HBeAg-positive Hepatitis Research Articles

The impact of ethnicity on chronic hepatitis B infection course and outcome: big data analysis from Israel

ABSTRACT Objectives: The effect of ethnicity on chronic hepatitis B virus (CHB) infection’s course and outcome has attracted little research. We aimed to compare different aspects of ethnic disparities in CHB patients, including prevalence, phenotypes, management, and outcome between two major ethnic groups in Israel. Design: We conducted a large retrospective cohort study utilizing the Leumit-Health-Service database. Electronic reports of almost 700,000 members from different ethnicities and districts throughout Israel from 2000 to 2019 were reviewed. Patients’ ethnicity was categorized based on the classification of the Israeli Central Bureau of Statistics into two main groups, Arabs and Jews. CHB diagnosis was based on ICD-9-CM codes and supportive serology results. Prevalence, clinical backgrounds, disease course, and patients’ outcomes were compared between both groups. Results: The prevalence of CHB in the Arab minority group was almost twice and a half-higher when compared to their Jewish counterparts (4.3% vs. 1.8%), but they had a lower rate of referral for HBsAg testing (7% vs. 7.9%). The Arab CHB patients were significantly younger at the time of diagnosis (37.6± 13.5 vs. 45.3± 15; P < 0.001). Male predominance was noted in both groups. The Arab patients had a higher rate of active hepatitis (HBeAg-positive and/or negative hepatitis) phase (36.4% vs. 29.8%; P = 0.01), as well as a significantly higher rate of HBeAg seroconversion (45.2% vs. 35.4%; P = 0.033). Nucleos/tide analogue treatment figures were similar, with most patients in both groups receiving a high barrier to resistance treatment. Patients’ outcome was similar in both groups as the rate of hepatocellular carcinoma, cirrhosis, and advanced fibrosis (after stratification analysis) were comparable between both groups. Conclusion: Marked by a prominently higher prevalence of HBV infection, patients in the Arab ethnic group had a lower rate of referral for HBsAg testing but received comparable management and had a similar outcome compared to their Jewish counterparts.

The Relationship Between Collagen Proportionate Area and Hepatitis B Surface Antigen Levels in E Antigen Positive Hepatitis B Cirrhosis.

Quantitative serum hepatitis B surface antigen (HbsAg) has been widely used as a biomarker for treatment response and prognosis in chronic hepatitis B infection, and has recently been found associated with liver histology in e-antigen positive patients. A histological measurement as a continuous variable-collagen proportionate area (CPA)-is appropriate to assess liver fibrosis degree and substages cirrhosis. We, therefore, aimed to explore the association between serum quantitative HBsAg and CPA in e antigenpositive hepatitis B cirrhosis. Liver fibrosis staging was evaluated by METAVIR semiquantitative scoring system, only patients with METAVIR fibrosis stage 4 were included. All liver sections were stained with picroSirius red for determination of collagen quantification by digital image analysis. Mean CPA value was 23.46%. The percentage of patients with different classification of CPA (30%) were 25.8%, 57.8%, and 16.4%, respectively. A modest correlation was found between CPA and serum HBsAg level (r = -0.306, P =.001). Hepatitis B surface antigen level is independently associated with CPA in multivariable linear regression analyses. Serum HBsAg levels can predict liver fibrosis determined by CPA in HBeAg-positive hepatitis B cirrhosis.

