• anti-hbc
• anti-hbe
• anti-hbs
• atypical serological markers
• chronic hepatitis b (chb)
• hbeag
• hbsag
• hbv
• hbv-dna

• Chronic hepatitis B
• Epithelial cell adhesion molecule
• Glutamine synthetase
• Hepatocellular carcinoma
• Risk factor
• p21

• Humans
• Carcinoma, Hepatocellular/pathology
• Hepatitis B, Chronic/complications
• Epithelial Cell Adhesion Molecule/metabolism
• Liver Neoplasms/pathology
• Glutamate-Ammonia Ligase/metabolism
• Hepatocytes/metabolism
• Cell Adhesion Molecules/metabolism
• Risk Factors

• Sub-Saharan Africa (SSA)
• infection
• malignancy
• oncogenesis
• virus

• 75N91019D00024 NCI NIH HHS
• HHSN261201500003I NCI NIH HHS

There are inadequate data and no histological evidence regarding the effects of antiviral treatment for hepatitis B e-antigen (HBeAg)-negative chronic hepatitis B (CHB) patients with normal or mildly elevated alanine aminotransferase (ALT). This study investigated the effects of antiviral treatment on these patients.

We retrospectively analysed the outcomes of antiviral treatment for HBeAg-negative CHB patients with normal or mildly elevated ALT who were treated with nucleoside/nucleotide analogues (NAs) for up to 96 weeks.

A total of 128 patients were enrolled; 74 patients had normal ALT and 54 patients had mildly elevated ALT. The total cumulative rates of viral suppression were 64.06%, 81.97%, and 96.39%, at weeks 24, 48, and 96, respectively. The cumulative rates of viral suppression for the normal and mildly elevated ALT groups were 67.85% and 58.97%, 86.39% and 76.31%, and 93.13% and 97.04% at weeks 24, 48, and 96, respectively. The serum HBV DNA levels at week 12 and hepatitis B surface antigen (HBsAg) levels at week 24 were significant predictors of the 96-week virological response. Of the 128 patients, 54 with normal ALT and 33 with mildly elevated ALT underwent FibroScan at baseline. Significant fibrosis (F ≥ 2) was found in 44.4% (n = 24) and 51.5% (n = 17) of the patients in the normal ALT group and mildly elevated ALT group, respectively. Compared with the values at baseline, liver stiffness values significantly decreased at week 48 (8.12 kPa vs. 6.57 kPa; p < 0.001) and week 96 (8.87 kPa vs. 6.43 kPa; p < 0.001), respectively.

HBeAg-negative CHB patients with normal ALT could benefit from antiviral therapy with NAs, similar to patients with mildly elevated ALT. Antiviral treatment is strongly recommended for HBeAg-negative CHB patients with normal ALT. Additionally, significant liver fibrosis is not rare in HBeAg-negative CHB patients with ALT less than two-times the upper limit of normal, and FibroScan should be performed regularly for these patients.

The online version contains supplementary material available at 10.1186/s12876-022-02471-y.

• Alanine aminotransferase
• Chronic hepatitis B
• FibroScan
• Hepatitis B virus DNA
• Nucleoside/nucleotide analogues

• Adenine/therapeutic use
• Antiviral Agents/therapeutic use
• Cost-Benefit Analysis
• Hepatitis B, Chronic/drug therapy
• Humans
• Organophosphonates/therapeutic use
• Tenofovir/therapeutic use
• Thailand
• Treatment Outcome

• chronic hepatitis B
• diagnostic performance
• liver fibrosis
• non-invasive diagnosis

• hbv dna
• hepatitis b e antigen
• hepatitis b surface antigen

• Adult
• Alanine Transaminase/blood
• Antiviral Agents/administration & dosage
• Drug Administration Schedule
• Female
• Hepatitis B e Antigens/blood
• Hepatitis B e Antigens/immunology
• Hepatitis B virus/drug effects
• Hepatitis B virus/immunology
• Hepatitis B, Chronic/drug therapy
• Hepatitis B, Chronic/immunology
• Hepatitis B, Chronic/virology
• Humans
• Male
• Middle Aged
• Prospective Studies
• Recurrence
• Seroconversion/drug effects
• Sustained Virologic Response
• Tenofovir/administration & dosage
• Time Factors

• Alanine aminotransferase
• Chronic liver disease
• Liver necroinflammatory grade
• Liver stiffness measurement

• advanced liver fibrosis
• cigarette smoking
• fibrosis regression
• hepatitis B virus infection

De novo combination of lamivudine (Lam) and adefovir (Adv) was not rarely used in clinical practice. However, head-to-head comparisons of entecavir (Etv) monotherapy with this combination in hepatitis B virus (HBV)-related compensated cirrhosis patients are unavailable. This study aimed to compare the efficacy and safety of Etv monotherapy with combination therapy in patients with HBV-related compensated liver cirrhosis.

