HBV genotypes in India: do they influence disease severity?

Aims:  Association of HBV genotypes (especially A and D) with severity of liver disease is controversial. We studied the influence of HBV genotypes on liver disease severity among Indian patients.
Methods:  We selected 247 HBV infected patients (42 acute hepatitis, 87 carriers, 44 chronic hepatitis B [CHB], 35 liver cirrhosis [LC] and 40 hepatocellular carcinoma [HCC]). Genotyping of stored sera was performed using genotype-specific enzyme-linked immunosorbent assay (ELISA) and restriction fragment length polymorphism (RFLP). The distribution of genotypes in disease states of differing clinical, histological and biochemical severity were compared.
Results:  The most common genotype was D (162/237, 68.3%), followed by A (61, 25.7%) and C (14, 5.9%). The distribution of HBV genotypes between patients with acute hepatitis and CHB (carriers + CHB + LC + HCC), or between carriers and disease states (CHB + LC + HCC), or between mild chronic infection (carriers + CHB) and complications of chronic HBV infection (LC + HCC) was similar. Eighty-seven patients had liver biopsy; the median histological activity index (HAI) and fibrosis stage at baseline were similar between genotype groups (four [1–9] genotype A [ n  = 28]), three (2–4) genotype C ( n  = 4) and four (1–10) genotype D ( n  = 55); P  = 0.33 for HAI score; (0.5 [0–6] genotype A, 0.5 [0–4] genotype C and 1 [0–6] genotype D; P  = 0.92 for fibrosis stage). The response to therapy was similar between the genotypes.
Conclusion:  Clinical, histological severity and therapeutic responses are similar among patients with HBV genotypes A and D.     

湖北地区乙型肝炎病毒基因型分布与临床的相关性

目的 了解湖北地区乙型肝炎病毒(HBV)基因型的分布及其与临床的相关性。 方法 选择湖北地区HBV DNA阳性的慢性HBV感染者190例,其中乙型肝炎表面抗原(HBsAg)携带者52例、慢性乙型肝炎56例、重型肝炎32例、肝硬化22例、原发性肝癌28例,应用多对型特异性引物-聚合酶链反应检测HBV的基因型。 结果 多对HBV型特异性引物法可快速准确鉴定HBV的基因型。190份HBV DNA阳性血清标本中,B基因型140例(73.7％),C基因型42例(22.1％),BC混合型8例(4.2％),未发现A、D和E基因型;B基因型在重型肝炎和肝癌患者中占绝对优势,分别为87.5％和89.3％,显著高于HBsAg携带者的67.3％;B基因型患者血清丙氨酸氨基转移酶水平(253.1±306.7)U／L高于C基因型患者的(154.1±192.9)U／L,差异有统计学意义(P<0.05);除HBsAg携带者外的慢性HBV感染者中,B基因型患者血清抗-HBe阳性率50.5％(53／105)显著高于C基因型的18.5％(5／27),P<0.01。 结论 多对型特异性引物同时进行聚合酶链反应的基因分型方法可用于HBV基因型的流行病学调查;湖北地区存在HBV的B、C和BC混合基因型,B型为本地区的优势基因型并在严重肝病和肝癌中的比例较高,基因型的分布可能有较大的地区差异。     

烟台地区慢性乙型肝炎患者病毒基因型分布与临床特征分析

目的了解烟台地区慢性乙型肝炎患者HBV基因型的分布及其与临床的关系。方法采用实时荧光定量PCR法,检测362例慢性乙型肝炎患者HBV基因型,并分析不同基因型之间性别、年龄及ALT、HBV DNA定量、HBeAg状态的差异。结果 362例标本中,B基因型7例（1.9%）,C基因型344例（95.0%）,非B非C型11例（3.0%）。B基因型患者年龄（36.29±17.54）岁,C基因型患者年龄（37±10.64）岁,非B非C型患者年龄（45.09±10.67）岁,P=0.050;两两比较提示C基因型患者年龄较非B非C型患者年龄低,P=0.015,余差异无统计学意义。不同基因型之间性别及ALT、HBV DNA定量、HBeAg状态的差异均无统计学意义。结论烟台地区慢性乙型肝炎患者HBV以基因C型为主,存在少量基因B型及非B非C型。不同基因型患者年龄可能存在差异。     

