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。     

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.     

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。     

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。     

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。     

乙型肝炎病毒基因分型及临床应用研究

目的了解常州地区乙型肝炎病毒基因型分布特征,探讨其基因型与肝功能损伤、病毒复制水平及对拉米夫定疗效的关系. 方法采用巢式聚合酶链反应 (nest-PCR), 扩增乙型肝炎病毒S基因区, 用末端标记方法对PCR产物标记并直接测序, 测序结果和GenBank中登录的标准基因型序列相比较. 结果对该地区146份不同HBV感染者血清HBV DNA进行了基因分型,B型51份 (34.9%),C型95份(65.1%),未发现B、C以外其他基因型;丙氨酸转氨酶(ALT)水平分别为383.8±335.7IU和364.3±333.7 IU,(t=0.335,P>0.05)、HBV DNA含量分别为107.795±1.22和107.69±1.19拷贝/毫升(t=0.138,P>0.05)、HBeAg 阳性数分别为36/51和64/95,(χ2=0.159,P>0.05);104例慢性乙型肝炎中B型为43例、C型为61例,28例肝硬化和肝癌患者检出B型4例、C型24例,二组比较χ2=7.65,P<0.01;23例B基因型患者和45例C基因型患者接受48周以上拉米夫定治疗,48周后反跳者B型为18例,C型为14例,χ2=13.49,P<0.001.结论本地区HBV DNA基因型为B型和C型;二种基因型丙氨酸转氨酶水平、病毒复制水平和HBeAg表达水平差异均无显著性;C基因型与肝硬化和肝癌关系密切;拉米夫定对C基因型患者的疗效强于B型.     

原发性肝癌与乙型肝炎肝硬化HBV DNA水平、HBV基因型的比较研究

目的 比较原发性肝癌与乙型肝炎肝硬化患者的血清HBV DNA水平、HBV基因型差别。方法 对210例原发性肝癌（HCC）患者及220例乙型肝炎肝硬化（HBV LC）患者的血清HBVDNA水平及HBV基因型进行分析,比较病毒学和基因型差异。结果 210例HCC患者和220例HBV LC患者HBV DNA检测阳性率分别为84.3％（177/210）、94.5％（ 208/220）;HBV DNA定量为（5.06±1.01） log10拷贝/ml和（5.36±1.13）log10拷贝/ml,HBV LC患者均高于HCC患者（P＜0.01）;HCC组和HBV LC组均以C基因型为主,两组B,C基因型分布无明显差异。结论 HCC患者血清HBV DNA水平低于HBV LC患者。两组HBV基因型分布无明显差异,均以C基因型为多。     

Comparison of genotypes C and D of the hepatitis B virus in Japan: a clinical and molecular biological study

The genotype-related differences between genotype C and genotype D of the hepatitis B virus (HBV) remain unknown. The relationship was studied between the HBV genotypes and their clinical features, paying special attention to genotypes C and D. Serum samples from 413 HBV carriers were genotyped using an enzyme immunoassay (EIA) and by restriction fragment length polymorphism. The nucleotide sequences at the basic core promoter (BCP) and precore (PreC) regions were analysed by direct sequencing. The full genome sequences of three HBV genotype D cases were also examined. Almost all carriers with HBV genotype D were asymptomatic carriers (84.2%). Genotype D was not found in patients with liver cirrhosis and hepatocellular carcinoma. In contrast, carriers with genotype C had mainly chronic liver disease (63.2%; P<0.001). The ratio of hepatitis B e antigen (HBeAg)/anti-HBe was significantly higher in genotype C than in genotype D in the young age-matched group (P<0.01). The mutation at BCP (T1762, A1764) was significantly lower in genotype D than in genotype C among HBeAg-negative patients (P<0.05). The HBV full-genome sequences are very similar to certain HBV genotype D sequences from Europe. In conclusion, genotype C was associated with chronic liver disease, whereas genotype D was related to asymptomatic carriers with earlier HBeAg seroconversion. Thus, the outcome of chronic HBV infection may be different in persons infected with HBV genotypes C and D.     

