• Humans
• Cameroon/epidemiology
• Blood Donors/statistics & numerical data
• Adult
• Hepatitis B virus/genetics
• Hepatitis B virus/isolation & purification
• Hepatitis B/epidemiology
• Hepatitis B/virology
• Hepatitis B/blood
• Male
• Female
• Middle Aged
• Genotype
• Adolescent
• Cross-Sectional Studies
• Hepatitis B Surface Antigens/blood
• Hepatitis B Surface Antigens/genetics
• DNA, Viral/genetics
• DNA, Viral/blood
• Young Adult
• Incidence
• Hepatitis B Antibodies/blood
• Viral Load

• Deutscher Akademischer Austauschdienst

• HBV S region
• Hepatitis B Virus
• Mutation
• Occult HBV infection

• Humans
• Hepatitis B Surface Antigens/genetics
• Hepatitis B Surface Antigens/immunology
• Hepatitis B virus/genetics
• Hepatitis B virus/immunology
• Mutation
• Female
• DNA, Viral/genetics
• Male
• Adult
• Middle Aged
• Hepatitis B/virology
• Amino Acid Substitution
• Genotype
• Young Adult
• Aged

• BJYAYY-CY2019-11 Beijing Youan Hospital affiliated to Capital Medical University incubates young and middle-aged talents

The coexistence of hepatitis B virus (HBV) and hepatitis B surface antibodies (anti-HBs) in occult hepatitis B virus infection (OBI) is a contradictory phenomenon, and the underlying mechanism is not fully understood. The characteristics of pre-S/S mutations in OBI genotypes B and C (OBI_B and OBI_C) in the presence or absence of anti-HBs were analyzed extensively in this study. Methodology. The amino acid substitutions of envelope proteins of 21 OBI strains, including 4 HBs (+) OBI_B, 6 HBs (−) OBI_B, 6 HBs (+) OBIc, and 5 HBs (−) OBI_C samples, were analyzed and fully compared among groups of HBV genotypes and the presence of anti-HBs.

The mutation rates in pre-S1, pre-S2, and S proteins of OBI_C were significantly higher than wild-type HBV (wt-HBV) genotype C strains, but only the mutation rate of S protein in OBI_B was significantly higher compared to wild-type HBV genotype B. The mutation rates in S protein of anti-HBs (−) OBI were higher than anti-HBs(+) OBI samples (4.40% vs. 2.43% in genotype B, P > 0.05; 6.81% vs. 3.47% in genotype C, P < 0.05). For these high-frequency substitutions in the pre-S/S region, the mutations sN40S and sK122R were found in 27.3% and 45.5% of anti-HBs (−) OBI strains, respectively. 7 substitutions were uniquely found in OBI_C strains and 9 substitutions were commonly detected in OBI_B and OBI_C strains.

These results suggested that the mutations might occur randomly and were not selected by antibody pressure.

• Occult-infected pregnant mothers
• active HBV immunization
• perinatal transmission
• silent HBV infection
• vaccine escape mutation

The characteristics of a large sample size of the full-length genome of occult hepatitis B virus (HBV) infection (OBI) have not been extensively explored in China. Voluntary blood donors who were HBsAg-negative/HBV NAT-positive (HBsAg−/HBV NAT+) were identified by blood screening and recruited. Blood samples were tested for HBV serologic markers, viral loads, and PCR to identify OBI. HBV full-length genomes were obtained by amplifying two fragments using nested PCR. The characterization of OBI strains was based on sequence analyses compared with HBsAg+ strains obtained from the same donor population. Of the 50 full-length genomes of 172 identified OBI strains, 33 were classified as genotype B (OBI_B) and 17 strains as genotype C (OBI_C). Significantly higher nucleotide variabilities were observed in the Pre-S2/S promoter region (SP2) and core upstream regulatory sequence (CURS) in OBI_B than in their HBsAg+ controls (P < 0.05). Both OBI_B and OBI_C showed higher amino acid (aa) variabilities in Pol and Pre-S/S regions than their controls (P < 0.05). In addition, 19 novel OBI-related mutations were found spanning the four open reading frames (ORFs) of the HBV genome. Four novel deletions and one novel insertion were also found in OBI_C strains. Several novel OBI-related mutations spanning the four ORFs of the virus were identified by characterizing a large sample size of the full-length OBI genome, which may affect the production of HBsAg and contribute to the occult infection of HBV.

