• ERS
• GRP78
• HBV
• hepatocellular carcinoma
• truncated HBsAg

• Humans
• Endoplasmic Reticulum Chaperone BiP
• Endoplasmic Reticulum Stress
• Liver Neoplasms/virology
• Liver Neoplasms/pathology
• Liver Neoplasms/genetics
• Hepatitis B virus/genetics
• Hepatitis B virus/physiology
• Hepatitis B virus/pathogenicity
• Carcinoma, Hepatocellular/virology
• Carcinoma, Hepatocellular/genetics
• Heat-Shock Proteins/genetics
• Heat-Shock Proteins/metabolism
• Apoptosis
• Carcinogenesis/genetics
• Hepatocytes/virology
• Reactive Oxygen Species/metabolism
• Mutation
• Cell Proliferation
• Male
• Signal Transduction
• Female
• Middle Aged

• This work was supported by National Key Research and Development Program of China (No.2022YFC2304800), 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (No. ZYGD23030), and National Natural Science Foundation of China (No. 82172254).

• HBsAg
• ROS
• hepatitis B virus
• rtA181T mutation
• rtA181V mutation

• Humans
• Hepatitis B virus/genetics
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/drug therapy
• Hepatitis B, Chronic/drug therapy
• Antiviral Agents/therapeutic use
• Mutation Rate
• Liver Neoplasms/genetics
• Liver Neoplasms/drug therapy
• Mutation
• Genes, Tumor Suppressor
• DNA, Viral/genetics
• Hepatitis B Surface Antigens/genetics

• Capital Health Research and Development Special grants
• Chinesisch-Deutsches Forschungsprojekt im Sonderprogramm zu COVID-19 (C-0012) and Key Programs of Beijing Municipal Education Commission of China
• National Key Research and Development Program of China
• Third Round of Public Welfare Development and Reform Pilot Projects of Beijing Municipal Medical Research Institutes

• carcinoma
• chronic
• genotype
• hepatitis
• hepatitis B virus
• hepatocellular
• mutation
• signal transduction

Activation of chronic hepatitis B virus (HBV) infection is an important cause of acute-on-chronic liver failure (ACLF). However, the effect of HBV-ACLF episode on hepatocellular carcinoma (HCC) occurrence remains largely unknown.

A total of 769 HBV-ACLF patients and 2114 HBV-related chronic liver disease (HBV-CLD) patients diagnosed between August 1998 and December 2011 were enrolled in this prospective cohort study. Of the HBV-CLD patients, 380 received lifetime antiviral treatment with nucleos(t)ide analogues. Propensity score matching was applied to reduce baseline differences between HBV-ACLF and HBV-CLD cohorts.

The survival rate of HBV-ACLF patients was 53.6%, 50.3%, 47.8%, and 46.2% at 90-day, 1-year, 5-year, and 10-year, respectively. The cumulative incidence of HCC was lower in HBV-ACLF cohort with 369 eligible patients survived for >90 days than in HBV-CLD cohort with the 380 patients (5.77/1,000 vs. 9.78/1,000 person-years, p = 0.0497). HBV-ACLF episode decreased HCC risk regardless of liver cirrhosis, and in patients without family history of HCC. Multivariate Cox analyses indicated that male, increasing age, liver cirrhosis, and platelet count (≤100 × 10⁹/L) increased, whereas HBV-ACLF episode decreased, HCC risk independently. In the propensity score-matched cohorts, HBV-ACLF episode reduced HCC incidence (10.20/1,000 vs. 4.66/1,000 person-years, p = 0.0326). The area under curve of nomogram was 0.812 for 3-year HCC probability.

HBV-ACLF episode decreases HCC occurrence in chronic HBV patients. Older age and liver cirrhosis independently increased HCC occurrence. A nomogram-enrolled episode of ACLF reliably predicts the occurrence of HCC.

• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/pathology
• Hepatitis C/complications
• Hepatitis, Viral, Human
• Humans
• Liver Neoplasms/genetics
• Liver Neoplasms/pathology
• MicroRNAs
• Non-alcoholic Fatty Liver Disease/pathology
• Viral Proteins

• National Natural Science Foundation of China

Hepatitis B virus (HBV) is DNA-based virus, member of the Hepadnaviridae family, which can cause liver disease and increased risk of hepatocellular carcinoma (HCC) in infected individuals, replicating within the hepatocytes and interacting with several cellular proteins. Chronic hepatitis B can progressively lead to liver cirrhosis, which is an independent risk factor for HCC. Complications as liver decompensation or HCC impact the survival of HBV patients and concurrent HDV infection worsens the disease. The available data provide evidence that HBV infection is associated with the risk of developing HCC with or without an underlying liver cirrhosis, due to various direct and indirect mechanisms promoting hepatocarcinogenesis. The molecular profile of HBV-HCC is extensively and continuously under study, and it is the result of altered molecular pathways, which modify the microenvironment and lead to DNA damage. HBV produces the protein HBx, which has a central role in the oncogenetic process. Furthermore, the molecular profile of HBV-HCC was recently discerned from that of HDV-HCC, despite the obligatory dependence of HDV on HBV. Proper management of the underlying HBV-related liver disease is fundamental, including HCC surveillance, viral suppression, and application of adequate predictive models. When HBV-HCC occurs, liver function and HCC characteristics guide the physician among treatment strategies but always considering the viral etiology in the treatment choice.

• Hepatitis B virus surface antigen
• circle sequencing
• drug-resistant mutation
• truncated mutation
• tryptophan

• Adolescent
• Adult
• Algorithms
• Amino Acid Motifs
• Antiviral Agents/pharmacology
• Antiviral Agents/therapeutic use
• Codon
• Drug Resistance, Viral
• Evolution, Molecular
• Female
• Genes, Viral
• Hepatitis B Surface Antigens/chemistry
• Hepatitis B Surface Antigens/genetics
• Hepatitis B virus/chemistry
• Hepatitis B virus/drug effects
• Hepatitis B virus/genetics
• Hepatitis B, Chronic/drug therapy
• Hepatitis B, Chronic/virology
• Humans
• Male
• Middle Aged
• Mutation
• Quasispecies
• RNA-Directed DNA Polymerase/genetics
• Sequence Analysis, DNA
• Tryptophan/genetics
• Young Adult

• Antiviral therapy
• Finite therapy
• Functional cure
• Hepatitis B surface antigen
• Hepatitis B virus
• Monitor
• Outcome
• Predictor
• Relapse
• Treatment discontinuation

Hepatocellular carcinoma (HCC) recurrence is the major obstacle concerning patients’ survival. Tertiary prevention by antiviral therapies could reduce HCC recurrence rate in both chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infected patients. In chronic hepatitis B (CHB) patients, nucleos(t)ide analogues (Nuc) provide a more effective HCC tertiary prevention effect than an interferon (IFN)-based regimen. In chronic hepatitis C (CHC) patients, the tertiary prevention effect by direct acting antiviral agents (DAAs) was reported non-inferior to that by IFN-based therapy. Chronic hepatitis C patients left untreated had the worst survival benefit as well as shorted recurrence-free interval than those treated by either type of antiviral regimen. Although the risk of HCC recurrence could only be decreased but not diminished by antiviral therapies due to host and microenvironmental factors beyond virus infection, antiviral therapy helps to preserve and improve liver function which makes multi-modality anticancer treatment feasible to improve survival.

Hepatocellular carcinoma (HCC) ranks as a leading cause of common cancer and cancer-related death. The major etiology of HCC is due to chronic hepatitis virus including HBV and HCV infections. Scheduled HCC surveillance in high risk populations improves the early detection rate and the feasibility of curative treatment. However, high HCC recurrence rate still accounts for the poor prognosis of HCC patients. In this article, we critically review the pathogenesis of viral hepatitis-related hepatocellular carcinoma and the evidence of tertiary prevention efficacy by current available antiviral treatment, and discuss the knowledge gap in viral hepatitis-related HCC tertiary prevention.

