Distribution of hepatitis B virus (HBV) genotypes among HBV carriers in the Cote d'Ivoire: complete genome sequence and phylogenetic relatedness of HBV genotype E

The characteristics of hepatitis B virus (HBV) genotype E are not well known because only a few studies have been carried out by complete genome analysis. The aim of this study was to elucidate the distribution of HBV genotypes in Cote d'Ivoire, and to clarify the genotype-related characteristics of genotype E. The distribution of HBV genotypes among 48 HBV carriers in Cote d'Ivoire was determined using serological and genetic methods. The characteristics of genotype E were evaluated by complete genome sequences, and further investigations of small S gene, basic core promoter (BCP) mutation, and precore mutation were undertaken. HBV genotype distribution among the 48 carriers was 6.3% for genotype A, 6.3% for genotype D, and 87.4% for genotype E. Complete genomes of two genotype E strains were sequenced, and found to have 98.2% to 99.2% homology at the nucleotide level when compared with genotype E strains reported previously. In 24 genotype E carriers, the precore mutation was detected in 75% of the patients without HBeAg, in contrast to only 25% of the patients with HBeAg (P < 0.05). All 24 strains have T at nucleotide 1858 in the precore region. In contrast, BCP double mutation was detected in 17% of the patients with HBeAg, and 33% of the patients without HBeAg. These results indicated as the following: (1) genotypes A, D, and E of HBV exist in Cote d'Ivoire and genotype E is the most prevalent; (2) genotype E spread with low genetic diversity over the complete genome in West Africa; (3) HBV precore and/or BCP double variants were common among the patients with genotype E infections.     

Variations in the functional domain of basal core promoter of hepatitis B virus among Eastern Indian patients with prevalence of genotypes A, C, and D among the same ethnic population

Mutations in the basal core promoter (BCP) and precore (PC) regions are associated with persistent and intermittently high hepatitis B virus (HBV) replication in several patients. The variability in the functional domains of BCP and PC region of HBV and their association with disease progression and clinical outcome were assessed in Eastern India, an unique region where three HBV genotypes, A, D, and C are prevalent among the same ethnic group. PCR amplification and direct sequencing of BCP and PC region was done on sera obtained from 130 HBsAg positive subjects with different clinical presentations. Associations of the apparent risk factors with clinical advancement were evaluated by statistical methods including multiple logistic regression analyses (MLR). HBV genotype A was present in 33.08%, C in 25.38%, and D in 41.54% cases. Genotypes A and C were associated with higher rate of T1762/A1764 mutations than the most predominant genotype D. HBeAg negative state was associated with considerably higher rate of C1753 mutation. T1762/A1764 along with C1753 was common among cirrhosis and T1762/A1764 without C1753 was frequent among chronic liver disease cases. No significant association was found between A1896 point mutation and clinical status. Multivariate analysis revealed that T1762/A1764 double mutation, HBV/A, age ≥25 years, C1753 and A1899 were critical factors for clinical advancement while age ≥25 years and C1753 as significant predictor for cirrhosis in comparison with chronic liver disease. In conclusion, the analysis of the BCP variability may help in monitoring the progression towards advanced liver disease in Eastern Indian patients.     

Basal core promoter, precore region mutations of HBV and their association with e antigen, genotype, and severity of liver disease in patients with chronic hepatitis B in India

