中国慢性HBV感染者基因型分布及其临床意义Meta分析*

目的 探讨中国乙型肝炎病毒（HBV）基因型分布及其临床意义。方法 在万方数据库和NCBI数据库检索有关中国HBV基因型分布的研究论文,将中国分为不同HBV感染流行区,分析不同地区、民族和肝脏疾病类型人群HBV基因A、B、C、B/C、D型和其他基因型（非A~D基因型和非B/C混合型）分布。采用Meta分析基因型分布特点及其临床意义。结果 在我国,HBV基因型主要以B基因型和C基因型为主,区域1（北部地区）HBV 基因A、B、C、B/C、D型和其他型分别为0.1%、22.2%、69.1%、3.8%、0.5%和1.5%,其中C基因型比例显著高于其它区域（P<0.05）;区域2（中部地区）HBV 基因A、B、C、B/C、D型和其他型分别为0.2%、62.6%、27.4%、3.8%、0.5%和2.4%,其中B基因型比例显著高于其它区域（P<0.05）;区域3（南部地区）HBV 基因A、B、C、B/C、D型和其他型分别为0.6%、36.3%、49.4%、2.8%、2.6%和3.4%,其中C基因型比例显著高于区域2的27.4%（P<0.05）;区域4（青藏高原）感染HBV B基因型、C基因型、D基因型和其他基因型分别为6.0%、22.5%、11.7%和59.3%,其中C/D混合型比例显著高于其他区域（P<0.05）;藏族人群C/D混合型比例（49.3%）显著高于其他民族（P<0.05）,哈萨克族D基因型比例（58.1%）显著高于其他民族（P<0.05）; C基因型与慢性乙型肝炎、HBV相关性肝硬化和肝癌显著相关（OR=1.979、OR=3.888、OR=4.399,P<0.001）。结论 不同地区和民族HBV基因型分布显著不同,B基因型可能是中国HBV起源基因,而感染C基因型更有可能引起严重的肝脏疾病。     

The clinical implications of hepatitis B virus genotype: Recent advances

Outcomes of chronic hepatitis B virus (HBV) infection are heterogeneous. Estimates of annual incidence of cirrhosis and hepatocellular carcinoma (HCC) are 2-10% and 1-3%, respectively. Several viral factors, including HBV genotype, viral load and specific viral mutations, have been associated with disease progression. Among these, HBV genotype is not only predictive of clinical outcomes but has also been associated with response to interferon treatment. Currently, at least 10 HBV genotypes and several subtypes have been identified; they have distinct geographic distribution. Acute infection with genotypes A and D results in higher rates of chronicity than genotypes B and C. Compared to genotype A and B cases, patients with genotypes C and D have lower rates of spontaneous hepatitis B e antigen (HBeAg) seroconversion; when this occurs, it tends to be delayed. HBV genotype C has a higher frequency of basal core promoter (BCP) A1762T/G1764A mutation, pre-S deletion and is associated with higher viral load than genotype B. Similarly, genotype D has a higher prevalence of BCP A1762T/G1764A mutation than genotype A. These observations suggest important pathogenic differences between HBV genotypes. These may contribute to more severe liver disease, including cirrhosis and HCC with genotypes C and D HBV infection. In addition, genotype A and B patients have better responses to interferon-based therapy than genotypes C and D, but there are few consistent differences for direct HBV antivirals. In conclusion, genotyping of chronic HBV infections can help practicing physicians identify those at risk of disease progression and determine optimal anti-viral therapy.     

拉米夫定对湖北地区乙型肝炎病毒基因型的影响

目的研究拉米夫定对湖北地区乙型肝炎病毒基因型的影响及其临床意义。方法采用多对型特异性引物-聚合酶链反应检测160例慢性乙型肝炎患者血清HBV基因型;采用基因芯片技术对86例拉米夫定治疗18个月的慢性乙型肝炎患者进行酪氨酸—蛋氨酸—天冬氨酸—天冬氨酸(YMDD)基序、G1896A、A1814C、A1792T和G1764A单碱基变异检测。结果160例慢性乙型肝炎患者,B基因型127例(79%),C基因型24例(15%),BC混合型9例(6%),未发现A、D和E基因型。拉米夫定治疗的86例患者中,17例(19.7%)发生YMDD变异,B型14例,C型2例,BC混合基因型1例,其中6例发生多重变异,包括B型4例,C型2例;HBeAg/HBeAb血清转换率B型41例(68.3%)高于C型8例(40%)(P<0.05)。另外17例患者,经拉米夫定治疗后,HBVDNA仍阳性,亦未发现YMDD变异株。结论湖北地区HBV存在B、C和BC混合基因型,B型为本地区优势基因型,B型在拉米夫定治疗中更易发生YMDD变异;未变异者,血清HBeAg/HBeAb转换率高。     

