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.

Clinical features of chronic hepatitis B patients with YMDD mutation after lamivudine therapy

Objective: To study the clinical features of chronic hepatitis B (CHB) patients with tyrosine-methionine-aspartateaspartate (YMDD) mutation after lamivudine therapy. Methods: This investigation was a retrospective study of 63 CHB patients with YMDD mutation during lamivudine therapy. Clinical data, including period and types of YMDD mutation; hepatitis B virus (HBV) DNA levels and alanine aminotransferase (ALT) levels before and after YMDD mutation were measured. YMDD mutation in the HBV DNA polymerase gene was determined using polymerase chain reaction (PCR) and direct sequencing. HBV DNA quantification was determined using real-time PCR. Relevant serum markers of HBV were measured. The follow-up period was 12 months after YMDD mutation. Results: YMDD mutation occurred 7～44 months (median, 21.5 months) after the start of lamivudine therapy. The majority of the cases (42/63, 66.6%) had YMDD mutants detected between 12 and 24 months. Four types of YMDD mutation were observed in this study, rtL180M/M204V mutation was the predominant type (26/63, 41.3%). A proportion of patients (16/63, 25.4%; 12/63, 19.1%) had higher HBV DNA levels and ALT levels (after mutation vs before mutation),respectively. Conclusion: The majority of patients with YMDD mutants had similar or lower HBV DNA levels and ALT levels compared with baseline values. This subset of patients might have benefited from the continued lamivudine therapy. The patients with increased ALT and HBV DNA levels (breakthrough hepatitis) should benefit from the addition of a newer nucleotide analogue (e.g. adefovir).

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.

Mutation analyses of integrated HBV genome in hepatitis B patients

Little has been learnt in the last 30 years about detection of HBV genome as well as its mutation analysis between hepatitis B fathers （HBF） and their children. In this study, we used nest polymerase chain reaction （PCR）, fluorescence in situ hybridization （FISH）, and DNA sequencing analysis, to examine the integrated HBV genome in paraffin-embedded testis tissues, which were taken as samples from HBE and in peripheral blood mononuclear cells （PBMC） from 74 cases of HBFs and their children who were born after their fathers＇ HBV infection （caHBF）. We found that HBV DNA existed in testis tissues, mainly in the basilar parts of the seminiferous tubules, and also in PBMC of HBE It was also documented that there were point mutations of poly-loci, insertions and deletions of nucleotides in integrated HBV genomes, and the types of gene mutations in the HBFs were similar to those in caHBE This study addresses the major types of gene mutations in integrated HBV genome in human patients and also presents reliable evidence of possible genetic transmission of hepatitis B.

YMDD mutations in patients with chronic hepatitis B untreated with antiviral medicines

AIM: To polymerase P region (YMDD) mutations of hepatitis B virus gene (HBV DNA) in patients with chronic hepatitis B (CHB) untreated with antiviral medicines and to explore its correlation with pre-c-zone mutations, HBV genotypes and HBV DNA level, and to observe its curative effect.METHODS: A total of 104 cases (38 cases in group of familial aggregation and 66 cases in group of non-familial aggregation) were randomly chosen from 226 patients with CHB who did not receive the treatment of lamivudine (LAM)and any other antivirus drugs within the last one year.Their serum YMDD mutations were detected by microcosmic nucleic acid and cross-nucleic acid quantitative determination,HBV genotypes by PCR-microcosmic nucleic acid crossELISA, HBV DNA quantitative determination and fluorescence ration PCR analysis, hepatitis B virus markers (HBVM) by ELISA. LAM was taken by 10 patients with YMDD mutations and its curative effect was observed.RESULTS: Twenty-eight cases (26.9%) had YMDD mutations, of them 11 cases (28.9%) were in familial aggregation group (38 cases) and 17 cases (25.8%) in nonfamilial aggregation group (66 cases) with no significant difference between the two groups. Twenty-seven point one percent (16/59) cases were positive for HBeAg YMDD mutations, and 26.7% (12/45) cases were negative for HBeAg and positive for anti-HBe. There was also no significant difference between the two groups. Different YMDD incidence rate existed in different HBV genotypes.HBV DNA level did not have a positive correlation with the incidence of YMDD mutations. LAM was effective for all patients with mutations.CONCLUSION: Wild mutant strains in HBV and their incidence rate have no significant difference between familial aggregation and non-familial aggregation. It may have no significant relationship between YMDD mutations and pre-c-zone mutations. HBV DNA level may not have a positive correlation with YMDD mutations. LAM is clinically effective for CHB patients with YMDD mutations.

