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。     

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。     

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。     

乙型肝炎病毒基因型C亚型和核心启动子、前C/核心区基因变异的关系

目的 研究慢性乙型肝炎病毒（HBV）感染者中HBV基因型C亚型（HBV／C）的核心启动子、前C／核心区基因变异情况，分析HBV／C亚型的病毒学特征。方法 用酶联免疫法（ELISA）筛选出79例HBV／C，再用聚合酶链反应．限制性酶长度多态性分析方法（PCR-RFLP）进行HBV／C亚型分析；同时针对HBV核心启动子、DreC／核心区基因进行半巢式PCR及PCR产物直接测序。结果 ①79例HBV／C中，33例（41．8％）为HBV／C1亚型，46例（58．2％）为HBV／C2亚型。②HBV／C1亚型仅见于来自中国南方的患者（P〈0．0001）。③A1898位点变异仅见于HBV／C1亚型（P=0．056），V1753位点变异在HBV／C1亚型中多见（P〈0．05）；HBV／C2以T1858（90％）、A1896（40％）位点变异多见（P〈0．008）。T1762／A1764位点变异在HBV／C两种亚型中均常见。④肝细胞癌（HCC）患者中，V1753和T1762／A1764变异最常见（P〈0．05）。结论 HBV／CI和HBV／C2在中国有明显的地区差异；V1753合并T1762／A1764双变异与发展为HCC相关，尤其在HBV／C1患者。     

乙型肝炎病毒C启动子区C1673T/C1799G联合突变的意义

目的 探讨HBV(乙型肝炎病毒)C启动子区(CP) C1673T/C1799G联合变异的生物学和临床意义.方法 136名慢性HBV感染者,包括无症状携带者(ASC) 25例,慢性乙型肝炎(CHB)38例,慢性重型乙型肝炎(CSHB) 24例,乙肝肝硬化(LC) 36例,肝细胞肝癌(HCC)13例,用半巢氏PCR的方法结合直接测序法检测HBV基因亚型及CP区变异,分析C1673T/C1799G联合变异在不同基因亚型中的发生率及与HBV复制、e抗原表达和不同慢性HBV感染疾病谱的关系.结果 本组病例中,Ba亚型110例,Bj亚型1例,C1亚型7例,C2亚型8例,C1673T/C1799G联合变异发生率为80.9％,其中在Ba亚型中为96.4％,C1亚型为14.3％,C2亚型为12.5％,Ba亚型与C1和C2亚型比较,差异有统计学意义(P ＜0.0001).变异组HBV DNA载量与非变异组比较差异无统计学意义(P＞0.05);e抗原阳性组变异率为71.4％,e抗原阴性组为87.5％,两组比较差异有统计学意义(P＜0.05).从ASC、CHB、CSHB、LC到HCC组,变异的发生率差异无统计学意义(P＞0.05).结论 C1673T/C17991G联合变异常见于Ba基因亚型,该变异不影响HBV DNA的复制水平,可能与不同慢性HBV感染疾病谱无关.     

HBV基因型与前C/C启动子变异及抗病毒疗效的关系

目的 了解深圳市乙型肝炎病毒（HBV）基因分型情况，探讨HBV基因型与前C／C启动子变异、乙肝的病程进展及抗病毒疗效的关系。方法 用单克隆抗体ELISA法（mAbs ELISA）对深圳市165例HBV感染者进行HBV基因分型；随机抽取24例慢性乙型肝炎（CUB）患者，用基因芯片技术检测HBV前C／C启动子变异；回顾性分析HBV基因型与干扰素、贺普丁抗HBV疗效的关系。结果 ①165例患者中，以B型106例（64.2％）和C型48例（29．1％）为主。慢性无症状乙肝病毒携带者（ASC）组B型占95．4％，肝硬化（LC）组C型占64．7％（P〈0．05）。②24例CHB患者中，16例（10例B型，6例C型）发生HBV前C／C启动子变异：前C区变异（nt1896、1862）者10例（B型9例，C型1例）。基本C区启动子变异（BCP）变异（nt1762、1764）者6例（B型1例，C型5例）。③用干扰素治疗的27例HBeAg（＋）CHB患者，达到完全应答者B型11例（62．5％）较C型1例（9．1％）多见（P〈0．05）。用贺普丁治疗的29例HBeAg（＋）CHB患者，持续应答者B型15例（78．9％）较C型3例（30．0％）多见（P〈0．05）。结论 ①深圳市HBV基因分型以B型为主，C型次之。②C型较B型易发生BCP变异，发生肝硬化机会较高，且对于扰素及贺普丁疗效较差。     

