Mechanism of intrauterine infection of hepatitis B virus

AIM:To explore the possible mechanism of intrauterineinfection of hepatitis B virus (HBV).METHODS:HBV DNA was detected in vaginal secretionand amniotic fluid from 59 HBsAg-positive mothers and invenous blood of their newborns by PCR.HBsAg and HBcAgin placenta were determined by ABC immunohistochemistry.RESULTS:The rate of HBV intrauterine infection was 40.1%(24/59).HBV DNA was detected in 47.5% of amniotic fluidsamples and 52.5% of vaginal secretion samples respectively.HBsAg and HBcAg were detected in placentas from HBsAg-positive mothers.The concentration of the two antigensdecreased from the mother's side to the fetus's side,in thefollowing order:maternal decidual cells > trophoblastic cells>villous mesenchymal cells > villous capillary endothelialcells.However,in 4 placentas the distribution was in thereverse order.HBsAg and HBcAg were detected in amnioticepithelial cells from 32 mothers.CONCLUSION:The main route of HBV transmission frommother to fetus is transplacental,from the mother side ofplacenta to the fetus side.However,HBV intrauterineinfection may take place through other routes.     

Persistent occult hepatitis B virus infection： Experimental findings and clinical implications

Hepatitis B virus （HBV） is a highly pathogenic virus that causes chronic liver diseases in millions of people globally. In addition to a symptomatic, serologically evident infection, occult persistent HBV carriage has been identified since nucleic acid amplification assays of enhanced sensitivity became introduced for detection of hepadnaviral genomes and their replicative intermediates. Current evidence indicates that occult HBV infection is a common and long-term consequence of resolution of acute hepatitis B. This form of residual infection is termed as secondary occult infection （SOI）. The data from the woodchuck model of HBV infection indicate that exposure to small amounts of hepadnavirus can also cause primary occult infection （POI） where virus genome, but no serological makers of exposure to virus, are detectable, and the liver may not be involved. However, virus replicates at low levels in the lymphatic system in both these forms. We briefly summarize the current understanding of the nature and characteristics of occult hepadnaviral persistence as well as of its documented and expected pathological consequences.     

The “return” of hepatitis B

INTRODUCTION Hepatitis B virus (HBV) infection is a global health problem. This infection is especially endemic in Asia, South Pacific Region, sub-Saharan Africa and South America[1]. It is estimated that over 350 million people worldwide are chronically …     

Immunogenicity of recombinant hepatitis B virus vaccine in patients with and without chronic hepatitis C virus infection： A case-control study

AIM： To compare the response of standard hepatitis B virus （HBV） vaccination between patients with chronic hepatitis C virus （HCV） infection and healthy individuals. METHODS： This is a prospective case-control study. A total of 38 patients with chronic HCV infection and 40 healthy controls were included. Vaccination was performed by injection of 20μg recombinant HBsAg into the deltoid muscle at mo 0,1 and 6. Anti-HBs concentration was determined 3 mo after the last dose and compared between the two groups. The response pattern was characterized as （1） high-response when the anti-HBs antibody titer was 〉 100 IU/L, （2） low-response when the titer was 10-100 IU/L. and （3） no-response when the titer was 〈 10 IU/L. RESULTS： In the patient group, there were 10/38 （26.3%） non-responders, 8/38 （21.1%） Iow-responders and 20/38 （52.6%） high-responders. The corresponding values in the control group were 2/40 （5.0%）, 7/40 （17.5%） and 31/40 （77.5%）, respectively. The response pattern was statistically different between the two groups. In multivariate analysis, smoking was a significant confounder, while HCV infection lost its significant correlation with lower antibody response. CONCLUSION： Patients with chronic HCV infection tend to respond weakly to HBV vaccination compared to healthy individuals, though this correlation is not independent according to multivariate analysis.     

Transmission of hepatitis C virus: Self-limiting hepatitis or chronic hepatitis?

It has been suggested that hepatitis C virus(HCV)is selectively transmitted to a new host as an infectious clone from multiple HCV variants(quasispecies)in the donor.Most individuals with HCV infection develop chronic hepatitis,but approximately 15%-40%of them clear the virus spontaneously and the hepatitis is resolved in a self-limiting manner in the acute phase of infection.This difference in the outcome of acute hepatitis C is attributable to both viral characteristics and genetic regulation of infection.In particular,the evolutionary dynamics of the infecting virus and host genetic polymorphisms pertaining mainly to the immune system,including polymorphisms in the region of the Interleukin 28B gene encoding interferon-λ-3,are associated with susceptibility to HCV infection.     