Treatment-naïve patients with HBV-related compensated liver cirrhosis were recruited to receive either Etv monotherapy or a de novo combination of Lam and Adv. Data were collected at baseline and every 6 months thereafter.

A total of 578 patients (485 in Etv group, 93 in combination group) were included. Baseline characteristics were comparable between the two groups. At the end of 1, 2, and 3 years, HBV DNA was undetectable in 82.7%, 96.2%, and 94.3% of patients in the Etv group and 88.9%, 81.7%, and 84.6% in the combination group, respectively (all P>0.05). The cumulative virological breakthrough rate at 1, 2, and 3 years was 2.7%, 6.7%, and 9.8% in the Etv group and 2.9%, 13.3%, and 32.2% in the combination group, respectively (P=0.003). After propensity-score adjustment for age, sex, and baseline HBeAg, ALT, and total bilirubin, virological breakthrough was higher in the de novo combination of Lam and Adv (HR 2.83, 95% CI 1.37–5.86; P<0.01). The cumulative rate of liver-related events, including decompensation and hepatocellular carcinoma, at 1, 2, and 3 years was 2.9%, 4.2%, and 6.1% in the Etv group and 2.2%, 2.2%, and 6.7% in combination group, respectively (P=0.83). Biochemical response and serological response were similar between the groups.

Etv treatment had less virological breakthrough and potentially higher HBV-DNA suppression than de novo combination of Lam and Adv during 3 years in treatment-naïve HBV-related compensated liver cirrhosis.

• adefovir
• compensated HBV-related cirrhosis
• de novo combination
• entecavir
• lamivudine
• real-world
• virological breakthrough

Nonalcoholic fatty liver disease (NAFLD) is becoming a worldwide epidemic, and is frequently found in patients with chronic hepatitis B (CHB). We investigated the impact of histologically proven hepatic steatosis on the risk for hepatocellular carcinoma (HCC) in CHB patients without excessive alcohol intake.

Consecutive CHB patients who underwent liver biopsy from January 2007 to December 2015 were included. The association between hepatic steatosis (≥ 5%) and subsequent HCC risk was analyzed. Inverse probability weighting (IPW) using the propensity score was applied to adjust for differences in patient characteristics, including metabolic factors.

Fatty liver was histologically proven in 70 patients (21.8%) among a total of 321 patients. During the median (interquartile range) follow-up of 5.3 (2.9–8.3) years, 17 of 321 patients (5.3%) developed HCC: 8 of 70 patients (11.4%) with fatty liver and 9 of 251 patients (3.6%) without fatty liver. The five-year cumulative incidences of HCC among patients without and with fatty liver were 1.9% and 8.2%, respectively (P=0.004). Coexisting fatty liver was associated with a higher risk for HCC (adjusted hazards ratio [HR], 3.005; 95% confidence interval [CI], 1.122–8.051; P=0.03). After balancing with IPW, HCC incidences were not significantly different between the groups (P=0.19), and the association between fatty liver and HCC was not significant (adjusted HR, 1.709; 95% CI, 0.404–7.228; P=0.47).

Superimposed NAFLD was associated with a higher HCC risk in CHB patients. However, the association between steatosis per se and HCC risk was not evident after adjustment for metabolic factors.