• hepatocellular carcinoma
• single nucleotide polymorphism
• spectrin repeat containing nuclear envelop protein 1
• targeted exome sequencing
• transitional cell carcinoma

• 107-2314-B-182-004-MY3 Ministry of Science and Technology (MOST), Taiwan
• CMRPG3K1401 Linkou Chang Gung Memorial Hospital

• Amino acid substitution
• Autoimmune hepatitis
• Occult HBV infection

Absolute quantification of HBV-DNA by sequence-encoded Quantitative Invader assay in a single tube without using calibration curves.

• HBV DNA
• HBeAg-negative chronic infection
• HBsAg seroclearance
• HBsAg seroconversion
• cohort

• chronic hepatitis B
• hepatitis B surface antigen
• hepatocellular carcinoma
• seroclearance

Occult hepatitis B infections (OBI) represent a reservoir of undiagnosed and untreated hepatitis B virus (HBV), hence the need to identify mutations that lead to this phenotype. Functionally characterizing these mutations by in vitro studies is time-consuming and expensive. To bridge this gap, in silico approaches, which predict the effect of amino acid (aa) variants on HBV protein function, are necessary. We developed an algorithm for determining the relevance of OBI-associated mutations using in silico approaches. A 3 kb fragment of subgenotypes A1 and D3 from 24 chronic HBV-infected (CHB) and 24 OBI participants was analyzed. To develop and validate the algorithm, the effects of 68 previously characterized occult-associated mutations were determined using three computational tools: PolyPhen2, SNAP2, and PROVEAN. The percentage of deleterious mutations (with impact on protein function) predicted were 52 (76.5%) by PolyPhen2, 55 (80.9%) by SNAP2, and 65 (95.6%) by PROVEAN. At least two tools correctly predicted 59 (86.8%) mutations as deleterious. To identify OBI-associated mutations exclusive to Botswana, study sequences were compared to CHB sequences from GenBank. Of the 43 OBI-associated mutations identified, 26 (60.5%) were predicted by at least two tools to have an impact on protein function. To our knowledge, this is the first study to use in silico approaches to determine the impact of OBI-associated mutations, thereby identifying potential candidates for functional analysis to facilitate mechanistic studies of the OBI phenotype.

• Africa
• Botswana
• HBV
• Hepatitis B
• in-silico analysis
• mutations
• occult hepatitis B virus

• D43 TW009610 FIC NIH HHS
• D43 TW010543 FIC NIH HHS
• P30 DK078392 NIDDK NIH HHS

The presence of HBV DNA in the liver (with detectable or undetectable HBV DNA in the serum) of individuals tested HBsAg negative by currently available assays is defined occult B Infection (OBI). It remains a potential transmission threat and risk to HBV chronic infection. The purpose of this study was to determine the OBI prevalence among HBsAg negative subjects and to characterize associated genotypes.

Blood samples of 219 HBsAg-negative subjects tested by ELISA were collected. HBV DNA was investigated in all samples. Viral loads were determined using quantitative real-time PCR. All samples were screened for HBV markers (anti-HBc, anti-HBe, HBsAg). The Pre-S/S region of the HBV genome was sequenced. The database was analyzed using the SPSS and Epi info software. Phylogenetic analysis was performed using the BioEdit and MEGA software.

Of the 219 samples, 20.1% were anti-HBc positive, 1.8% HBeAg and 22.8% were anti-HBe positive. Fifty-six (56) (25.6%) of the samples had a detectable HBV DNA and viral loads ranging from 4 IU/mL to 13.6 10⁶ IU/mL. Sixteen of them (16/56) had a viral load < 200 IU/mL, resulting in an OBI prevalence of 7.3% (16/219) in our study. The remaining 40 subjects had viral loads > 200 IU/mL, resulting in a “false OBI” prevalence of 18.3% (40/219). HBV genotype E was predominant followed by the quasi-sub-genotype A3. A single “false OBI” strain had the characteristic mutation G145R. Other mutations were observed and all located in the major hydrophilic region (MHR) of the S gene.

