Effects of Entecavir on Hepatitis B Virus Covalently Closed Circular DNA in Hepatitis B e Antigen-Positive Patients with Hepatitis B

The aim of this study was to assess the effect of 48-week entecavir therapy on serum and intrahepatic hepatitis B virus, covalently closed circular DNA (HBV cccDNA) levels in hepatitis B e antigen (HBeAg)-positive patients. A total of 120 patients with HBeAg-positive chronic hepatitis were treated with entecavir for 48 weeks. Serum HBV markers, total HBV DNA, and HBV cccDNA levels were measured at baseline and week 48. Biopsies from 20 patients were available for both intrahepatic total HBV DNA and cccDNA testing at these timepoints. HBV cccDNA levels were decreased from a median level of 5.1×10⁶ copies/mL at baseline to a median level of 2.4×10³ copies/mL at week 48. Reduction magnitudes of HBV cccDNA in patients with normalized alanine aminotransferase levels and those undergoing HBeAg seroconversion were significantly greater than those in alanine aminotransferase-abnormal and HBeAg positive patients. Intrahepatic HBV cccDNA was decreased significantly after 48 weeks of treatment, but could not be eradicated. In conclusion, treatment of HBeAg-positive hepatitis B patients with entecavir for 48 weeks decreased serum and intrahepatic HBV cccDNA significantly, and the magnitude of HBV cccDNA reduction was related to total HBV DNA decrease, alanine aminotransferase normalization, and HBeAg seroconversion.     

抗原抗体复合物型治疗性疫苗(乙克)临床研究中患者血清乙型肝炎病毒表面抗原下降的分析与启示

近年来全球慢性乙型肝炎(chronic hepatitis B,CHB)防治指南提出了“功能性治愈”(functional cure)的概念,即患者经过治疗达到血清乙型肝炎病毒表面抗原(hepatitis B virus surface antigen,HBsAg)消失,但现有抗病毒治疗很难实现这一目标。本研究对既往临床试验中经抗原抗体复合物型治疗性疫苗(乙克)治疗后的CHB患者HBsAg下降情况进行了归纳分析,结果显示,经乙克治疗随访后达到乙型肝炎e抗原(hepatitis B e antigen,HBeAg)血清学转换者的HBsAg下降高达0.95log₁₀IU/mL,显著高于未达到HBeAg血清学转换者的0.32log₁₀IU/mL(P<0.01),而经氢氧化铝佐剂治疗随访后发生HBeAg血清学转换(0.49log₁₀IU/mL)者与未发生HBeAg血清学转换者(0.36log₁₀IU/mL)之间HBsAg下降无统计学差异。乙克组治疗过程中,丙氨酸氨基转移酶(alanine aminotransferase,ALT)骤升(ALT flare)在HBsAg下降>1.0log₁₀IU/mL者中较多见,氢氧化铝组未观察到此现象。回归分析显示,乙克治疗后HBsAg下降的影响因素有患者出现HBeAg血清学转换、感染的HBV为B基因型、治疗过程中ALT出现10倍增高,以及基线血清HBsAg为高水平。结果提示,乙克诱导的特异性免疫对降低CHB患者血清HBsAg水平有一定效果,采用“抗病毒药物治疗＋针对HBsAg的中和性抗体被动免疫＋乙克主动免疫”的“三明治”治疗策略可能会提高“功能性治愈”率。     