135例乙型肝炎病毒感染者基因分型及其临床分布

目的研究乙型肝炎病毒（HBV）感染者中HBV基因分型及其临床分布情况。方法应用基因型和亚型特异性引物聚合酶链反应（PCR）法，对鲁西地区135例HBV感染者血清进行HBV基因型及亚型分型。结果未分型11例，已分型124例。其中C型111例（C2基因亚型87例、非C1／C2亚型24例）；B型11例，其中Ba型8例、Bj型3例；B／C混合型2例均为BaC2亚型混和感染。在肝硬化和重度慢性乙型肝炎中C型所占比例较高，分别为100％、88％；无症状携带者中B型所占比例较高为8．51％；HBV基因型分型与性别无关。结论鲁西地区HBV感染者以C基因型为主，其中C2亚型占优势。     

Hepatitis B virus genotypes and G1896A precore mutation in 486 Spanish patients with acute and chronic HBV infection

This study aims to determine the prevalence of hepatitis B virus (HBV) genotypes (A-F) and their association with the G1896A precore mutation in 486 patients positive for HBV surface antigen. Genotypes were determined by RFLP and precore mutation by real-time PCR. Genotypes D (48.1%) and A (39.5%) were the most common, followed by F (4.1%) and B, C and E (<1%). The A to D ratio (A:D) was 1.4 in HBeAg+ chronic hepatitis B (CHB), 0.6 in HBeAg- CHB and 1.4 in HBeAg- inactive carriers. Distribution of these genotypes was different between HBeAg+ CHB and HBeAg- CHB (P = 0.02), and between HBeAg- CHB and HBeAg- inactive carriers (P = 0.009). Genotype A was the most prevalent in HBeAg+ CHB with elevated alanine aminotransferase (ALT) (68.6%) and genotype D in HBeAg+ CHB with fluctuating ALT (60.7%). There was a difference in genotype prevalence between chronic and acute infection (P = 0.03). The precore mutant correlated with high levels of HBV-DNA in genotype d HBeAg- CHB. Genotype D is not as highly prevalent in Spanish patients as would be expected in a Mediterranean area. The unequal prevalence of genotypes between acute and chronic infection suggests that genotype A is associated with a higher tendency to cause chronic infection.     

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.     

Clinical relevance of hepatitis B virus genotype in children with chronic infection and hepatocellular carcinoma

BACKGROUND & AIMS: The aim of this study was to investigate the influence of hepatitis B virus (HBV) genotypes on the clinical outcome of chronic childhood HBV infection and hepatocellular carcinoma (HCC). METHODS: A total of 460 HBV carrier children were followed-up for 15 years and 26 children with HBV-related HCC were recruited. HBV genotyping was examined at enrollment and the latest follow-up of these carrier children and at diagnosis in HCC children. Viral load was checked at enrollment for the carrier children. These carriers were grouped based on their initial hepatitis B e antigen (HBeAg) and antibody to hepatitis B e antigen (anti-HBe) status. The HBeAg positive (+) group was divided further into an HBeAg(+/+) group and HBeAg(+/-) group, depending on whether spontaneous HBeAg seroconversion occurred during the follow-up period. RESULTS: Genotype B constituted 73%, 86%, and 76% in the HBeAg(+/+), HBeAg(+/-), and anti-HBe(+) groups, respectively. Genotype C was found in 27%, 8%, and 6% in the HBeAg(+/+), HBeAg(+/-), and anti-HBe(+) group, respectively. Genotype C carriers were more prevalent in the HBeAg(+/+) group than the other 2 groups (P = .01), and had a delayed HBeAg seroconversion compared with the genotype B carriers (P < .001). Changes of genotype during the follow-up period were rare (2.8%). In those with HCC, genotype B was also the major type (74%). There was no difference in the baseline viral load between genotypes B and C. CONCLUSIONS: Although HBV genotype B dominates in children with chronic HBV infection and HCC in Taiwan, genotype C delays HBeAg seroconversion in pediatric chronic HBV infection.     

Multicentre study of hepatitis B virus genotypes in France: correlation with liver fibrosis and hepatitis B e antigen status

The clinical significance of hepatitis B virus (HBV) genotypes is still under debate. The aims of this study were to assess the distribution of HBV genotypes in France and to identify the associations between HBV genotypes and patient demographics, severity of liver disease and HBeAg status in patients referred to tertiary care centres. This was a French, multicentre, retrospective study on 262 patients with chronic HBV infection. HBV genotypes were determined using INNO-LiPA. Liver fibrosis damage was evaluated by histological analysis of biopsy samples. Patients were mainly male (74%), of Caucasian (65%), Asian (17%) or African (18%) ethnicity and 36% were HBeAg positive. All A-G genotypes were found, the most frequent being genotypes D (27%) and A (24%), followed by E (13%) and C (12%), and B (7%). Mixed genotypes were detected in 16% of the cases. Genotype A was associated with sexual contact (P < 0.001) and genotype D with transfusion (P < 0.001) and HBe antibody positivity (P = 0.03).The distribution of HBV genotypes differed with regard to the ethnicity, and may reflect migration patterns. Genotypes A and D were the most frequent in France. Genotype A was associated with HBeAg positivity and genotype D with HBe antibody positivity. In our European patients, we find no clear association between a given HBV genotype and liver disease severity.     