Prevalence of sero-markers and non-invasive assessment of liver cirrhosis in patients with Hepatitis B virus infection in Freetown, Sierra Leone: a cross-sectional study

BackgroundHepatitis B virus (HBV) is a major global health problem. Although sub-Saharan Africa has a high proportion of the global burden of HBV, the epidemiology and clinical features of HBV in this region are poorly characterized, and access to diagnostic and treatment services remain limited.MethodsWe conducted a retrospective study of HBV-infected children and adults of all age groups who were evaluated at public and private health facilities in Freetown, Sierra Leone between January 2017 and January 2019. We assessed their clinical presentation, HBV sero-markers, stages of liver disease, prevalence of cirrhosis by non-invasive tools, and the proportion of treatment eligible patients using the criteria recommended by the World Health Organization’s 2015 treatment guidelines for HBV. Logistic regression was used to identify predictors of liver cirrhosis.Results163 HBV patients included in the study, with mean age 32.6 years and 65.0% (106) being males. Most (84.0%) were asymptomatic at presentation. The majority (69.9%) were classified as having HBeAg-negative chronic infection (or inactive HBsAg carrier phase), 24.5% were in the HBeAg-negative immune active phase, 3.1% had HBeAg positive hepatitis, and 2.5% were HBsAg negative. The median Aspartate aminotransferase to Platelet Ratio (APRI) and Fibrosis-4 (FIB-4) scores were 0.37 and 0.80, respectively. The prevalence of cirrhosis was 7.6% and 6.2%, estimated by the APRI and FIB-4 scores, respectively. About 20.0% of patients were eligible for treatment with antiviral agents. Based on APRI scores, the presence of any symptom [adjusted odds ratio (aOR) 20.0, 95% confidence interval (CI) (4.1–85.9); p < 0.001], elevated direct bilirubin [aOR 12.1, 95% CI (1.9–63.0); p = 0.003], and elevated total bilirubin [aOR 16.1, 95% CI (3.2–80.8); p = 0.001] were independent predictors of cirrhosis.ConclusionAlthough most patients with HBV infection were asymptomatic, the prevalence of liver cirrhosis and proportion of patients requiring antiviral treatment were substantial. This small study from a hyperendemic setting in Sierra Leone suggests that routine population-based screening may increase early detection and linkage of HBV patients to care before development of complications. Larger studies are needed to confirm our findings.

Клинико-лабораторная характеристика больных хроническим гепатитом В в зависимости от HBeAg-статуса на территории Кыргызской Республики

Клинико-лабораторная характеристика больных хроническим гепатитом В в зависимости от HBeAg-статуса на территории Кыргызской Республики

Establishment of Coamplification at Lower Denaturation Temperature PCR/Fluorescence Melting Curve Analysis for Quantitative Detection of Hepatitis B Virus DNA, Genotype, and Reverse Transcriptase Mutation and Its Application in Diagnosis of Chronic Hepatitis B

Dynamic and real-time hepatitis B virus (HBV) DNA, genotype, and reverse transcriptase mutation analysis plays an important role in diagnosing and monitoring chronic hepatitis B (CHB) and in assessing the therapeutic response. We established a highly sensitive coamplification at lower denaturation temperature PCR (COLD-PCR) coupled with probe-based fluorescence melting curve analysis (FMCA) for precision diagnosis of CHB patients. The imprecision with %CV and detection limit of HBV DNA detected by COLD-PCR/FMCA were 2.58% to 4.42% and 500 IU/mL, respectively. For mutation, the imprecision and detection limit were 3.35% to 6.49% and 1%, respectively. Compared with Sanger sequencing, the coincidence rates of genotype and mutation were 96.0% and 82.5%, respectively, whereas the inconsistent data resulted from a low proportion (<20%) of mixed genotypes or mixed mutations. The mutation ratio in HBV infection patients was as follows: hepatitis B e antigen (HBeAg)-positive infection (0/0.0%)<HBeAg-negative infection (16/4.5%)<HBeAg-positive hepatitis (30/5.5%)<HBeAg-negative hepatitis (36/6.5%). In patients with entecavir therapy, the proportion of mutation at baseline or week 4 in virologic response (VR) group was <4%, whereas in the partial VR group, it was mostly≥4%. COLD-PCR/FMCA provides a novel tool with high sensitivity, convenience, and practicability for the simultaneous quantification of HBV DNA, genotype, and mutation. It might be used for distinguishing the different phases of HBV infection and predicting VR of CHB patients.