Spontaneous mutations of hepatitis B virus (HBV) could influence the severity of liver disease. Since the basal core promoter (BCP) and the precore (Pc) regions are important for viral replication, these regions were examined for naturally occurring mutations and were correlated with the genotype, e antigen status, and severity of liver disease. In 82 patients with histologically confirmed chronic hepatitis B, the BCP and Pc regions were sequenced and aligned with known wild-type sequences. Sequence based HBV genotyping was done and HBV DNA was quantified. Thirty-three (40%) patients had decompensated chronic liver disease and the remaining patients had chronic hepatitis B. Forty-six (56%) patients were HBeAg positive. HBV genotype A was found in 28%, D in 65%, and B/C in 7.3%. The Pc G1896A mutation was more common in HBeAg-negative (33% vs. 2%, P < 0.01) patients and was genotype D specific. The Pc G1862T mutation was detected more often in HBeAg-positive than HBeAg-negative (37% vs. 11%, P < 0.01) patients and was genotype A specific (P < 0.01). BCP mutations at the 1,762/64 nucleotide positions were common in HBeAg negative than positive (36% vs. 13%, P < 0.05) and were equally common in different genotypes. TA 1-3 region mutations of the BCP were significantly higher in HBeAg-negative as compared to HBeAg-positive patients (78% vs. 26%, P < 0.01). BCP mutations had significantly higher HBV DNA levels. It is concluded that Pc G1862T mutant is Genotype A-specific but is not always associated with e antigen. The TA 1-3 rich mutations of BCP region are also associated with the absence of e antigen in Indian patients.     

Molecular epidemiological study of hepatitis B virus infection in two different ethnic populations from the Solomon Islands

The Solomon Islands is a multi-ethnic nation with a high rate of hepatitis B virus (HBV) infection. The prevalence relative to ethnicity was examined in relation to HBV infection, genotypes, and mutations. Asymptomatic populations (n = 564, 308 Melanesian and 118 Micronesian) from the Western Province were enrolled. Positive samples for Hepatitis B surface antigen (HBsAg) were examined for serological status, genotyping, viral load, and mutations of the basic core promoter (BCP) and pre-core (Pre-C) regions. The positive rate for HBsAg was 21.5%. The major Melanesian genotype was C (HBV/C), whereas the major Micronesian genotype was D (HBV/D). The prevalence of Hepatitis B e antigen (HBeAg) in serum was lower in carriers of HBV/D than of HBV/C. While the prevalence of the BCP mutation (T(1762)A(1764)) tended to be higher in HBV/C, that of the Pre-C mutation (T(1846)) was significantly higher in HBV/D (P < 0.0001). Genetic distance and phylogenetic analyses based on complete genome sequences were also carried out for two strains of HBV/C and two strains of HBV/D, and the findings were compared with those in the DDBJ/EMBL/GenBank database. The full-length sequence revealed that strains from the Solomon Islands were classified into subgenotype C3 (HBV/C3) and D4 (HBV/D4), and that the HBV/D strains were related closely to those from Papua New Guinea. HBV infection in the Solomon Islands is hyperendemic, and the genotype is ethnicity-specific. HBeAg appears to clear from the serum in young adulthood in HBV/D infection, which may be influenced by genotype-dependent features in relation to viral mutations.     

Prevalence of basal core promoter and precore mutations in Chinese chronic hepatitis B patients and correlation with serum HBeAG titers

The A1762T and G1764A mutations in the basal core promoter (BCP) region and the G1896A mutation in the precore (PC) region of hepatitis B virus (HBV) genome are found commonly in HBeAg‐negative patients. Experiments in vitro suggest that BCP and PC mutation reduce and abolish HBeAg expression, respectively. In the present study, the prevalence of the BCP and PC mutations were determined in 207 patients with HBeAg positive chronic hepatitis B from China and correlated with the titers of serum HBeAg. None of the patients received antiviral therapy. The HBV genotype was determined by direct sequencing of the HBsAg gene. The BCP and PC mutations were detected by the polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) and confirmed by DNA sequencing. The HBeAg titer was measured by the microparticle enzyme immunoassay. Fifty‐one of the 207 patients (24.6%) were infected with genotype B and the remainder with genotype C. The BCP mutations were detected in 103 patients (50%) while the PC mutation was present in 43 (20.8%). Thirteen patients (6.3%) harbored both BCP and PC mutations. No significant difference in the titers of HBeAg was found between patients infected with the two HBV genotypes, but the presence of either the BCP or PC mutation was associated with reduced HBeAg titer (P < 0.05). The presence of both the BCP and PC mutations was accompanied by even lower HBeAg titer (P < 0.05). These findings confirm that in patients with HBeAg, the BCP and PC mutations reduced the expression of HBeAg. J. Med. Virol. 81:807–814, 2009. © 2009 Wiley‐Liss, Inc.     

