Hepatitis B E Antigen Positive Patients Research Articles

M1 macrophages may be effective adjuvants for promoting Th‑17 differentiation in HBeAg positive hepatitis patients with ALT ≤2ULN.

Hepatitis B virus (HBV) infection can activate macrophages to accelerate liver disease progression, including inflammation and fibrosis. However, the exact mechanism remains undetermined. The present study assessed the effects of macrophage polarization and the related cytokines on Th‑17 differentiation in HBeAg positive individuals with a HBV infection, and also evaluated the potential association of Th‑17 cell frequency with the severity of liver injury. A cross‑sectional study design was used to collect the clinical parameters, blood samples and liver tissue samples of patients with alanine transaminase £2x upper limit of normal and confirmed hepatitis B who underwent liver puncture in Qishan Hospital between January 2019‑December 2021. Macrophage and Th‑17 cell related factors were assayed using ELISA. The expression and quantification of cell surface antigen and intracellular markers in cells were assessed using flow cytometry. Pathological staining, including hematoxylin and eosin, reticular fiber staining and immunohistochemical staining were used to assess inflammation and fibrosis in the liver tissue. In the peripheral blood of patients with HBV infection, the number of CD14+ macrophages was significantly increased compared with the healthy control, especially in the hepatitis B e antigen (HBeAg) positive group. CD14+ macrophages were predominantly of the M1 type based on the assessment of the phenotype using flow cytometry and cytokine secretion. Furthermore, the percentage of M1 phenotype and related cytokines were positively correlated with Th‑17 differentiation. IL‑17A secreted by Th‑17 was positively correlated with the degree of liver inflammation and fibrosis, as well as with the severity of liver disease, which indicated that the differentiation of Th‑17 may be involved in the progression of liver disease. HBeAg may promote Th‑17 differentiation and IL‑17A production by M1 macrophages to accelerate the pathogenesis of liver inflammation and fibrosis in CHB patients.

An optimized mode of interferon intermittent therapy help improve HBsAg disappearance in chronic hepatitis B patients.

BackgroundTo investigate the effect of intermittent interferon therapy mode on the disappearance of hepatitis B surface antigen (HBsAg) in chronic hepatitis B (CHB) patients.MethodsThis is a retrospective cohort study in CHB patients who were suspended from pegylated interferon α (PEG-IFNα) therapy due to a plateau in HBsAg decline during the initial treatment period, and resumed interferon therapy after an interval of 3–6 months. Patients received entecavir or tenofovir during the interval period. Hepatitis B virus (HBV) virological and serological indexes, clinical biochemical indexes, and blood routine tests were performed at the baseline and every 3 months during follow-up of initial interferon treatment. A functional cure was analyzed as a primary outcome.ResultsA total of 304 patients treated with intermittent PEG-IFNα were included in the statistical analysis, including 215 men and 89 women, aged 37.97 ± 8.53 years, and 73 hepatitis B e antigen (HBeAg)-negative and 231 HBeAg positive patients. In total 59 patients (19.41%) achieved HBsAg disappearance through the initial, intermittent, and retreatment of PEG-IFNα treatment, of whom 43 patients (14.14%) achieved HBsAg seroconversion. Early HBsAg response to initial treatment was significantly associated with HBsAg response at 12 and 24 weeks of retreatment. After the intermission period, the incidence of HBsAg disappearance in patients with early HBsAg response in the retreatment period was 43.87%. The baseline HBsAg and 12-week HBsAg response in the retreatment period had higher predictive value than the initial treatment HBsAg response.ConclusionThe initial, intermittent, and retreatment mode of interferon can help to improve the HBsAg disappearance rate in CHB patients.Clinical trial registration[www.ClinicalTrials.gov], identifier [NCT04028856].

Nucleoside/nucleotide analog consolidation therapy in hepatitis B e-antigen positive chronic hepatitis B patients: Three years should be preferred.