• carcinogenesis
• cirrhosis
• direct acting antiviral agents
• interferon
• nucleos(t)ide analogues
• sustained virologic response

• Hepatitis B virus (HBV)
• Nucleos(t)ide analogs resistance mutations
• Surface truncation mutation
• Viral replication

• HBV DNA
• HBV S gene
• HBV genotype
• HBV markers
• HBsAg
• Mutation site

• Adult
• Age Factors
• Amino Acid Sequence
• Asymptomatic Infections
• Carrier State/blood
• Carrier State/immunology
• DNA Replication
• DNA, Viral/isolation & purification
• Female
• Genes, Viral/genetics
• Genotype
• Hepatitis B Antigens/blood
• Hepatitis B Surface Antigens/blood
• Hepatitis B virus/genetics
• Hepatitis B, Chronic/blood
• Hepatitis B, Chronic/immunology
• Humans
• Male
• Middle Aged
• Mutation
• Sequence Analysis, DNA

Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the second leading cause of cancer deaths globally. The high prevalence of HCC is due in part to the high prevalence of chronic HBV infection and the high mortality rate is due to the lack of biomarkers for early detection and limited treatment options for late stage HCC. The observed individual variance in development of HCC is attributable to differences in HBV genotype and mutations, host predisposing germline genetic variations, the acquisition of tumor-specific somatic mutations, as well as environmental factors. HBV genotype C and mutations in the preS, basic core promoter (BCP) or HBx regions are associated with an increased risk of HCC. Genome-wide association studies have identified common polymorphisms in KIF1B, HLA-DQ, STAT4, and GRIK1 with altered risk of HBV-related HCC. HBV integration into growth control genes (such as TERT), pro-oncogenic genes, or tumor suppressor genes and the oncogenic activity of truncated HBx promote hepatocarcinogenesis. Somatic mutations in the TERT promoter and classic cancer signaling pathways, including Wnt (CTNNB1), cell cycle regulation (TP53), and epigenetic modification (ARID2 and MLL4) are frequently detected in hepatic tumor tissues. The identification of HBV and host variation associated with tumor initiation and progression has clinical utility for improving early diagnosis and prognosis; whereas the identification of somatic mutations driving tumorigenesis hold promise to inform precision treatment for HCC patients.

• genotype
• hepatitis B virus
• hepatocellular carcinoma
• mutation
• single nucleotide polymorphisms

Although hepatitis B virus (HBV) is still one of the most common etiological factors for hepatocellular carcinoma (HCC), the association between the HBV mutations and the clinical characteristics and prognosis of HBV-related HCC patients (HBV-HCC) after surgical resection remains largely unknown.

A cohort of 131 consecutive patients who received hepatectomy for HBV-HCC were retrospectively enrolled. The HBV genotype and 14 genomic mutations, which have been reported to relate to HCC in liver samples, were sequenced. The associations between the genomic mutations and clinical characteristics and outcomes were analyzed.

Both A1762T/G1764A mutation and Pre S deletion related to worse overall survival (OS, p=0.040 and p<0.001, respectively) and disease-free survival (DFS, p=0.040 and p<0.001, respectively), G1899A mutation related to worse OS (p=0.030), A1762T/G1764A mutation correlated with tumor size (r=0.204, p=0.019), G1899A mutation correlated with vascular invasion (r=0.332, p<0.001), and Pre S deletion correlated with alpha-fetoprotein (AFP; r=0.254, p=0.003) positively. Multivariate analysis with Cox proportional hazards model revealed that both A1762T/G1764A mutation and Pre S deletion were independent prognostic factors for OS (hazard ratio [HR]=3.701, 95% CI=1.390–9.855, p=0.009, and HR=4.816, 95% CI=2.311–10.032, p<0.001, respectively) and DFS (HR=3.245, 95% CI=1.400–7.521, p=0.006, and HR=2.437, 95% CI=1.311–4.530, p<0.001, respectively), and patients with dual mutations were found to have the worst OS and DFS (p<0.001 and p<0.001, respectively). Patients with A1762T/G1764A mutation or Pre S deletion were more likely to have early recurrence (p=0.042 and p=0.019, respectively).