广西乙型肝炎病毒基因分型及其临床意义的研究

目的 了解广西乙型肝炎病毒(HBV)基因型流行情况及其临床意义。方法 用套式PCR扩增检测广西南部和北部[桂南和桂北]的各型乙型肝炎患者和慢性无症状HBV携带者共161份血清HBV DNA，阳性者用限制性片段长度多态性(RFLP)方法、直接测序法或克隆测序法进行基因分型。结果 广西HBV各种基因型分布比例：基因型A占3．7％，基因型B 21．7％，基因型C 72．7％、基因型D 1．2％；未发现基因型E、F、G和H。基因型C在慢性肝炎、肝硬化和原发性肝癌患者组中流行呈增加趋势，基因型B的流行与基因型C比较呈相反趋势(主要在慢性无症状HBV携带者和急性肝炎流行率相对较高)；基因型C组的HBeAg阳性率显著高于基因型B组，而基因型C组抗—HBe阳性率显著低于基因型B组。在基因型C组的肝脏损伤(ALT)比基因型A和B组更为严重；而在慢性无症状HBV携带者组中，基因型C在桂南的流行率显著高于桂北，基因型B的情况则相反。结论 ①广西主要流行的HBV主要为基因型B和C，桂南主要为HBV基因型C，桂北则主要为HBV基因型B，提示广西HBV基因型由于其流行分布的不同与广西肝癌发病率桂南高于桂北有关。②基因型C与较严重的肝脏疾病如肝癌的发生有关。③首次发现广西的急性肝炎、慢性肝炎存在少量的HBV基因型A型、D型和B C的混合型的流行。     

Genotypes and phylogenetic characterization of hepatitis B and delta viruses in Egypt

Hepatitis B virus (HBV) and hepatitis D virus (HDV) sequences among HBV carriers from Egypt have not been evaluated sufficiently. The genotypes of HBV isolated from 105 serum samples from Egyptian carriers were determined. Four complete genomes and 11 entire preS1/S2/S genes were sequenced and evaluated. All serum samples were classified into HBV genotype D using serologic and genetic methods. The length of four complete nucleotide sequences was 3,182 bp. In all 15 samples, the common 33 nucleotides (11 amino acids) deletions in the preS1 region specific for HBV genotype D were observed. In the phylogenetic analysis based on the complete nucleotide sequences, all samples were clustered with the HBV isolates reported from previously Western and Mediterranean countries with nucleotide homology ranging from 96.0-98.0%. Of 75 HBsAg positive samples, anti-HDV was found in 15 (20%), and HDV RNA was detected in 9 of 15 (60%). The proportion of the patients with liver disease was higher in HBV carriers of anti-HDV positive with HDV RNA than in HBV carriers of anti-HDV positive without HDV RNA (P < 0.05). In the phylogenetic analysis based on the sequences in nucleotide position 853-1267 of HDV, nine samples were classified into HDV genotype I with the nucleotide homology ranging from 88.3-92.1% (mean; 90.5%) and clustered with HDV strains reported previously from Ethiopia, Somalia, Egypt, and Lebanon. These results indicate that HBV genotype D and HDV genotype I are most prevalent in Egypt, and HDV co-infection in HBV carriers is related to severity of liver disease.     