Hepatitis B viral factors and clinical outcomes of chronic hepatitis B

Hepatitis B virus (HBV) infection is an important health problem and the major cause of chronic hepatitis, cirrhosis as well as hepatocellular carcinoma (HCC) worldwide. The natural history of chronic HBV infection can be divided into 4 dynamic phases in HBV carriers who acquire the virus early in life. In general, the frequency and severity of hepatitis flares in the immune clearance or reactivation phase predict disease progression in HBV carriers, and early HBeAg seroconversion typically confers a favorable outcome. In contrast, late or absent HBeAg seroconversion after multiple hepatitis flares accelerates the progression of chronic hepatitis to cirrhosis. Recently, several hepatitis B viral factors predictive of clinical outcomes have been identified. For example, serum HBV DNA level at enrollment is the best predictor of adverse outcomes (cirrhosis, HCC and death from liver disease) in adults with chronic HBV infection. In addition, HBV genotype C, basal core promoter (BCP) mutant and pre-S deletion mutant are associated with increased risk of HCC development. In conclusion, hepatitis B viral factors such as serum HBV DNA level, genotype and mutants have already been clarified to influence disease progression of chronic hepatitis B. Further studies are needed to investigate the pathogenic mechanism of each viral factor.     

Analysis of precore/core covariances associated with viral kinetics and genotypes in hepatitis B e antigen-positive chronic hepatitis B patients

Hepatitis B virus (HBV) is one of the most common DNA viruses that can cause aggressive hepatitis, cirrhosis and hepatocellular carcinoma. Although many people are persistently infected with HBV, the kinetics in serum levels of viral loads and the host immune responses vary from person to person. HBV precore/core open reading frame (ORF) encoding proteins, hepatitis B e antigen (HBeAg) and core antigen (HBcAg), are two indicators of active viral replication. The aim of this study was to discover a variety of amino acid covariances in responses to viral kinetics, seroconversion and genotypes during the course of HBV infection. A one year follow-up study was conducted with a total number of 1,694 clones from 23 HBeAg-positive chronic hepatitis B patients. Serum alanine aminotransferase, HBV DNA and HBeAg levels were measured monthly as criteria for clustering patients into several different subgroups. Monthly derived multiple precore/core ORFs were directly sequenced and translated into amino acid sequences. For each subgroup, time-dependent covariances were identified from their time-varying sequences over the entire follow-up period. The fluctuating, wavering, HBeAg-nonseroconversion and genotype C subgroups showed greater degrees of covariances than the stationary, declining, HBeAg-seroconversion and genotype B. Referring to literature, mutation hotspots within our identified covariances were associated with the infection process. Remarkably, hotspots were predominant in genotype C. Moreover, covariances were also identified at early stage (spanning from baseline to a peak of serum HBV DNA) in order to determine the intersections with aforementioned time-dependent covariances. Preserved covariances, namely representative covariances, of each subgroup are visually presented using a tree-based structure. Our results suggested that identified covariances were strongly associated with viral kinetics, seroconversion and genotypes. Moreover, representative covariances may benefit clinicians to prescribe a suitable treatment for patients even if they have no obvious symptoms at the early stage of HBV infection.     

恩替卡韦治疗HBeAg 阳性乙型肝炎临床观察

目的:探讨恩替卡韦治疗HBeAg阳性乙型肝炎的疗效与安全性。方法:140例慢性乙肝患者随机分为2组:观察组予恩替卡韦0.5 mg/d,对照组予拉米夫定100 mg/d,疗程均为48周。观察两组HBV DNA阴转率、ALT复常率、HbeAg血清转换率以及不良反应发生情况。结果:在治疗12周后,观察组与对照组HBV DNA阴转率分别为47.1%、22.9%(P<0.01),ALT复常率分别为51.4%、31.4%(P<0.05),在治疗48周后,观察组与对照组HBV DNA阴转率分别为88.6%、48.6%(P<0.01),ALT复常率分别为90.0%、72.9%(P<0.01)。HbeAg血清转换率无统计学差异,两组患者未见严重不良反应。结论:恩替卡韦治疗HBeAg阳性乙肝患者,较拉米夫定起效快、作用强,且安全性好。     