FRI-156-Hyperactivation and proliferation of B cells in hbeag positive hepatitis B patients revealed by high throughput RNA sequencing

FRI-156-Hyperactivation and proliferation of B cells in hbeag positive hepatitis B patients revealed by high throughput RNA sequencing

Effects of tenofovir and telbivudine on HBV RNA in pregnant women with different genotypes of HBeAg-positive hepatitis B in Guizhou Province

Objective: To investigate whether HBV genotype influences HBV DNA and RNA responses to tenofovir(TDF) and telbivudine(LDT) in pregnant women with HBeAg-positive in Guizhou. Methods: This was a retrospective analysis of 75 pregnant women hepatitis B with HBsAg and HBeAg double-positive(19-38 years old, median age 26 years old), who were enrolled in the Department of Infectious Diseases and Obstetrics Clinic of the Affiliated Hospital of Guizhou Medical University from May 2016 to July 2017.Blood samples were collected at 12-24, 28-32 and 36-40 weeks of pregnancy for analyses of genotype, including hepatitis B surface antigen(HBsAg), hepatitis B e antigen (HBeAg), HBV DNA, HBV RNA and liver function, alanine transaminase(ALT), aspartate transaminase(AST), total bilirubin(TBiL), total bile acids(TBA), cholinesterase(CHE), alkaline phosphatase (ALP). Continuous variable was adopted by means of mean±standard deviation, and categorical variables were used for statistical analysis. Results: The HBV genotype was B in 64.0%(48/75)and C in 36.0%(27/75). The TDF and LDT groups showed no differences in demographic and clinical characteristics, including liver function tests, HBsAg, HBeAg, log(10)HBV DNA and log(10)HBV RNA.TDF groups, pre-treatment: HBV DNA (4.8±2.0), HBV RNA (6.4±1.1); at 4 weeks of treatment: HBV DNA (4.0±0.8), HBV RNA (6.0±0.9); at the end of treatment: HBV DNA (3.1±0.7), HBV RNA (5.5±0.8). LDT groups, pre-treatment HBV DNA (5.1±2.0), HBV RNA(6.5±0.9); at 4 weeks of treatment: HBV DNA (4.4±1.2), HBV RNA(6.5±0.8); at the end of treatment: HBV DNA(3.5±1.2), HBV RNA (6.1±0.7). Compared with pre-treatment (12-24 weeks), the TDF and LDT group showed significant reductions in log(10)(HBV DNA) and log(10)(HBV RNA) at 36-40 weeks ( P<0.05). Under the influence of excluding other variables, the genotype had a certain influence on the HBV RNA load.That was, HBV RNA in patients with the C genome decreased by 0.54 units(log(10)) at the end of the treatment compared to patients with the B genome, and the P value was less than 0.05. Conclusion: B and C genotypes are predominant in pregnant women with hepatitis B in Guizhou Province. B-type viruses are more easily controlled when different genotypes are treated with nucleotide analogues.

A Noninvasive Score to Predict Liver Fibrosis in HBeAg-Positive Hepatitis B Patients with Normal or Minimally Elevated Alanine Aminotransferase Levels.