To assess the role of consolidation therapy after cessation of nucleoside/nucleotide analogs (NAs) for off-treatment outcome and to explore the optimal consolidation period in hepatitis B e-antigen (HBeAg) positive chronic hepatitis B (CHB) patients. We undertook a prospective, observational cohort study including HBeAg positive CHB patients discontinuing NAs. Virological relapse was the primary endpoint of the current study and was defined as a serum hepatitis B virus DNA more than 104 copies/ml (another assay was carried out for confirmation at least 2weeks later). Propensity score matching analysis was used to balance the baseline characteristics between HBeAg positive CHB patients with different consolidation periods. A total of 190 HBeAg positive CHB patients were included. Fifty-four patients relapsed during follow-up and the cumulative relapse rates at years 1, 3, 5, and 10 were 19.5%, 24.1%, 27.2%, and 32.1%, respectively. Most patients (61.1%) relapsed in the first 6months. After propensity score matching, significantly lower cumulative relapse rates were observed in patients with consolidation period ≥36months compared with patients with consolidation period more than 36months (29.3% vs. 52.8% at year 10; p=0.012). Cessation of NAs after HBeAg seroconversion and long-term consolidation is generally safe and feasible in HBeAg positive CHB patients. Three years of consolidation should be preferred in clinical practice.

Abnormal IL-10 levels were related to alanine aminotransferase abnormalities during postpartum in HBeAg positive women with chronic hepatitis B.

Alanine transaminase (ALT) abnormalities are common in chronic hepatitis B (CHB) carriers during postpartum period. Disturbances in cytokines are considered to be associated with hepatitis Flares. There are limited data on cytokines changes in HBeAg positive patients with ALT abnormalities.This is an observational study. Pregnant patients with hepatitis B e-antigen (HBeAg) positive were enrolled from January 2014 to September 2018. Patients were assigned into three groups based on ALT levels in postpartum 6 to 8 weeks: ALT in normal range, ALT in 1 to 2-fold upper limits of normal (ULN) and ALT >2-fold ULN. Serum cytokines, ratios of regulatory T cells, and the concentration of cortisol were collected and compared among the three groups.Of the 135 mothers enrolled, 80.7% (109/135) completed the postpartum 6-week study. 13.8% (15/109) patients had postpartum ALT higher than 2ULN, 27.5% (30/109) patients had ALT in 1 to 2ULN and 58.7% (64/109) patients had ALT in normal range. Compared to control group, patients with ALT >2ULN had a higher IL-10 level (P < .05). No differences of IL-10 levels were found in the comparison of other inter comparison among three groups. No differences were found in the levels of other collected serum cytokines, cortisol, and regulatory T cells among three groups. On multivariate analysis, abnormal IL-10 level was independent risk factor for postpartum ALT elevating >2ULN. At the same time, the incidence of postpartum ALT elevated >2ULN were higher in patients with abnormal elevation IL-10 level than in patients with normal IL-10 level (14/68 vs 1/41, P = .008).CHB patients with postpartum ALT abnormalities show higher IL-10 level and postpartum ALT abnormalities were mainly occurred in patients with abnormal IL-10 level. IL-10 may be an underlying predictor and treatment target of hepatitis B, and further studies are needed.

Clinical Features of Hepatitis B e-antigen Positive Chronic Hepatitis B Patients co-existing Precore and/or Basal Core Promoter Mutations

Aim: Characterize the clinical features of treatment-naive hepatitis B e-antigen (HBeAg)-positive chronic hepatitis B (CHB) patients harboring either precore (PC) or basal core promoter (BCP; PC/BCP) mutations. Methods: Alanine aminotransferase, HBsAg, HBV-DNA, HBV genotypes, PC/BCP mutations and liver stiffness measurement were assessed for 186 treatment-naive HBeAg-positive CHB patients. Results: PC/BCP mutations were found in 40.31% of the treatment-naive HBeAg-positive CHB patients. Patients with PC/BCP mutations showed significantly higher alanine aminotransferase and liver stiffness measurement levels. The serum HBsAg and HBV DNA levels in patients with BCP mutations were significantly lower than those in patients with wild-type virus. PC/BCP mutations were more prevalent in patients in immune clearance phase than those in immune tolerance phase. Conclusion: The emergences of PC/BCP mutations possibly indicate that HBeAg positive patients are experiencing the phase of immune clearance.

Relationship between serum quantitative HBsAg and HBV DNA levels in chronic hepatitis B patients.

