Hepatitis B virus genotypes in precision medicine of hepatitis Brelated hepatocellular carcinoma:Where we are now

Hepatitis B virus(HBV)infection is a major player in chronic hepatitis B that may lead to the development of hepatocellular carcinoma(HCC).HBV genetics are diverse where it is classified into at least 9 genotypes(A to I)and 1 putative genotype(J),each with specific geographical distribution and possible different clinical outcomes in the patient.This diversity may be associated with the precision medicine for HBV-related HCC and the success of therapeutical approaches against HCC,related to different pathogenicity of the virus and host response.This Editorial discusses recent updates on whether the classification of HBV genetic diversity is still valid in terms of viral oncogenicity to the HCC and its precision medicine,in addition to the recent advances in cellular and molecular biology technologies.

Hepatitis B virus genotypes:Global distribution and clinical importance

At least 600000 individuals worldwide annually die of hepatitis B virus(HBV)-related diseases,such as chronic hepatitis B(CHB),liver cirrhosis(LC),and hepatocellular carcinoma(HCC).Many viral factors,such as viral load,genotype,and specific viral mutations,are known to affect disease progression.HBV reverse transcriptase does not have a proofreading function,therefore,many HBV genotypes,sub-genotypes,mutants,and recombinants emerge.Differences between genotypes in response to antiviral treatment have been determined.To date,10 HBV genotypes,scattered across different geographical regions,have been identified.For example,genotype A has a tendency for chronicity,whereas viral mutations are frequently encountered in genotype C.Both chronicity and mutation frequency are common in genotype D.LC and progression to HCC are more commonly encountered with genotypes C and D than the other genotypes.Pathogenic differences between HBV genotypes explain disease intensity,progression to LC,and HCC.In conclusion,genotype determination in CHB infection is important in estimating disease progression and planning optimal antiviral treatment.

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Hepatitis B virus genotypes and genome characteristics in China

AIM:To analyze the hepatitis B virus(HBV) characters in China,as well as the correlation between several HBV mutation and hepatitis symptoms.METHODS:A total of 1148 HBV genome sequences from patients throughout China were collected via the National Center For Biotechnology Information database(information including:genotype,territory and clinical status).HBV genotypes were classified by a direct reference from the Genbank sequence annotation,phylogenetic tree and online software analysis(http://www.ncbi.nlm.nih.gov/projects/genotyping/formpage.cgi).The phylogenetic tree was constructed based on the neighbor-joining method by MEGA5.0 software.HBV sequences were grouped based on phylogenetic tree and the distance between the groups was calculated by using the computer between group mean distance methods.Seven hundred and twelve HBV sequences with clear annotation of clinical symptoms were selected to analyses the correlation of mutation and clinical symptoms.Characteristics of sequences were analyzed by using DNAStar and BioEdit software packages.The codon usage bias and RNA secondary structures analysis were performed by RNAdraw software.Recombination analysis was performed by using Simplot software.RESULTS:In China,HBV genotype C was the predominant in Northeastern,genotype B was predominant in Central Southern areas,genotype B and C were both dominant in Southwestern areas,and the recombinant genotype C/D was predominant in Northwestern areas.C2 and B2 were identified as the two major sub-genotypes,FJ386674 might be a putative sub-genotype as B10.The basal core promoter double mutation and pre-C mutation showed various significant differences between hepatitis symptoms.In addition to ATG,many other HBV initiation codons also exist.HBV has codon usage bias;the termination codon of X,C and P open reading frames(ORF) were TAA,TAG,and TGA,respectively.The major stop codons of S-ORF were TAA(96.45%) and TGA(83.60%) in B2 and C2 subtype,respectively.CONCLUSION:This study recapitulated the epidemiology of HBV in China,and the information might be meaningful critical for the future prevention and therapy of HBV infections.