The study reported a prevalence of 7.3% of occult hepatitis B infection. It confirms the predominance of genotype E and the existence of a subgroup of quasi-sub-genotype A3 of HBV in Burkina Faso. It further provides information on the presence of “false OBI.” This study has found mutations in the major hydrophilic region (MHR) of the pre-S/S gene of HBV.

• Genotypes
• HBV
• OBI
• Real-time PCR
• Sequencing

Mutation in the hepatitis B virus surface antigen (HBsAg) may affect the efficiency of diagnostic immunoassays or success of vaccinations using HBsAg. Thus, antigenicity and immunogenicity analyses of the mutated HBsAg are necessary to develop novel diagnostic tools and efficient vaccinations. Here, the in vitro antigenicity of three wild-type HBsAg open reading frames (ORFs) (adr4, W1S [subtype adr] and W3S [subtype adr]) isolated from clinically infected patients and nineteen synthesized single/double/multiple amino acid-substituted mutants were tested with commercial ELISA kits. Immunofluorescence staining of transfected cells and Western blot analysis confirmed that these ORFs were expressed at comparable levels in HEK-293 cells. W1S and adr4 were clearly detected, whereas W3S could not be detected. Using the same commercial immunoassay kit, we found that the single mutants, K120P and D123T, were marginally reactive, whereas W3S-aW1S and the double mutant, K120P/D123T, exhibited antigenicity roughly equivalent to the wild-type wako1S. On the other hand, the single mutants of W1S, P120K and T123D, significantly impaired the reactivity, while W1S-aW3S and the double mutant of W1S, P120K/T123D, resulted in a complete loss of antigenicity. In addition, ELISA revealed reduced HBs antigenicity of two mutants, W1S N146G and W1S Q129R/G145R. These commercial ELISA-based antigenic reactivities of HBsAg were also strongly correlated with the predicted Ai alterations of affected amino acids due to the specific mutation. In conclusion, this study showed for the first time that lysine (K120) and aspartate (D123) simultaneously affected HBsAg antigenicity, leading to diagnostic failure. These findings will improve diagnostic assays and vaccine development.

• Amino Acid Substitution
• Enzyme-Linked Immunosorbent Assay
• Fluorescent Antibody Technique
• HEK293 Cells
• Hepatitis B/diagnosis
• Hepatitis B Surface Antigens/genetics
• Hepatitis B Surface Antigens/immunology
• Hepatitis B virus/genetics
• Humans
• Immunoassay
• Mutation
• Open Reading Frames

Hepatitis B virus (HBV) carrying the rtA181T/sW172* mutation conferred cross-resistance to adefovir and lamivudine. Cell-based and clinical studies indicated that HBV carrying this mutation had an increased oncogenic potential. Herein, we created transgenic mouse models to study the oncogenicity of the HBV pre-S/S gene containing this mutation. Transgenic mice were generated by transfer of the HBV pre-S/S gene together with its own promoter into C57B6 mice. Four lines of mice were created. Two of them carried wild-type gene and produced high and low levels of HBV surface antigen (HBsAg) (TgWT-H and L). The other two carried the sW172* mutation with high and low intrahepatic expression levels (TgSW172*-H and L). When sacrificed 18 months after birth, none of the TgWT mice developed hepatocellular carcinoma (HCC), whereas 6/26 (23.1%) TgSW172*-H and 2/24 (8.3%) TgSW172*-L mice developed HCC (TgWT vs TgSW172* P=0.0021). Molecular analysis of liver tissues revealed significantly increased expression of glucose-regulated protein 78 and phosphorylated extracellular signal-regulated kinases 1 in TgSW172* mice, and decreased expression of B-cell lymphoma-extra large in TgSW172*-H mice. Higher proportion of apoptotic cells was found in TgSW172*-H mice, accompanied by increased cyclin E levels, suggesting increased hepatocyte turnover. Combined analysis of complimentary DNA microarray and microRNA array identified microRNA-873-mediated reduced expression of the CUB and Sushi multiple domains 3 (CSMD3) protein, a putative tumor suppressor, in TgSW172* mice. Our transgenic mice experiments confirmed that HBV pre-S/S gene carrying the sW172* mutation had an increased oncogenic potential. Increased endoplasmic reticulum stress response, more rapid hepatocyte turnover and decreased CSMD3 expression contributed to the hepatocarcinogenesis.