• Fatty liver
• Hepatitis B virus
• Liver cancer
• Metabolic syndrome
• Nonalcoholic fatty liver disease (NAFLD)

• genetic variability
• hepatitis B virus
• immune responses
• immune system
• interferon
• persistent infection

• Adolescent
• Child
• Child, Preschool
• Female
• Genotype
• Hepatitis B Core Antigens/genetics
• Hepatitis B Core Antigens/immunology
• Hepatitis B e Antigens/genetics
• Hepatitis B virus/genetics
• Hepatitis B virus/immunology
• Hepatitis B, Chronic/immunology
• Hepatitis B, Chronic/virology
• Humans
• Infant
• Longitudinal Studies
• Male
• Mutant Proteins/genetics
• Mutant Proteins/immunology
• Selection, Genetic
• Seroconversion
• Young Adult

Since 2005 there have been several reports of hepatitis B outbreak in the state of Kerala in southern India. Objective of this study was to analyze such outbreaks and to explore hypothesis pertaining the transmission mode.

Retrospective observational study involving cases of acute hepatitis B acquired between 1 January 2015 and 31 December 2015 and their family members residing in Mazhuvanoor village in Ernakulam district of Kerala State in southern India.

59 houses were included in the survey. The number of patients diagnosed to have acute viral hepatitis B was 59. Majority (66.10%) were over 50 years old. There were no cases below the age of 15 years. All 59 patients claimed to have been bitten frequently by a fly which was identified as “deer fly” belonging to the genus Chrysops.

Given the current understanding of mechanical transmission of pathogens in both humans and animals by insects belonging to the Tabanidae family which also includes Chrysops, it is plausible that the same mechanism may hold true for hepatitis B also. However this needs to be proven in further studies both at the laboratory level and at field studies.

Purpose: This study aimed to identify the active components of Fuzheng Huayu (FZHY) formula and the mechanism by which they inhibit the viability of hepatic stellate cells (HSCs) by a combination of network pharmacology and transcriptomics.

Methods: The active components of FZHY formula were screened out by text mining. Similarity match and molecular docking were used to predict the target proteins of these compounds. We then searched the STRING database to analyze the key enriched processes, pathways and related diseases of these target proteins. The relevant networks were constructed by Cytoscape. A network analysis method was established by integrating data from above network pharmacology with known transcriptomics analysis of quiescent HSCs-activated HSCs to identify the most possible targets of the active components in FZHY formula. A cell-based assay (LX-2 and T6 cells) and surface plasmon resonance (SPR) analysis were used to validate the most possible active component-target protein interactions (CTPIs).

Results: 40 active ingredients in FZHY formula and their 79 potential target proteins were identified by network pharmacology approach. Further network analysis reduced the 79 potential target proteins to 31, which were considered more likely to be the target proteins of the active components in FZHY formula. In addition, further enrichment analysis of 31 target proteins indicated that the HIF-1, PI3K-Akt, FoxO, and chemokine signaling pathways may be the primary pathways regulated by FZHY formula in inhibiting the HSCs viability for the treatment of liver fibrosis. Of the 31 target proteins, peroxisome proliferator activator receptor gamma (PPARG) was selected for validation by experiments at the cellular and molecular level. The results demonstrated that schisandrin B, salvianolic acid A and kaempferol could directly bind to PPARG, decreasing the viability of HSCs (T6 cells and LX-2 cells) and exerting anti-fibrosis effects.

Conclusion: The active ingredients of FZHY formula were successfully identified and the mechanisms by which they inhibit HSC viability determined, using network pharmacology and transcriptomics. This work is expected to benefit the clinical application of this formula.

• Fuzheng Huayu formula
• liver fibrosis
• network pharmacology
• pharmacological mechanism
• transcriptomics

• Diagnosis
• Europe
• hepatitis B
• hepatitis C
• immunisation
• standard of care

Systemic inflammatory response syndrome (SIRS) and model for end-stage liver disease (MELD) predict short-term mortality in patients with cirrhosis. Prediction of mortality at initial hospitalization is unknown in black African patients with decompensated cirrhosis.

This study aimed to look at the role of MELD score and SIRS as the predictors of morbidity and mortality at initial hospitalization.

In this retrospective cohort study, we enrolled 159 patients with cirrhosis (median age: 49 years, 70.4% males). The role of Child–Pugh–Turcotte (CPT) score, MELD score, and SIRS on mortality was determined by the Kaplan–Meier method, and the prognosis factors were assessed with Cox regression model.