Therapeutic implications of hepatitis B virus genotypes.

BACKGROUND/AIMS: Hepatitis B virus (HBV) is a global health problem. In addition to the implementation of universal hepatitis B vaccination, effective and individualized treatment of chronic hepatitis B to prevent progression into end-stage liver diseases and hepatocellular carcinoma is still needed. HBV has been designated eight genotypes (A-H) based on genome sequence divergence. The epidemiology of HBV genotypes and their implications on the responses to antiviral therapy have become increasingly recognized in both Asian and Western countries. METHODS: Published data are thus reviewed. Results: Each genotype has its distinct geographical and ethnic distribution. Genotypes A and D occur frequently in Africa, Europe, and India, while genotypes B and C are prevalent in Asia. Genotype E is restricted to West Africa, and genotype F is found in Central and South America. The distribution of genotypes G and H is less clear. Accumulating evidence indicates a better sustained response to conventional interferon in patients with genotype B than those with C, and in patients with genotype A than those with D. In contrast, conflicting results exist regarding the response to pegylated interferon. On the other hand, the therapeutic responses to nucleoside/nucleotide analogues are comparable among patients with different HBV genotypes. The impact of HBV subgenotypes, mixed genotype infections, and recombinants of different genotypes on the response to antiviral treatments awaits further examinations. CONCLUSION: Remarkable clinical and pathogenic differences do exist among HBV genotypes; however, researches on molecular and virologic mechanisms underlying the clinical phenotypes of different HBV genotypes are urgently needed.     

蚌埠地区乙型肝炎病毒基因分型及临床意义

目的 了解蚌埠地区乙型肝炎患者的病毒(HBV)基因型分布情况,并探讨其临床意义。方法 选择在我院就诊的乙型肝炎患者268例,采用荧光定量PCR测定乙肝患者的病毒载量并进行基因分型,同时分析基因型与患者年龄及HBeAg的关系。结果 268份血清标本中有202株为C基因型,占75.37%(202/268),46株为B基因型,20株为B+C型;C基因型的病毒载量和HBeAg阳性率明显高于其他基因型,B基因型感染者的年龄相对较轻。结论 蚌埠地区的乙型肝炎患者基因型以C型为主,B基因型次之,基因型与乙肝患者HBeAg阳性率、年龄等临床指标有一定的相关性。     

Impact of the hepatitis B virus genotype and genotype mixtures on the course of liver disease in Vietnam

Eight genotypes (A-H) of hepatitis B virus (HBV) have been identified. However, the impact of different genotypes on the clinical course of hepatitis B infection remains controversial. We investigated the frequency and clinical outcome of HBV genotypes and genotype mixtures in HBV-infected patients from Vietnam, Europe, and Africa. In addition, we analyzed the effects of genotype mixtures on alterations in in vitro viral replication. In Asian patients, seven genotypes (A-G) were detected, with A, C, and D predominating. In European and African patients, only genotypes A, C, D, and G were identified. Genotype mixtures were more frequently encountered in African than in Asian (P = .01) and European patients (P = .06). In Asian patients, the predominant genotype mixtures included A/C and C/D, compared to C/D in European and A/D in African patients. Genotype A was more frequent in asymptomatic compared with symptomatic patients (P < .0001). Genotype C was more frequent in patients with hepatocellular carcinoma (HCC; P = .02). Genotype mixtures were more frequently encountered in patients with chronic hepatitis in comparison to patients with acute hepatitis B (P = .015), liver cirrhosis (P = .013), and HCC (P = .002). Viral loads in patients infected with genotype mixtures were significantly higher in comparison to patients with a single genotype (P = .019). Genotype mixtures were also associated with increased in vitro HBV replication. In conclusion, infection with mixtures of HBV genotypes is frequent in Asia, Africa, and Europe. Differences in the replication-phenotype of single genotypes compared to genotype-mixtures suggest that co-infection with different HBV-genotypes is associated with altered pathogenesis and clinical outcome.     