Noninvasive fibrosis tests are highly needed but have not been well studied in chronic hepatitis B patients with normal or minimally elevated alanine aminotransferase (ALT) levels. This study is aimed at developing a noninvasive score system to predict liver fibrosis in these patients. HBeAg-positive chronic hepatitis B patients with ALT levels of <80 IU/l and liver histology (n = 290) were assigned to training (n = 203) or validation (n = 87) groups. Training group patients were divided into nonsignificant (F0–1) and significant fibrosis (F2–4) according to METAVIR stages. Logistic regression was performed to identify factors for liver fibrosis and develop a score system. The capacity of the score to identify the severity of fibrosis was displayed by receiver operating characteristic curve (ROC) and area under ROC (AUROC) values. Multivariate logistic regression showed that HBeAg (ratios of the sample to the cutoff values (S/CO)) and liver stiffness measurement (LSM; kilopascals (kPa)) were independent factors of liver fibrosis. A score system composed of HBeAg and LSM by assigning a point of 1, 2, or 3 to different HBeAg and LSM levels, respectively, was developed. The scores 2-3, 4, and 5-6 of the sum of HBeAg and LSM points indicated nonsignificant, indeterminate, and significant fibrosis, respectively. The score system had an AUROC of 0.880 and showed similar performance in validation group patients. The accuracy for identifying significant and nonsignificant fibrosis was 77.14% in validation group patients and 71.26% in the entire group of patients. It is suggested that this noninvasive score system can accurately predict hepatic fibrosis and may reduce the need for liver biopsy in HBeAg-positive patients with normal or minimally elevated ALT levels.

Prediction value of serum HBV large surface protein in different phases of HBV infection and virological response of chronic hepatitis B patients

BackgroundSerum HBV large surface protein (HBV-LP) is an envelope protein that has a close relationship with HBV DNA level. This study is to explore the prediction value of HBV-LP in different phase of HBV infection and during antiviral therapy in chronic hepatitis B (CHB) patients. MethodsA retrospective study was conducted in 2033 individuals, which included 1677 HBV infected patients in different phases and 356 healthy controls. HBV-LP, HBV serum markers and HBV DNA were detected by ELISA, CMIA and qRT-PCR, respectively. 85 CHB patients receiving PegIFNα or ETV were divided into virological response (VR) and partial virological response (PVR). The dynamic changes of HBV DNA and HBV-LP were observed. ResultsThe level of HBV-LP in 2033 individuals was shown as: HBeAg-positive hepatitis > HBeAg-positive infection > HBeAg-negative hepatitis > HBeAg-negative infection > healthy controls. HBV-LP was positive in all patients whose HBV DNA > 1.0E + 06 IU/ml. When HBsAg was <0.05 IU/ml or >1000 IU/ml, HBV DNAs were all negative if HBV-LP < 1.0 S/CO. When HBsAg was between 0.05 IU/ml and 1000 IU/ml, the consistency of HBV-LP with HBV DNA was 100% in case of HBV-LP > 4.0 S/CO in HBeAg-positive patients and HBV-LP > 2.0 S/CO in HBeAg-negative ones. During antiviral therapy, baseline HBV-LP was lower in VR patients than that in PVR patients. The optimal cut-off points to predict VR by baseline HBV-LP were 32.4 and 28.6 S/CO for HBeAg-positive and HBeAg-negative hepatitis patients, respectively. ConclusionsHBV-LP may be a useful marker for distinguishing the different phases of HBV infection. Moreover, baseline HBV-LP level can be used for predicting VR of CHB patients.

Quantification of large and middle proteins of hepatitis B virus surface antigen (HBsAg) as a novel tool for the identification of inactive HBV carriers

ObjectiveAmong individuals with chronic hepatitis B, those with hepatitis B e-antigen (HBeAg)-negative chronic hepatitis (CHB) can be difficult to distinguish from those with HBeAg-negative chronic HBV infection, also referred to...

A cohort study on the epidemiological characteristics of HBeAg sero-clearance in HBeAg positive chronic hepatitis B patients in Jiangsu province from 2012 to 2014