Molecular identification of hepatitis B virus genotypes/subgenotypes:Revised classification hurdles and updated resolutions

The clinical course of infections with the hepatitis B virus (HBV) substantially varies between individuals, as a consequence of a complex interplay between viral, host, environmental and other factors. Due to the high genetic variability of HBV, the virus can be categorized into different HBV genotypes and subgenotypes, which considerably differ with respect to geographical distribution, transmission routes, disease progression, responses to antiviral therapy or vaccination, and clinical outcome measures such as cirrhosis or hepatocellular carcinoma. However, HBV (sub)genotyping has caused some controversies in the past due to misclassifications and incorrect interpretations of different genotyping methods. Thus, an accurate, holistic and dynamic classification system is essential. In this review article, we aimed at highlighting potential pitfalls in genetic and phylogenetic analyses of HBV and suggest novel terms for HBV classification. Analyzing full-length genome sequences when classifying genotypes and subgenotypes is the foremost prerequisite of this classification system. Careful attention must be paid to all aspects of phylogenetic analysis, such as bootstrapping values and meeting the necessary thresholds for (sub)genotyping. Quasi-subgenotype refers to subgenotypes that were incorrectly suggested to be novel. As many of these strains were misclassified due to genetic differences resulting from recombination, we propose the term “recombino-subgenotype”. Moreover, immigration is an important confounding facet of global HBV distribution and substantially changes the geographic pattern of HBV (sub)genotypes. We therefore suggest the term “immigro-subgenotype” to distinguish exotic (sub)genotypes from native ones. We are strongly convinced that applying these two proposed terms in HBV classification will help harmonize this rapidly progressing field and allow for improved prophylaxis, diagnosis and treatment.

Characteristics of general distribution of hepatitis B virus genotypes in China

BACKGROUND: Based on differences in the virus nucleotide sequence, hepatitis B virus (HBV) genotypes are presently divided into genotypes A-H. The geographic distributions of HBV genotypes differ in countries and regions. To determine the general characteristics of their distributions in the mainland of China, we reviewed articles on HBV genotypes published in China. METHODS: The Wanfang Database and the CNKI Database were searched for original articles involving HBV in China, and then the data from the articles were classified according to genotype and latitude and analyzed using SPSS 11.0. RESULTS: The main HBV genotypes were C, B and BC, and their rates were 50.99%, 35.58%, 6.07%, respectively; other genotypes were rare. There was a negative correlation between latitude and the rate of genotype B (r=-0.782, P<0.01), while a positive correlation existed between latitude and the rate of genotype C (r=0.646, P<0.01). No correlation was observed between latitude and the rates of other genotypes (r=0.294, P>0.05). CONCLUSIONS: In China, HBV genotype C predominates, followed by genotype C and mixed genotype BC; genotypes A, D and others are rare. With an increasing latitude, the distribution of genotype B decreases gradually, while that of genotype C tends to increase. The other genotypes do not show any changes.

Genotypes and viral variants in chronic hepatitis B: A review of epidemiology and clinical relevance

The Hepatitis B Virus(HBV) has a worldwide distribu-tion and is endemic in many populations. It is constantly evolving and 10 genotypic strains have been identified with varying prevalences in different geographic regions. Numerous stable mutations in the core gene and in the su-rface gene of the HBV have also been identified in untreated HBV populations. The genotypes and viral variants have been associated with certain clinical featu-res of HBV related liver disease and Hepatocellu-lar carcinoma. For example Genotype C is associated withlater hepatitis B e antigen(HBe Ag) seroconversion, and more advanced liver disease. Genotype A is associated with a greater risk of progression to chronicity in adu-lt acqu-ired HBV infections. Genotype D is particu-larly associated with the precore mu-tation and HBe Ag negative chronic hepatitis B(CHB). The genotypes prevalent in parts of West Africa, Central and Sou-th America, E, F and H respectively, are less well stu-died. Viral variants especially the Basal Core Promotor mutation is associated with increased risk of fibrosis and cancer of the liver. Althou-gh not cu-rrently part of rou-tine clinical care, evalu-ation of genotype and viral variants may provide u-sefu-l adju-nctive information in predicting risk abou-t liver related morbidity in patients with CHB.