Serum hepatitis B surface antigen (HBsAg) level has been developed as an important marker to predict treatment outcome recent years. The authors aimed to identify the correlation between quantitative HBsAg and hepatitis B virus (HBV) DNA level in chronic hepatitis B (CHB) patients and explore whether quantitative HBsAg can be used as a surrogate marker of serum HBV DNA for CHB patients. One hundred seventy-three patients were included in this study. Patients were divided into two groups: Hepatitis B e antigen (HBeAg) positive and negative patients. There was a positive correlation between quantitative HBsAg and HBV DNA level in HBeAg positive patients (r = 0.509, P < 0.001) and poor correlation in HBeAg negative patients (r = 0.176, P = 0.096). Interestingly, completely no correlation (r = -0.01, P = 0.994) was found in younger HBeAg negative patients (<40 years old), whereas in older HBeAg negative patients (>40 years old) there is a positive correlation (r = 0.448, P = 0.003). Mean HBsAg titer and Alanine aminotransferase (ALT) level were significantly higher in HBeAg positive group (3.81 log10 IU/mL; 105 IU/mL) than in negative group (2.85 log10 IU/mL; 32 IU/mL) (P < 0.001). We concluded that quantitative HBsAg could reflect HBV DNA level in HBeAg positive patients, but could not surrogate for HBV DNA level in HBeAg negative patients. Our study improves understanding of the relationship between HBsAg titers and HBV DNA levels in CHB patient and may have implications for future treatment algorithms evaluating the HBsAg titers in both HBeAg positive and negative patients.

Correlation of Quantitative Assay of HBsAg and Hepatitis B Virus DNA Levels Among Chronic HBV Patients Attending Pathologist Lancet Laboratory in Nairobi, Kenya

Background: Hepatitis B Virus (HBV) viral load measurements is recommended for diagnosis and monitoring of patients on treatment for Chronic Hepatitis B (CHB). However, these diagnostic techniques are molecular-based and expensive and unavailable to majority of the Kenyan population. Quantitation of hepatitis B surface antigen (HBsAg) by automated chemiluminescent micro-particle immunoassay has been proposed as a surrogate marker. Objectives: This study showed the correlation between HBsAg and HBV DNA levels among patients with CHB attending a referral Laboratory in Nairobi, Kenya. Methods: One hundred and seventy-three (173) patients were enrolled while excluding Hepatitis C Virus (HCV) and Hepatitis D Virus (HDV) positive patients. Results: The mean age of the study patients was 37.2 years, 112 (64.7%) were male, and 142 (82.1%) were hepatitis B e antigen (HBeAg) negative while 31/173 (17.9%) were HBeAg positive. The mean HBV DNA level was 2.89 log10 IU/mL and 41 (23.7%) had a baseline HBV DNA level of > 2000 IU/mL. By Mann-Whitney test, HBV DNA levels differed significantly between HBeAg positive and negative patients (P = 0.001), as did HBsAg titer (P = 0.032). Unfortunately, according to the Spearman test, there was a weak correlation between HBsAg and HBV DNA levels (P = 0.024 and r = 0.171). Conclusions: Patients with HBeAg negative test results had lower levels of HBsAg and lower levels of HBV DNA. Serum quantitation of HBsAg may not replace serum HBV DNA levels among patients with CHB in Nairobi Kenya.

Alpha-interferon treatment in hepatitis B.

Pegylated interferon-α (PEG-IFN-α) is a first line option in the treatment of chronic hepatitis B. Compared with nucleos(t)ide analogues (NAs), therapy with PEG-IFN-α has the advantages of finite treatment duration and higher rates of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) seroconversion, but the disadvantage of greater adverse effects. Choosing PEG-IFN-α requires careful evaluation of the likelihood of achieving a sustained off-treatment response. Sustained off-treatment response with PEG-IFN-α can be predicted by baseline factors in HBeAg positive disease. These include genotype A or B, low viral load, high alanine aminotransferase (ALT), older age and female gender. On the other hand, no pre-treatment factors have been identified that can reliably predict response in HBeAg negative disease. Using on-treatment quantitative HBsAg levels, failure of a long term response can be identified with high negative predictive value (NPV). However, no combination of on treatment parameters have been identified so far that can precisely forecast successful treatment. Up until recently, there was little evidence supporting the use of combining PEG-IFN with NAs. The addition of PEG-IFN in patients who already have viral suppression with NAs therapy appears superior to continuing NAs alone in achieving a sustained response. Also, tenofovir disoproxil fumarate (TDF) in combination with PEG-IFN has been reported to enable significantly higher HBsAg loss than with either monotherapy alone. This occurred in both HBeAg positive and negative patients across all genotypes. In spite of recent developments, rates of HBsAg loss are still only in the order of 10% and so cure remains elusive. Further research is required to identify the optimal combination or sequential therapy regimen, and the subgroups with the highest rates of response so that they can be targeted.