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。     

海府地区慢性HBV感染不同免疫状态患者基因分型、病毒变异研究

目的 了解海府地区慢性HBV感染不同免疫状态患者基因分型、病毒变异及其相互之间的关联性.方法 入选对象为海府地区慢性HBV感染患者,依照HBV感染自然史分为4组:慢性无症状HBV携带组、HBeAg(+)CHB组、HBsAg-IaC组、HBeAg(-)CHB组,各50例,PCR-RELP、PCR-反向点杂交法检测所有样本基因型、病毒变异.结果 ①4组患者B基因型感染分布比率分别为:60％、56％、62％、60％;C基因为:38％、38％、34％、32％;D基因为:2％、6％、0、6％;B+C基因为:0、0、4％、2％.各型基因在4组患者中感染同比分布差异无统计学意义(P＞0.05).4组之间优势基因均为B、C基因,尤以B基因感染为主.②4组患者均存在PC、BCP区变异,其中HBeAg(-)CHB组患者变异比例最高,其次为HBeAg(+)CHB组,与HBsAg-IaC组相较,差异有统计学意义(x2=24.73、18.32、6.78、3.84;P=6.59E-07、1.87E-05、0.009、0.049).③B、C型基因感染患者均存在PC、BCP区变异.PC、BCP区变异结果中C基因型发生比例较B基因型高,分别为:43.66％比15.97％、33.80％比10.92％,两者相较差异有统计学意义(x2=17.59、14.84,P=2.74E-05、0.000).结论 海府地区慢性HBV感染优势基因为B、C基因,尤以B基因为主,4种免疫状态均存在PC、BCP区变异.C基因型感染患者及HBeAg(-)CHB患者存在高PC、BCP区变异,可能更易引起严重的肝细胞炎症、坏死和纤维化修复、病毒的高复制及流行,因此,对患者基因分型及病毒变异进行有效监控,将为海府地区慢性HBV感染者的管理开辟新的途径,具有很高的临床实用价值.     

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。     

黑龙江省乙型肝炎病毒拉米夫定耐药株YMDD变异与基因型、BCP区变异的相关性研究

目的 探讨黑龙江省乙型肝炎病毒(HBV)拉米夫定耐药株YMDD变异与基因型、HBV BCP变异之间的相关性.方法 对收集的245例经拉米夫定治疗的慢性乙型肝炎患者血清标本,采用多重PCR法检测HBV的基因型;荧光标记杂交双探针PCR融解曲线法(FH-PCR-MC)检测HBV YMDD变异及变异类型;巢式PCR法扩增HBV C基因区,测序分析BCP位点变异并进行统计学分析.结果 在HBV YMDD野生株、变异株中,基因型B、C、B与C混合型分别为8.8％、89.2％、2.0％;6.3％、93％、0.7％,基因型构成比无统计学的差异.HBV BCP的变异率在YMDD野生株与变异株分别为69.6％、76.9％,无统计学的差异.在HBV YMDD野生株中,HBV B基因型BCP的变异率22.2％,C基因型BCP的变异率73.6％存在统计学差异(P＜0.01),但在YMDD变异株中,无统计学的差异.在YIDD、YVDD变异株HBV BCP变异率分别为83.0％和64.6％,存在统计学的差异(P＜0.05).结论 在HBV YMDD野生株中,与B基因型相比,C基因型更易发生BCP变异;YMDD变异株中,BCP变异率在B、C基因型间无统计学差异,BCP变异在变异类型间(YIDD、YVDD)存在统计学差异;与YVDD变异株相比较,YIDD变异株易发生HBV BCP的变异.     

沈阳地区家庭聚集性感染HBV的家庭HBV前C区基因突变率及其临床意义的研究

目的 研究沈阳地区家庭聚集性感染乙型肝炎病毒的家庭HBV前C区1896位G→A基因突变率及其临床意义。方法 采用PCR—RFLP法检测HBV前C区1896位G→A基因突变。结果 患者及其家庭成员HBV前C区1896位G→A基因突变发生率分别为56．3％和40．5％，明显高于患者配偶25．0％的突变发生率，且配偶中抗-HBs阳性率为26．3％。同时，这种突变在慢性乙型肝炎患者中的发生率为52．4％，在HBV携带者中的发生率为44．4％，在慢性重型肝炎患者中的发生率仅为20．0％。结论 HBV前C区1896位G→A基因突变的发生，可能与HBV的持续感染有关。     

Hepatitis B virus (HBV) subgenotypes C2 and B2 differ in lamivudine- and adefovir-resistance-associated mutational patterns in HBV-infected Chinese patients