EFFECTS OF MUTATIONS IN THE POLYMERASE GENE OF HEPATITIS B VIRUS GENOME ON LAMIVUDINETHERAPY

Objective To explore the offects of mutations in tyrosine-methionine-aspartic acid-aspartic acid (YMDD) motif of the polymerase in the hepatitis B virus (HBV) genome on lamivudine antiviral therapy. Methods Partial HBV DNA segment containing the YMDD motif in the P gene wes obtained through amplifi- cation by polymerase chain reaction (PCR )from 19 chronic hepatitis B patients with serum HBV DNA positive at the 48th week treatment with lamivudine and subjected to automatic sequencing. Influences of vartants with YMDD mutations on lamivudine therapy were seen by observing the dynamic changes of serum HBV DNA and ALT levels. Results Serum HBV DNA breakthrough was found in 3 out of 10 individuals with detection of the YMDD mutations at the 48th week and in 5 at the 52th week, 2 of the 5 patients accompanied by serum ALT re-elevation, whereas of 9 subjects without YMDD mutations, 2 experenced an HBV DNA breakthrough at the 48th week and 1 of them had a conversion from HBV DNA positive DNA positive to negative at the 52th week. Patients with detectable HBV DNA level had a fluctuating level of serum ALT all time during the treatment. Conclusion Detection of mutations in the YMDD motif of polymerase gene in HBV genome during the lamivudine therapy will be helpful to monitoring its therapeutic outcomes.

Quantitative evaluation of hepatitis B virus mutations and hepatocellular carcinoma risk:a meta-analysis of prospective studies

Background： The temporal relationship between hepatitis B virus （HBV） mutations and hepatocellular carcinoma （HCC） remains unclear. Methods： We conducted a meta-analysis including cohort and nested case-control studies to prospectively examine the HCC risk associated with common variants of HBV in the PreS, Enhancer Ⅱ, basal core promoter （BCP） and precore regions. Pertinent studies were identified by searching PubMed, Web of Science and the Chinese Biological Medicine databases through to November 2014. Study-specific risk estimates were combined using fixed or random effects models depending on whether significant heterogeneity was detected. Results： Twenty prospective studies were identified, which included 8 cohort and 12 nested case-control studies. There was an increased risk of HCC associated with any PreS mutations with a pooled relative risk （RR） of 3.82 [95% confidence interval （CI）： 2.59-5.61]. The pooled-RR for PreS deletion was 3.98 （95% CI： 2.28-6.95）, which was higher than that of PreS2 start codon mutation （pooled-RR=2.63, 95% CI： 1.30-5.34）. C1653T in Enhancer Ⅱ was significantly associated with HCC risk （pooled-RR=l.83; 95% CI： 1.21-2.76）. For mutations in BCP, statistically significant pooled-RRs of HCC were obtained for T1753V （pooled- RR=2.09; 95% CI： 1.49-2.94） and AI762T/G1764A double mutations （pooled-RR=3.11; 95% CI： 2.08- 4.64）. No statistically significant association with HCC risk was observed for G1896A in the precore region （pooled-RR=0.77; 95% CI： 0.47-1.26）. Conclusions： This study demonstrated that PreS mutations, C1653T, T1753V, and A1762T/G1764A, were associated with an increased risk of HCC. Clinical practices concerning the HCC risk prediction and diagnosis may wish to focus on patients with these 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.

慢性乙型肝炎患者HBV DNA YMDD变异的检测及意义

目的 了解慢性乙型肝炎患者HBVDNAYMDD变异的存在情况及意义。方法 检测 90例慢性乙型肝炎患者HBVDNAYMDD变异 ,对发生HBVDNAYMDD变异的 2 0例患者的肝功能、HBeAg、HBVDNA及HBVDNAYMDD变异情况进行分析。结果 90例慢性乙型肝炎患者中检出HBVDNAYMDD变异共 2 0例 (阳性率 12 0 0 % ) ,已服用拉米夫定者 3 6例 ,检出YMDD变异 9例 (2 5 0 0 % ) ,未服用拉米夫定患者 5 4例 ,检出YMDD变异 11例 (阳性率 2 0 3 7% )。在 2 0例YMDD变异患者中有 5例HBeAg阴性 ;2 0例YMDD变异患者HBVDNA在 3 0 2 1× 10 5～ 2 3 69× 10 8(5 41× 10 7± 7 75× 10 7)copies/ml ,ALT 3 4～ 12 16(2 88 2 0± 3 3 8 0 7)IU/L ,TB 8 9～ 3 2 6 7(4 8 74± 72 2 0 ) μmol/L。 结论 YMDD变异株可在拉米夫定治疗过程中出现 ,也可天然存在 ,YMDD变异可与前C基因变异同时存在 ,提示HBV的变异常常是多位点的 ;YMDD变异株HBV复制处于中～高度水平 ;YMDD变异株的致病性轻重不等 ,肝功能可为正常 ,也可是轻度～高度等不同程度异常。

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.