Hepatitis B virus infection and coronary atherosclerosis： Results from a population with relatively high prevalence of hepatitis B virus

AIM: To investigate the possible association between hepatitis B virus (HBV) infection and angiographically proven coronary artery disease (CAD) in a population with relatively high prevalence of HBV. METHODS: Sera from 434 patients who underwent coronary angiography were tested for HBV antigens (HBsAg, HBeAg) and antibodies (Anti-HBs, Anti-HBc and Anti-HBe) by ELISA. RESULTS: Seventy-seven percent (224/291) of the patients with CAD and 73.4% (105/143) of the patients without angiographic evidence of atherosclerosis were seropositive for HBV (P>0.05). However, C-reactive protein (CRP) levels were significantly higher in patients with CAD (P - 0.008), while lower in HBV seropositive population (P= 0.043 and P=0.021 after adjustment for conventional risk factors). CONCLUSION: Our results suggested HBV infection negatively correlates with CRP levels, but seems not to be associated with coronary atherosclerosis.     

Exonuclease Ⅰ and Ⅲ improve the detection efficacy of hepatitis B virus covalently closed circular DNA

Background: Hepatitis B virus covalently closed circular DNA(HBV ccc DNA) is an important biomarker of hepatitis B virus infection. However, the current methods are not specific and sensitive. The present study aimed to develop a specific and sensitive assay method for the quantification of HBV ccc DNA. Methods: Exonuclease Ⅰ(Exo Ⅰ) Exonuclease Ⅲ(Exo Ⅲ) and specific primer probes are used in real-time PCR. The virus particles isolated from peripheral blood mononuclear cells were used as negative control and HBV1.3 recombinant plasmid 3.2 kb circular DNA fragment was used as positive control. The methods of cccDNA detection were evaluated in cell lines, plasmid, animal model, patient serum and liver biopsies. Results: A linear range of 10 1 –10 7 copies/assay using specific primers for HBV cccDNA was established. HBV cccDNA were only detected in cell lines, animal model and liver tissue. It cannot be detected in serum samples. Intrahepatic HBV cccDNA level had good correlation with intrahepatic total HBV DNA level( r = 0.765, P 0.001). Conclusions: The real-time quantitative PCR is an effective and feasible method for sensitive and specific detection of low copy number of ccc DNA. The novel detection method is fast, provides high sensitivity and specificity and can be used in clinical practice.     

Significant correlation between expression level of HSP gp96 and progression of hepatitis B virus induced diseases

AIM:Gp96,also known as Grp94,is a member of heatshock protein (HSP) family and binds repertoires of peptidesthereof eliciting peptide-specific T cell immune responses.It predominantly locates inside the endoplasmic reticulum(ER) with some cell surface expression in certain cancerouscells.Previous studies have shown that gp96 expressionlevel was up-regulated in tumor cells,including hepatocellularcarcinoma (HCC).However,relationship between theextent of gp96 expression and disease progression especiallyHBV-induced chronic infection,cirrhosis and hepatocellularcarcinoma,has not been addressed before.As primary HCCcan be induced and progressed from chronic hepatitis Bvirus (HBV) infection and HBV-induced cirrhosis,wedesigned an immunohistochemical experiment to test thecorrelation between gp96 expression level and HBV-induceddisease progression,from chronic HBV infection,cirrhosisto HCC.METHODS:We chose liver samples from different patientsof hepatitis B virus induced diseases,including chronichepatitis B (77 patients),cirrhosis (27 patients) and primaryHCC (30 patients),to test the expression level of gp96 indifferent affected groups.Formalin-fixed,and paraffin-embedded liver tissues taken from these patients wereimmuno-stained by using an anti-gp96 monoclonal antibodyfor the expression level of gp96 protein in the sections.Inaddition,Western blotting of whole cell lysates derived fromestablished human embryonic liver cell lines and severalhuman HCC cell lines (Huh7,HepG2,SSMC-7721) wascompared with the expression of gp96.RESULTS:We found that the extent of elevated gp96expression was significantly correlated with the diseaseprogression,and was the highest in HCC patients,lowestin chronic HBV infection and was that of the cirrhosis inthe middle.CONCLUSION:Increased expression of gp96 might be usedas a diagnostic or prognostic bio-marker for the HBV infectionand HBV-induced diseases.     