Previous in vivo studies have suggested that nucleic acid polymers (NAPs) may reduce circulating levels of HBsAg in the blood by blocking its release from infected hepatocytes and that this effect may have clinical benefit. NAP treatment, was evaluated in two clinical studies in patients with HBeAg positive chronic HBV infection. The REP 101 study examined REP 2055 monotherapy in 8 patients and the REP 102 study examined REP 2139-Ca, in monotherapy in 12 patients, 9 of which transitioned to short term combined treatment with pegylated interferon alpha 2a or thymosin alpha 1. In both studies NAP monotherapy was accompanied by 2–7 log reductions of serum HBsAg, 3–9 log reductions in serum HBV DNA and the appearance of serum anti-HBsAg antibodies (10–1712 mIU / ml). Eight of the 9 patients transitioning to combined treatment with immunotherapy (pegylated interferon or thymosin alpha 1) in the REP 102 study experienced HBsAg loss and all 9 patients experienced substantial increases in serum anti-HBsAg antibody titers before withdrawal of therapy. For 52 weeks after removal of REP 2055 therapy, rebound of serum viremia (HBV DNA > 1000 copies / ml, HBsAg > 1IU / ml) was not observed in 3 / 8 patients. Suppression of serum virema was further maintained for 290 and 231 weeks in 2 of these patients. After withdrawal of all therapy in the 9 patients that transitioned to combination therapy in the REP 102 study, 8 patients achieved HBV DNA < 116 copies / ml after treatment withdrawal. Viral rebound occurred over a period of 12 to 123 weeks in 7 patients but was still absent in two patients at 135 and 137 weeks of follow-up. Administration tolerability issues observed with REP 2055 were rare with REP 2139-Ca but REP 2139-Ca therapy was accompanied by hair loss, dysphagia and dysgeusia which were considered related to heavy metal exposure endemic at the trial site. These preliminary studies suggest that NAP can elicit important antiviral responses during treatment which may improve the effect of immunotherapy. NAPs may be a potentially useful component of future combination therapies for the treatment of chronic hepatitis B.

Trial Registration: ClinicalTrials.gov NCT02646163 and NCT02646189

• HBV preS/S variability
• anti-HBV treatment
• hepatitis B Virus

Occult hepatitis B virus infection (OBI), characterized as the persistence of hepatitis B virus (HBV) surface antigen (HBsAg) seronegativity and low viral load in blood or liver, is a special form of HBV infection. OBI may be related mainly to mutations in the HBV genome, although the underlying mechanism of it remains to be clarified. Mutations especially within the immunodominant “α” determinant of S protein are “hot spots” that could contribute to the occurrence of OBI via affecting antigenicity and immunogenicity of HBsAg or replication and secretion of virion. Clinical reports account for a large proportion of previous studies on OBI, while functional analyses, especially those based on full-length HBV genome, are rare.

• Hepatitis B virus
• Occult
• Variation
• Hepatitis B surface antigen

• Biomarkers/blood
• Genetic Variation
• Genome, Viral
• Genotype
• Hepatitis B/blood
• Hepatitis B/diagnosis
• Hepatitis B/epidemiology
• Hepatitis B/virology
• Hepatitis B Surface Antigens/blood
• Hepatitis B virus/genetics
• Hepatitis B virus/immunology
• Hepatitis B virus/pathogenicity
• Host-Pathogen Interactions
• Humans
• Mutation
• Phenotype
• Prevalence
• Prognosis
• Viral Load