Long-term follow up of peginterferon-α-2a treatment of hepatitis B e-antigen (HBeAg) positive and HBeAg negative chronic hepatitis B patients in phase II and III studies.

We analyzed the 5-year post-treatment response to peginterferon α-2a (PEG IFN-α-2a) in hepatitis B e-antigen (HBeAg) positive and negative chronic hepatitis B patients. One hundred and thirty-seven chronic hepatitis B (CHB) patients receiving 90μg or 180μg of PEG IFN-α-2a for 24 or 48weeks in phase II or III studies were enrolled in the study, including 100 HBeAg positive patients and 37 HBeAg negative patients; 121 patients (88.4%) had genotype C. Of the 137 patients, 94 received additional antiviral therapy because of viral reactivation and 43 did not receive any additional antiviral treatment during follow up. Five years upon PEG IFN-α-2a treatment, 32 patients (23.4%) who did not receive any additional antiviral agent after PEG IFN-α-2a therapy achieved a good response (normal serum alanine aminotransferase, low-level hepatitis B virus [HBV] DNA, and HBeAg negativity). Female sex and low HBV DNA levels by the end of treatment were independently associated with favorable 5-year post-treatment responses. Forty-eight-week administration of PEG IFN-α-2a showed a better response (26.4%) than 24-week administration (18.0%). Six patients (4.3%), four males and two females, cleared hepatitis B surface antigen (HBsAg) during the 5-year follow-up period. The 48-week administration of PEG IFN-α-2a achieved better biochemical and virological responses than the 24-week administration, particularly in younger females. The 5-year post-treatment response rate was 23.4%; however, more than two-thirds of the patients received additional antiviral therapy because of viral reactivation after PEG IFN-α-2a treatment. HBsAg clearance was noted in six patients (4.3%). PEG IFN-α-2a is effective in young female patients.

Mutations in pre-core and basic core promoter regions of hepatitis B virus in chronic hepatitis B patients.

To investigate the frequency of mutations in pre-core (pre-C) and basic core promoter (BCP) regions of hepatitis B virus (HBV) from Shanxi Province, and the association between mutations and disease related indexes. One hundred chronic hepatitis B patients treated at Shanxi Province Hospital of Traditional Chinese Medicine were included in this study. PCR-reverse dot blot hybridization and mismatch amplification mutation assay (MAMA)-PCR were used to detect the mutations in the HBV pre-C and BCP regions. HBV DNA content and liver function were compared between patients with mutant HBV pre-C and BCP loci and those with wild-type loci. The consistency between PCR-reverse dot blot hybridization and MAMA-PCR for detecting mutations in the HBV pre-C and BCP regions was assessed. Of the 100 serum samples detected, 9.38% had single mutations in the pre-C region, 29.17% had single mutations in the BCP region, 41.67% had mutations in both BCP and pre-C regions, and 19.79% had wild-type loci. The rates of BCP and pre-C mutations were 65.7% and 34.3%, respectively, in hepatitis B e antigen (HBeAg) positive patients, and 84.6% and 96.2%, respectively, in HBeAg negative patients. The rate of pre-C mutations was significantly higher in HBeAg negative patients than in HBeAg positive patients (χ (2) = 26.62, P = 0.00), but there was no significant difference in the distribution of mutations in the BCP region between HBeAg positive and negative patients (χ (2) = 2.43, P = 0.12). The presence of mutations in the pre-C (Wilcoxon W = 1802.5, P = 0.00) and BCP regions (Wilcoxon W = 2906.5, P = 0.00) was more common in patients with low HBV DNA content. Both AST and GGT were significantly higher in patients with mutant pre-C and BCP loci than in those with wild-type loci (P < 0.05). PCR-reverse dot blot hybridization and MAMA-PCR for detection of mutations in the BCP and pre-C regions had good consistency, and the Kappa values obtained were 0.91 and 0.58, respectively. HBeAg negative patients tend to have HBV pre-C mutations. However, these mutations do not cause increased DNA copies, but associate with damage of liver function.