乙肝病毒基因型及病毒变异对慢性肝病进展的影响

目的进一步研究HBV基因型及病毒变异与慢性肝病进展的关系。方法用聚合酶链式反应-限制性片段长度多态性（PCR-RFLP）以及部分PCR产物测序的方法对401例慢性HBV感染者，包括112例HCC患者（HCC组）。129例无症状携带者（ASC组），70例肝硬化患者（LC组）和90例慢性肝炎患者（CH组）进行HBV基因分型以及BCP和PC变异检测。结果401例慢性HBV感染者中181例发生B基因型感染，220例发生C型感染。HCC组中C型分布高于其他3个疾病组；C基因型感染者BCP变异多于B基因型；B基因型感染者PC变异多于C基因型：同时BCP变异发生率随着病程进展而递增：在ASC组、CH组、LC组和HCC组里的BCP变异阳性率分别为22．4％、35．0％、50．0％、74．1％。C1与C2亚型相比，C1有较高BCP变异阳性率，而C2有较高PC变异发生率。结论BCP变异与肝病进程存在依从关系，因此BCP变异的检测对慢性HBV感染的疾病进展和临床结局的评估有重要意义。     

Analysis of the complete hepatitis B virus genome in patients with genotype C chronic hepatitis in relation to HBeAg and anti-HBe

To investigate the relationship between viral factors and the development of chronic hepatitis B, the entire hepatitis B virus (HBV) genome of chronic carriers at different disease stages were analyzed. Eighty genotype C HBV carriers including 12 hepatitis B e antigen (HBeAg) positive asymptomatic carriers (Group A), 49 HBeAg positive patients with chronic liver diseases (Group B) and 19 anti-HBe positive patients with chronic liver diseases (Group C) were studied. HBV nucleic acid from serum samples was sequenced directly and compared with GenBank reference sequences HBV X01587 and M12906. On phylogenetic analysis, 76 cases were genotype C2. Of the 76 genotype C2 cases, the nucleotide and amino acid substitution rates in the precore/core region were significantly higher in Groups B and C than in Group A, also in Group C than in Group B. The nucleotide substitution rates in the full genome and the core promoter region were significantly higher in Group C than in Group A, also in group C than in Group B. The nucleotide and amino acid substitution rates in the X region were significantly higher in Group C than in Group A. The amino acid substitution rate in the pre-S2 region was significantly higher in Group C than in Group B. Deletion mutations were found mainly in Groups B and C. This whole genome analysis of HBV chronic carriers suggested that the nucleotide substitutions and deletions in HBV were closely associated with the pathogenesis of chronic HBV infection.     

Characteristics of core promoter and precore stop codon mutants of hepatitis B virus in Vietnam

In Asia, genotypes B and C are the most common genotypes of hepatitis B virus (HBV); and genotype C causes more severe liver disease. Core promoter/precore (CP/PC) mutants, known to be linked to these genotypes, could have an impact on the progression and severity of liver disease. Sera of 115 patients, including 39 acute and 76 chronic Vietnamese HBV infected patients, were tested for their liver profile, HBeAg, HBV genotypes, and HBV DNA level. Fragments of 282 nucleotides covering CP/PC were amplified, sequenced, and analysed. In the acute group, CP/PC mutants accounted for 38.4 and 25.6%, respectively. Genotype B was found to be predominant (74.3%, P < 0.05) and linked to the PC mutant (A1896) (P < 0.05). In the chronic group, CP/PC mutants accounted for 61.7 and 32.8%. CP mutants, especially the T1762/A1764 double mutant, were found to correlate with genotype C (81%, P < 0.001), liver cirrhosis, and hepatocellular carcinoma (P < 0.05). Therefore, genotype C in Vietnam, which carried high rate of C-1858 (70%), could play an important role in causing severe chronic liver disease.     