At initial hospitalization, 74.2%, 20.1%, and 37.7% of the patients with cirrhosis showed the presence of ascites, hepatorenal syndrome, and esophageal varices, respectively. During the in-hospital follow-up, 40 (25.2%) patients died. The overall incidence of mortality was found to be 3.1 [95% confidence interval (CI): 2.2–4.1] per 100 person-days. Survival probabilities were found to be high in case of patients who were SIRS negative (log-rank test= 4.51, p=0.03) and in case of patients with MELD score ≤16 (log-rank test=7.26, p=0.01) compared to the patients who were SIRS positive and those with MELD score >16. Only SIRS (hazard ratio (HR)=3.02, [95% CI: 1.4–7.4], p=0.01) and MELD score >16 (HR=2.2, [95% CI: 1.1–4.3], p=0.02) were independent predictors of mortality in multivariate analysis except CPT, which was not relevant in our study. Patients with MELD score >16 experienced hepatorenal syndrome (p=0.002) and encephalopathy (p=0.001) more frequently than that of patients with MELD score ≤16. SIRS was not useful in predicting complications.

MELD score and SIRS can be used as tools for the prediction of mortality in black African patients with decompensated cirrhosis.

• Africa
• MELD
• SIRS
• cirrhosis
• mortality

• Adult
• Aged
• Antigens, Neoplasm/analysis
• Antigens, Neoplasm/blood
• Antiviral Agents/therapeutic use
• Area Under Curve
• Biomarkers, Tumor/analysis
• Biomarkers, Tumor/blood
• Carcinoma, Hepatocellular/blood
• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/metabolism
• Carrier Proteins/analysis
• Carrier Proteins/blood
• Case-Control Studies
• Female
• Glycoproteins/analysis
• Glycoproteins/blood
• Hepatitis B Surface Antigens/analysis
• Hepatitis B Surface Antigens/blood
• Hepatitis B, Chronic/complications
• Hepatitis B, Chronic/drug therapy
• Humans
• Liver Cirrhosis/complications
• Liver Neoplasms/blood supply
• Liver Neoplasms/drug therapy
• Liver Neoplasms/metabolism
• Male
• Middle Aged
• Prognosis
• ROC Curve
• alpha-Fetoproteins/analysis

Development of an safe and efficient in vivo gene delivery method is indispensable for molecular biology research and the progress in the following gene therapy. Over the past few years, hydrodynamic gene delivery (HGD) with naked DNA has drawn increasing interest in both research and potential clinic applications due to its high efficiency and low risk in triggering immune responses and carcinogenesis in comparison to viral vectors. This method, involving intravenous injection (i.v.) of massive DNA in a short duration, gives a transient but high in vivo gene expression especially in the liver of small animals. In addition to DNA, it has also been shown to deliver other substance such as RNA, proteins, synthetic small compounds and even viruses in vivo. Given its ability to robustly mimic in vivo hepatitis B virus (HBV) production in liver, HGD has become a fundamental and important technology on HBV studies in our group and many other groups. Recently, there have been interesting reports about the applications and further improvement of this technology in other liver research. Here, we review the principle, safety, current application and development of hydrodynamic delivery in liver disease studies, and discuss its future prospects, clinical potential and challenges.

• HBV
• gene delivery
• gene therapy
• hydrodynamic injection
• liver diseases

To assess the diagnostic value of FIB-4, aspartate aminotransferase-to-platelet ratio index (APRI), and liver stiffness measurement (LSM) in patients with hepatitis B virus infection who have persistently normal alanine transaminase (PNALT).

We enrolled 245 patients with chronic hepatitis B: 95 in PNALT group, 86 in intermittently elevated alanine transaminase (PIALT1) group [alanine transaminase (ALT) within 1-2 × upper limit of normal value (ULN)], and 64 in PIALT2 group (ALT > 2 × ULN). All the patients received a percutaneous liver biopsy guided by ultrasonography. LSM, biochemical tests, and complete blood cell counts were performed.

The pathological examination revealed moderate inflammatory necrosis ratios of 16.81% (16/95), 32.56% (28/86), and 45.31% (28/64), and moderate liver fibrosis of 24.2% (23/95), 33.72% (29/86), and 43.75% (28/64) in the PNALT, PIALT1, and PIALT2 groups, respectively. The degrees of inflammation and liver fibrosis were significantly higher in the PIALT groups than in the PNALT group (P < 0.05). No significant difference was found in the areas under the curve (AUCs) between APRI and FIB-4 in the PNALT group; however, significant differences were found between APRI and LSM, and between FIB-4 and LSM in the PNALT group (P < 0.05 for both). In the PIALT1 and PIALT2 groups, no significant difference (P > 0.05) was found in AUCs for all comparisons (P > 0.05 for all). In the overall patients, a significant difference in the AUCs was found only between LSM and APRI (P < 0.05).