Association of -238G／A polymorphism of tumor necrosis factor-alpha gene promoter region with outcomes of hepatitis B virus infection in Chinese Han population

AIM: To clarify whether -238G/A polymorphism of tumor necrosis factor-a (TNF-a) gene promoter region was associated with outcomes of hepatitis B virus (HBV) infection in Han population of northern China, and to analyze the geneenvironment interaction between -238G/A polymorphism and cigarette smoking or alcohol consumption. METHODS: A case-control study was conducted to analyze the association of TNF-a gene promoter polymorphism with HBV infection outcomes. A total of 207 patients with chronic hepatitis B (HB) and 148 cases of self-limited HBV infection from Ditan Hospital and Shunyi District Hospital in Beijing, respectively were recruited. History of smoking and alcohol drinking was inquired by a questionnaire. The -238G/A polymorphism of TNF-a gene promoter was genotyped by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP). RESULTS: The frequencies of GG and GA genotypes were 98.07% and 1.93% in chronic HB patients and 93.24% and 6.76% in self-limited HBV infection individuals, respectively (X^2=5.30, P=-0.02). The frequency of G allele was significantly higher in patients with chronic HB that in individuals with self-limited HBV infection (99.03% vs 96.62%, X^2=5.20, P=0.02). Only modestly increased risk of onset of chronic HB was found in smokers (OR=1.40, 95% CI： 0.87-2.28, P=0.14) and drinkers (OR=-1.26, 95%CI： 0.78-2.05, P=-0.32). There was a positive interaction between genotype GG and cigarette smoking with an interaction index (Ⅱ) of 2.95, or alcohol consumption with an Ⅱ of 1.64. CONCLUSION: The -238G/A polymorphism of TNF-a gene promoter region is independently associated with different outcomes of HBV infection.     

Evolution of hepatitis B management in kidney transplantation

Chronic hepatitis B virus(HBV)infection adversely influences the clinical outcomes of renal transplant recipients owing to increased hepatic complications.Management of HBV infection in kidney transplant recipients presents a challenge to clinicians,especially in endemic regions.Interferon precipitates renal allograft dysfunction.Treatment with lamivudine,the first oral nucleoside analogue available,resulted in effective viral suppression,reduced liver-related complications,and improved patient survival so that medium-term data showed comparable patient survival rates between hepatitis B surface antigen-positive and HBsAg-negative kidney transplant recipients in the era of effective antiviral therapies.Entecavir has replaced lamivudine as first-line therapy for treatment-na?ve subjects in view of the propensity for drug resistance with the latter.Management of HBV infection in kidney transplant patients needs to take into consideration the nephrotoxicity of nucleoside/tide analogues such as adefovir and tenofovir.Prevention of HBV-related complications in kidney transplant recipients starts much earlier prior to transplantation,with vaccination of patients with chronic kidney disease and donor-recipient matching with regard to HBV status.In addition to anti-viral treatment,patients with chronic HBV infection must have regular surveillance for liver cancer and assessment for the development of cirrhosis.     

Molecular analysis of hepatitis B virus isolates in Mexico: Predominant circulation of hepatitis B virus genotype H

AIM:To determine the genotypes in Mexican hepatitis B virus (HBV) isolates and characterize their precore and core promoter mutations.METHODS: Forty-nine HBV isolates of Mexico obtained from sera of 15 hepatitis patients, 6 hemodialysis patients, 20 men seeking HIV testing, and 8 AIDS patients were analyzed. HBV isolates were amplified by PCR,and genotyped by line probe assay (INNO-LiPA HBV Genotyping; INNOGENETICS N V, Ghent, Belgium).HBV genotype confirmation was performed by DNA sequencing part of the sAg region. Precore and core promoter mutation characterization was performed by line probe assay (INNO-LiPA HBV PreCore; INNOGENETICS N.V.; Ghent, Belgium).RESULTS: Overall, HBV genotype H was found in 37(75.5%) out of the 49 isolates studied. HBV genotypes G, A, and D were found in 5 (10.2%), 4 (8.2%), and 3(6.1%) isolates, respectively. HBV genotype H was predominant in isolates from hemodialysis patients (100%),hepatitis patients (80%), and men seeking HIV testing (75%), and accounted for half of infections in AIDS patients (50%). Six (12.2%) out of the 49 HBV isolates showed both wild type and mutant populations at precore codon 28. These mixed wild type and precore murant populations were observed in one HBV genotype A isolate and in all HBV genotype G isolates. A dual variant core promoter mutation was observed in 1 (2%) of the isolates, which was genotype H.CONCLUSION: HBV genotype H is highly predominant in HBV isolates of Mexico followed by genotypes G, A and D. A low frequency of precore and core promoter mutations is observed in HBV Mexican isolates.     