Relationship between hepatocellular carcinoma and hepatitis B virus genotype with spontaneous YMDD mutations

AIM: To investigate the relationship between hepatitis B virus (HBV) genotype with spontaneous YMDD mu-tations and hepatocellular carcinoma (HCC) in HBV-related cirrhosis. METHODS: We investigated 264 liver cirrhosis pa-tients who were not treated with antiviral drugs, in-cluding 81 patients with HCC. YMDD mutations were detected by fluorescent hybridization bioprobe poly-merase chain reaction (PCR) and melting curve assay using the Diagnosis Kit for HBV YMDD Mutation. Serum HBV genotypes were detected by real-time PCR using genotype-specific TaqMan probes. Statistical analysis was performed according to data type using the t test, χ2 test and unconditional logistic regression analysis. RESULTS: In the HCC group, genotype C strains, spon-taneous YMDD mutations, and genotype C strains with YMDD mutations were detected in 33 (40.74%), 13 (16.05%) and 11 (13.58%) patients, respectively. In the liver cirrhosis (LC) group, HBV genotype C strains,spontaneous YMDD mutations, and genotype C strains with YMDD mutations were detected in 33 (18.03%), 7 (3.83%) and 2 (1.09%) patients, respectively. The dif-ferences in genotype C strains, spontaneous YMDD mu-tations, and genotype C strains with YMDD mutations between the two groups were statistically significant (χ2=15.441, P=0.000; χ2=11.983, P=0.001; P=0.000). In the HCC and LC groups, there were seven patients infected by genotype B strains with YMDD mutations and 13 by genotype C strains with YMDD mutations. Further research revealed that HCC oc-curred in 2 patients infected by genotype B strains with YMDD mutations and 11 infected by genotype C strains with YMDD mutations. The difference was statistically significant (P=0.000). Unconditional logistic regres-sion analysis revealed that patients infected by geno-type C strains with spontaneous YMDD mutations had a 7.775-fold higher risk for the development of HBV-related HCC than patients infected by other type HBV strains (P=0.013, 95%CI: 1.540-39.264). CONCLUSION: Genotype C strains with spontaneous YMDD mutations are an independent risk factor for HCC in LC patients and are important for early warning of HCC.

Relationship between HBV genotypes and anti-viral therapeutic efficacy of interferon-alpha

BACKGROUND: Much evidence demonstrates that the genotypes of hepatitis B virus (HBV) present differences in pathogenicity and outcomes owing to differences in genetic structure. This study aimed to investigate the influences of HBV genotypes on the anti-viral therapeutic efficacy of interferon-alpha (IFN-alpha) in chronic hepatitis B patients, and to determine the relationship between HBV genotypes and levels of viral replication or gene variations. METHODS: The chronic hepatitis B patients who were treated with IFN-alpha were selected randomly. Anti-viral therapeutic efficacy was monitored in these patients. The HBV genotypes were detected by PCR microplate hybridization ELISA. The levels of serum HBV-DNA were determined by fluorescence quantitative PCR. HBV gene variation at pre-C and basic core promoter (BCP) regions were assayed by gene chip technology. RESULTS: Genotypes B and C were predominant in 94 chronic hepatitis B patients. A, E and F genotypes were not found in these patients. The HBV-DNA levels of genotype C and mixed genotypes were significantly higher than those of genotype B. The response to IFN-alpha in patients with genotype B was markedly better than in those with genotypes C and D, and the complete response to IFN-alpha was only observed in genotype B. The response to IFN-alpha in patients with mixed genotypes was the least sensitive. The negative transition of HBeAg was correlated with variations in the HBV pre-C and BCP regions in patients with partial or no response to IFN-alpha. The variation rates of HBV pre-C and BCP regions were clearly higher in genotype C than in genotype B. CONCLUSIONS: The results suggest that HBV genotype is correlated with the serum levels of HBV-DNA, HBV gene variations and therapeutic efficacy of IFN-alpha. The regular detection of HBV genotypes in the clinic will be of benefit for disease prognosis and planning of anti-viral therapeutic strategies.

Hepatitis B virus infection and genotype in asymptomatic people from 10 ethnic groups in Yunnan, China

AIM: To evaluate the infection and genotype distribution of hepatitis B virus(HBV) in ethnic groups in Yunnan, China.METHODS: Two thousand five hundred and eightyfour asymptomatic local people from 10 ethnic groups were investigated in Yunnan, China. Infection and genotype distribution were evaluated by serological and genetic methods. Genotyping was verified by sequencing. Ethnic genotype distribution was compared by proportion test. RESULTS: Four types of infection model based on HBV serum markers were identified, and the average HBV infection rate was 5.7% in those asymptomatic local people. The genotype prevalence was 59.6% for B, 21.1% for C and 19.3% BC; subgenotypes Ba, Cs and Ce were identified in this study. Hepatitis B surface antigen-positive rate and the proportion of genotype B were significantly lower in ethnic groups with a northern origin compared to those with a southern origin(50% vs 73.9%, P = 0.037; 4.2% vs 10.5%, P = 0.000).CONCLUSION: Genotype B is dominant and genotype BC has high occurrence in asymptomatic local ethnic groups in Yunnan. HBV infection status and genotype distribution may associate with ethnic origin.