APRI and FIB-4 are not the ideal noninvasive hepatic fibrosis markers for PNALT patients. LSM is superior to APRI and FIB-4 in PNALT patients because of the influence of liver inflammation and necrosis.

• Liver stiffness measurement
• Hepatitis B virus
• FIB-4
• Aspartate aminotransferase-to-platelet ratio index
• Normal
• Alanine aminotransferase

• Adult
• Alanine Transaminase/blood
• Aspartate Aminotransferases/blood
• Biomarkers
• Biopsy, Needle/methods
• Elasticity Imaging Techniques
• Female
• Fibrosis
• Hepatitis B virus/isolation & purification
• Hepatitis B, Chronic/blood
• Hepatitis B, Chronic/diagnosis
• Hepatitis B, Chronic/pathology
• Hepatitis B, Chronic/virology
• Humans
• Liver/diagnostic imaging
• Liver/pathology
• Liver Cirrhosis/blood
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/pathology
• Liver Cirrhosis/virology
• Male
• Middle Aged
• Platelet Count
• Retrospective Studies
• Ultrasonography, Interventional
• Young Adult

Background: HBV (Hepatitis B Virus) and HCV (Hepatitis C Virus) infections are more prevalent in vulnerable populations than the general population. The objective of this study was to investigate the prevalence of HBV and HCV infection in HIV-positive patients (GI), chronic renal failure (CRF) patients (GII) and coagulation disorder individuals (GIII). Methods: A cross-sectional study was conducted from June 2014 to March 2015. Serum samples were tested for markers of hepatitis B and C by enzyme-linked immunosorbent assay (ELISA). Sociodemographic, epidemiological, clinical and laboratory data and accompanying statistical analyses were performed using Epi Info™ 7. Results: A total of 348 individuals were recruited, i.e., 154 HIV-positive, 143 CRF and 51 coagulopathy patients. Among them, more than 66% were men, and the predominant age group was 26–35 years in GI and 56–65 years in GIII. Most patients had more than 8 years of education (66.2% in GI, 60.6% in GIII and 46.1% in GII), with a family income between 100–400 dollars in more than 48% of patients. The prevalence of the HBsAg marker was 3.9%, 7% and 3.9%, total anti-HBc was 28.6%, 55.9% and 31.4%, and anti-HCV was 1.3%, 12.6% and 47% for GI, GII and GIII, respectively. However, the prevalence of anti-HBs was greater than 70% in all groups. Conclusions: This study shows a high prevalence of HBV and HCV among specific groups compared to the general population. Factors such as age, income, number of sexual partners, sexually transmitted disease burden, blood transfusion history or blood products and blood transfusions before 1994 were associated with a higher prevalence for these infections.

• coagulopathy
• haemodialysis
• hepatitis B virus
• hepatitis C virus
• human immunodeficiency virus 1
• prevalence

• Adult
• Aged
• China/epidemiology
• Cohort Studies
• Environmental Exposure/adverse effects
• Female
• Hepatitis B, Chronic/epidemiology
• Hepatitis B, Chronic/etiology
• Hepatitis B, Chronic/physiopathology
• Humans
• Life Style
• Male
• Middle Aged
• Risk Factors
• Sex Characteristics

• chronic hepatitis b infection
• necroinflammatory activity
• renin-angiotensin-aldosterone axis
• serum angiotensin-converting enzyme

• Hepatitis B
• access to prophylaxis and treatment
• linkage to care
• screen-and-treat-programs

• Hepatitis B virus
• cell-based therapies
• cytokine therapy
• immune-based innovations
• immunopathogenesis
• therapeutic vaccination

• Chronic hepatitis B
• HBeAg-negative
• Persistently normal ALT

• HBV DNA quantitative
• HBV, hepatitis B virus
• HBeAg
• HBeAg, hepatitis B early antigen
• HBsAg
• IC, immune clearance phase
• IT, immune tolerance phase
• LR, low-replicative phase
• hepatitis B virus
• quantitative HBsAg