Molecular and serological characterization of occult hepatitis B infection in blood donors from Mexico

Occult hepatitis B virus (HBV) infection (OBI) is characterized by presence of HBV DNA in blood or liver tissue without detectable HBV surface antigen (HBsAg), with or without antibodies to hepatitis B core antigen (anti-HBc) or antibodies against HBsAg (anti-HBs). A molecular and serological characterization was done of OBI in blood donors from Yucatan, Mexico. HBV DNA was found in 24 (6.4%) of the 372 evaluated samples. Anti-HBs was present in 15/24 samples (62.5%), and no significant difference was observed between HBV DNA positivity and anti-HBs levels. HBV genotype H was detected in 66.7% of samples, followed by genotypes D (20.8%) and F (8.3%). Amino acid substitutions were identified in the core region of nine samples, and most of these changes were located in immunodominant epitopes. No precore stop codon 28 mutant (W28Stop) was identified among the analyzed HBV isolates. In conclusion, genotype H is the main circulating HBV strain among OBI blood donors from Yucatan, Mexico. Mutations in the core region may contribute to viral persistence.     

乙型肝炎病毒基因型对乙型肝炎病毒变异的影响

目的探讨乙型肝炎病毒(HBV)基因型对病毒前核心区(前C区,nt1896)及基本核心启动子(BCP,nt1762/1764)变异的影响.方法416例血清HBsAg阳性、HBV DNA定量大于1.0×104拷贝/ml的患者,采用微流基因芯片检测HBV基因型、前C区及BCP变异.结果416例HBV感染者中406例有基因分型结果:B型20.9%、C型65.9%、BC混合型10.8%,10例患者未分出基因型.302例为HBeAg(-)且HBV DNA( )患者,其中248例(82.12%)有前C区或BCP变异,41.06%为前C区变异,31.12?P变异,2种同时变异为9.94%.B型患者前C区变异率为22.9%(20/87),与C型患者前C区变异率39.4%(108/274)及B、C混合型变异率40.0%相比均有显著差异(P＜0.01).在BCP变异及双变异,C型患者变异率均大于B型患者,但差异无统计学意义(P＞0.05).B、C混合型患者前C区及BCP变异率与C型相似.结论HBV基因型可影响病毒前C区及BCP变异,以C型为著.     

Epidemiological study of hepatitis B virus genotypes, core promoter and precore mutations of chronic hepatitis B infection in Hong Kong

BACKGROUND/AIMS: We conducted a population study to document the prevalence of hepatitis B virus (HBV) genotypes in Hong Kong. METHODS: HBV genotypes, core promoter (CP) and precore mutations were determined in 776 asymptomatic patients. RESULTS: 92.6% patients had single genotype [B (32.5%), C (62.5%)]. 99.1% of genotype B was subtype Ba. Patients with age <50 years had a lower prevalence of genotype B than patients with age >51 years (32.5% vs. 41%, respectively, P=0.028). Compared to patients with genotype C, patients with genotype B had a higher cumulative rate (P=0.018) and younger age (40.1 vs. 34.2 years, respectively, P=0.018) of HBeAg seroconversion. There were no differences in the HBV DNA levels between patients with genotypes B and C, and with wild-type and mutants of CP and precore regions. By multivariate analysis, patients with genotype C and with CP mutations had higher alanine aminotransferase (ALT) levels. CONCLUSIONS: B and C were the two most common HBV genotypes in Hong Kong. The former had a higher chance of earlier HBeAg seroconversion and lower ALT levels. The prevalence of genotype B was lower in patients with age <50, probably related to influx of immigrants from China since 1949.     