The prevalence of hepatitis B virus preS deletions occurring naturally in Korean patients infected chronically with genotype C

Although Korea is one of the endemic areas for hepatitis B virus infection (HBV), the prevalence of deletions in HBV preS region occurring naturally have not been determined. In the present study, the prevalence of preS deletions was determined in terms of clinical state and HBeAg serostatus in 120 patients with different clinical features [59 HBeAg positive, 61 HBeAg negative; 38 asymptomatic carriers, 21 patients with chronic hepatitis, 21 patients with liver cirrhosis, 40 patients with hepatocellular carcinoma (HCC)]. A total of 37 strains (30.8%) harbored deletions in the preS region. Overall, the frequencies of preS deletions tended to increase gradually according to the degree of the clinical severity of liver disease. The prevalence of preS1 deletions in HCC patients tended to be higher than in patients with liver cirrhosis (32.5% vs. 19%). The prevalence of preS2 deletions in HBeAg negative patients was significantly higher than in HBeAg positive patients (23% vs. 6.8%). The type of deletion encountered most frequently was one disrupting the preS1 start codon [14/37 strains (37.8%)], which showed a very high prevalence in HCC patients (9/40, 22.5%; HCC vs. asymptomatic carriers, P=0.048). These results suggest that there might be the discrepancy between preS1 and preS2 mutations in the mechanism of enhancing the progression of chronic liver disease, especially the development of HCC and to maintain tolerance during the stage of immune tolerance. Specific deletion of the type disrupting preS1 start codon may play important roles in hepatocarcinogenesis, at least in Korean patients with chronic HBV infection.     

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。     

Clinical and virological characteristics of hepatitis B virus subgenotypes Ba, C1, and C2 in China

Hepatitis B virus (HBV) subgenotypes Ba, C1 (Cs), and C2 (Ce) are the most prevalent HBV variants in China. To investigate the virological characteristics of these subgenotypes and their clinical implications, we enrolled a cohort of 211 patients in the Guangdong Province of China, including 132 with chronic hepatitis B virus infection (CH), 32 with liver cirrhosis (LC), and 47 with hepatocellular carcinoma (HCC) according to clinical examination, liver function test, and ultrasonograph results. Overall, HBV Ba was found in 51.2% (108/211), HBV C1 in 33.6% (71/211), and HBV C2 in 15.2% (32/211) of the cases. The distribution of HBV genotype C was greater among patients in the LC and HCC groups than among patients in the CH group, while the distribution of HBV genotype B was greater among the CH patients than among the LC and HCC patients. No significant differences in clinical features were found among patients with HBV Ba, C1, and C2. Virologically, HBV C1 had the strongest association with the A1762T G1764A double mutation, while the mutation at position 1896 resulting in A (1896A) was uncommon. In contrast, HBV Ba had the highest frequency of 1896A but the lowest of A1762T G1764A, and HBV C2 had intermediate frequencies of these mutations. Mutations of 1653T and 1753V were specifically associated with HBV C2 and C1, respectively. Multivariate analyses showed that the 1653T, 1753V, and A1762T G1764A mutations and patient age significantly increased the risk of HCC development. In conclusion, HBV Ba, C1, and C2 have different mutation patterns in the enhancer II/core promoter/precore region. Therefore, genotyping and detecting the 1653T and 1753V mutations, in addition to the A1762T G1764A double mutation, might have important clinical implications as predictive risk factors for hepatocarcinogenesis.     

慢性乙型肝炎病毒基因型与临床病理相关性分析

目的 了解慢性乙型肝炎病毒基因型与临床及病理表现的相互关系.方法对92例慢性乙型肝炎患者进行HBV基因分型,并与其临床生化结果、病毒定量和肝组织病理进行相关性分析.结果 B基因型16例(17.4%),C基因型71例(77.2%),B+C混合型3例(3.2%),未分出型2例(2.2%),其中B和C基因型在丙氮酸转氨酶水平分别为(82.6±82)U/L和(84.7±71.5)U/L,病毒复制水平Log值分别为(5.8±1.4)和(5.9±1.5),C型患者中有8例病理诊断为肝炎肝硬化,但均无统计学意义.结论 B型和C型慢性肝炎患者在丙氨酸转氨酶、病毒复制、HBeAg表达水平及肝脏病理炎症和纤维化程度间差异无统计学意义.     

Molecular epidemiology of hepatitis B virus in Asia

Although safe and effective vaccines against hepatitis B virus (HBV) have been available for three decades, HBV infection remains the leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) worldwide, especially in Asian countries. HBV has been classified into at least 9 genotypes according to the molecular evolutionary analysis of the genomic DNA sequence and shown to have a distinct geographical distribution. Novel HBV genotypes/subgenotypes have been reported, especially from Southeast Asian countries. The clinical characteristics and therapeutic effectiveness of interferon (IFN) and nucleos(t)ide analogues vary among different HBV genotypes. Mutations at T1653C in subgenotype C2 from Japan and South Korea, C/A1753T and C1858T in subgenotype C1 from Vietnam, and C1638T and T1753V in subgenotype B3 from Indonesia were reported to be associated with advanced liver diseases including HCC. Genotype distribution in Japan has been changed by an increasing ratio of subgenotype A2 in chronic hepatitis B. While a large number of epidemiological and clinical studies have been reported from Asian countries, most of the studies were conducted in developed countries such as Taiwan, China, South Korea and Japan. In this review, the most recent publications on the geographical distribution of genetic variants of HBV and related issues such as disease progression and therapy in Asia are updated and summarized.     