沈阳地区乙型肝炎病毒基因型分子流行病学研究

目的 研究沈阳地区乙型肝炎病毒基因型分布和特点。方法 应用半巢式聚合酶链反应（PCR）扩增乙型肝炎病毒P基因，将PCR产物应用ABI377自动测序仪直接做核苷酸序列分析，并用DNA STAR软件进行种系发生分析及基因型鉴定。结果 HBV DNA标准株P基因片段可进行基因分型。在沈阳地区慢性HBV感染者中可检出基因型B、C和D，检出率分别为22％、50％和28％，基因型C分布与基因型B、D的差异有统计学意义，在慢性乙型肝炎患者和慢性HBV携带者间各基因型间分布比较中差异无统计学意义。结论 通过测定HBV DNAP基因序列片段可进行HBV DNA基因分型。沈阳地区乙型肝炎病毒基因型有基因型B、C和D型，其中基因型C为优势基因型。     

Age-specific prevalence and significance of hepatitis B e antigen and antibody in chronic hepatitis B virus infection in Taiwan: a comparison among asymptomatic carriers, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma

The age-specific prevalence of hepatitis B e antigen (HBeAg) and its antibody (anti-HBe) were studied by radioimmunoassay, and compared in a large series of patients with chronic hepatitis B virus (HBV) infection, including 268 asymptomatic carriers, 389 chronic hepatitis, 114 liver cirrhosis, and 278 hepatocellular carcinoma (HCC). The prevalence of HBeAg/anti-HBe in asymptomatic carriers and patients with chronic hepatitis correlated closely with age as HBeAg prevalence decreased and anti-HBe prevalence increased with increasing age (P less than 0.0005), and is probably due to high infection rate at young age in Taiwan. The prevalence of HBeAg in patients with both cirrhosis and HCC are much significantly lower and had no correlation with age. Two peaks of age-specific prevalence of HBeAg and anti-HBe were observed in patients with HCC, implicating two patterns of HBV infection in these patients. The difference in the prevalence of HBeAg and anti-HBe might indicate that asymptomatic carriers, chronic hepatitis, liver cirrhosis, and HCC are sequential sequelae of HBV infection.     

Genotype and variations in core promoter and pre-core regions are related to progression of disease in HBV-infected patients from Northern Vietnam

Vietnam is one of the countries with a high rate of hepatitis B virus (HBV) infection, but there are only a few reports about relation of HBV genotypes and mutations to clinical course in Northern Vietnam. The characteristics of HBV and its relationship to clinical outcome in patients from Northern Vietnam were analyzed. Serum samples were collected from 183 HBV-infected Vietnamese patients. They were clinically categorized into 4 groups: hepatocellular carcinoma (HCC), liver cirrhosis (LC), chronic hepatitis (CH), and asymptomatic carriers (ASC). HBV serology, alpha-fetoprotein, HBV genotypes, HBV-DNA level and mutations in the core promoter and pre-core regions of HBV-DNA were examined. The majority of sera contained HBV genotype B (67.8%) and C (27.9%). The median age was matched between genotype B and C (38.2 vs. 42.9 years). The rates of HBeAg seroconversion and G1896A for genotype B were significantly higher than those for genotype C (P<0.05). Genotype C had a higher HBV-DNA level than genotype B. C1858 was frequent, especially in genotype C (62.7%). The most prevalent genotype in ASC and CH was genotype B. The presence of the mutation A1762T/G1764A correlated with disease progression. The triple mutation T1753C/A1762T/ G1764A was quite common and was more prevalent in LC and HCC than in CH and ASC. In Northern Vietnamese, HBV genotypes B and C were prevalent. Genotype C and mutations in the core promoter region were associated with progressive, severe liver diseases.     