Urinary nuclear magnetic resonance spectroscopy of a Bangladeshi cohort with hepatitis-B hepatocellular carcinoma: A biomarker corroboration study.

To establish if a distinct urinary metabolic profile could be identified in Bangladeshi hepatitis-B hepatocellular carcinoma (HCC) patients compared to cirrhosis patients and controls. Urine samples from 42 Bangladeshi patients with HCC (39 patients with hepatitis-B HCC), 47 with cirrhosis on a background of hepatitis B, 46 with chronic hepatitis B, and seven ethnically-matched healthy controls were analyzed using nuclear magnetic resonance (NMR) spectroscopy. A full dietary and medication history was recorded for each subject. The urinary NMR data were analyzed using principal component analysis (PCA) and orthogonal partial least squared discriminant analysis (OPLS-DA) techniques. Differences in relative signal levels of the most discriminatory metabolites identified by PCA and OPLS-DA were compared between subject groups using an independent samples Kruskal-Wallis one-way analysis of variance (ANOVA) test with all pairwise multiple comparisons. Within the patient subgroups, the Mann-Whitney U test was used to compare metabolite levels depending on hepatitis B e-antigen (HBeAg) status and treatment with anti-viral therapy. A Benjamini-Hochberg adjustment was applied to acquire the level of significance for multiple testing, with a declared level of statistical significance of P < 0.05. There were significant differences in age (P < 0.001), weight (P < 0.001), and body mass index (P < 0.001) across the four clinical subgroups. Serum alanine aminotransferase (ALT) was significantly higher in the HCC group compared to controls (P < 0.001); serum α-fetoprotein was generally markedly elevated in HCC compared to controls; and serum creatinine levels were significantly reduced in the HCC group compared to the cirrhosis group (P = 0.004). A three-factor PCA scores plot showed clustering of the urinary NMR spectra from the four subgroups. Metabolites that contributed to the discrimination between the subgroups included acetate, creatine, creatinine, dimethyamine (DMA), formate, glycine, hippurate, and trimethylamine-N-oxide (TMAO). A comparison of relative metabolite levels confirmed that carnitine was significantly increased in HCC; and creatinine, hippurate, and TMAO were significantly reduced in HCC compared to the other subgroups. HBeAg negative patients showed a significant increase in creatinine (P = 0.001) compared to HBeAg positive patients in the chronic hepatitis B subgroup, whilst HBeAg negative patients showed a significant decrease in DMA (P = 0.004) in the cirrhosis subgroup compared to HBeAg positive patients. There were no differences in metabolite levels in HCC patients who did or did not receive antiviral treatment. Urinary NMR changes in Bangladeshi HCC were identified, corroborating previous findings from Egypt and West Africa. These findings could form the basis for the development of a cost-effective HCC dipstick screening test.

Efficacy of entecavir therapy for hepatitis B e-antigen positive chronic hepatitis B patients with prior exposure to interferon or nucleoside/nucleotide analogues.

AimThe efficacy of entecavir (ETV) in treatment‐experienced chronic hepatitis B (CHB) patients remains unclear. We evaluated the therapeutic responses and virological breakthrough following ETV treatment in hepatitis B e‐antigen (HBeAg) positive CHB patients with prior exposure to interferon or nucleoside/nucleotide analog and treatment‐naive patients.MethodsThis was a retrospective, multicenter study of treatment (&gt;1 year) with 0.5 mg ETV in 248 treatment‐naive and 48 treatment‐experienced HBeAg positive CHB patients (70.5% male; mean age, 40.5 years). The rates of undetectable hepatitis B virus (HBV) DNA, HBeAg loss and virological breakthrough were analyzed.ResultsThe median duration of ETV treatment was 27.3 months (range, 18.4–34.5). The rate of HBeAg loss was 41.9% (104/248) in treatment‐naive and 45.8% (22/48) in treatment‐experienced patients. The baseline serum HBV DNA and alanine aminotransferase levels were significant predictors for HBeAg loss (P = 0.01 and P = 0.04, respectively). There was no statistical difference between the groups in the rates of undetectable HBV DNA and HBeAg loss at any time point. Virological breakthrough occurred in 1.6% (4/248) of treatment‐naive and 8.3% (4/48) of treatment‐experienced patients. The four treatment‐experienced patients with virological breakthrough had received prior lamivudine treatment. After excluding those treated with interferon, lamivudine‐experienced patients had significantly greater virological breakthrough compared with treatment‐naive patients (log–rank test, P = 0.034; univariate Cox regression, P = 0.047).ConclusionETV treatment efficacy, including virological response and HBeAg loss, was comparable between treatment‐naive and treatment‐experienced HBeAg positive CHB patients. Lamivudine‐experienced patients had a higher risk of virological breakthrough than treatment‐naive patients.