Objective: To understand the epidemiological characteristics and influencing factors related to HBeAg sero-clearance in chronic hepatitis B patients so as to provide evidence for regular management on chronic HBV patients. Methods: From 2012 to 2014, a cohort study was conducted among HBeAg positive chronic HBV patients in Jiangsu province. Association between the characteristics and incidence of HBeAg sero-clearance was analyzed by Cox regression method. The changing trend on HBV DNA between patients with HBeAg sero-clearance and those with persistent HBeAg positive status was compared by repeated measure data variance analysis method. Results: In 2012, there were 721 HBeAg positive hepatitis B patients aged (45.2 ± 14.2) years enrolled in this study. By 2014, the follow-up observation period was 1 058 person-years, and 393 cases had lost their HBeAg status, with the rate as 37.2/100 person-years. The HBeAg sero-clearance rate was 32.4/100 person-years in hepatitis B patients who received antiviral treatment. The probability of HBeAg clearance in HBeAg positive hepatitis B patients aged ≥60 year (62.0/100 person-years) was higher than those of aged <20 year (7.0/100 person-years). The rate of HBeAg sero-clearance in HBeAg positive patients with HBV DNA <20 000 IU/ml (75.8/100 person-years) was higher than those whose HBV DNA were ≥200 000 IU/ml (16.1/100 person-years). By Cox regression analysis, the HBV DNA level was an important influencing factor on the progress of HBeAg sero-clearance. Patients with HBV DNA levle as ≥200 000 IU/ml, had a lower HBeAg clearance rate (HR=0.18, 95%CI: 0.13-0.23, P<0.001). Compared to the persistent HBeAg positive group, HBV DNA showed a more dramatic fall in the HBeAg-lost group (P<0.001). Conclusion: The rate of HBeAg sero-clearance among HBeAg positive hepatitis B patients was correlated with age and HBV DNA status of the patients that called for comprehensive management and intervention programs to develop for the HBeAg positive hepatitis B patients with different characteristics.

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.

703 Multidrug-Resistant Chronic Hepatitis B -Impact on Therapy Outcome

BACKGROUND: The occurrence of Hepatitis B virus (HBV) polymerase mutations was a major limitation of chronic hepatitis B (CHB) treatment until the introduction of entecavir (ETV) and tenofovir (TDF). Cross-resistance to ETV is well documented in the presence lamivudine (LAM) resistance mutations and ETV specific mutations. To date, no mutations that confer resistance to TDF have been described, nevertheless adefovir (ADF)-associated resistance mutation N236T proved to confer low-level resistance to TDF in studies in vitro. METHODS AND AIMS: Retrospective analysis of HBV monoinfected patients treated with TDF or ETV that performed viral mutations testing (mostly INNO-LiPA hybridization assays, Innogenetics, Belgium) in a single center. Evaluation of the efficacy of antiviral therapy in the presence of multidrug-resistantmutants (MDR). RESULTS: In a group of 181CHBpatients treated with TDF or ETV (5% combination TDF+ETV), 89 (49%) had HBV polymerase gene mutation analysis. Sixty-eight patients (76% of tested) presented several mutations including N236T and 8% had only nucleoside resistant strains. MDR were detected in 9% of naive patients and 49.5% of previously treated patients. Fifty-three (78%) of the MDRHBV patients were treated with TDF and 15 (22%) were taking ETV. MDR were more frequent in HBeAg positive hepatitis (p 250 IU/mL at the beginning of therapy (p=0.002) and baseline HBV viral load >100000 IU/mL (p=0.008) were predictive of MDR presence. During therapy, patients without MDR achieved more HBeAg negativation (p=0.007), anti-HBe seroconversion (p=0.019) and more frequently achieved HBV DNA suppression (p=0.003). Globally, mean treatment duration until HBV DNA undetectability was 24.8 months with MDR versus 8.2 months without (p<0.001). In MDR CHB patients, treatment with TDF was associated with greater HBV DNA supression than ETV (p<0.001), and shorter time to undetectability (18.9 versus 45.2 months, p=0.001). In multivariate analysis, baseline MDR (p<0.001), HbeAg positive (p<0.001) and viremia (p=0.043) were independently associated with longer time to HBV DNA undetectability. CONCLUSIONS: Multidrug-resistant CHB was detected in 9% of naive patients and in half of those previously treated. Its occurrence was associated with more difficult to treat CHB and slower treatment response. TDF was more effective than ETV in MDR HBV patients. This impact in antiviral therapy could have implications in CHB management, particularly in severe cases with decompensated cirrhosis and/or indication for liver transplantation.