HBV genotype C is independently associated with cirrhosis in community-based population

AIM:To determine the association of hepatitis B virus (HBV) genotypes with probable cirrhosis and fatty liver in community-based populations.METHODS: A multi-stage cluster probability sampling method was applied to recruit 10 167 subjects aged between 6 and 72 years from our epidemiological bases in Eastern China. After excluding the subjects co-infected with hepatitis C or hepatitis D viruses, the hepatitis B surface antigen (HBsAg)-positive subjects were examined for HBV genotype, serum viral load, alanine aminotransferase (ALT), hepatitis B e antigen (HBeAg) status, and ultrasonographic changes. Logistic regression models were used to determine the factors associated with probable cirrhosis and fatty liver.RESULTS: Of 634 HBsAg-positive subjects with HBV genotype determined, 82 had probable cirrhosis (ultrasonographic score ≥5), 42 had ultrasonographic fatty liver. Probable cirrhosis was only found in the HBeAg-negative subjects, and more frequently found in the subjects with genotype C than in those with genotype B (14.8% vs 8.0%, P=0.018). In HBeAg-negative subjects, high viral load was frequently asso-ciated with abnormal ALT level, while ALT abnormality was more frequent in those with probable cirrhosis than those without (19.5% vs 7.8%, P=0.001). Univariate analysis showed that age, sex, HBV genotypes, and viral load were not significantly associated with ultrasonographic fatty liver, whereas ALT abnormality was significantly related to ultrasonographic fatty liver (OR=4.54,95% CI:2.11-9.75, P<0.001). Multivariate analysis demonstrated that HBV genotype C, age (≥45 years), male sex, and ALT abnormality were independently associated with probable cirrhosis (AOR=2.30,95% CI:1.26-4.19; AOR =1.81,95% CI:1.10-2.99;AOR=1.74,95% CI:1.03-2.95; AOR=2.98,95% CI:1.48-5.99, respectively).CONCLUSION: A crude prevalence of probable cirrhosis is 12.9% in the community-based HBV-infected subjects. HBV genotype C is independently associated with probable cirrhosis in the HBeAg-negative subjects.

HBV endemicity in Mexico is associated with HBV genotypes H and G

Hepatitis B virus(HBV)genotypes have distinct genetic and geographic diversity and may be associated with specific clinical characteristics,progression,severity of disease and antiviral response.Herein,we provide an updated overview of the endemicity of HBV genotypes H and G in Mexico.HBV genotype H is predominant among the Mexican population,but not in Central America.Its geographic distribution is related to a typical endemicity among the Mexicans which is characterized by a low hepatitis B surface antigen seroprevalence,apparently due to a rapid resolution of the infection,low viral loads and a high prevalence of occult B infection.During chronic infections,genotype H is detected in mixtures with other HBV genotypes and associated with other co-morbidities,such as obesity,alcoholism and co-infection with hepatitis C virus or human immunodeficiency virus.Hepatocellular carcinoma prevalence is low.Thus,antiviral therapy may differ significantly from the standard guidelines established worldwide.The high prevalence of HBV genotype G in the Americas,especially among the Mexican population,raises new questions regarding its geographic origin that will require further investigation.

Hepatitis B virus genotypes:an overview

BACKGROUND:Hepatitis B virus(HBV)infection is a major cause of mortality and morbidity globally.The quest continues to identify viral factors that influence disease progression and severity as well as responses to treatment of HBV infection.Based on variations in HBV,the virus has been divided into a number of genotypes. DATA SOURCES:Review of published literature on HBV genotypes. RESULTS:HBV genotypes are likely to be important in determining the severity and progression of HBV-induced liver disease as well as responses to different anti-viral agents. CONCLUSION:Although HBV genotyping is not yet recommended for routine use in treating HBV infection, available data suggest that,as in hepatitis C virus infection, HBV genotyping is also likely to become a routine investigation for HBV treatment,perhaps in the not too distant future.