Low Serum Hepatitis B Surface Antigen Level Predicts Compensated Cirrhosis Caused by Chronic Hepatitis B in HBeAg Positive Patients in East China.

Backgrounds:Serum hepatitis B surface antigen (HBsAg) levels are associated with fibrosis in patients with chronic hepatitis B (CHB) infection.Objectives:The aim of our study was to evaluate serum HBsAg level as a biomarker for compensated cirrhosis in hepatitis B e antigen (HBeAg) positive CHB patients.Patients and Methods:Two-hundred and one HBeAg-positive Chinese CHB patients with or without cirrhosis were enrolled in this retrospective study. Cirrhosis was diagnosed based on liver biopsy. Furthermore, patients with decompensated cirrhosis were excluded. A statistical analysis was performed regarding the association between serum HBsAg level and compensated cirrhosis.Results:Patients with compensated cirrhosis had a significantly lower mean serum HBsAg level compared to those without cirrhosis (3.27 Log10 IU/mL VS 4.17 Log10 IU/mL, P < 0.001). Furthermore, examining the correlation with compensated cirrhosis revealed that lower level of serum HBsAg was a significant factor in multivariate analysis. The area under the receiver operating characteristics curve of serum HBsAg was 0.856 for compensated cirrhosis. A positive predictive value of 66.2% and negative predictive value of 90.7% were obtained with a cut-off value of < 3.60 Log10 IU/mL (4000 IU/mL) of serum HBsAg. Moreover, the rate of compensated cirrhosis increased to 75.0% after combining with APRI > 2.Conclusions:In HBeAg positive CHB patients, low serum HBsAg level is a useful predictor of compensated cirrhosis.

HBeAg-negative chronic hepatitis patients should be monitored more strictly: a cross-sectional retrospective study on antiviral treatment-naïve patients.

To investigate the prevalence and characteristics of hepatitis B e antigen (HBeAg) negative/treatment naïve subjects with low hepatitis B virus (HBV) DNA levels (<10(4) copies/ml) and low alanine aminotransferase (ALT) levels (<2 × upper limit of normal) in patients with HBV-related hepatocellular carcinoma (HCC). A total of 226 treatment naïve patients diagnosed with HBV-related HCC, divided into five Barcelona Clinic Liver Cancer (BCLC) stages, were enrolled and retrospectively analyzed. Virological parameters including hepatitis B surface antigen (HBsAg), HBeAg, HBV DNA levels, and laboratory parameters including ALT and aspartame aminotransferase were accessed at the time of HCC was diagnosed. Comparison between HBeAg positive patients and HBeAg negative patients was performed using a χ(2) test. While laboratory parameters correlated with BCLC stages, virological parameters did not. HBeAg negative patients were more prevalent than HBeAg positive patients (160, 70.8% vs. 66, 29.2%). HBsAg and HBV DNA levels in HBeAg negative patients were significantly lower than that in HBeAg positive patients (all P < 0.001). Of the 160 HBeAg negative patients, 74 (46.25%) had low HBsAg, 76 (47.5%) had low DNA levels, and 35 (21.9%) patients had low DNA and normal ALT levels. In treatment naïve patients with HBV-related HCC, the majority (70.8%) were HBeAg negative patients. More than one fifth of HBeAg negative patients had low HBV DNA levels and normal ALT levels, indicating more strict monitoring for HBeAg negative patients is needed.

Lower mutation frequency of BCP/precore regions in e antigen-negative chronic HBV-infected children instead of adults patients.