HBeAg阳性患者中乙型肝炎病毒基因型分布及YMDD变异位点分析

目的通过研究乙型肝炎患者HBV基因型的分布及YMDD变异位点的分布特点,了解两者之间的关系,探讨临床意义。方法选取在我院门诊和住院部就诊的HBeAg阳性并经拉米夫定治疗两年以上的慢性乙型肝炎患者137例,用实时荧光PCR方法检测HBV DNA分型情况,用LDR方法检测YMDD位点变异情况。结果 137例患者中21例未能检测出基因型,其中男性17例,女性4例;其余116例标本确定了感染病毒的基因型,包括男性94例,女性22例;其中A型2例(1.72%)、B型19例(16.38%)、C型91例(78.45%)、D型4例(3.45%);分型成功率为84.67%(116/137)。116例标本中有41例患者的感染病毒中检测到了YMDD变异位点,变异发生率为35.35%。其中B基因型中检出7例(36.84%);C基因型中检出33例(36.26%);D基因型中检出1例(25.0%);A基因型中未检测出变异位点。B、C基因型中变异位点的检出率高于D型,但各基因型之间差异无统计学意义(χ2=1.392,P>0.05)。在41例变异中,其中I突变占60.9%,V突变占31.7%,I/V共生突变占7.4%。结论兰州大学第一医院所在地区患者中HBV基因型主要以C型为主,其次是B型,也有少量D、A型存在;B、C基因型的YMDD位点发生突变的几率相近。突变几率与基因型无关。     

广东省东莞地区慢性乙型肝炎患者HBV基因型分析

目的探讨东莞地区乙型肝炎患者HBV基因型的分布特点。方法采用PCR-微板核酸杂交-ELISA法检测HBVA—F基因型，采用荧光定量-聚合酶链反应法检测血清HBVDNA定量。结果在295例乙型肝炎患者中检出HBV基因型247例（83．7％），其中HBV基因C型占62．3％（154／247）、B型15．4％（38／247）、D型6．9％（17／247）、B／C混合型4．9％（12／247）、C／D混合型5．3％（13／247）、B／D混合型5．3％（13／247），48例未检出基因型；基因C型感染者之间无性别差异（x^2=0．043，P〉0．05）；各基因型患者血清HBVDNA水平无显著性相差，但与48例未检出基因型者比，后者HBVDNA水平明显降低（P〈0．01）。结论PCR-微板核酸杂交-ELISA法检测HBV基因型具有特异、敏感、简单和实用的特点，东莞地区乙型肝炎患者HBV基因型以C型为主，混合型比例相对较高，HBV复制强弱与病毒基因型无关。     

Hepatitis B virus genotypes in the United States: results of a nationwide study

BACKGROUND & AIMS: Hepatitis B virus (HBV) genotypes may be related to severity of liver disease and treatment response. The aims of this nationwide study were to determine the prevalence of HBV genotypes in the United States and the association between HBV genotypes and patient demographics, mode of infection, and clinical status. METHODS: A total of 694 consecutive chronic HBV-infected patients seen in 17 U.S. liver centers during a 1-year period were enrolled. Demographic, clinical, and laboratory data were collected. Sera were tested for HBV genotyping, precore, and core promoter variants by line-probe assays. RESULTS: All 7 HBV genotypes (A-G) were found, with genotypes A and C the most common. The prevalence of HBV genotypes was different in different regions of the United States. A strong correlation was found between HBV genotypes and ethnicity. HBV genotype A was prevalent among white and black patients, whereas genotypes B and C were most common among Asian patients. The predominant genotype among patients born in the United States, Europe, the Far East, and Southeast Asia were A, D, C, and B, respectively. Genotypes A and C were associated with a higher prevalence of hepatitis B e antigen. Precore variant was detected in 27% of patients and core promoter variant in 44% of patients. CONCLUSIONS: Our study suggests that the epidemiology of HBV infection in the United States may have changed over time as a result of immigration from countries with a high prevalence of HBV infection. HBV genotypes may account for the heterogeneity in disease manifestations among patients with chronic HBV infection.     