We aimed to study the prevalence and clinical implications of hepatitis B virus (HBV) subgenotypes in Chinese patients. A total of 4,300 patients, mainly from northern China, were enrolled, including 182 patients with acute hepatitis B and 4,118 patients with chronic HBV infection who had been exposed to nucleoside or nucleotide analogs. HBV genotypes/subgenotypes were determined by direct sequencing of the HBV S/Pol region. The prevalence rates were 0.40% for HBV/B1, 14.30% for HBV/B2, 0.25% for HBV/B3, 0.35% for HBV/B4, 1.05% for HBV/C1, 81.72% for HBV/C2, 0.93% for HBV/C3, 0.16% for HBV/C4, and 0.84% for HBV/D. In chronic HBV infection, patients with HBV/B2 were younger and had lower ΗBeAg positive rates than patients with HBV/C2. The incidence of lamivudine-resistant mutations was significantly higher in HBV/C2 compared to HBV/B2 (27.9% versus 19.8%; P<0.01), and the significant difference was observed only for rtM204I and not rtM204V. In addition, compensatory mutations were more frequently detected in HBV/C2. The incidence of adefovir-resistant mutations was similar between the two subsets, but HBV/C2 inclined to show rtA181V (3.6% for C2 versus 0.9% for B2; P<0.01), while HBV/B2 inclined to show rtN236T (4.5% for versus 2.5% for C2; P<0.01). The ratios of HBV/B2 to HBV/C2 infection were 1.7 (110/65), 5.7 (2,653/463), 7.5 (520/69), 8.0 (48/6), and 15.3 (183/12) for acute hepatitis B, chronic hepatitis B, liver cirrhosis, acute-on-chronic liver failure, and hepatocellular carcinoma, respectively. In conclusion, HBV/C2 and HBV/B2, two prevalent subgenotypes, differ in lamivudine- and adefovir-resistance-associated mutational patterns. HBV/C2-infected patients are more likely to have disease progression than HBV/B2-infected ones.     

Hepatitis B virus genotyping, core promoter, and precore/core mutations among Afghan patients infected with hepatitis B: a preliminary report

In spite of hepatitis B virus (HBV) vaccination, HBV infection remains an important public health problem worldwide. Although the HBV genotype distribution has been determined in some parts of South Central Asia, no survey has been conducted to determine the HBV genotype in Afghanistan. Twelve Afghan patients infected with HBV living in Afghanistan were enrolled in this study. Partial HBsAg and basic core promoter, precore, and core (BCP/preC/C) regions were amplified and subjected for direct sequencing. In parallel, precore G1896A mutation was also determined by an amplification-created restriction site method. Results revealed HBV genotype D (95% bootstrap value), sub-genotype D1 (98% bootstrap value), and subtype ayw2 in all Afghan isolates. Afghan isolates clustered in a separate branch in the D1 sub-genotype called D1', while supported by 82% bootstrap value. The percentage of intra-genotypic distance among Afghan isolates was 1.05% and inter-genotypic distance with the other genotype D was 2.87% and with other genotypes was 7.50%-11.1%. The wild-type, mixed infection, and precore mutant were found in six, two, and four HBV isolates, respectively. The A1762T/G1764A BCP dual mutation was found in one isolate. Three isolates presented single mutation in the BCP dual mutation region, whereas two showed a novel G1764T mutation. In conclusion, this preliminary study revealed HBV genotype D, sub-genotype D1, and subtype ayw2 of HBV among hepatitis B infected patients from Afghanistan. Further investigation should be carried out.     

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.     

Characterization of hepatitis B virus mutations in untreated patients co‐infected with HIV and HBV based on complete genome sequencing

Co‐infection of HBV with HIV results in an accelerated course of HBV‐associated chronic liver disease. Several studies have shown that viral mutations are related to disease progression in mono‐infection with HBV. However, it is unclear whether HBV mutation patterns might differ between co‐infected and mono‐infected patients. To compare the frequencies and mutation patterns in the HBV genome between co‐infection and mono‐infection. Twenty‐four treatment‐naïve co‐infected and 31 treatment‐naïve mono‐infected Thai patients were included. HBV mutations were characterized by whole genome sequencing of virus serum samples. The clinical features and frequency of known clinically significant mutations were compared between the two groups. No significant difference between the groups was found with respect to sex, age and HBeAg. However, HBV DNA levels were significantly higher in co‐infected patients. The distribution of HBV genotypes was comparable between the two groups and restricted mostly to sub‐genotypes C1 and B2. An isolate with recombinants of genotypes G/C1 was also identified in a patient with co‐infection. There was no difference in the prevalence of mutations in the enhancer II/basal core promoter/precore region, pre‐S/S and polymerase genes between the two groups. In conclusion, dual infections tend to engender increased HBV DNA levels. There was no major difference in the frequencies of common HBV mutations between co‐infected and mono‐infected patients. Thus, HBV mutations may not contribute to disease pathogenesis in Thai patients with co‐infection. J. Med. Virol. 85:16–25, 2012. © 2012 Wiley Periodicals, Inc.     