PEG-IFN-α-2a combined with Liuweiwuling tablets for treatment of patients with HBeAg positive hepatitis B

PEG-IFN-α-2a combined with Liuweiwuling tablets for treatment of patients with HBeAg positive hepatitis B

Caspase-cleaved fragments of cytokeratin-18 as a marker of inflammatory activity in chronic hepatitis B virus infection

BackgroundThe differential diagnosis between inactive carrier and active hepatitis is important in patients with chronic hepatitis B (CHB) virus infection. Serum cytokeratin (CK)-18 fragments (M30-antigen) are proposed as biomarkers of apoptosis. ObjectivesWe investigated whether serum M30-antigen levels might help to characterize the various phases of CHB and predict the state of significant inflammation in patients with CHB. Study designA total of 339 CHB patients who underwent liver biopsy, were included. Serum M30-antigen levels were compared between inactive carriers (n=21), patients with HBeAg-negative hepatitis (n=95), HBeAg-positive hepatitis (n=141) and liver cirrhosis (n=82). ResultsSerum M30-antigen levels were correlated significantly not only with AST (r=0.544, p<0.001) and ALT (r=0.315, p<0.001) and but also inflammatory grading score on liver biopsy (r=0.240, p<0.001). Serum M30-antigen level in HBeAg-negative CHB was significantly higher than that of inactive HBV carrier (399.78U/L vs 148.90U/L, p<0.001). Multivariate analysis showed that AST (p<0.001), albumin (p=0.009) and M30-antigen (p=0.020) were the independent predictors of significant inflammation. Combined serum M30-antigen level (>344U/L) and AST (>78IU/L) measurement provided the most accurate identification of significant inflammation, showing 38.2% sensitivity, 96.1% specificity, 91.0% positive predictive value and 56.1% negative predictive value. ConclusionsSerum M30-antigen can be a predictive marker for distinguishing between inactive carrier and HBeAg-negative CHB. Serum M30 levels are associated with the presence of significant inflammation, especially in patients with normal or minimally elevated ALT in CHB patients.

IL28B Polymorphism Correlates with Active Hepatitis in Patients with HBeAg-Negative Chronic Hepatitis B

Background & AimsThe clinical relevance of single nucleotide polymorphisms (SNPs) near the IL28B gene is controversial in patients with hepatitis B virus (HBV) infection. This study aimed to investigate the role of viral and host factors, including IL28B genotypes, in the natural course of chronic hepatitis B (CHB).MethodsThe study enrolled consecutive 115 treatment-naive CHB patients. HBV viral loads, genotypes, precore and basal core promotor mutations, serum hepatitis B surface antigen (HBsAg) and interferon-gamma inducible protein 10 (IP-10) levels as well as four SNPs of IL28B were determined. Serial alanine transaminase (ALT) levels in the previous one year before enrollment at an interval of three months were recorded. Factors associated with active hepatitis, defined as persistent ALT >2× upper limit of normal (ULN) or a peak ALT level >5× ULN, were evaluated.ResultsThe prevalence of rs8105790 TT, rs12979860 CC, rs8099917 TT, and rs10853728 CC genotypes were 88.3%, 87.4%, 88.4% and 70.9%, respectively. In HBeAg-positive patients (n = 48), HBV viral load correlated with active hepatitis, while in HBeAg-negative patients (n = 67), rs10853728 CC genotype (p = 0.032) and a trend of higher IP-10 levels (p = 0.092) were associated with active hepatitis. In multivariate analysis, high viral load (HBV DNA >108 IU/mL, p = 0.042, odds ratio = 3.946) was significantly associated with HBeAg-positive hepatitis, whereas rs10853728 CC genotype (p = 0.019, odds ratio = 3.927) was the only independent factor associated with active hepatitis in HBeAg-negative population.ConclusionsHBV viral load and IL28B rs10853728 CC genotype correlated with hepatitis activity in HBeAg-positive and HBeAg-negative CHB, respectively. Both viral and host factors play roles in disease activity during different phases of CHB.