• Chronic hepatitis B (CHB)
• Cirrhosis
• Entecavir (ETV)
• Lamivudine (LAM)
• Telbivudine (TBV)

• Adult
• Antiviral Agents/therapeutic use
• Biopsy
• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/pathology
• Early Detection of Cancer
• Elasticity Imaging Techniques
• Female
• Hepatitis B, Chronic/drug therapy
• Hepatitis B, Chronic/pathology
• Humans
• Liver/pathology
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/pathology
• Liver Neoplasms/diagnosis
• Liver Neoplasms/pathology
• Male
• Middle Aged
• Republic of Korea
• Retrospective Studies
• Risk Assessment
• Tertiary Care Centers

• HBV
• HCC
• MicroRNA
• biomarker
• hepatitis B virus
• hepatocellular carcinoma
• miR-126

• Genome characterization
• Hepatitis B virus
• Hepatitis delta virus
• Intrafamilial transmission
• Molecular epidemiology
• Serology

• Developing Countries
• HIV
• Hepatitis B

• Etiology
• Hepatocellular carcinoma
• Risk factors

• Cirrhosis
• Helicobacter pylori
• hepatitis B
• thrombocytopenia

• Adult
• Aged
• Aged, 80 and over
• Biomarkers
• Female
• Helicobacter Infections/complications
• Helicobacter Infections/diagnosis
• Helicobacter Infections/microbiology
• Helicobacter pylori
• Hepatitis B, Chronic/complications
• Humans
• Liver Cirrhosis/complications
• Liver Cirrhosis/etiology
• Male
• Middle Aged
• Platelet Count
• Risk Factors
• Severity of Illness Index
• Thrombocytopenia/diagnosis
• Thrombocytopenia/etiology
• Thrombocytopenia/therapy
• Treatment Outcome
• Young Adult

AIM: To investigate the virological relapse rate in hepatitis B e antigen (HBeAg)-negative patients after antiviral therapy discontinuation and analyze the factors associated with virological relapse.

METHODS: Among patients diagnosed with chronic hepatitis B infection between May 2005 and July 2010, 204 were eligible for analysis. The Kaplan-Meier method and log-rank test were used to calculate the cumulative rate of relapse and compare cumulative relapse rates between groups. The Cox proportional hazards regression model was used to evaluate the predictive factor of virological relapse.

RESULTS: The 2 and 1 year cumulative risks of virological relapse after antiviral therapy discontinuation were 79.41% (162/204) and 43.82% (71/162), respectively. Multivariate analysis revealed that only post treatment hepatitis B surface antigen (HBsAg) level was associated with virological relapse (P = 0.011). The cumulative risk of virological relapse was higher in the patients with HBsAg levels ≥ 1500 IU/L than in those with HBsAg levels < 1500 IU/L (P = 0.0013). The area under the curve was 0.603 (P = 0.033). The cutoff HBsAg value for predicting virological relapse was 1443 IU/L.

CONCLUSION: We found that the virological relapse rate remained high after antiviral therapy discontinuation in the HBeAg-negative patients and that the post treatment HBsAg levels predicted virological relapse.

• Chronic hepatitis B
• Virological relapse
• Hepatitis B surface antigen

• Adult
• Antiviral Agents/administration & dosage
• Area Under Curve
• Biomarkers/blood
• Chi-Square Distribution
• Drug Administration Schedule
• Female
• Hepatitis B Surface Antigens/blood
• Hepatitis B, Chronic/blood
• Hepatitis B, Chronic/diagnosis
• Hepatitis B, Chronic/drug therapy
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Multivariate Analysis
• Odds Ratio
• Predictive Value of Tests
• Proportional Hazards Models
• ROC Curve
• Recurrence
• Retrospective Studies
• Risk Factors
• Time Factors
• Treatment Outcome
• Young Adult

• Acute WHV infection
• Hepadnavirus
• Replication markers
• WHV7
• WHVNY
• Woodchuck hepatitis virus strain

• Animals
• Antibodies, Viral/blood
• Female
• Hepatitis B/blood
• Hepatitis B/veterinary
• Hepatitis B/virology
• Hepatitis B Virus, Woodchuck/genetics
• Hepatitis B Virus, Woodchuck/physiology
• Male
• Marmota/virology
• Rodent Diseases/blood
• Rodent Diseases/virology
• Virus Replication