HBV DNA genomic mutations in A1762T/G1764A and Pre S deletion were associated with worse prognoses and early recurrence for HBV-HCC patients after surgery.

• hepatitis B virus
• hepatocellular carcinoma
• mutation
• prognosis

It has been reported that the emergence of HBV rtA181T/sW172* mutant could result in a dominant secretion defect of HBsAg and increase the risk of HCC development. This study was designed to reveal the role and possible pathogenic mechanism of truncated mutant HBsAg in tumorigenesis of HBV rtA181T/sW172* mutant.

As compared to wide type or substituted mutant HBsAg, the ratio of cell clones was significant higher in L02 cells stable expressing truncated mutant HBsAg. Injection of L02 cells stable expressing truncated mutant HBsAg into the dorsal skin fold of nude mice resulted in increased primary tumor growth compared to L02 cells stable expressing wide-type and substituted mutant HBsAg. In HBV replication L02 cell lines, the key molecular involved in TGF-β/Smad pathway was also investigated. We found that the mRNA and protein levels of Smad3/2, CREB and CyclinD1 were significantly higher and TGFBI level was significantly lower in cells stably expressing truncated mutant HBsAg as compared to cells stably expressing wide-type and substituted mutant HBsAg. Additionally, after administration of TGF-β1 (increasing TGFBI level), the volume of tumor is obviously reduced in nude mice with injection of L02 cells stable expressing truncated HBsAg.

The emergence of sW172* mutant may increase the tumorigenesis of HBV, and its mechanism may be associated with down-regulated expression of TGFBI in TGF-β/Smad signaling pathway.

• Hepatitis B virus mutation
• TGFBI
• Truncated mutant HBsAg
• Tumorigenises
• rtA181T/sW172* mutation

• Neutrophil–to–lymphocyte ratio
• chronic hepatitis B
• peginterferon

• Core promoter mutations
• Genome replication
• Hepatitis B surface antigen
• Hepatitis B virus
• Liver cancer
• PreS deletions

• Asian People
• Cell Line, Tumor
• Genetic Variation
• Genome, Viral
• Genotype
• Hepatitis B virus/classification
• Hepatitis B virus/genetics
• Hepatitis B virus/isolation & purification
• Hepatitis B virus/physiology
• Hepatitis B, Chronic/complications
• Hepatitis B, Chronic/virology
• Humans
• Liver Cirrhosis/complications
• Liver Cirrhosis/virology
• Liver Neoplasms/virology
• Mutation
• Sequence Analysis
• Virus Replication

• R01 AI116639 NIAID NIH HHS
• R21 AI103648 NIAID NIH HHS
• R21 AI107618 NIAID NIH HHS
• R21 AI113394 NIAID NIH HHS

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.

Hepatocellular carcinoma (HCC), one of the leading causes of cancer deaths in the world, is offering a challenge to human beings, with the current modes of treatment being a palliative approach. Lack of proper curative or preventive treatment methods encouraged extensive research around the world with an aim to detect a vaccine or therapeutic target biomolecule that could lead to development of a drug or vaccine against HCC. Biomarkers or biological disease markers have emerged as a potential tool as drug/vaccine targets, as they can accurately diagnose, predict, and even prevent the diseases. Biomarker expression in tissue, serum, plasma, or urine can detect tumor in very early stages of its development and monitor the cancer progression and also the effect of therapeutic interventions. Biomarker discoveries are driven by advanced techniques, such as proteomics, transcriptomics, whole genome sequencing, micro- and micro-RNA arrays, and translational clinics. In this review, an overview of the potential of tissue- and serum-associated HCC biomarkers as diagnostic, prognostic, and therapeutic targets for drug development is presented. In addition, we highlight recently developed micro-RNA, long noncoding RNA biomarkers, and single-nucleotide changes, which may be used independently or as complementary biomarkers. These active investigations going on around the world aimed at conquering HCC might show a bright light in the near future.