• Adult
• Age Factors
• Aged
• Carcinoma, Hepatocellular/epidemiology
• Carcinoma, Hepatocellular/immunology
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/virology
• DNA, Viral/analysis
• Data Collection
• Female
• Hepacivirus/genetics
• Hepacivirus/isolation & purification
• Hepatitis B/diagnosis
• Hepatitis B/epidemiology
• Hepatitis B/immunology
• Hepatitis B Surface Antigens/analysis
• Hepatitis B virus/genetics
• Hepatitis B virus/isolation & purification
• Hepatitis C/diagnosis
• Hepatitis C/epidemiology
• Hepatitis C/immunology
• Humans
• Liver Cirrhosis/epidemiology
• Liver Neoplasms/epidemiology
• Liver Neoplasms/immunology
• Liver Neoplasms/pathology
• Liver Neoplasms/virology
• Male
• Middle Aged
• Risk Factors
• Sex Factors
• Taiwan/epidemiology

Hepatitis B virus (HBV) has a worldwide distribution and is endemic in many populations. Due to its unique life cycle which requires an error-prone reverse transcriptase for replication, it constantly evolves, resulting in tremendous genetic variation in the form of genotypes, sub-genotypes, and mutations. In recent years, there has been considerable research on the relationship between HBV genetic variation and HBV-related pathogenesis, which has profound implications in the natural history of HBV infection, viral detection, immune prevention, drug treatment and prognosis. In this review, we attempted to provide a brief account of the influence of HBV genotype on the pathogenesis of HBV infection and summarize our current knowledge on the effects of HBV mutations in different regions on HBV-associated pathogenesis, with an emphasis on mutations in the preS/S proteins in immune evasion, occult HBV infection and hepatocellular carcinoma (HCC), mutations in polymerase in relation to drug resistance, mutations in HBV core and e antigen in immune evasion, chronicalization of infection and hepatitis B-related acute-on-chronic liver failure, and finally mutations in HBV x proteins in HCC.

• Hepatitis B virus
• Genotype
• Variation
• Pathogenesis

• Antineoplastic Agents/adverse effects
• Genetic Variation
• Genome, Viral
• Genotype
• Hepatitis B/drug therapy
• Hepatitis B/etiology
• Hepatitis B/virology
• Hepatitis B virus/genetics
• Hepatitis B virus/pathogenicity
• Humans
• Immunosuppression Therapy/adverse effects
• Mutation
• Recurrence
• Viral Proteins/genetics
• Virulence/genetics

Previous studies have demonstrated that nucleic acid polymers (NAPs) have both entry and post-entry inhibitory activity against duck hepatitis B virus (DHBV) infection. The inhibitory activity exhibited by NAPs prevented DHBV infection of primary duck hepatocytes in vitro and protected ducks from DHBV infection in vivo and did not result from direct activation of the immune response. In the current study treatment of primary human hepatocytes with NAP REP 2055 did not induce expression of the TNF, IL6, IL10, IFNA4 or IFNB1 genes, confirming the lack of direct immunostimulation by REP 2055. Ducks with persistent DHBV infection were treated with NAP 2055 to determine if the post-entry inhibitory activity exhibited by NAPs could provide a therapeutic effect against established DHBV infection in vivo. In all REP 2055-treated ducks, 28 days of treatment lead to initial rapid reductions in serum DHBsAg and DHBV DNA and increases in anti-DHBs antibodies. After treatment, 6/11 ducks experienced a sustained virologic response: DHBsAg and DHBV DNA remained at low or undetectable levels in the serum and no DHBsAg or DHBV core antigen positive hepatocytes and only trace amounts of DHBV total and covalently closed circular DNA (cccDNA) were detected in the liver at 9 or 16 weeks of follow-up. In the remaining 5/11 REP 2055-treated ducks, all markers of DHBV infection rapidly rebounded after treatment withdrawal: At 9 and 16 weeks of follow-up, levels of DHBsAg and DHBcAg and DHBV total and cccDNA in the liver had rebounded and matched levels observed in the control ducks treated with normal saline which remained persistently infected with DHBV. These data demonstrate that treatment with the NAP REP 2055 can lead to sustained control of persistent DHBV infection. These effects may be related to the unique ability of REP 2055 to block release of DHBsAg from infected hepatocytes.