应用扩增受阻突变检测系统（ARMS）检测HBV基因型

目的建立扩增受阻突变检测系统（ARMS）检测乙型肝炎病毒（HBV）基因型方法,并对慢性乙型肝炎（CHB）患者HBV基因型进行分析。方法通过对HBV全基因组序列比对分析,设计ARMS特异性引物和探针体系,建立检测HBVB和C基因型方法,对50例临床标本进行检测。结果50例临床样本中,B型的检出率为26％（13例）,C型为74％（37例）,其实验结果与测序结果完全一致。常州及周边地区乙型肝炎病毒C基因型HBV为优势株。C基因型患者A1762T／G1764A突变率为62％,明显高于B型。结论ARMS检测HBV基因型,快速、准确;常州及周边地区HBV基因型主要为B、C型,且C型携带A1762T／G1764A双突变率较高,与较为严重的肝病相关。     

秦皇岛市各型肝炎病毒感染的血清流行病学研究

对１９９２年至１９９５年在秦皇岛市各医院住院的３２６例肝病患者进行各型肝炎病毒感染的血流流行病学分析，表明在慢性肝炎、肝硬化和原当性肝细胞肝癌中未检出甲型肝炎病毒抗体、乙型肝炎病毒在ＣＨ、ＬＣ和ＨＣＣ的感染率分别为７７．７８％，８４．２１％和９４．２９％，而在急性肝炎中的感染率为２１．５９％。     

Increased hepatocarcinogenic potential of hepatitis B virus genotype A in Bantu-speaking sub-saharan Africans

Genotypes A, D, and E of the hepatitis B virus (HBV) circulate in southern Africa, with genotype A predominating. Their hepatocarcinogenic potential in Bantu-speaking sub-saharan Africans is, however, unknown. Using a case/control format, we investigated the hepatocarcinogenic potential of these genotypes and subgenotype A1 of genotype A, which accounts for the great majority of genotype A isolates. HBV isolates from 111 unselected Bantu-speaking sub-saharan Africans with hepatocellular carcinoma (HCC) and 111 matched asymptomatic chronic carriers, serving as controls, were genotyped using the method of [Lindh et al. (1997): J Infect Dis 175:1285-1293]. Subgenotypes of genotype A were determined using an in-house restriction fragment length polymorphism assay. Genotype A was present in 96 (86.5%) of patients with HCC and 76 (68.5%) of the carriers, giving a 4.5-fold (95% confidence limits: 1.86, 10.90) increased risk of HCC in carriers infected with genotype A compared with those infected with non-A genotypes. HCC patients infected with genotype A were significantly younger than those infected with non-A genotypes (P = 0.02). The distributions between these two groups according to sex, geographic background, and tribe were not significantly different. Subgenotype A1 was present in all of the 77 cancer patients and 69 of 70 carriers analyzed, yielding a relative risk of 4.21 (95% confidence limits: 1.73,10.23) of HCC in those infected with subgenotype A1 compared with those infected with non-A genotypes. Genotype A has a greater hepatocarcinogenic potential than non-A genotypes in Bantu-speaking sub-saharan Africans and this is entirely attributable to subgenotype A1.     

Association of serum soluble human leukocyte antigen-G levels with chronic hepatitis B virus infection

Human leukocyte antigen-G is involved in immunotolerogenic, inflammatory and carcinogenic process. This study investigated serum soluble HLA-G (sHLA-G) levels in patients with chronic hepatitis B virus (HBV) infection according to the infection phases and clinical diagnoses. The study included 223 patients with chronic HBV infection [phases: 38 immune-tolerant (IT), 83 immune clearance (IC), 30 non/low-replicative (LR) and 72 HBeAg negative hepatitis (ENH); diagnoses: 38 asymptomatic HBV carriers (ASC), 98 chronic hepatitis (CH), 46 cirrhosis (LC) and 41 hepatocellular carcinoma (HCC)], 62 HBV infection resolvers and 66 healthy controls. The sHLA-G levels in patients were elevated compared with resolvers and healthy controls (P < 0.001). According to phases, sHLA-G levels were higher in IC and ENH than in IT (P = 0.017 and P = 0.001, respectively). Serum sHLA-G levels were also higher in ENH than in LR (P = 0.008). According to diagnoses, sHLA-G levels in HCC were significantly increased compared with LC, CH and ASC (P = 0.010, P < 0.001 and P < 0.001, respectively). Serum sHLA-G levels were higher in CH than in ASC (P = 0.039). The sHLA-G levels in IC, ENH and CH were correlated with alanine aminotransferase levels (P = 0.011, P = 0.010 and P < 0.001, respectively). It is concluded that sHLA-G is involved in the pathogenesis of chronic HBV infection and correlates with infection phases and clinical diseases, suggesting the value in evaluating disease activity and defining clinical diagnosis.     