HBeAg‐positive hepatitis delta: virological patterns and clinical long‐term outcome

The presence of the hepatitis B virus (HBV)-eAg in patients with hepatitis B is associated with higher HBV replication and with an increased risk to develop liver-related clinical endpoints defined as liver related death, liver transplantation, development of hepatocellular carcinoma and hepatic decompensation. The aim of this study was to investigate the role of HBeAg in patients co-infected with the hepatitis D virus (HDV). We studied virological markers of HBV and HDV infection and as well as biochemical and clinical features of liver disease in a cohort of 534 anti-HDV-positive patients. In addition, we compared the clinical long-term outcome of HBeAg-positive HDV-infected patients with HBeAg-negative control patients matched for age, gender and baseline-MELD score. HBeAg-positive hepatitis delta was detected in 71 of 534 patients (13.3%). HBeAg positivity was associated with a higher biochemical disease activity and higher HBsAg levels in HDV co-infected patients. Sixty one per cent of the HBeAg-positive HDV-infected patients presented with HBV DNA levels below 2000 IU/ml, at least once during follow-up. Both HBeAg-positive and -negative patients showed a similar severe clinical long-term course with about half of the patients developing a liver-related clinical complication after a median follow-up period of 51 months (range: 9-193 months). HBV DNA levels are low in both HBeAg-negative and HBeAg-positive patients suggesting suppressive effects of HDV on HBV irrespective of the phase of HBV infection. The clinical long-term outcome of HBeAg-positive patients is not different to HBeAg-negative patients infected with the HDV.

Lamivudine plus adefovir vs. entecavir in HBeAg‐positive hepatitis B with sequential treatment failure of lamivudine and adefovir

Few studies have adequately examined the efficacy of lamivudine plus adefovir (LAM+ADV) combination therapy vs. entecavir (ETV) monotherapy in HBeAg-positive hepatitis B patients who fail to respond to sequential treatment with LAM and ADV. We compared directly the efficacy of LAM+ADV vs. ETV in such patients and assessed prognostic factors associated with a virologic response at month 12. In total, 72 HBeAg-positive patients who showed resistance (n = 33) or a suboptimal virologic response (n = 39) to ADV monotherapy with resistance to LAM therapy underwent rescue therapy (31 LAM+ADV and 41 ETV). All patients were followed for at least 12 months. Following 12 months of treatment, in the LAM+ADV and ETV groups, a virologic response was observed in 7/31 (22.6%) and 8/41 (19.5%; P = 0.777) patients; ALT normalization occurred in 11/13 (84.6%) and 16/18 (88.9%; P = 0.566); HBeAg seroconversion in 1/31 (2.3%) and 4/41 (9.8%; P = 0.341) and a virologic breakthrough in 3/31 (9.0%) and 5/41 (12.1%; P = 0.452) respectively. Independent prognostic factors associated with a virologic response were the baseline HBV-DNA level (OR = 0.37; 95% CI 0.17-0.80; P = 0.011) and the duration of prior ADV monotherapy (OR = 0.89; 95% CI 0.83-0.95; P = 0.044). Neither LAM+ADV nor ETV was adequately effective in patients with sequential LAM and ADV treatment failure. Thus, when chronic hepatitis B patients show resistance or suboptimal response to ADV monotherapy, early modification of treatment should be considered.