Prevalence and clinical implications of hepatitis B virus genotypes in southern Taiwan

BACKGROUND: Hepatitis B virus (HBV) infection is a major health problem. HBV genotypes may be associated with progression of liver disease. The distribution and clinical implications of HBV genotypes in southern Taiwan are evaluated. METHODS: We used a polymerase chain reaction-restriction fragment length polymorphism genotyping method to determine HBV genotypes. RESULTS: The genotype distribution for 265 patients with chronic HBV infection was as follows: A, 3 (1%); B, 158 (60%); C, 90 (34%); D, 7 (2.5%); E, 0: F, 0; and unclassified, 7 (2.5%). Compared with genotype B patients, genotype C patients had a higher hepatitis B e antigen positive rate and higher fibrosis score. There was no significant difference in the mean age between genotype B and genotype C patients with hepatocellular carcinoma (HCC). However, when patients were stratified by age, the prevalence of genotype C was significantly higher in young HCC patients (<50 years of age) than in age-matched asymptomatic carriers (40% versus 10%, P < 0.001). Using multivariate analysis, the significant risk factors for advanced liver disease (cirrhosis or HCC) for patients with chronic HBV infection were old age, male gender and genotype C. CONCLUSIONS: These results suggest that genotype C is associated with more severe liver diseases than the B variant.     

山西省HBV基因型及亚型分布调查

目的了解山西省乙型肝炎病毒(HBV)的基因型及亚型分布情况。方法对136例乙型肝炎表面抗原(HBsAg)阳性者血清采用PCR-PFLP结合基因型特异性引物-PCR法进行HBV基因型及亚型检测。结果 136例HBV感染者的血清标本经PCR-PFLP分析,B基因型18例,均为Ba亚型,占13.2%;C基因型113例,占83.1%,除4例未分型外均为Ce亚型;D基因型5例,占3.7%。经型特异性引物-PCR分析,18例HBV B基因型中有4例为B/C基因型混合感染;5例经PCR-PFLP确定的D基因型病毒经型特异性引物法分析有2例扩增出E基因型条带。C、B基因型病毒感染者的平均年龄分别为(39.5±13.1)岁和(30.5±14.1)岁,差异有统计学意义(P<0.05);与B基因型相比,C基因型病毒感染者的HBeAg阴转率减慢。结论山西省HBV基因型主要为C(Ce),有少量的B(Ba)和D基因型,且存在B/C混合基因型,且可能存在D和E基因型病毒的重组体;与B基因型比较,感染C基因型病毒更难被机体清除,疾病更易慢性化。     

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.     

Is There Any Value to Hepatitis B Virus Genotype Analysis?

Hepatitis B may cause a varying spectrum of diseases ranging from an asymptomatic or mild anicteric acute illness, to severe or fulminant hepatitis. Similarly, the outcome of chronic hepatitis B is variable. Viral factors associated with outcome of chronic hepatitis B virus (HBV) infection include hepatitis B e antigen status, HBV DNA, genotype, and HBV variants. HBV genotypes and subgenotypes have been associated with differences in clinical and virological characteristics, indicating that they may play a role in the virus-host relationship. A total of ten hepatitis B virus genotypes have been defined with a distinct geographical distribution. Hitherto, genotypes A, B, C and D have been studied most extensively. The HBV genotype appears to influence not only the natural history of HBV related liver disease but also the response to HBV treatment. HBV genotypes are also linked with both core promoter and BCP mutations. Progression to chronic infection appears to occur more frequently following acute infection with genotypes A and D than with the other studied genotypes. Genotypes A and B appear to have higher rates of spontaneous HBeAg seroconversion. More advanced liver disease and progression to HCC is more often seen in chronic infection with genotypes C and D in contrast to genotypes A and B. More specifically, genotypes A1, C, B2–B5 and H appear to be associated with more serious complications than genotypes A2, B1 and B6. These observations suggest important pathogenic differences between HBV genotypes. Genotypes A and B have higher response rates to interferon based therapy than genotypes C and D. Knowledge of HBV genotype enables clinicians to identify those patients at increased risk of disease progression whilst aiding the selection of appropriate antiviral therapy. Genotyping and monoclonal subtyping can provide useful information for epidemiological studies. In conclusion, genotyping of chronic HBV infections can help practicing physicians identify those at risk of disease progression and determine optimal anti-viral therapy.     