乙型肝炎病毒增强子I／X基因启动子变异与HBV慢性感染疾病谱的关系

目的探讨乙型肝炎病毒增强子I（HBVEnhI）／X基因启动子变异与乙型肝炎病毒慢性化感染疾病谱的关系。方法随机收集275例HBV感染者的血清标本,包括慢性乙型肝炎（CHB）100例,肝硬化（LC）74例,肝细胞癌（HCC）101例。以入选病例的基因型为分组,采用半巢式PCR的方法扩增HBVEnhI／X基因启动子并测序,测序结果与HBV参照序列比对,确定变异位点,使用x^2检验和多变量logistic回归进行数据分析。结果①HBV基因分型结果：HBVB基因型患者158例（61．48％）,包括CHB70例,LC36例,HCC52例;HBVC基因型患者117例（38．52％）,包括CHB30例,LC38例,HCC49例。②HBVB基因型A1123Y变异在LC组明显高于CHB组（30．56％vs．8．58％,x^2=8．533,P=0．005,A=4．693,95％CI[1．567～14．056]）,HCC组明显高于CHB组（28．85％vs．8．58％,x^2=8．607,P=0．003,OR=4．324,95％CI[1．544～12．109]）;A1317G变异在HCC组明显高于CHB组（30．77％VS．7．14％,x^2=11．687,P=0．001,A=5．778,95％CI[1．955—17．076]）。HBVC基因型T1323C变异在HCC组明显高于CHB组（30．61％vs．6．67％,x^2=6．318,P=0．012,A=6．176,95％CI[1．301-29．331]）。③多变量logistic回归分析发现A1317G（A=5．706,95％CI[1．770～18．837],P=0．004）和T1323C（A=5．810,95％CI[1．114～30．306],P=0．037）变异是HCC发生的独立危险因素。结论乙型肝炎病毒增强子I／X基因启动子突变与肝硬化、肝癌的发生有关,对变异位点的检测有助于预测肝硬化和肝癌的发生。     

慢性乙型肝炎患者病毒基因型分布及与临床关系

目的了解邯郸市乙肝病毒基因型分布情况，并探讨其与临床的关系。方法采用PCR—RFLP方法对邯郸108份HBV感染者的血清进行基因型分型，并结合转氨酶和HBV—DNA结果，分析乙肝病毒基因型的临床意义。结果邯郸市慢性乙肝人群感染的HBV主要以C基因型为主，占93．5％，B基因型占6、5％。不同性别感染基因型差异无统计学意义。肝生化指标ALT、AST、TB比较提示c基因型患者的肝脏炎症似乎比B型患者重，但差异无统计学意义。C基因型的患者血清HBeAg阳性率高于B基因型。C基因型的患者血清HBV—DNA略高于B基因型，但无统计学差异。结论邯郸市慢性乙肝人群感染的HBV主要以C基因型为主。C基因型患者血清HBeAg阳性率高于B基因型，C基因型患者与B基因型相比肝脏炎症较重，HBV—DNA略高，但差异无统计学意义。     

Preponderance of hepatitis B virus genotype B contributes to a better prognosis of chronic HBV infection in Okinawa,Japan

The present study was designed to examine the distribution of hepatitis B virus (HBV) genotypes among patients at various stages of chronic liver disease type B in Okinawa Prefecture, Japan, where the prevalence of hepatitis B surface antigen is the highest in Japan despite the lowest mortality rate from primary liver cancer. Serum samples from 227 HBV carriers were determined for HBV genotype by polymerase chain reaction (PCR)-restriction fragment length polymorphism. Five of 227 sera were negative for HBV DNA by nested PCR and were excluded from the genotype analysis. Genotype B was predominant in asymptomatic carriers (45/67, 67%), whereas genotype C was predominant in chronic liver disease: 49% (50/103) in patients with chronic hepatitis, 63% (20/32) in patients with cirrhosis, and 60% (12/20) in patients with hepatocellular carcinoma. The distribution of genotype B decreased with increasing liver disease severity. However, this tendency was seen among patients aged less than 50 years old, whereas the prevalence of genotype B was similar among carriers with various liver diseases who were older than age 50. In conclusion, HBV genotype B was prevalent and less frequent among patients with advanced liver disease, particularly in patients aged less than 50 years. These findings suggest that the preponderance of genotype B is responsible for the low mortality rate of primary liver cancer associated with HBV seen in Okinawa Prefecture, despite having the highest HBV carrier rate in Japanese.