Correlation of the occurrence of YMDD mutations with HBV genotypes,HBV-DNA levels,and HBeAg status in Chinese patients with chronic hepatitis B during lamivudine treatment

BACKGROUND:Continuous lamivudine therapy is associated with high rates of YMDD mutations,which are the main causes of drug resistance.The current study explores the association of the emergence of YMDD mutations with pretherapy HBV genotype,HBV-DNA levels,HBeAg status,and serum alanine aminotransferase(ALT) levels in Chinese patients receiving lamivudine therapy for chronic hepatitis B.METHODS:A total of 319 chronic hepatitis B patients who received lamivudine therapy for more than a year were enrolled in this study.YMDD mutations,HBV genotype,HBV-DNA levels,HBeAg status,and ALT levels were determined prior to their lamivudine treatment and every three months for a year of this therapy.RESULTS:Among the 319 patients,137(42.95%) were infected with genotype B and 182(57.05%) with genotype C.Up to 94 patients(29.47%) developed YMDD mutations within one year of lamivudine therapy.Furthermore,50 patients with HBV genotype B and 44 patients with genotype C developed YMDD mutations(36.50% vs 24.18%,P<0.05).Logistic regression analysis showed that pretherapy HBV genotype,HBV-DNA levels,and HBeAg status are independent factors for the emergence of YMDD mutations(HBV genotype:OR=2.159,95% CI 1.291-3.609,P=0.003;HBV-DNA:OR=1.653,95% CI 1.231-2.218,P=0.001;HBeAg:OR=2.021,95% CI 1.201-3.399,P=0.008).CONCLUSIONS:HBV genotype,HBV-DNA levels,and HBeAg status at baseline are the independent factors associated with the emergence of YMDD mutations among Chinese patients receiving lamivudine therapy for chronic hepatitis B.These findings are helpful to the development of therapeutic strategies for these patients.

Profile, spectrum and significance of hepatitisB virus genotypes in chronic HBV-infected patients in Yunnan, China

BACKGROUND: There are significant variations in the geographical distribution of hepatitis B virus (HBV) genotypes throughout the world, and some genotypes are associated with different clinical outcomes. Eight genotypes of human HBV (designated A-H) have been reported. The present study was designed to examine the distribution of HBV genotypes among patients at various stages of chronic type B liver disease in Yunnan Province, China, and to explore its significance and the relationship of HBV genotype with gender and age, clinical spectrum of chronic HBV infection, and viral replicative activity. METHODS: Serum samples from 126 patients with chronic HBV infection from Yunnan Province, including 26 chronic asymptomatic HBV carriers (ASC), 61 patients with chronic hepatitis B (CHB) (21 mild, 30 moderate and 10 severe), 20 patients with chronic fulminant hepatic failure (CFHF), 12 patients with HBV-related liver cirrhosis (LC) and 7 patients with HBV-related hepatocellular carcinoma (HCC) were analyzed using reverse dot blot (RDB) methodology, which is based on the reverse hybridization principle for HBV genotyping. The relations of HBV genotype with gender and age, clinical patterns, and serological data of the patients were analyzed. RESULTS: In this series, genotypes A, B, C, and D were found. 38.1% patients (48/126) belonged to B, 54.8% (69/126) to C, 0.8% (1/126) to D, 1.6% (2/126) to a mixture of B and C, and 1.6% (2/126) to a mixture of A and C. 3.2% patients (4/126) had unknown genotypes. No other genotypes (E, F, G, and H) were found. Genotypes B and C were predominant. There was a statistically significant difference in the distributions of genotypes C and B (chi(2)=7.04, P=0.008), and C was the dominant genotype in all patient categories. The rate of genotype B in the mild CHB group was significantly higher than that in the moderate and severe groups (chi(2)=12.16, P=0.0001; chi(2)=11.98, P=0.001, respectively), the ASC group (chi(2)=5.46, P=0.02), the CFHF group (chi(2)=5.53, P=0.019), and the LC/HCC group (chi(2)=12.13, P=0.001). The rate of genotype C in the LC/HCC group and the severe CHB group were significantly higher than that in the mild group (chi(2)=9.95, P=0.002; chi(2)=8.78, P=0.003, respectively). HBV DNA positivity and HBeAg positivity were higher in genotype C than in genotype B (chi(2)=9.81, P=0.002; chi(2)=3.85, P=0.05, respectively). The prevalence of genotype C showed an increasing trend in lowest-, middle- and highest-level groups of HBV replication (25.0%, 70.0%, and 55.6%, respectively); in contrast, the prevalence of genotype B showed an opposite trend in the same order (62.5%, 30.0%, and 37.0%, respectively). The rate of genotype C in the highest-level group of HBV replication was higher than genotype B (chi(2)=7.45, P=0.006). The rate of genotype C in the over-30 age group was higher than that in the below-30 age group (chi(2)=3.7, P=0.05). There was no difference between the sexes (P>0.05). More severe liver damage was found in genotype C than in genotype B (P<0.05). CONCLUSIONS: The predominant HBV genotypes in chronic HBV-infected patients are B and C, and C is the most prevalent genotype in Yunnan Province, China. HBV genotype C is associated with the development of more severe liver disease and a higher level of HBV viral replication, and genotype B has a relatively good progress.