Clinical characteristics of hepatitis B virus infection in middle school students born after the universal infant vaccination program in Shanghai, China

The aim of this study was to investigate the prevalence of hepatitis B surface antigen (HBsAg) and clinical characteristics of middle school students infected with hepatitis B virus (HBV) after initiation of the HBV immunization program in China. A total of 82,156 serum samples were collected from students in 33 junior schools and 25 senior schools. HBsAg was tested by ELISA. Samples from HBsAg-positive students were collected and analyzed for HBV serum markers, alanine aminotransferase (ALT), HBV DNA levels, and HBV genotypes. The overall prevalence of HBsAg was 1.11% in middle school students in Shanghai, China. The prevalence of HBsAg in students born during the immunization program to HBsAg-positive mothers was significantly higher than that in students born during the universal vaccination program (1.47% vs 0.78%, P < 0.01). Only HBV genotypes B and C were found in these infections, and genotype C was the dominant one. Twenty-one (13.0%) of 162 HBsAg-positive students had active hepatitis B, and 18 were hepatitis B e antigen (HBeAg) positive. The universal infant vaccination program has reduced the prevalence of HBsAg significantly. HBeAg-positive hepatitis B, however, needs to be monitored among the students in whom vaccination failed.

Prevalence and virological profiles of hepatitis B infection in human immunodeficiency virus patients

To determine the prevalence of hepatitis B virus (HBV) in adult human immunodeficiency virus (HIV) patients with CD4+ T-cell count less than 500/mm(3) and without antiretroviral therapy; to describe different HBV-HIV coinfection virological profiles; and to search for factors associated with HBs antigen (HBsAg) presence in these HIV positive patients. During four months (June through September 2006), 491 patients were received in four HIV positive monitoring clinical centers in Abidjan. HIV-1 or HIV-1 and 2 positive patients, age ≥ 18 years, CD4+ T-cell count < 500/mL and formal and signed consent of the patient. Realized blood tests included HIV serology, CD4+ T-cell count, quantitative HIV RNA load and HBV serological markers, such as HBsAg and HBc antibody (anti-HBcAb). We performed HBeAg, anti-HBe antibody (anti-HBeAb), anti-HBc IgM and quantitative HBV DNA load in HBsAg positive patients. Anti-HBsAb had been tested in HIV patients with HBsAg negative and anti-HBcAb-positive. HBV DNA was also tested in 188 anti-HBcAb positive patients with HBsAg negative status and without anti-HBsAb. Univariate analysis (Pearson χ(2) test or Fischer exact test) and multivariate analysis (backward step-wise selection logistic regression) were performed as statistical analysis. Mean age of 491 patients was 36 ± 8.68 years and 73.3% were female. Type-1 HIV was found in 97% and dual-type HIV (type 1 plus type 2) in 3%. World Health Organization (WHO) clinical stage was 1, 2, 3 and 4 respectively in 61 (12.4%), 233 (47.5%), 172 (35%) and 25 patients (5.1%). Median CD4+ T-cell count was 341/mm(3) (interquartile range: 221-470). One hundred and twelve patients had less than 200 CD4+ T-cell/mm(3). Plasma HIV-1 RNA load was elevated (≥ 5 log(10) copies/mL) in 221 patients (45%). HBsAg and anti-HBcAb prevalence was respectively 13.4% and 72.9%. Of the 66 HBsAg positive patients, 22 were inactive HBV carriers (33.3%), 21 had HBeAg positive hepatitis (31.8%) and 20 had HBeAg negative hepatitis (30.3%). HBeAg and anti-HBeAb were indeterminate in 3 of them. Occult B infection prevalence (HBsAg negative, anti-HBcAb positive, anti-HBsAb negative and detectable HBV DNA) was 21.3%. Three parameters were significantly associated with the presence of HBsAg: male [odds ratio (OR): 2.2; P = 0.005; 95% confidence interval (CI): 1.3-3.8]; WHO stage 4 (OR: 3.2; P = 0.01; 95% CI: 1.3-7.9); and aspartate aminotransferase (AST) level higher than the standard (OR: 1.9; P = 0.04; 95% CI: 1.02-3.8). HBV infection prevalence is high in HIV-positive patients. HBeAg positive chronic hepatitis and occult HBV infection are more frequent in HIV-positive patients than in HIV negative ones. Parameters associated with HBsAg positivity were male gender, AIDS status and increased AST level.