Prevalence and resistance pattern of genotype G and H in chronic hepatitis B and HIV co-infected patients in Mexico

Objective. We estimated the prevalence and identified the resistance pattern of HBV genotypes H and G in HBV monoinfected and HIV co-infected patients.Material and methods. A cross-sectional prevalence and analytic study were performed in chronic hepatitis B patients at the Hospital de Infectologia, La Raza National Medical Center in Mexico City. Chronic HBV monoinfected and HIV co-infected patients were included. HBeAg, HBV viral load and genetic analysis of mutations were collected; CD4+ cells count from HIV co-infected patients and HIV RNA were measured. We calculated the prevalence and exact 95% binomial confidence interval and the Odds ratios (OR) with 95% confidence intervals to assess the relationship between the presence of risk factors and HBV genotypes H or G.Results. We enrolled 77 patients, 67 men and 10 women with 37 HIV co-infected patients. The distribution of HBV genotypes was: HBV genotype H 55 (71% [95% CI 60% to 80%]), HBV genotype G 16 (20.7%), HBV genotype F 4 (5.1%) and HBV genotype A 2 (2.6%). The most frequent mutations presented in 8 HIV co-infected patients and one mono-infected patient with antiretroviral therapy (ART) experience were rtM204V and six of them showed genotype G (6/9). Mono-infected HBV patients exposed more probability to HBV genotype H than co-infected HIV patients OR 13.0 (CI 95% 3.40-49.79), p = 0.0001. In contrast co-infected patients presented less possibility to have genotype H, 0.56 (CI 95% 0.42-0.75).Conclusions. This study confirms the high prevalence of HBV genotype H in Mexico; furthermore, our results suggest that HBV genotype G predominates in co-infected patients. As well, rtM204V and rtL180M mutations are common in HBV-HIV co-infected patients with genotype G and ART experience.     

Preliminary report of hepatitis B virus genotype prevalence in Iran

AIM: To determine the prevalence of hepatitis B virus (HBV) genotypes in Iranian hepatitis B surface antigen (HBsAg) carriers, chronic hepatitis B and cirrhotic patients. METHODS: A total of 109 HBsAg-positive patients were included in this study. HBV genotypes were determined by using INNO-LiPA methodology which is based on the reverse hybridization principle. RESULTS: The distribution of patients with different stages of liver disease was as follows: 95 (86.4%) chronic hepatitis, 11 (10%) liver cirrhosis, and 3 (2.7%) inactive carrier. Of the chronic hepatitis and liver cirrhosis patients, 26.4% were HBeAg-positive while 70% were HBeAg-negative. Genotype D was the only detected type found in all patients. CONCLUSION: Classifying HBV into genotypes has to be cost-effective and clinically relevant. Our study indicates that HBV genotype D prevails in the Mediterranean area, Near and Middle East, and South Asia. Continued efforts for understanding HBV genotype through international co-operation will reveal further virological differences of the genotypes and their clinical relevance.     

Viral genotype and hepatitis B virus DNA levels are correlated with histological liver damage in HBeAg-negative chronic hepatitis B virus infection

OBJECTIVES: We aimed to study the relationship between the hepatitis B virus (HBV) genotypes, core promoter/precore stop codon mutations, and histological liver damage among hepatitis B e antigen (HBeAg)-negative patients. METHODS: Liver biopsy specimens of 55 HBeAg-negative chronic HBV-infected patients were studied. A histological activity index was scored for degree of necroinflammation (HAI-NI) and fibrosis (HAI-F) as described by Knodell et al. HBV DNA was determined by a cross-linking assay and polymerase chain reaction (PCR) at the core promoter/precore region and the S region. PCR-positive samples were directly sequenced for core promoter and precore mutations and examined by restriction fragment length polymorphism for genotyping. RESULTS: Forty-one males and 14 females at a median age of 43 were studied. HBV DNA was detectable in 32 (58%) and 37 (67%) patients by the cross-linking assay and PCR, respectively, at the time of liver biopsy. The median (range) HAI-NI and HAI-F scores were 5 (1-10) and 2 (0-4), respectively. HBV DNA detectable by either the cross-linking assay or PCR was associated with a higher HAI-NI score. Eleven and 31 patients had genotypes B and C HBV, respectively. Genotype C HBV was associated with higher HAI-NI than genotype B HBV. Core promoter mutations and precore stop codon mutation were detected in 74% and 40% patients, respectively, but they were not associated with higher HAI-NI or HAI-F scores. CONCLUSIONS: Detectable HBV DNA and genotype C HBV, but not core promoter or precore stop codon mutations, are associated with more severe liver damage in HBeAg-negative patients.     