• Animals
• Antiviral Agents/therapeutic use
• Cytokines/biosynthesis
• Ducks
• Hepatitis Virus, Duck/isolation & purification
• Hepatitis, Viral, Animal/drug therapy
• Hepatitis, Viral, Animal/pathology
• Hepatitis, Viral, Animal/virology
• Oligodeoxyribonucleotides/therapeutic use
• Picornaviridae Infections/drug therapy
• Picornaviridae Infections/pathology
• Picornaviridae Infections/virology

The aim was to extract factors from virologic and biochemical profiles at baseline and 24 weeks of treatment to predict HBeAg seroconversion in patients treated with ETV.

HBeAg positive chronic hepatitis B patients receiving ETV naïve-treatment were enrolled. HBV DNA, ALT, and serological markers were prospectively monitored every 6 months for 240 weeks. The cumulative rates of virologic response (VR), biochemical response (BR), and HBeAg seroconversion were determined, and potential predictors for HBeAg seroconversion were identified through uni/multivariate analysis.

Two hundred twenty nine patients were eligible for this study. The cumulative rates of VR, BR, and HBeAg seroconversion at 240 weeks were 88.4 %, 100 %, and 36.7 %, respectively. Multivariate analysis showed that HBV DNA (OR, 2.8, p = 0.003), ALT (OR, 2.6, p = 0.005) at baseline, undetectable HBV DNA within 24 weeks (OR = 3.2, p < 0.001), and body mass index (BMI) ≥24kg/m² (OR = 0.038, p = 0.013) were associated with HBeAg seroconversion. A prediction model for probability of HBeAg seroconversion was constructed. Patients can be classified into high (>40 %), intermediate (20–40 %), or low (≤20 %) groups based on the calculated probability of HBeAg seroconversion. The cumulative rates of HBeAg seroconversion were different among the three groups (p < 0.001). About 58 % patients in the high probability group achieved HBeAg seroconversion while almost 90 % patients within the low group remained HBeAg positive.

A combination of HBV DNA, ALT and BMI values at baseline, and undetectable HBV DNA level within 24 weeks can predict HBeAg seroconversion. Both viral and metabolic factors likely determine HBeAg status with ETV treatment.

CTR20132358

Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). The HBV mutations, which include point mutation, deletion, insertion and truncation mutation of HBV gene in 4 open reading frames (S, C, P, X), are closely associated with HCC pathogenesis. Some mutations accumulated during chronic HBV infection could be regarded as a biomarker to predict the occurrence of HCC. The detection of the mutations in clinical practice could be helpful for defining better preventive and therapeutic strategies and, moreover, predicting the progression of liver disease.

• Hepatitis B virus
• Mutations
• Hepatocellular carcinoma
• Carcinogenesis
• Chronic hepatitis B

• clearance
• mutation
• occult hepatitis B
• spontaneous HBsAg loss

• Hepatitis B
• Mutation
• Virus Diseases

The correlation between chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) has been well-established. But the roles of viral factor remain uncertain. Only HBV X gene and nonsense mutations of S gene (C-terminal truncation of HBV surface protein) have been demonstrated to have transforming activity. Whether they play a significant role in hepatocarcinogenesis is still uncertain.

Twenty-five HBV-related HCC patients were positive for hepatitis B core antigen (HBcAg) in the cancerous parts of their HCC liver tissues by immunohistochemistry studies, and had available tissue for whole HBV genome sequence analysis. The results were compared with 25 gender and age-matched HBcAg negative HCCs. Plasmids encoding HBV S gene nonsense mutations identified from HBcAg (+) HCC tissue were constructed to investigate their cell proliferation, transformation activity and the oncogenic potentials by xenograft study and in vivo migration assay.