HBV基因型与HBx基因变异的研究

目的分析慢性HBV感染者血清中HBV基因型和HBx基因多态性,探讨HBx基因变异与HBV基因型的关系。方法采用型特异性引物PCR法对110份慢性HBV感染者血清中HBV基因型进行检测。采用巢式PCR、单链构象多态性与异源双链分析、以及基因测序和生物信息学方法分析HBx基因突变。结果在110份慢性HBV感染者血清中,检出B型、C型和混合型B＋C,分别占57份（56.8%）、49份（44.6%）和4份（3.6%）。与参考序列相比,B型与C型HBx基因都存在点突变,且C型点突变数明显多于B型（t=-12.599,P〈0.05）。结论慢性HBV感染者HBx基因突变与HBV基因型密切相关。     

HBV基因型与HBV感染慢性化、重症化的关系

目的 探讨HBV基因型与HBV感染后慢性化、重症化的关系.方法 应用型特异性引物聚合酶链反应法,对中国2922例HBV感染者进行HBV基因型检测,比较各临床类型HBV感染者基因型分布差异及各基因型HBV感染者肝功能和病毒学差异.结果 2922例HBV感染者中,基因型B、C、B/C、D分别占15.9%、83.5%、0.41%、0.21%.与慢性肝炎比较急性肝炎B基因型所占比例较高（P=0.003）,肝硬化和肝细胞性肝癌C基因型所占比例较高（P值均为0.000）,慢加急性肝衰竭与慢性肝炎比较基因型分布差异无统计学意义.急性肝炎和慢性肝炎B、C基因型患者HBeAg 阳性率、HBV DNA病毒载量、肝功能生化指标差异无统计学意义.慢加急性肝衰竭、肝硬化、肝细胞性肝癌组C基因型较B基因型患者HBeAg阳性率更高（P值分别为0.000、0.024、0.003）,肝细胞性肝癌C基因型患者HBV DNA病毒载量高于B基因型患者（P=0.025）,慢加急性肝衰竭和肝细胞性肝癌组C基因型较B基因型患者胆碱酯酶更低（P值为0.0004、0.02）.结论 中国HBV感染者的HBV基因型以B、C基因型为主,少量的B/C、D基因型;C基因型较B基因型HBV感染者更易发生慢性化和进展为肝硬化和肝细胞性肝癌,但未观察到基因型对慢加急性肝衰竭发生的差异.急性和轻症HBV感染者B、C基因型未显示对病情的明显影响,但重症和终末期HBV感染者C基因型较B基因型患者HBeAg阳性率、HBV DNA病毒载量更高,肝功能损害更严重.     

Characterization of Full-Length Genomes of Hepatitis B Virus Quasispecies in Sera of Patients at Different Phases of Infection

Hepatitis B virus (HBV) infection results in different clinical presentation due to different levels of immune response. Our study aimed to characterize HBV full-length genome quasispecies (QS) in patients with different phases of infection to better understand its pathogenesis. Forty treatment-naive HBV-infected patients were enrolled, including 10 cases of acute hepatitis B (AHB), 9 cases of immunotolerant (IT) HBV carriers, 11 cases of chronic hepatitis B (CHB), and 10 cases of acute-on-chronic liver failure (ACLF). The present study was conducted by clone-based sequencing. QS heterogeneity within each open reading frame was calculated. The mutation frequency index (MFI) and amino acid variations within the large HBsAg, HBcAg, and HBxAg regions were analyzed based on the different infection phases. In total, 606 HBV full-length sequences were obtained. HBV QS had higher heterogeneity in ACLF and CHB than that in IT among chronically infected individuals. AHB patients had the lower QS heterogeneity at onset than those with chronic infection. ACLF patients had the highest frequency of mutations in the core promoter and precore region. A triple mutation (A1762T/G1764A/G1896A) was observed more frequently in genotype C than in genotype B. The MFI indicated that specific peptides of the studied regions had more frequent mutations in ACLF. Furthermore, several amino acid variations, known as T- and B-cell epitopes, were potentially associated with the immunoactive phase of infection. More HBV genome mutations and deletions were observed in patients with more severe diseases, particularly in specific regions of the core and preS regions, the clinical significance and mechanism of which need to be further investigated.