Hepatitis B virus taxonomy and hepatitis B virus genotypes

Hepatitis B virus(HBV) is a member of the hepadnavirus family.Hepadnaviruses can be found in both mammals(orthohepadnaviruses) and birds(avihepadnaviruses).The genetic variability of HBV is very high.There are eight genotypes of HBV and three clades of HBV isolates from apes that appear to be additional genotypes of HBV.Most genotypes are now divided into subgenotypes with distinct virological and epidemiological properties.In addition,recombination among HBV genotypes increases the variability of HBV.This review summarises current knowledge of the epidemiology of genetic variability in hepadnaviruses and,due to rapid progress in the field,updates several recent reviews on HBV genotypes and subgenotypes.

HBV genotype characterization and distribution in patients with HBV-related liver diseases in Zhejiang Province, P. R. China: possible association of co-infection with disease prevalence and severity

BACKGROUND: There are 8 well-documented genotypes of hepatitis B virus (HBV) at this time point. Genotyping can be accomplished based on a partial sequence of hepatitis B virus (HBV) genome such as the pre-S or S gene. Several methods have been developed and used for HBV genotyping including direct sequencing, restriction fragment length polymorphism, line probe assay and enzyme-linked immunoassay. Recently, a novel, rapid and cost-effective genotyping method based on PCR amplification assay using type-specific primers that can identify all six major genotypes has been developed. This study was undertaken to characterise HBV genotypes and investigate the association between the prevalence of different genotypes and the severity of HBV-induced liver diseases. METHODS: Serum samples from carriers of HBV and patients with HBV-related liver diseases from Zhejiang Province were screened for viral serological markers using commercially available radioimmunoassay (RIA) and enzyme linked immunosorbent assay (ELISA) kits. Serum HBV DNA load was determined by real-time detection PCR. A type-specific primer based the nested-PCR method was employed in the HBV genotyping. The genotype results obtained were confirmed by direct sequencing of nested PCR amplicons of the pre-S region. Ten samples of each genotype (B and C) were sequenced. RESULTS: The survey on a cohort of 125 HBV carriers in and around Hangzhou City, Zhejiang Province showed the existence of HBV genotypes A (0.8%), B (48%), C (40.8%), D (0.8%), mixed B and C (9.6%) and an absence of E and F genotypes. Distribution of HBV genotypes in patients with liver diseases revealed a statistically insignificant higher prevalence of genotype B in mild chronic hepatitis (CH). Among the three genotypes B, C and mixed B/C infections 11 (73.3%), 3 (20%) and 1 (6.7%), (P< 0.05), respectively in subjects with moderate CH, genotype B was significantly predominant. The infection patterns for genotypes B, C and B/C mixed in (i) liver cirrhosis (LC) 4 (23.5%), 10 (58.8%) and3 (17.7%) and (ii) hepatocellular carcinoma (HCC) 2 (28.6%), 5(71.4%) and 0 (0.0%) respectively revealed a marked association of C genotype with liver disease; however, the association was statistically insignificant (P >0.05). Differences in positive rate of HBeAg for the three genotypes B, 16(30.8%), C, 27(51.9%), and mixed B/C, 9(17.3%) were significant (P < 0. 05 ) , with genotype C showing predominance. CONCLUSIONS : These findings show an interesting distribution of HBV A-D genotypes in Zhejiang Province. Furthermore, our results indicate a novel and markedly high prevalence of mixed B/C genotype infections in subjects with severe CH and LC, and a possible association of mixed B/C infections with the severity of liver diseases in this region of China's Mainland.