HBcAg (+) HCC patients were significantly associated with cirrhosis and small tumor size (≦2 cm) when compared with HBcAg (−) HCC patients. Southern blot analyses revealed freely replicative forms of HBV in the cancerous parts of HBcAg(+) HCC. Three nonsense mutations of S gene (sL95*, sW182*, and sL216*) were identified in the HBcAg(+) HCC tumor tissues. sW182* and sL216* were recurrently found in the 25 HBcAg (−) HCC tumor tissue, too. Functional studies of the above 3 non-sense mutations all demonstrated higher cell proliferation activities and transformation abilities than wild type S, especially sW182*. Tumorigenicity analysis by xenograft experiments and in vitro migration assay showed potent oncogenic activity of sW182* mutant.

This study has demonstrated potent oncogenic activity of nonsense mutations of HBV S gene, suggesting they may play an important role in hepatocarcinogenesis.

• Blotting, Southern
• Carcinoma, Hepatocellular/complications
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/virology
• Cell Transformation, Neoplastic/genetics
• Codon, Nonsense/genetics
• Endoplasmic Reticulum/metabolism
• Hepatitis B/complications
• Hepatitis B virus/genetics
• Hepatitis B virus/metabolism
• Humans
• Immunohistochemistry
• Liver Neoplasms/complications
• Liver Neoplasms/pathology
• Liver Neoplasms/virology
• Plasmids/genetics
• Sequence Analysis, DNA
• Viral Fusion Proteins/genetics

• Chronic hepatitis B
• Hepatitis B surface antigen
• Interferon
• Nucleosides
• Nucleotides
• Prediction of sustained virological response
• Quantification

• Adult
• Aged
• Female
• Hepatitis B e Antigens/blood
• Hepatitis B virus/drug effects
• Hepatitis B virus/immunology
• Hepatitis B virus/physiology
• Hepatitis B, Chronic/blood
• Hepatitis B, Chronic/drug therapy
• Hepatitis B, Chronic/immunology
• Humans
• Male
• Middle Aged
• Species Specificity
• T-Lymphocytes/drug effects
• T-Lymphocytes/immunology

The aims of this study were to compare results from a Taiwanese sub-study of the GLOBE 2303 telbivudine study and evaluate the HBV DNA kinetics.

Forty-one Taiwanese patients were treated for an additional 2 years with telbivudine. Efficacy endpoints were the same as the GLOBE study. The correlations of reductions in HBV DNA levels at Week 24 were evaluated.

All 7 HBeAg-positive patients with undetectable HBV DNA levels at Week 24 sustained this response at Year 4 with rates of ALT normalization 71%, HBeAg seroconversion 57%, and cumulative resistance 0%. Out of 16 HBeAg-negative patients with undetectable HBV DNA levels at Week 24, 11 (78%) sustained this response at Year 4 with rates of ALT normalization 83% and cumulative resistance 8.7%. There were significant correlations between reductions of DNA of ≥5 log₁₀ copies/mL at Week 24 with maintained PCR negativity at Years 2–4 and a lack of resistance at Year 2.

Long-term telbivudine efficacy in Taiwanese patients was comparable to the GLOBE 2303 study. A reduction in HBV DNA levels by ≥5 log₁₀ copies/mL at Week 24 represented the optimal cut-off point, which may predict favourable outcomes in patients with high baseline HBV DNA levels.

ClinicalTrials.gov Identifier: NCT00142298 (http://clinicaltrials.gov/).

• Adolescent
• Adult
• Animals
• Antibodies, Monoclonal, Murine-Derived
• Carrier State/virology
• Cell Line, Tumor
• DNA Mutational Analysis
• DNA, Viral/blood
• Female
• Genotype
• Hepatitis B Surface Antigens/genetics
• Hepatitis B Surface Antigens/immunology
• Hepatitis B virus/genetics
• Hepatitis B virus/immunology
• Humans
• Male
• Mice
• Middle Aged
• Mutation
• Phenotype
• RNA, Viral/biosynthesis
• Viral Envelope Proteins/genetics
• Viral Envelope Proteins/immunology
• Viral Envelope Proteins/metabolism
• Virion/genetics
• Virion/metabolism
• Young Adult