• HCC
• biomarker
• liver
• lncRNA
• miRNA
• prevention
• prognosis
• therapeutic

• Epigenetics
• HBx protein
• Hepatitis B virus (HBV)
• Hepatocellular carcinoma (HCC)
• miRNAs
• preS mutants

• Carcinoma, Hepatocellular/etiology
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/pathology
• Cell Transformation, Neoplastic/genetics
• DNA, Neoplasm/genetics
• DNA, Viral/genetics
• Hepatitis B/complications
• Hepatitis B/pathology
• Hepatitis B/virology
• Hepatitis B virus/genetics
• Hepatocytes/pathology
• Hepatocytes/virology
• Humans
• Liver Neoplasms/etiology
• Liver Neoplasms/metabolism
• Liver Neoplasms/pathology
• Mutation

• HBV
• Replication
• Variability

Hepatitis B virus (HBV) affects approximately two billion people worldwide and more than 240 million people in the world are currently chronic carrier that could develop serious complications in the future, like liver cirrhosis and hepatocellular carcinoma. Although an extended HBV immunization program is being carried out since the early ‘80s, representing effective preventive measure, leading to a dramatic reduction of HBV hepatitis incidence, globally HBV infection still represents a major public health problem. The HBV virus is a DNA virus belongs to the Hepadnaviridae family. The HBV-DNA is a circular, partial double strand genome. All coding information is on the minus DNA strand and it is organized into four open reading frames. Despite hepatitis B virus is a DNA virus, it has a high mutation rate due to its replicative strategy, that leads to the production of many non-identical variants at each cycle of replication. In fact, it contains a polymerase without the proofreading activity, and uses an RNA intermediate (pgRNA) during its replication, so error frequencies are comparable to those seen in retroviruses and other RNA viruses rather than in more stable DNA viruses. Due to the low fidelity of the polymerase, the high replication rate and the overlapping reading frames, mutations occur throughout the genome and they have been identified both in the structural and not structural gene. The arise of mutations being to develop of a whole of viral variants called “quasi-species” and the prevalent population, which favors virus replication, was selected by viral fitness, host’s immune pressure and external pressure, i.e., vaccination or antiviral therapy. Naturally occurring mutations were found both in acute and chronic subjects. In the present review we examine and discuss the most recent available data about HBV genetic variability and its significance.

• Hepatitis B virus
• Mutations
• Open reading frames
• Molecular biology tools
• Liver disease

• Drug Resistance, Viral/genetics
• Genome, Viral
• Hepatitis B/drug therapy
• Hepatitis B/epidemiology
• Hepatitis B/virology
• Hepatitis B virus/drug effects
• Hepatitis B virus/genetics
• Humans
• Mutation
• Viral Proteins/genetics

• HBV mutations
• cohort analysis
• pretreatment histology
• ultra-deep sequencing

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

• antiviral therapy
• chronic hepatitis B
• efficacy
• tenofovir disoproxil fumarate

AIM: To investigate the loci of adefovir dipivoxil (ADV)-induced resistance in hepatitis B virus (HBV) isolates and optimize the management of ADV-treated patients.

METHODS: Between June 2008 and August 2010, a cross-sectional control study was conducted comprising 79 patients with chronic HBV infection-related liver disease who had been administered ADV monotherapy. Patients underwent liver imaging. Serum DNA extracts were analyzed for HBV DNA levels, genotypes, and serology markers, and deep sequencing of the HBV P gene was performed.

RESULTS: ADV-resistant patients were found either with a single mutated locus, or with coexisting mutated loci. The most prevalent mutations were rtA181T, rtV214A, and rtN236T. Twenty-six patients had more than two mutated loci. The mutants were distributed among the patients without any significant affinity for gender, age, end-stage of liver disease, complications of non-alcoholic fatty liver disease, or HBV DNA levels. Patients with the rtA181T mutant were primarily infected with genotype C and e-antigen negative HBV, while patients with the rtN236T mutant were primarily infected by genotype B HBV (χ² = 6.004, 7.159; P = 0.023, 0.007). The duration of treatment with ADV was shorter in the single mutant group compared with the multi-mutant group (t = 2.426, P = 0.018).