乙型肝炎病毒基因型与病毒复制的关系

检测慢性乙型肝炎患者血清乙型肝炎病毒(HBV)基因型和病毒载量(HBV-DNA定量),探讨它们之间的关系。用微板核酸杂交-ELISA方法对HBV进行基因分型,用PCR荧光定量检测血清HBV-DNA水平,共318例。检测到HBV B型111例(35％);C型128(40％);混合型(B+C,C+D,B+C+D)45例(14％);D型2例;F型2例;未分型30例(9.4％);没有发现A、E型。结果发现,C型和混合型HBV的血清DNA水平高于B型(1.14×107vs2.2×107vsl.60×106拷贝/ml,P<0.05);而混合型HBV的血清DNA水平与C型无差别(P=0.127)。研究提示,我国HBV以B,C两基因型为主,HBV基因型可能是影响HBV复制的重要因素之一。     

肝癌患者血清中乙型肝炎病毒基因分型及临床意义

目的:探讨血清中乙型肝炎病毒(HBV)基因型及HBV DNA水平与肝细胞癌的关系。方法:应用巢式聚合酶链反应扩增乙型肝炎病毒与基因,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,应用荧光定量PCR法检测HBV DNA水平。对61例肝癌、65例慢性乙型肝炎、10例乙型肝炎病毒携带者进行了检测。结果:136例中B基因型59例(43.4%)、C基因型77例(56.6%),随着病情加重,C基因型比例逐渐增高;不同基因型HBV感染的肝癌患者间HBV DNA水平差异有显著意义,P<0.05;在慢性乙型肝炎患者中,HBV DNA水平差异无显著性意义。结论:本地区乙型肝炎病毒以B、C基因型为主,乙型肝炎病毒C基因型及高水平的HBV DNA感染与肝癌的发生相关。     

新疆维吾尔族慢性乙型肝炎患者HBV基因型分布及其特点

目的探讨新疆维吾尔族慢性乙型肝炎患者HBV基因型分布及其特点。方法采用型特异性引物巢式PCR法对127例维吾尔族慢性乙型肝炎患者进行基因分型,并测序验证。结果基因D型占39．4%（50/127）,基因B型占22．0%（28/127）,基因C型占16．5%（21/127）,基因BD混合型占9．4%（12/127）,基因CD混合型占8．7%（11/127）,基因BCD混合型占3．9%（5/127）; HBeAg阳性与HBeAg阴性的维吾尔族慢性乙型肝炎患者基因型分布,差异无统计学意义（x^2= 6．033,P＞0．05）;不同年龄维吾尔族慢性乙型肝炎患者HBV基因型分布差异无统计学意义（x^2= 3．137,P＞0．05）;不同性别维吾尔族慢性乙型肝炎患者HBV基因型分布差异亦无统计学意义（x^2= 8．058,P＞0．05）。结论新疆维吾尔族慢性乙型肝炎患者HBV基因型以D型占优势,其次可见B、C型及BD、CD、BCD混合型。同一疾病谱的慢性HBV感染者基因型分布可能与宿主HBeAg状态、年龄、性别无明显关系。     

Does hepatitis B virus (HBV) genotype influence the clinical outcome of HBV infection?

Between 5 and 10% of adults infected with the hepatitis B virus (HBV) develop a chronic infection lasting longer than 6 months, which may lead to advanced liver disease. HBV can be classified into six genotypic families: A, B, C, D, E and F, but only genotypes A and D are significantly represented in western Europe, where they account for some 90% of cases of infection with HBV. In the present study, we investigated a possible association between HBV genotype A or D and clinical outcome of the infection. We compared the prevalence of these genotypes in a group of patients with chronic active hepatitis to that of a group with acute resolving hepatitis. In patients with chronic active hepatitis, genotype A was found in 28 of 35 patients and genotype D in only four. The remaining three patients were infected with genotype non-A, non-D. In contrast, genotype D was found in 24 of 30 patients with acute hepatitis, whilst genotype A was found in only three patients of this group. Three were infected with genotype non-A, non-D. Our results show a clear association between genotype A and chronic outcome (Ficher's exact test: two-sided P -value, P < 0.0001). They suggest that HBV genotypes may play a role in the virus–host relationship. Possible mechanisms for such a role are discussed.     