To describe the Hepatitis B e antigen(HBeAg) seroconversion related mutation profiles of the basal core promoter(BCP)/precore regions in e antigen seroconverted child patients, a cohort of 245 child patients with CHB and a control patients group of 92 adult patients with CHB were recruited. The mutation frequencies of six nucleotides or nucleotide combinations including nucleotide (nt)1896, nt1762/1764, nt1752, nt1846, nt1899 and nt1753 showed significant differences between HBeAg positive and HBeAg-negative child patients groups. The frequencies of these HBeAg seroconversion-related mutations were significantly lower in HBeAg-negative children with CHB than in HBeAg-negative adults with CHB, especially for the mutation G1896A (41.1% vs 91.7%, P<0.001), and the average number of BCP/precore region mutations in samples from HBeAg-negative child patients was also obviously lower than in HBeAg-negative adult patients(3.62±3.03 vs 4.89±2.09, P<0.001), suggesting less impact of mutations in the BCP/precore region on HBeAg seroconversion in child patients than adult patients.

Effects of Entecavir on Hepatitis B Virus Covalently Closed Circular DNA in Hepatitis B e Antigen-Positive Patients with Hepatitis B

The aim of this study was to assess the effect of 48-week entecavir therapy on serum and intrahepatic hepatitis B virus, covalently closed circular DNA (HBV cccDNA) levels in hepatitis B e antigen (HBeAg)-positive patients. A total of 120 patients with HBeAg-positive chronic hepatitis were treated with entecavir for 48 weeks. Serum HBV markers, total HBV DNA, and HBV cccDNA levels were measured at baseline and week 48. Biopsies from 20 patients were available for both intrahepatic total HBV DNA and cccDNA testing at these timepoints. HBV cccDNA levels were decreased from a median level of 5.1×106 copies/mL at baseline to a median level of 2.4×103 copies/mL at week 48. Reduction magnitudes of HBV cccDNA in patients with normalized alanine aminotransferase levels and those undergoing HBeAg seroconversion were significantly greater than those in alanine aminotransferase-abnormal and HBeAg positive patients. Intrahepatic HBV cccDNA was decreased significantly after 48 weeks of treatment, but could not be eradicated. In conclusion, treatment of HBeAg-positive hepatitis B patients with entecavir for 48 weeks decreased serum and intrahepatic HBV cccDNA significantly, and the magnitude of HBV cccDNA reduction was related to total HBV DNA decrease, alanine aminotransferase normalization, and HBeAg seroconversion.

Hepatitis B Core Antigen in Hepatocytes of Chronic Hepatitis B: Comparison between Indirect Immunofluorescence and Immunoperoxidase Method.

BackgroundHepatitis B virus (HBV) infection has many faces. Precore and core promoter mutants resemble inactive carrier status. The identification of hepatitis B core antigen (HBcAg) in hepatocytes may have variable clinical significance. The present study was undertaken to detect HBcAg in chronic hepatitis B (CHB) patients and to assess the efficacy of detection system by indirect immunofluorescence (IIF) and indirect immunoperoxidase (IIP).Materials and methodsThe study was done in 70 chronic HBV-infected patients. Out of 70 patients, eight (11.4%) were hepatitis B e antigen (HBeAg) positive and 62 (88.57%) were HBeAg negative. Hepatitis B core antigen was detected by indirect immunofluorescence (IIF) and indirect immunoperoxidase (IIP) methods in liver tissue.ResultsAll HBeAg positive patients expressed HBcAg by both IIF and IIP methods. Out of 62 patients with HBeAg-negative CHB, HBcAg was detected by IIF in 55 (88.7%) patients and by IIP in 51 (82.26%) patients. A positive relation among viral load and HBcAg detection was also found. This was more evident in the case of HBeAg negative patients and showed a positive relation with HBV DNA levels.ConclusionHepatitis B core antigen can be detected using the IIF from formalin fixed paraffin block preparation and also by IIP method. This seems to reflect the magnitudes of HBV replication in CHB.How to cite this articleRaihan R, Tabassum S, Al-Mahtab M, Nessa A, Jahan M, Kabir CMS, Kamal M, Aguilar JC. Hepatitis B Core Antigen in Hepatocytes of Chronic Hepatitis B: Comparison between Indirect Immunofluorescence and Immunoperoxidase Method. Euroasian J Hepato-Gastroenterol 2015;5(1):7-10.