• P20 RR016443 NCRR NIH HHS
• R01 CA166213 NCI NIH HHS
• NCI R01CA166213 NCI NIH HHS
• NCRR P20RR016443 PHS HHS

• Adult
• Age Factors
• Aged
• Aged, 80 and over
• Alanine Transaminase/blood
• Female
• Hepatitis B Antigens/blood
• Hepatitis B, Chronic/blood
• Hepatitis B, Chronic/pathology
• Humans
• Liver/pathology
• Liver Cirrhosis/blood
• Liver Cirrhosis/pathology
• Male
• Middle Aged
• Severity of Illness Index
• Young Adult

Studies on molecular mechanisms of the persist infection of hepatitis B virus have been hampered by a lack of a robust animal model. We successfully established a simple, versatile, and reproducible HBV persist infection model in vitro and in vivo with the circularized HBV DNA. The cells and mice were transfected or injected with circularized HBV DNA and pAAV/HBV1.2, respectively. At the indicated time, the cells, supernatants, serum samples, and liver tissues were collected for virological and serological detection. Both in vitro and in vivo, the circularized HBV DNA and pAAV/HBV1.2 could replicate and transcribe efficiently, but the infection effect of the former was superior to the latter (p < 0.05). The injection of circularized HBV genome DNA into the mice robustly supported HBV infection and approximately 80% of HBV infected mice established persistent infection for at least 10 weeks. This study demonstrated that the infection efficiency and replication ability of the circularized structure of HBV DNA overmatched that of the expression plasmid containing the linear structure of HBV DNA in vitro and in vivo. Meanwhile, this research results could provide useful tools and methodology for further study of pathogenic mechanisms and potential antiviral treatments of human chronic HBV infection in vitro and in vivo.

• Alanine Transaminase/metabolism
• Animals
• Cell Line
• DNA, Viral/chemistry
• DNA, Viral/metabolism
• Disease Models, Animal
• Genetic Vectors/metabolism
• Hepatitis B/metabolism
• Hepatitis B/pathology
• Hepatitis B Core Antigens/metabolism
• Hepatitis B Surface Antigens/metabolism
• Hepatitis B virus/genetics
• Humans
• Interleukin-6/genetics
• Interleukin-6/metabolism
• Liver/metabolism
• Liver/pathology
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Nude
• Real-Time Polymerase Chain Reaction
• Tumor Necrosis Factor-alpha/genetics
• Tumor Necrosis Factor-alpha/metabolism
• Virus Replication

The core promoter and proximal precore regions are the most complex portions of the hepatitis B virus (HBV) genome. These regions cooperatively regulate viral replication and differentially regulate the synthesis of the viral proteins E, core, and X. Multiple mutations in these regions are associated with the persistency of viral infection and the development of cirrhosis and hepatocellular carcinoma (HCC). In South Korea, nearly all HBVs are classified as HBV genotype C2; the majority of these viruses have the basal core promoter double mutation, a precore stop mutation, or both. These mutations may play a role in the alteration of viral and clinical features, and abundant and complex mutations are particularly prevalent in the core promoter and proximal precore regions. We previously demonstrated that the accumulation of ≥ 6 mutations at eight key nucleotides located in these regions (G1613A, C1653T, T1753V, A1762T, G1764A, A1846T, G1896A, and G1899A) is a useful marker to predict the development of HCC regardless of advanced liver disease. In addition, certain mutation combinations were predominant in cases with ≥ 4 mutations. In cases with ≤ 5 mutations, a low Hepatitis B e antigen titer (< 35 signal to noise ratio) was indicative of HCC risk. Viral mutation data of the single HBV genotype C2 suggest that the combined effect of the number and pattern of mutations in the core promoter and proximal precore regions is helpful in predicting HCC risk.

• Hepatitis B virus
• Point mutation
• Hepatitis B virus X protein
• Hepatocellular carcinoma
• Cancer screening

• Chronic HBV infection
• West Africa
• challenges

• 3′-untranslated region
• Chronic infection
• Hepatitis B virus
• Programmed cell death-1
• Single nucleotide polymorphism