贵州乙型肝炎病毒基因型分布及意义分析

目的调查贵州乙型肝炎病毒（HBV）基因型分布。方法选择贵阳、遵义、凯里、都匀慢性HBV感染者693例，其中无症状携带者（ASC）292例，慢性肝炎（CH）276例，肝硬化（LC）76例，肝细胞肝癌（HCC）49例。用S基因限制性片段长度多态性确定基因型，比较主要基因型的地区分布及其与临床的关系。结果693例中，B基因449例（64．79％），C型233例（33．62％），A型6例（0．87％）。D型5例（0．72％），未发现E、F基因型。B型的分布：凯里最高（96．40％），遵义、都匀其次（78．79％、76．19％），贵阳最低（53．66％）。C型的分布，贵阳（45．68％）高于都匀（23．80％）、遵义（13．13％）及凯里（3．96％），差异有统计学意义（P≤0．01）。与B型相比，C型感染者平均年龄大；ALT水平高；HBeAg阳性率低（P≤0．01）。除ASC组外，B、C2种基因型在CH、LC和HCC中的分布差异有统计学意义（P均〈0．01）。结论贵州存在A、B、C、D4种HBV基因型，但以B型为主，C型其次，A型、D型仅占很小比例。B、C基因型在贵州不同地区的分布有一定差异。与B型相比，C型感染者肝脏损害的程度较重。     

Genetic characteristics of hepatitis B virus genotypes as a factor for interferon-induced HBeAg clearance

The factors determining the responsiveness of different hepatitis B virus (HBV) genotypes to interferon treatment are not fully understood. We investigated the relationship between HBV genetic characteristics and the outcome of short (16 weeks) or prolonged (32 weeks) treatment with standard interferon-alpha in a prospectively followed cohort of 103 patients across Europe with HBeAg positive chronic hepatitis B. INNO-LiPA assays and HBV DNA sequencing were used to determine HBV genotypes, mutations in the core promoter and precore/core regions. After 16-weeks interferon-alpha treatment, the rate of HBeAg clearance was higher in genotype A versus all other genotypes (P = 0.014), or genotype D alone (P = 0.05). The HBV genome analysis revealed that: (i) after 16-weeks treatment, an HBV subpopulation with core promoter mutations emerged or increased (P < 0.001) only in genotype A; (ii) the core gene of genotype A has the lowest number of amino acid variations in comparison with genotypes B, C, or D. Logistic regression analysis identified genotype A as a positive predictor of short (16 weeks) treatment response (P = 0.001; odds ratio 6.19, 95 confidence interval 1.94-19.8), having a greater impact than baseline HBV DNA or alanine aminotransferase (ALT) levels. In contrast, the response to prolonged interferon-alpha treatment was not different between HBV genotypes. These results suggest that HBV genotype A responds earlier to interferon treatment than other genotypes, which is associated with its molecular characteristics. The optimal duration of interferon-based therapies in chronic hepatitis B may vary between different HBV genotypes.     

Clinical and molecular characterization of chronic hepatitis B in Albania: a country that is still highly endemic for HBV infection

Albania is a Mediterranean country, still with a high endemicity level of hepatitis B virus (HBV) infection. The chronic hepatitis B profile was characterized in this geographical area and used as a model to investigate the impact of endemicity level on the prevalence of the two major forms of chronic hepatitis B (HBeAg-positive and HBeAg-negative chronic hepatitis B). A cross-sectional study was conducted among 62 chronic hepatitis B patients consecutively admitted to the most important tertiary health care center for the diagnosis and treatment of liver disease in Albania. HBV-DNA was measured with an in-house PCR with a sensitivity of 10(4) copies/ml which uses primers encompassing the pre-core/core region. PCR products were subjected to sequencing and oligohybridization assay. Of the 62 patients, 75.8% had HBeAg-negative chronic hepatitis B. Genotype D was found in all 39 patients with detectable HBV viremia, for whom the heterogeneity of the region modulating HBeAg expression was assessed. Basic core promoter (BCP) mutations (1762/1764) were observed more often in anti-HBe-positive and older patients. In more than 90% of the HBeAg-negative chronic hepatitis B patients with detectable viremia, HBV that carries the G to A pre-core mutation at nucleotide 1896 was found. Patients with HBeAg-positive chronic hepatitis B were younger than HBeAg-negative chronic hepatitis B patients, and for symptomatic and asymptomatic liver-disease patients, the age of peak prevalence was at least 10 years lower for HBeAg-positive chronic hepatitis B patients. In conclusion, the virological and clinical pattern of chronic hepatitis B in Albania is similar to that observed in other Mediterranean countries; it seems to be independent of the HBV endemicity level.     