Hepatitis B virus genotypes in chronic liver disease patients from New Delhi, India

INTRODUCTION Approximately, two billion people in the world have been infected by Hepatitis B virus (HBV), 350 million of whom are chronic carriers of the virus[1,2]. Worldwide HBV isolates have been classified into eight genotypes: A, B, C, D, E, F, G an…     

血清皮质醇水平与重型肝炎预后的相关性

目的探讨重型肝炎患者血清皮质醇水平与预后的关系,为临床判断预后及探讨治疗提供理论依据。方法对临床诊断的重型肝炎患者进行血清皮质醇、TNFα含量检测;比较重型肝炎、急性肝炎和慢性肝炎患者血清皮质醇水平的差异以及重型肝炎患者中死亡组和存活组的差异;检测血清皮质醇含量与TNFα含量的相关性。结果重型肝炎患者血清皮质醇水平明显低于急、慢性肝炎患者,尤以死亡组患者更为明显;血清皮质醇水平与TNFα含量呈显著负相关。结论重型肝炎患者存在肾上腺皮质功能不全,且与患者预后密切相关。     

Hepatitis B viral genotypes: clinical relevance and molecular characteristics

Hepatitis B virus (HBV) infection is a global health problem and the clinical outcome of chronic HBV infection depends on the frequency and severity of hepatitis flares in the immune clearance phase. Currently, four subtypes and seven genotypes of HBV are identified and most have specific geographic distributions. The impact of HBV genotypes on the clinical outcome of chronic HBV infection has been partially clarified. In Taiwan, genotype C is associated with more severe liver disease and genotype B is associated with the development of hepatocellular carcinoma (HCC) in young non-cirrhotic patients. In contrast, genotype B has a relatively good prognosis in Japan and China and is rarely associated with the development of HCC. Similarly, genotype D is associated with more severe liver disease than genotype A in India and may predict occurrence of HCC in young patients. Although superinfection of HBV on top of hepatitis B carriers occurs in Taiwan, it is rarely associated with acute exacerbations. As to the response to antiviral treatment, genotypes C and D are associated with a lower response rate to interferon therapy compared with genotypes B and A. In addition, the subtype adw is reported to be associated with a higher risk of lamivudine resistance than ayw. In HBV subtype adw-infected HCC patients, genotype B responds better to embolization therapy and has a lower rate of HCC recurrence than genotype C. In summary, pathogenic and therapeutic differences do exist among HBV genotypes and determining the genotype in patients with chronic HBV infection would help gain further information for etiologic, clinical, virologic and anthropologic investigations. Further studies to clarify the molecular virological factors that contribute to these differences are awaited.     

江苏省启东市乙型肝炎病毒基因型与肝癌及核心启动子突变的关系

目的 对江苏省启东市肝癌高发区的HBV流行株进行基因型别鉴定,并分析其与肝癌的相关性. 方法自启东市肝癌高发区的182份血清标本中抽提HBV DNA,以PCR方法扩增HBV全基因或X基因,测序后与基因库中已知基因型的参照序列共同构建基因进化树,根据序列在进化树中的位置进行型别鉴定.率的比较采用χ 2检验或Fisher精确概率法. 结果对包含24例HBV携带者、11例慢性乙型肝炎患者及13例肝癌患者在内的48例患者的血清HBV全基因测序结果显示,44例(91.7%)为C2基因型,4例(8.3%)为B2基因型,未见A、D、E、F、G、H等型别,也未见B/C重组病毒.以X基因测序方法对182例患者血清标本的鉴定结果显示,C2和B2型分别占92.9%(169例)和5.5%(10例),另有1.6%(3例)为B2/C2混合感染.启东地区C基因型的感染率明显高于邻近上海地区的78.9%(χ2=12.252,P<0.01).在81例肝癌和77例肝炎患者中,B、C基因型HBV的分布差异并无统计学意义(P>0.05).核心启动子区T1762/A1764联合突变在C基因型中的发生率为70.3%,明显高于B基因型中的30.8%(P<0.05);T1766和A1768突变则仅见于C基因型病毒中. 结论启东地区HBV感染以C2基因型为主,但其与肝癌的发生未见明显相关性.C基因型中较易出现核心启动子突变.     

双环醇治疗慢性乙型肝炎的临床研究

初步探讨双环醇治疗慢性乙型肝炎的保肝、抗病毒效果 ,并比较双环醇对不同基因型的乙肝患者的疗效。选取 33例慢性乙型肝炎患者 ,口服双环醇 2 5mg每日 3次 ,6个月。治疗前测乙型肝炎病毒基因型 ,治疗结束后分析不同基因型乙肝患者ALT、AST、HBeAg、HBVDNA变化。复常率ALT2 1例 (6 3 6 % ) ,AST15例 (4 5 5 % ) ,转阴率HBeAg :11例 (33 3% ) ,HBVDNA :9例 (2 7 3% )。B型和C型抗病毒总有效率分别是 5例 (4 1 7% )、8例 (4 0 0 % )。双环醇治疗慢性乙型肝炎有较好的保护肝细胞抑制乙肝病毒的效果。基因型B型和C型患者对双环醇疗效比较无显著差异