家庭聚集性慢性HBV感染者HBV YMDD自然变异的调查

目的:探讨家庭聚集性慢性HBV感染者HBVYMDD自然变异发生情况以及影响其变异的因素.方法:筛选34个共95例有乙型肝炎家庭聚集现象且未经抗病毒治疗的慢性乙型肝炎(chronic hepatitis B,CHB)患者作为家庭组,进行YMDD检测;随机选择82例无乙型肝炎家庭聚集现象且未接受过抗病毒治疗的CHB患者作为对照组,进行YMDD检测.结果:家庭组95例中有51例(53.68%)检测到YMDD自然变异,对照组82例中有21例(25.61%)检测到YMDD自然变异;YMDD自然变异检出率有显著性差异(P<0.05).结论:有乙型肝炎家族聚集史慢性HBV感染者的YMDD自然变异率较没有乙型肝炎家族聚集史慢性HBV感染者的YMDD自然变异率高.

慢性乙型肝炎患者应用拉米夫定治疗发生HBV YMDD变异的研究

目的 探讨慢性乙型肝炎（CHB）患者应用拉米夫定治疗发生HBV YMDD变异后与患者血清HBVDNA载量关系的临床意义.方法 选择46例应用拉米夫定治疗并发生HBV YMDD变异的CHB患者,另选择未发生HBV YMDD变异的CHB患者作对照组.探讨血清HBVDNA载量与HBV YMDD变异类型、变异发生时间的关系.结果 CHB患者接受拉米夫定治疗前,HBV YMDD变异组HBVDNA载量明显高于HBV YMDD未变异组（P〈0.01）.HBV YMDD变异类型（YVDD、YIDD、YVDD/YIDD）的分布与血清HBVDNA载量无相关性.HBVDNA载量与发生HBV YMDD变异的时间有相关性.随着HBVDNA载量的升高,发生HBV YMDD变异的时间越来越早.结论 应用荧光定量PCR方法检测血清HBVDNA载量和HBV YMDD变异,可动态观察CHB患者拉米夫定治疗后发生HBV YMDD变异的情况,对临床治疗和观察预后具有重要的临床意义.

干扰素联合拉米夫定治疗慢性乙型肝炎耐药后HBV YMDD变异及HBV前S2蛋白变化的研究

目的:探讨干扰素联合拉米夫定治疗慢性乙型肝炎产生耐药后HBV发生YMDD变异及HBV膜蛋白前S2的变化。方法:应用实时荧光定量PCR检测联合应用干扰素及拉米夫定治疗慢性乙肝产生耐药后血清中HBV YMDD变异;同时应用ELISA方法检测产生耐药与未产生耐药患者的血清HBV膜蛋白前S2。结果:产生耐药后突变66例,未突变51例,野生株33例。突变66例中YIDD突变7例;YVDD突变8例;YMDD/YIDD突变12例;YMDD/YVDD突变17例,YMDD/YIDD/YVDD突变22例。产生耐药组HBV-S2阳性78例,与未产生耐药组(HBV-S2阳性32例)相比,差异有显著性(P<0.05)。结论:产生耐药后YMDD发生突变,突变率为44%,以YMDD/YIDD/YVDD突变为主,且HBV-S2的表达增加,说明耐药后HBV病毒出现活动性复制,发生耐药机制主要为YMDD变异。

HBV YMDD变异者采用阿德福韦和恩替卡韦治疗144周临床比较

目的评价阿德福韦(ADV)和恩替卡韦(ETV)治疗慢性乙型肝炎HBV YMDD变异患者144周的疗效和安全性。方法 2005年6月至2007年6月在门诊和住院的经拉米夫定(LAM)治疗后出现HBV YMDD变异的慢性乙型肝炎患者120例,随机分为4组,A组单用ADV 10mg/d治疗144周;B组采用ADV 10mg/d和LAM 100 mg/d联合治疗12周,后单用ADV 10mg/d治疗132周;C组采用ADV 10 mg/d和LAM 100 mg/d联合治疗144周;D组接受ETV1 mg/d治疗144周。结果治疗144周时四组患者HBeAg血清转换率比较,差异均无统计学意义(P>0.05)。C组患者ALT复常率、HBV DNA达到检测水平以下的百分率与A组、B组、D组比较,差异均有统计学意义(P<0.05);四组患者144周的基因型耐药率分别为30%(9/30)、26.7%(8/30)、3.3%(1/30)、40%(12/30)(x^2=11.556,P<0.05)。结论慢性乙型肝炎患者发生HBV YMDD变异后采用ADV与LAM联合治疗更安全有效。