The relationship between HBV lamivudine resistance and HBV genotypes or basic core promoter mutations

OBJECTIVE: To investigate the relationship between HBV Iamivudine resistance and HBV genotypes or basic core promoter (BCP) mutations. METHODS: The common coated probes were synthesized according to the conserved regions of the preC gene of hepatitis B virus (HBV). Different colorized probes were chosen from the sequences of different genotypes of HBV (A to F), BCP and YMDD wild types and mutants, respectively. HBV DNA levels, HBV genotypes, BCP and YMDD resistants were analyzed by PCR microplate hybridization ELISA at the zero and 6th month after the patients were treated with lamivudine. RESULTS: HBV genotyping results showed that HBV types B, C, D accounted for about 30%, 36% and 23% patients respectively. Thirteen BCP mutations (type B in 1 patient, type C in 8 and type D in 4) were found before treatment with lamivudine. HBV DNA levels were lower than 100 pg/ml in 2 patients anti higher than 100 pg/ml in 11. 9.4% of the HBV patients (5/43; type C in 3 and type D in 2) showed YMDD resistants and 4 BCP mutations at the same time. CONCLUSION: Oral treatment of lamivudine decreases the level of serum HBV DNA. The appearance of HBV YMDD resistants is related to certain HBV genotypes, and most of them are BCP mutations.

T3098C and T53C Mutations of HBV Genotype C Is Associated with HBV Infection Progress

Objective To analyze the association between mutation（s） in preS region of HBV and hepatitis B disease progress in Chinese patients with genotype C chronic HBV infection. Methods Ninety-three patients with chronic genotype C HBV infection, including 24 asymptomatic carriers （ASC）, 26 patients with chronic hepatitis B （CHB）, 22 patients with liver cirrhosis （LC） and 21 HCC patients were investigated. Levels of HBV DNA, HBeAg, alanine aminotransferase （ALT）, asparate transaminase （AST） were measured. HBV preS region was analyzed by PCR direct sequencing. Results The prevalence of preS T3098C and T53C mutations ofgenotype C HBV was significantly higher in LC and HCC patients than ASC and CHB patients. The rate ofT3098C mutation in ASC, CHB, LC, and HCC patients were 0.00% （0/24）, 3.85% （1/26）, 9.09% （2/22）, and 30.77% （8/22）, respectively （P=0.0015）, while the rate of T53C mutation was I2.50% （3/24）, 3.85% （1/26）, 40.91% （9/22）, and 42.31% （11/26）, respectively （P=0.0012）. Conclusion The frequency of genotype C HBV preS T3098C and T53C mutations is associated with hepatitis B infection progression.

Hepatitis B virus genotypes and lamivudine resistance mutations in Jordan

AIM:To investigate and identify prevalent hepatitis B virus(HBV) genotypes and to explore lamivudine-resistant mutations among treated and untreated patients in Jordan.METHODS:A total of 107 cases with chronic hepatitis B were recruited from different medical centers in Jordan.Serological tests were preformed for all cases using a microparticle enzyme immunoassay.HBV Genotyping was performed for 70 cases using Line probe genotyping assay.The YMDD mutations were explored for 20 cases(4 were lamivudine naive) using the INNO-LiPA HBV DR assay.RESULTS:Genotype D was the only detected genotype.A total of 6 YMDD mutations were detected in 5 treated patients(31%) while one mutation was detected in the naive patients.Seventeen percent of cases were positive for HBeAg and had statistically significant higher levels of serum aminotransferases.CONCLUSION:HBV genotype D appears to be the only circulating type in Jordanian patients.The YMDD mutations were detected in 31% of lamivudine-treated cases with similar patterns to those found in the literature.We also found a relatively low prevalence of HBeAg expression among examined cases(17%).Awareness of these serologic,genotypic and resistance patterns might help in the formulation of management plans and for predicting clinical outcomes.Further larger scale studies are needed to confirm our results and to examine possible associations among clinical,serologic,and genetic patterns of HBV infections in Jordan.