A male patient with severe acute hepatitis who was domestically infected with a genotype H hepatitis B virus in Iwate, Japan

Although all eight genotypes of hepatitis B virus (HBV) strains are circulating in Japan, no cases of acute hepatitis with foreign HBV strains of genotype H have thus far been reported in Japan. Here, we report a 35-year-old Japanese patient with severe acute hepatitis who was domestically infected with genotype H HBV. On admission, he had a high HBV load of 1.0 × 10⁹ copies/ml, elevated levels of total bilirubin (7.0 mg/dl) and alanine aminotransferase (3606 IU/l), and reduced prothrombin activity of 39.0%. The HB-JAIW05 isolate obtained in the present study was composed of 3215 nucleotides and had the highest similarity of 99.7% with the reported genotype H HBV isolate recovered from a Japanese blood donor. The HB-JAIW05 isolate had neither precore (A1896) nor core promoter (T1762/A1764) mutations. However, upon comparison with the consensus sequence of ten reported HBV isolates of the same genotype, the HB-JAIW05 isolate had 17 nucleotide substitutions including five missense mutations in the P gene, which may be related to vigorous replication of HBV in this case. He had no history of traveling abroad, but had had extramarital sexual contact with two Japanese women living in Iwate, Japan, 2 weeks and 2 months before the disease onset, respectively. Our results suggest that rare HBV genotypes such as H may be spreading in Japan via sexual contact. Further molecular epidemiological studies on HBV to clarify the exact changing profiles of de novo HBV infection in Japan in relation to genotype and genomic variability are warranted.     

Classifying genotype F of hepatitis B virus into F1 and F2 subtypes

AIM: To explore the propriety of providing hepatitis B virus(HBV) genotypes F and H with two distinct genotypes.METHODS: Eleven HBV isolates of genotype F (HBV/F)were recovered from patients living in San Francisco,Japan, Panama, and Venezuela, and their full-length sequences were determined. Phylogenetic analysis was carried out among them along with HBV isolates previously reported.RESULTS: Seven of them clustered with reported HBV/F isolates in the phylogenetic tree constructed on the entire genomic sequence. The remaining four flocked on another branch along with three HBV isolates formerly reported as genotype H. These seven HBV isolates, including the four in this study and the three reported, had a sequence divergence of 7.3-9.5% from the other HBV/F isolates,and differed by ＞ 13.7% from HBV isolates of the other six genotypes (A-E and G). Based on a marked genomic divergence, falling just short of ＞8% separating the seven genotypes, these seven HBV/F isolates were classified into F2 subtype and the former seven into F1 subtype provisionally. In a pairwise comparison of the S-gene sequences among the 7 HBV/F2 isolates and against 47HBV/F1 isolates as well as 136 representing the other six genotypes (A-E and G), two clusters separated by distinct genetic distances emerged.CONCLUSION: Based on these analyses, classifying HBV/F isolates into two subtypes (F1 and F2) would be more appropriate than providing them with two distinct genotypes (F and H).     

Hepatitis B virus genotypes and clinical manifestation among hepatitis B carriers in Thailand

BACKGROUND: Hepatitis B virus (HBV) genotypes have distinct geographic distributions. The aim of the present study was to evaluate the distribution of HBV genotypes and their clinical relevance in Thailand. METHODS: Hepatitis B virus genotypes among 107 hepatitis B carriers residing in Thailand were evaluated using serologic and genetic methods. They were clinically classified into asymptomatic carriers with normal serum alanine transaminase (ALT) levels and patients with chronic liver disease, such as those with chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). RESULTS: Hepatitis B virus genotype distribution among the 107 patients was 25.2% for genotype B, 72.0% for genotype C and 2.8% for genotype D. The serum ALT levels, HBV-DNA and hepatitis B e antigen positivity were significantly higher in carriers infected with genotype C HBV than in those infected with genotype B (P < 0.05). The proportion of genotype B HBV was higher in asymptomatic carriers than in patients with CH and those who developed liver disease, such as LC and HCC (45.5, 16.9 and 25.0%, respectively; P < 0.05). In contrast, the proportion of genotype C HBV was higher in patients who developed liver disease and CH than in asymptomatic carriers (68.7, 83.0 and 50.0%, respectively; P < 0.05). Phylogenetic analysis based on entire genome sequences revealed three HBV isolates, which were classified into a subgroup of genotype C in isolates from South-East Asian countries. CONCLUSIONS: Genotypes B and C are the predominant types among hepatitis B carriers residing in Thailand and those genotypes influence the clinical manifestation in carriers with chronic hepatitis B infection.