HBV基因分型的研究进展

乙型肝炎病毒(HBV)感染是一个影响全球的健康问题.HBV有8种基因型,呈地域性分布.研究表明HBV基因型对慢性HBV感染的自然病程、临床结局、抗病毒治疗等具有影响.A基因型与C基因型与严重的肝损害相关;A基因型与B基因型对干扰素的应答率分别较D基因型与C基因型均更高;有研究发现HBV的基因型可能影响HBV的传播途径.然而,目前大多数临床资料来自亚洲及对B、C基因型的相关研究,基于基因型的地域性分布,对HBV基因型的全面认识,还有待进一步的国际化合作.     

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.     

YMDD mutations and genotypes of hepatitis B virus in northern China

The objective of this research was to determine the relationship between YMDD mutations and the genotypes of hepatitis B virus (HBV) during lamivudine treatment. HBV genotypes were determined by nested PCR with 6 pairs of HBV genotype-specific primers (A to F) in serum specimens from 142 hepatitis B patients receiving lamivudine antiviral therapy. YMDD mutations were detected by fluorescent hybridization bioprobe PCR and melting curve assay (FH-PCR-MC). Among 142 serum specimens, 13 samples were genotype B (9.2%), 125 samples were genotype C (88%), 4 samples were genotype D (2.8%), and 80 YMDD mutations were found. The YMDD mutation rates were 69.2 and 54.4% in genotype B and genotype C, respectively. There was no significant difference in the YMDD mutation rate between genotypes B and C. Nine genotype B sera with YMDD mutations were found, including 2 YIDD mutations and 7 YVDD (M + V) mutations. Sixty-eight genotype C sera with YMDD mutations were found, including 34 mutations I (M + I) and 17 mutations V (M + V). There was a significant difference in the YMDD mutation types between genotypes B and C. Our results suggested that the YMDD mutation rate was 56.3% in patients treated with lamivudine for 2-4 years. YIDD was the main mutation type. The YMDD mutation rate showed no significant difference between HBV types B and C (P > 0.05), while the YMDD mutation types showed a significant difference between HBV types B and C in Northern China (chi2 test = 4.6, P < 0.05).     

乙型肝炎病毒基因型检测及其临床应用

目的:探讨HBV基因型的检测及其在临床上的应用.方法:用微板核酸分子杂交-ELISA方法检测468例HBV DNA阳性的慢性乙型肝炎患者血清HBV基因型.分析HBV基因型与病毒复制、基本C基因启动子(BCP)变异、肝病病情轻重、干扰素疗效的关系.结果:深圳地区HBV基因型以B和C基因型为主,分别占25.0%和64.9%;C基因型的HBeAg阳性率(68.8%)高于B基因型的HBeAg阳性率(35.0%)(P＜0.01);C基因型的血清HBV DNA水平也明显高于B基因型(1g 6.74 copies/ml vs. 1g 5.44 copies/ml, P＜0.01);轻中度慢性肝炎以B基因型为主,而重度慢性肝炎以C基因型为主;B基因型对干扰素的有效应答率为47.2%,C基因型的有效应答率为28.9%,两组比较差异有显著性意义(P＜0.05).结论:HBV基因分型有助于临床判断病情、估计预后及抗病毒治疗疗效预测.     

Hepatitis B virus genotypes and subgenotypes in China

Eight Hepatitis B virus (HBV) genotypes (A to H) have been identified based on an intergenotype divergence of 8% or more in the entire nucleotide sequence. Subgenotypes have also been identified in different HBV genotypes. As a highly endemic area for HBV infection, the prevalence of chronic HBV infection in China is between 8 and 20% of the general population. Genotypes B and C were identified as the most common HBV strains and account for approximately 95% of Chinese patients. Further study confirmed all genotype B strains belong to subgenotype Ba. Two of genotype C subgenotypes, C1 (Cs) and C2 (Ce), were found in China and they showed different geographic distributions. Genotype A was very rarely found, while genotypes E, F, G and H have not beenreported until now. Two types of HBV C/Drecombinant viruses have been identified in west China and distinct geographic and ethnic distributions were observed. Significant differences were observed ( P  < 0.001) in the prevalence of A1896 and T1762/A1764 mutations among HBV Ba, C1 and C2 subgenotypes in Chinese patients. Accumulating evidence showed the response rate to antiviral therapy in Chinese patients is higher in genotype B than genotype C patients on interferon treatment, but no difference was observed on nucleoside/nucleotide analog treatment.     