恩替卡韦治疗HBeAg阳性乙型肝炎临床观察

目的：探讨恩替卡韦治疗HBeAg阳性乙型肝炎的疗效与安全性。方法：140例慢性乙肝患者随机分为2组：观察组予恩替卡韦0．5mg／d,对照组予拉米夫定100mg／d,疗程均为48周。观察两组HBVDNA阴转率、ALT复常率、HbeAg血清转换率以及不良反应发生情况。结果：在治疗12周后,观察组与对照组HBVDNA阴转率分别为47．1％、22．9％（P〈0．01）,ALT复常率分别为51．4％、31．4％（P〈0．05）,在治疗48周后,观察组与对照组HBVDNA阴转率分别为88．6％、48．6％（P〈0．01）,ALT复常率分别为90．0％、72．9％（P〈0．01）。HbeAg血清转换率无统计学差异,两组患者未见严重不良反应。结论：恩替卡韦治疗HBeAg阳性乙肝患者,较拉米夫定起效快、作用强,且安全性好。     

乙型肝炎病毒e抗原的生物学功能及血清学转换的免疫学基础

目前在临床乙型肝炎的治疗中,乙型肝炎病毒e抗原(HBeAg)消失及其抗体的出现已成为重要的疗效指标.本文回顾了HBeAg的发现及其生物学和医学意义,对HBeAg与乙型肝炎病毒核心抗原(HBcAg)的免疫原性进行了比较,阐述了HBeAg血清学转换的免疫学基础,并对出现HBeAg血清学转换的意义作了分析.     

聚乙二醇干扰素α-2b治疗61例e抗原阳性慢性乙型肝炎临床分析

目的探讨聚乙二醇化干扰素α-2b治疗e抗原(HBeAg)阳性慢性乙型肝炎的临床疗效和不良反应,同时探讨影响应答的相关因素。方法用聚乙二醇干扰素α-2b治疗61例HBeAg阳性慢性乙型肝炎,治疗期间定期监测血常规、生物化学指标、病毒学标志、甲状腺功能等。结果 48周,表面抗原(HBsAg)和HBeAg血清学转换率分别为5.26%、31.2%;血清HBV DNA阴转率为59.6%;ALT复常率为64.9%。随访半年,HBV DNA复发率为17.4%;HBeAg血清学转换者维持应答。治疗前ALT>5 ULN时,48周时HBeAg血清学转换率和HBV DNA阴转率明显高于ALT<5 ULN时,二者比较差异有统计学意义;而血清HBV DNA水平与其无明显相关性。结论聚乙二醇化干扰素α-2b具有免疫调节和抗病毒双重作用,48周时HBeAg血清学转换率和HBV DNA阴转率与治疗前血清ALT水平与相关,停药后具有持续应答效应。     

恩替卡韦联合胸腺肽α1治疗慢性乙型肝炎疗效研究

目的：观察和比较恩替卡韦联合胸腺肽α1治疗HBeAg阳性慢性乙型肝炎的疗效。方法：选取我院58例HBeAg阳性慢性乙型肝炎患者分成联合组和对照组。联合组28例,初始同时使用恩替卡韦及胸腺肽αl24周,之后停胸腺肽αl继续用恩替卡韦至48周。对照组30例,单用恩替卡韦0．5mg／d,48周。定期检测ALT复常率,HBVDNA转阴率,HBeAg／抗HBe血清转换率,肝纤维化组合,Fibroscan评分两组在治疗结束时进行疗效评价。结果：24周时两组ALT复常率无差异显著性（P〉0．05）,联合组和对照组HBVDNA阴转率在24周、48周时均差异有显著性（P〈0．05）。联合组与单用组HBeAg血清转换率在第24周、48周时,两组比较差异均有显著性（P〈0．05）。肝纤维化组合各指标（HA,LN,PIIIP,Ⅳ型胶原）,Fibroscan评分两组治疗48周后比较差异均有显著性（P〈0．05）,且两组治疗前后差异联合组更显著。治疗过程中,未发现明显副作用。结论：恩替卡韦联合胸腺肽d1治疗HBeAg阳性慢性乙型肝炎,安全性与耐受性良好,联合组在ALT复常率,HBeAg血清转换率和HBVDNA转阴率,抗肝纤维仲韵井种P昂荽楫干蕈闱凰巷卡韦组．     