单探针FQ-PCR法检测HBV YMDD变异

目的建立一种检测乙型肝炎YMDD变异株的方法。方法应用单探针实时荧光定量聚合酶链反应(FQ-PCR)法对46例HBV-DNA阳性的标本进行YMDD变异株的检测,同时对这46例标本进行基因测序。结果在46例HBV-DNA阳性的标本中,采用单探针FQ-PCR法检测出YMDD变异株16例占35%,采用基因测序法检测出17例占37%,2者比较无显著性差异(P>0.05)。结论单探针FQ-PCR法具有简便、快速、灵敏、经济的特点,特别适用于临床对YMDD变异株的检测,为临床用药提供及时的指导。

恩施地区乙型肝炎患者HBV DNA YMDD变异的检测

目的了解恩施地区慢性乙型肝炎（乙肝）患者HBV DNA YMDD变异的情况。方法检测该地区100例乙肝患者ALT水平、HBV DNA载量、HBV YMDD变异,对其HBV DNA YMDD变异情况进行分析。结果 100例乙肝患者中检出HBV DNA YMDD变异共15例（阳性率15%）,已服用拉米夫定者60例,检出YMDD变异12例（阳性率20%）,未服用拉米夫定患者40例,检出YMDD变异3例（阳性率7.5%）。15例YMDD变异患者HBV DNA在5.21×10^4-1.34×10^8copies/ml,ALT水平在38-1100U/L。结论恩施地区乙肝患者YMDD变异可在拉米夫定治疗过程中出现,也可天然存在;尚未发现恩施地区乙肝患者性别、年龄、HBV DNA载量。

Lamivudine resistance in children with chronic hepatitis B

Currently, although lamivudine(LAM) has a low genetic barrier, only interferon-alpha and LAM are available as a first-line treatment in children with chronic hepatitis B(CHB). LAM is a potent inhibitor of hepatitis B virusdeoxyribonucleic acid(HBV-DNA) polymerase replication by termination of the proviral HBV-DNA chain. LAM has a good safety and tolerability profile in CHB patients with hepatic decompensation. However, the main disadvantages of this HBV reverse transcriptase inhibitor are:(1) pre-existing covalently closed circular DNA cannot be eradicated by LAM, thus relapse after therapy withdrawal is frequent; and(2) although the longer LAMtreatment induced the higher seroconversion rate, the risk of viral resistance increased through the selection of YMDD(tyrosine, methionine, aspartate, aspartate) motif. Insufficient suppression of viral replication leads to the emergence of resistant strains that could result in virological breakthrough which is usually followed by biochemical breakthrough. Mutant strains affects additional resistance and cross resistance, leading to drug resistance in a significant number of CHB patients. In this case, efficacy of more powerful anti-viral agents with higher genetic barrier against development of resistance is diminished. Furthermore, strains that are resistant to LAM could bring about vaccine escape mutants, decreasing the efficacy of HBV vaccine. A more potent drug with a high genetic barrier to resistance needs to be approved as the first-line treatment option for CHB in children.

乙型肝炎治疗前后HBV YMDD变异与血清HBV-DNA定量水平的相关性

目的探讨拉米夫定治疗乙型肝炎前后YMDD变异与HBV-DNA定量水平之间的关系。方法 78例慢性乙型病毒性肝炎患者服用拉米夫定片,100mg/d,并随访2年。于治疗后每隔3个月采用全自动生化分析仪检测肝功能,用ELISA法检测乙肝五项指标,用荧光定量PCR方法检测HBV-DNA水平,用限制性片段长度多态分析法（PCR-RFLP）检测YMDD变异。结果 YMDD变异组治疗前血清HBV-DNA定量水平显著高于未产生YMDD变异组,产生变异的时间与血清HBV-DNA定量水平相关。结论慢性乙型病毒性肝炎患者治疗前血清病毒载量水平超高,应用拉米夫定治疗容易产生YMDD变异,且产生时间早。随着拉米夫定用药时间的延长,出现变异株的病例增加。