Hepatitis B genotypes and the response to interferon therapy

BACKGROUND/AIMS: Possible pathogenic differences among hepatitis B virus (HBV) genotypes have been observed; however, the response to interferon therapy among HBV genotypes remains unknown. We therefore analyzed the efficacy of interferon alfa in the treatment of chronic hepatitis B patients with different HBV genotypes. METHODS: Fifty-eight genotype B or C infected chronic hepatitis B patients who had been treated with interferon alfa-2b were retrospectively studied. The response to interferon was defined as normalization of serum aminotransferase level, loss of hepatitis B e antigen and HBV DNA 48 weeks post-treatment. RESULTS: Baseline data of both groups of patients were comparable; however, genotype C patients had a higher serum aminotransferase level and a higher frequency of core promoter mutation. The response rate was 41% and 15% in genotype B and C patients, respectively (p=0.045). In those with higher serum aminotransferase levels, the response rate was 50% and 17%, respectively (p=0.025). Additionally, younger age and genotype B infection may predict a better response to interferon alfa. CONCLUSIONS: HBV genotype C, compared to genotype B, is associated with a higher frequency of core promoter mutation, and a lower response rate to interferon alfa therapy.     

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.     

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。     

Hepatitis B Virus Genotypes: Clinical Relevance and Therapeutic Implications

At least ten hepatitis B virus (HBV) genotypes (A to J) with distinct geographic distributions have been recognized. HBV genotype is not only predictive of clinical outcome but also implicated in responsiveness to antiviral therapy, especially interferon-based regimens. HBV genotype-specific immunologic and virological pathogenesis may contribute to heterogeneous clinical outcomes in chronic hepatitis B patients. For example, patients with genotypes C and D infection have a lower rate of spontaneous HBeAg seroconversion. In addition, genotype C and D have a higher frequency of basal core promoter A1762T/G1764A mutation than genotype A and B. Genotypes C and D also carry a higher risk of cirrhosis and HCC development than genotype A and B. Therapeutically, genotype A and B patients have a better response to interferon-based therapy than genotypes C and D patients, but the response to nucleos(t)ide analogues is comparable across all HBV genotypes. In conclusion, genotyping of HBV can help practicing physicians identify chronic hepatitis B patients who are at risk of disease progression and optimize anti-viral therapy in clinical practice.     

Hepatitis B virus genotypes and the response to lamivudine therapy

Hepatitis B virus (HBV) can be classified into eight major genotypes (A-H) that have mainly a geographic distribution. The HBV genotype may influence disease progression, HBeAg seroconversion rates, response to antiviral treatment. The aim of study was to analyze the distribution and frequency of genotypes in patients with chronic hepatitis B. Response to lamivudine 100 mg daily therapy was examined in respect to genotype. Sixty six patients (45 (68,2%) male, 21 (31,8%) female) with chronic hepatits B were enrolled. HBV genotypes were assigned before treatment with INNO-LiPA HBV Genotyping, Innogenetics, N. V., Ghent assay, which is a line probe test based on the reverse hybridization principle. In baseline and after 12 months of treatment serological markers of HBV infection, alanine aminotransferase (ALT) activities and HBV DNA serum levels were tested. Patients with chronic hepatitis B were infected predominantly with genotype A. HBV genotype distribution was: 78,8% for genotype A, 13,6% for genotype D, 1,5% for mixed infection with genotypes A and D. Distribution of genotypes A and D was asymmetrically regardless of sex, HBeAg status, ALT and HBV DNA levels. Four (6,1%) specimens had indeterminate A results by LiPA. There were no significant differences between patients with genotypes A and D regarding age and sex. There were also no significant differences between these two groups regarding rates of HBeAg and anti-HBe positivity, ALT activity and viral load. Twenty months of lamivudine (100 mg daily) therapy resulted in significant decreases in serum HBV DNA and ALT activities in patients with genotype A as well as with genotype D. After 12 months of treatment there were no statistical differences in HBeAg seroconversion rates, ALT activities, viral loads, frequency of HBeAg and anti-HBe between genotypes A and D.