CONCLUSION: Drug-resistant HBV mutants are complex and diverse. Patients should receive the standard and first-line antiviral treatment, strictly comply with medication dosage, and avoid short-term withdrawal.

• Hepatitis B virus
• Adefovir dipivoxil
• Drug-resistant mutant
• Gene sequencing

• Adenine/analogs & derivatives
• Adenine/therapeutic use
• Adult
• Antiviral Agents/therapeutic use
• Chi-Square Distribution
• Cross-Sectional Studies
• DNA Mutational Analysis
• DNA, Viral/genetics
• Diagnostic Imaging/methods
• Drug Resistance, Viral/genetics
• Female
• Genotype
• Hepatitis B virus/drug effects
• Hepatitis B virus/genetics
• Hepatitis B, Chronic/diagnosis
• Hepatitis B, Chronic/drug therapy
• Hepatitis B, Chronic/virology
• High-Throughput Nucleotide Sequencing
• Humans
• Male
• Middle Aged
• Mutation
• Organophosphonates/therapeutic use
• Predictive Value of Tests
• Risk Factors
• Time Factors
• Treatment Outcome

AIM: To study the clinical outcome of antiviral therapy in hepatitis B-related decompensated cirrhotic patients.

METHODS: Three hundred and twelve patients with decompensated hepatitis B cirrhosis were evaluated in a prospective cohort. With two years of follow-up, 198 patients in the group receiving antiviral therapy with nucleos(t)ide analogues and 39 patients in the control group without antiviral treatment were analysed.

RESULTS: Among the antiviral treatment patients, 162 had a complete virological response (CVR), and 36 were drug-resistant (DR). The two-year cumulative incidence of hepatocellular carcinoma (HCC) in the DR patients (30.6%) was significantly higher than that in both the CVR patients (4.3%) and the control group (10.3%) (P < 0.001). Among the DR patients in particular, the incidence of HCC was 55.6% (5/9) in those who failed rescue therapy, which was extremely high. The rtA181T mutation was closely associated with rescue therapy failure (P = 0.006). The Child-Pugh scores of the CVR group were significantly decreased compared with the baseline (8.9 ± 2.3 vs 6.0 ± 1.3, P = 0.043).

CONCLUSION: This study showed that antiviral drug resistance increased the risk of HCC in decompensated hepatitis B-related cirrhotic patients, especially in those who failed rescue therapy.

• Hepatitis B
• Decompensated cirrhosis
• Nucleos(t)ide analogues
• Hepatocellular carcinoma
• Drug resistance

• Adult
• Aged
• Antiviral Agents/therapeutic use
• Carcinoma, Hepatocellular/epidemiology
• Carcinoma, Hepatocellular/virology
• Case-Control Studies
• China/epidemiology
• Drug Resistance, Viral/genetics
• Female
• Genotype
• Hepatitis B/complications
• Hepatitis B/diagnosis
• Hepatitis B/drug therapy
• Hepatitis B virus/drug effects
• Hepatitis B virus/genetics
• Humans
• Incidence
• Kaplan-Meier Estimate
• Liver Cirrhosis/virology
• Liver Neoplasms/epidemiology
• Liver Neoplasms/virology
• Male
• Middle Aged
• Mutation
• Prospective Studies
• Risk Factors
• Time Factors
• Treatment Failure

• Carcinogenesis
• HBV
• HBVx
• HCC

• HBV drug-resistance
• HBsAg secretion
• HBsAg stop codon
• HBsAg structure
• Treatment failure

• Carcinoma, Hepatocellular/etiology
• Carcinoma, Hepatocellular/pathology
• Genes, Viral/genetics
• Hepatitis B/complications
• Hepatitis B/genetics
• Hepatitis B/virology
• Hepatitis B virus/genetics
• Humans
• Liver Neoplasms/etiology
• Liver Neoplasms/pathology
• Mutation/genetics

• Adefovir dipivoxil
• Drug resistance mutations
• Genotype C
• Hepatitis B virus
• In vitro replication phenotype
• Secretion defect

• Carcinoma
• Hepatocellular
• Operative
• Recurrence
• Surgical Procedures
• Survival