Red cell distribution width as a potential index to assess the severity of hepatitis B virus‐related liver diseases

To investigate the association between red cell distribution width (RDW) and the severity of hepatitis B virus (HBV)-related liver diseases. Sixty-nine patients with chronic hepatitis B (CHB) and 61 patients with HBV-related liver cirrhosis were enrolled in the present study. Forty-one healthy individuals were included as controls. Hematological parameters, hepatitis B e-antigen (HBeAg) status, HBV DNA levels and liver biochemistry were analyzed. Child-Pugh scores and Model for End-Stage Liver Disease (MELD) scores of the patients with HBV-related liver cirrhosis were calculated. The RDW was significantly higher in patients with HBV-related liver cirrhosis as compared with CHB patients and healthy controls. RDW was slightly higher in CHB patients as compared with healthy controls. An increasing correlation of RDW with Child-Pugh grades was found. RDW was positively correlated with Child-Pugh scores and MELD scores. In patients with HBV-related liver cirrhosis, RDW was also positively correlated with total bilirubin and negatively correlated with hemoglobin and serum albumin concentration. However, no significant difference was found between HBeAg positive and negative patients and no significant correlation between RDW and HBV DNA levels was found. The RDW was elevated in CHB patients and patients with HBV-related liver cirrhosis and was positively correlated with the severity of HBV-related liver cirrhosis. RDW is a potential index to assess the severity of HBV-related liver diseases.

HBeAg negative variants and their role in the natural history of chronic hepatitis B virus infection.

Molecular virology methods including polymerase chain reaction, cloning and sequencing have revolutionised our understanding of viral genome variation. In the case of hepatitis B virus (HBV), sequencing studies have identified a number of virus variants normally found during the natural course of chronic infection. The appearance of the precore stop codon (with G-for-A substitution at position 1896) and basal core promoter (BCP) (with A-for-T and G-for-A, at positions 1762 and 1764, respectively) variants which reduce or abrogate hepatitis B e antigen (HBeAg) production, heralds the initiation of the seroconversion phase from HBeAg to anti-HBe positivity. The gradual removal of the tolerogenic effect of HBeAg leads to the awakening of the immune response (immune clearance phase). Most patients after HBeAg seroconversion become "inactive HBsAg carriers". However during the course of infection precore and/or BCP variants may emerge and be selected leading to HBeAg negative chronic hepatitis B (CHB) with high viremia levels (reactivation phase). The prevalence of HBeAg negative CHB has been increasing over the last few decades and has become the commonest type of HBV infection in many countries of the world. This probably reflects the aging of existing HBV carriers and the effective prevention measures restricting new HBV infections. Frequent acute exacerbations accompanied by high viral replication, elevated alanine aminotransferase levels and histological activity are a common feature of HBeAg negative CHB leading to cirrhosis much faster than in HBeAg positive CHB patients.

Serum HBV DNA level at week 12 is superior to viral response at week 24 in predicting long-term treatment outcome of telbivudine for chronic hepatitis B patients

Background Telbivudine, one of the five nucleos(t)ide antiviral drugs, was reported to be superior to lamivudine in a better biochemical, virological, and histological response for treatment-naive patients in the GLOBE trial. The aim of this study was to determine the antiviral potency, viral resistance, and the significance of early response for long-term telbivudine treatment. Methods We recruited 161 patients of chronic hepatitis B (CHB) on telbivudine between January 2009 and September 2011 in Macau, China. The serum hepatitis B virus DNA levels, hepatitis B e antigen (HBeAg) seroconversion, alanine aminotransferase (ALT) normalization, and viral resistance were analyzed. Results The median age and follow-up duration were 48 years and 16.9 months. All patients were followed up for at least 6 months, while data were collected for 132, 120, 95, and 53 patients at 12, 24, 48, and 96 weeks respectively. The cumulative HBeAg seroconversion rate was 20.8% and only three patients (1.9%) presented with telbivudine low level resistance. The ALT normalization rates were 76.9% at 48 weeks and 77.6% at 96 weeks. Undetectable HBV DNA was achieved by 1.8%, 31.6%, 60%, and 74.1% in HBeAg positive patients and 29.3%, 60.3%, 84%, and 84.6% in HBeAg negative patients at each time point. Week 12 HBV DNA level &lt;1000 copies/ml (&lt;200 IU/ml) was a better predictor of viral suppression at 2-year follow-up (P=0.001, OR=27.00) than undetectable HBV DNA level at week 24 (P=0.120, OR=4.81). Conclusions Two-year telbivudine treatment yielded high rates of viral suppression and ALT normalization. Serum HBV DNA level at week 12 is a superior predictor for long-term viral suppression.