Hepatitis B genotypes, precore and core promoter mutants circulating in Tunisia

Hepatitis B virus (HBV) is characterized by genetic heterogeneity, including genotypes and mutations. Eight genotypes (A-H) have been identified throughout the world with a characteristic geographical distribution. Previous studies also suggest that the viral genotypes may correlate with differences in clinical features of the infection. Two types of mutations were particularly described, precore and basal promoter mutations; they may play an important role in the clinical outcome of HBV infection. The aim of this study was to investigate the prevalence of HBV genotypes and HBV variants in Tunisia, and their eventual association with severity of liver disease. Using a molecular method, HBV genotypes, precore and basal core promoter mutations were determined in 56 asymptomatic carriers and in 82 patients with histologically verified chronic liver disease and hepatocellular carcinoma (HCC). Three genotypes (D, A, and E) were detected; the prevalence was 80%, 8%, and 9%, respectively. No significant difference was observed for genotype D with clinical status. HBV mutants were detected in 93% of cases, precore mutants were the most prevalent. Basal core promoter mutants were observed in 61% of cases, they were frequently characterized by a double mutation in 1762 and 1764. Co-infection by these two types of mutants was detected in 50% of cases. Genotype D was the most prevalent HBV genotype in Tunisia. High circulation of precore and basal core promoter mutants are common in chronic hepatitis B infection in Tunisia.     

Hepatitis B virus genotype C prevails among chronic carriers of the virus in Korea

Hepatitis B virus (HBV) is one of the major causative agents of chronic liver diseases in Korea. HBV has been classified into 8 genotypes by a divergence of >8% in the entire genomic sequence, and have distinct geographic distributions. There are limited data on the relevance between HBV genotypes and clinical outcomes in Korea. To investigate the clinical feature relating to HBV genotype in Korea, a total 120 serum samples with HBsAg (65 from Seoul and 55 from the other city in Korea) were obtained from each 30 chronic HBV carriers with asymptomatic carrier (ASC), chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). HBV genotype was determined by either enzyme-linked immunosorbent assay (ELISA) using monoclonal antibodies against genotype-specific epitopes in the preS2-region or the direct sequencing of small S gene. HBV genotypes were determined in 105 (87.5%) of 120 samples. HBV genotype C was identified in all HBV carriers with ASC, CH, LC, and HCC. Genotypes A, B, D, E, F and G were not detected in any of them. Genotype C HBV prevails predominantly among chronic carriers of the virus in Korea, irrespective of their clinical stages of liver disease and geographic origin.     

慢性乙肝病毒感染者基因分型及其临床意义

目的探讨江苏南通地区慢性乙肝病毒（HBV）感染者基因型分布状况及其临床相关性。方法采用多对型特异性引物巢式PCR法对220例南通地区血清HBV标志物和HBV-DNA阳性者,包括乙肝表面抗原携带者（ASC）30例,慢性乙型肝炎（CHB）97例,重型肝炎（CSH）29例,肝炎后肝硬化（LC）34例,肝细胞癌（HCC）30例,进行HBV基因型检测。结果220例中B型59例（26.8%）,C型150例（68.2%）,BC混合型11例（5.0%）;C基因型在CSH组、LC组、HCC组中的比例显著高于ASC组（P〈0.05）。B型、C型、BC混合型HBeAg阳性率分别为49.2%、54.0%和36.4%,差异无统计学意义（P〉0.05）。C型和BC混合型HBV-DNA载量显著高于B型,差异有统计学意义（P〈0.05）。结论南通地区HBV基因型以B、C型为主,C型为优势基因型,并与重型肝炎、肝硬化、肝癌的发生及血清HBV-DNA高载量相关。