chronic HBV infection

BackgroundBlood CXCR5+CD4+ T cells are defined as circulating T follicular helper (TFH) cells, which is required for effective humoral immunity. This study aimed to investigate the role of circulating TFH cells in patients with chronic hepatitis B virus (CHB) infection.MethodsThe frequency and phenotype of circulating TFH cells were monitored by flow cytometry in CHB patients and in healthy controls (HC). The expression of BCL-6, IL-21, IL-4, CXCR5, and IL-6R mRNA was analyzed using real-time PCR. Serum HBsAg, HBeAg, HBeAb, HBV DNA loads, ALT and AST were determined. The potential association of the frequency of TFH cells and their surface markers with clinical parameters was assessed.ResultsThe frequency of CXCR5+CD4+ T cells was increased in CHB patients and positively correlated with ALT and AST but not with HBV DNA loads. Moreover, an expansion of ICOS-, PD-1-, CD40L-, and IL-21R-expressing TFH cells occurred in CHB patients, but failed to correlate with ALT, AST and HBV DNA loads. Interestingly, the frequency of CXCR5+CD4+ T cells and ICOS+CXCR5+CD4+ T cells was significantly higher in HBeAg positive CHB patients than in HC. Additionally, the percentages of CXCR5+CD4+ T cells were positively correlated with AST, and ICOS-expressing CXCR5+CD4+ T cells were negatively correlated with HBV DNA loads. No significant differences in the frequency of CXCR5+CD4+ T cells were observed between inactive carrier (IC) patients and healthy controls. However, ICOS-, PD-1-, CD40L-expressing TFH cells were increased in IC patients and positively correlated with AST. Furthermore, the expression of BCL-6, IL-21, IL-4, CXCR5, and IL-6R mRNA in TFH cells was higher in CHB patients than in HC.ConclusionsThese data demonstrate that circulating TFH cells may participate in HBV-related immune responses. In addition to the frequency of TFH cells, the phenotype of these cells plays an important role in CHB patients.

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

Comparison of hepatitis B surface antigen and e antigen in predicting liver histology in hepatitis B e antigen-positive chronic hepatitis B patients.

The purpose of this study was to determine the relationship between hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) levels and liver histology in HBeAg-positive patients with chronic hepatitis B virus (CHB) infection. Serum HBsAg and HBeAg levels were analyzed, and liver biopsies were obtained from 203 HBeAg-positive CHB patients (62.6% males; median age 31.3years). The upper limit of normal (ULN) for ALT in this study was 30 and 19U/L for males and females, respectively. Histologic assessment was based on Scheuer classification. ALT <2 × ULN, fibrosis stage <S2, and necro-inflammation grade <G2 were noted in 70 (34.5%), 141 (69.5%), and 105 (51.7%) patients, respectively. Patients with significant histology (fibrosis stage ≥S2 and/or fibrosis stage of 1 plus inflammation grade ≥2) had significantly lower median HBsAg (13,998.4 and 42,186.5IU/mL, respectively, p<0.001) and HBeAg levels (540.5 and 1,206.8S/CO, respectively, p<0.001) than patients with insignificant histology. Among patients with ALT <2 × ULN, the area under the ROC curve for serum HBsAg and HBeAg levels was 0.76 and 0.70, respectively. Using a cutoff value of 17,558IU/mL for HBsAg and 875.6S/CO for HBeAg in patients with ALT <2×ULN, positive predictive values for insignificant histology were 87 and 86.8%, respectively, whereas the negative predictive values were 50 and 47.1%, respectively. Among HBeAg-positive patients with ALT <2 × ULN, high-serum HBsAg and HBeAg levels can equally accurately predict insignificant histology.

412 PREVALENCE, VIROLOGICAL AND CLINICAL CHARACTERISTICS OF CHRONIC HEPATITIS DELTA VIRUS INFECTION (CHD) IN ROMANIA

receiving anti-viral therapy could be used as a response marker at baseline (BL), or early during treatment to predict treatment outcome. Methods: A prototype array-based assay served (IMPACT – Immunological Multi-Parameter Chip Technology, Roche Diagnostics) to determine HBsAg, anti-HBs and complex levels. We tested a panel of serum samples of 40 HBeAg-positive and 44 HBeAg negative patients who received pegylated interferon and adefovir for 48 weeks and were followed subsequently for 2 years. Results: HBsAg loss occurred in 4 of 40 HBeAg positive and 7 of 44 HBeAg negative patients. Sixteen of 40 HBeAg positive patients lost HBeAg and 13 of them formed anti-HBe. At BL complexes were present in 83 (99%) patients, whereas free anti-HBs levels were only detectable in 5 patients. Complex levels at BL and WK 12 were higher in HBeAg positive patients with HBeAg loss, compared to patients who retained HBeAg (p =0.0046 and p=0.026 respectively). ROC analysis for HBeAg loss in HBeAg positive patients at BL and WK 12 showed AUC 0.77 (p =0.004) and AUC 0.73 (p =0.026) for complex levels and AUC 0.57 (non significant) and AUC 0.61 (non significant) for HBsAg levels. We saw no correlation in either HBeAg-positive or -negative patients between complex levels and HBsAg loss. Nor did we find any correlation between complex and HBsAg or anti-HBs levels. Discussion: We demonstrated for the first time that before and during treatment HBsAg/anti-HBs immune complex levels can predict HBeAg loss in HBeAg positive CHB patients treated with peg-interferon and adefovir. Complexes were present in almost all patients at BL and were higher in patients that lost HBeAg. In conclusion, determining HBsAg/anti-HBs immune complex levels before and early during treatment could select CHB patients with an optimal chance to achieve HBeAg loss.