Clinical characteristics and distribution of hepatitis B virus genotypes in Guangxi Zhuang population

AIM: To investigate the distribution of HBV genotypes and their YMDD mutations in Guangxi Zhuang population, China, and to study the relationship between HBV genotypes and clinical types of HB, ALT, HBV DNA, HBe system as well as the curative effect of Lamivudine (LAM) on hepatitis B.METHODS: A total of 156 cases were randomly chosen as study subjects from 317 patients with chronic hepatitis B (CHB). HBV genotypes were determined by PCR-microcosmic nucleic acid cross-ELISA. YMDD mutations were detected by microcosmic nucleic acid cross-nucleic acid quantitative determination. HBV DNA was detected by fluorescence ratio PCR analysis.LAM was given to 81 cases and its curative effect was observed by measuring ALT, HBV DNA load, HBeAg, and HBeAg/HBeAb conversion rate.RESULTS: HBV genotypes B, C, D, and non-classified genotypes were found in Guangxi Zhuang population.accounting for 25.6%, 47.4%, 58.3%, and 16.0%,respectively. Seventy-four cases were CD-, CB-, BD-mixed genotypes (47.7%). Forty-six (29.5%) cases had YMDD mutations. Genotype B was mostly found in mild and moderate CHB patients. Genotypes C, D and mixed genotype mostly occurred in severe CHB cases.Genotypes D and CD HBV-infected patients had higher ALT and HBV DNA than patients with other types of HBV infection. There was no significant difference among the genotypes in YMDD mutations, clinical types, ALT and HBV DNA level. Non-classified types geno had a significantly lower positive rate of HBeAg than other genotypes (x2= 12.841, P＜0.05). There was no significant difference in ALT recovery rate, HBV DNA load, HBeAg,and HBeAg/HBeAb conversion rate, 48 wk after LAM treatment between groups of genotypes D, CD, and nonclassified type.CONCLUSION: Genotypes B, C, and D, non-classified and mixed genotype of HBV are identified in the Guangxi Zhuang population. Variations in genotypes are associated with clinical severity and serum ALT levels, but not with YMDD mutation or HBV DNA load.Therapeutic effects of LAM on clinical parameters are not influenced by differences in genotypes. Further studies are needed to gain an in-depth understanding of the relationship between HBV genotypes and serum HBeAb and HBeAg.

Association of miRNA-122-binding site polymorphism at the interleukin-1 a gene and its interaction with hepatitis B virus mutations with hepatocellular carcinoma risk

This study was designed to investigate the contribution of miRNA-122-binding site polymorphism at the IL-1A gene and its multiplicative interactions with hepatitis B virus （HBV） mutations in the risk of hepatocellular carcinoma （HCC）. A total of 1021 healthy controls, 302 HBV surface antigen （HBsAg） seroclearance subjects, and 2011 HBsAg-positive subjects （including 1021 HCC patients） were enrolled in this study. Quantitative PCR was used to genotype rs3783553. HBV mutations were determined by direct sequencing. Multivariate logistic regression analyses were performed to test the associations of rs3783553, mutations, and their interactions with the risk of HCC. No significant association was found between rs3783553 and the risk of HCC among healthy controls, HBsAg seroclearance subjects, HBsAg-positive subjects without HCC, and all controls. Additionally, rs3783553 was not significantly associated with chronic HBV infection, liver cirrhosis, HBV e antigen seroconversion, abnormal alanine aminotransferase, and high viral load （ 〉 10^4 copies/ml）. However, the TTCA insertion allele of rs3783553 was significantly associated with an increased frequency of HBV C7A mutation compared with homozygous TTCA deletion carriers [（del/ins ＋ ins/ins） vs. del/del, adjusted odds ratio （OR）= 1.48, 95% confidence interval （CI）= 1.09-2.02, P = 0.013]. Multiplicative interaction of rs3783553 with HBV preS deletion significantly reduced the risk of HCC in males, with an adjusted OR of 0.64 （95% CI = 0.42-0.98; P = 0.041） after age and HBV genotype were adjusted. Although rs3783553 did not significantly affect genetic susceptibility to HBV-related HCC, its variant allele may predispose the host to selecting HBV C7A mutation during evolution and significantly reduce the risk of HCC caused by HBV preS deletion. This study provides an insight into the complex host-virus interaction in HBV-induced hepatocarcinogenesis and is helpful in determining HBsAg-positive subjects who are likely to develop HCC.