不同临床类型乙型病毒感染者外周血T 细胞亚群与血清HBV DNA 载量 及HBeAg 滴度相关性分析

目的:探讨慢性乙型肝炎病毒(HBV)感染患者外周血T细胞亚群与血清HBV DNA载量及HbeAg滴度的关系。方法:选取103名HBV感染患者和20名健康者为研究对象。流式细胞术检测外周血T细胞亚群,聚合酶链式反应及酶免疫分析法分别检测血清HBV DNA载量及HbeAg滴度。结果:慢性乙型肝炎患者和慢性HBV携带者外周血CD3+T、CD4+T淋巴细胞亚群百分数低于健康对照组,结果有统计学意义(P<0.05或0.01;而CD8+T细胞亚群则呈现相反趋势,结果亦有统计学意义(P<0.05或0.01)。HBeAg阴性组中,HBVDNA水平与CD8+T细胞亚群百分数呈正相关(r=0.567,P<0.01),与CD4+/CD8+T细胞亚群百分数比值呈负相关(r=-0.601,P<0.01),而与CD3+T、CD4+T细胞亚群百分数无相关性。HBeAg阳性组中,HBV DNA水平及HbeAg滴度与CD3+T、CD4+T、CD8+T细胞百分数及CD4+/CD8+T细胞百分数均无相关性(P>0.05)。结论:不同临床类型的慢性乙型肝炎病毒感染患者外周血T细胞亚群存在不同程度细胞免疫功能降低和细胞免疫调节异常。HbeAg阴性的HBV感染患者,其血清HBV DNA水平与外周血T淋巴细胞免疫存在相关性。     

不同临床类型乙型病毒感染者外周血T细胞亚群与血清HBVDNA载量及HBeAg滴度相关性分析

目的：探讨慢性乙型肝炎病毒（HBV）感染患者外周血T细胞亚群与血清HBVDNA载量及HbeAg滴度的关系。方法：选取103名HBV感染患者和20名健康者为研究对象。流式细胞术检测外周血T细胞亚群,聚合酶链式反应及酶免疫分析法分别检测血清HBVDNA载量及HbeAg滴度。结果：慢性乙型肝炎患者和慢性HBV携带者外周血CD3可、CD4T淋巴细胞亚群百分数低于健康对照组,结果有统计学意义（P〈0．05或0．01;而CD8＋T细胞亚群则呈现相反趋势,结果亦有统计学意义（P〈0．05或0．01）。HBeAg阴性组中,HBVDNA水平与CD8T细胞亚群百分数呈正相关（r=0．567,P〈0．01）,与CD47CD8＋T细胞亚群百分数比值呈负相关（r=-0．601,P〈0．01）,而与CD3＋T、CD4＋T细胞亚群百分数无相关性。HBeAg阳性组中,HBVDNA水平及HbeAg滴度与cD3＋1r、cD41、CD8叮细胞百分数及CD47CD8＋T细胞百分数均无相关性（P〉0．05）。结论：不同临床类型的慢性乙型肝炎病毒感染患者外周血T细胞亚群存在不同程度细胞免疫功能降低和细胞免疫调节异常。HbeAg阴性的HBV感染患者,其血清HBVDNA水平与外周血T淋巴细胞免疫存在相关性。     

荧光分子信标探针检测拉米夫定耐药基因的研究

建立荧光分子信标探针方法,探讨乙肝病毒对拉米夫定耐药的发生及病程进展。观察77例乙肝病人口服拉米夫定治疗前及治疗后12个月及24个月肝功能(ALT)及免疫学指标及检测HBVDNA含量,并采用PCR荧光分子信标技术检测YMDD耐药突变株(包括YIDDYVDD突变株)。结果表明,口服拉米夫定12个月或24个月,近半数病人血清HBVDNA转阴(小于01pgml),35%(2777)的病人出现e抗原血清转换或单纯e抗原转阴,而e抗原血清转换绝大多数发生于HBVDNA低于100pgml血清的病人。30%(2376)的病人出现YMDD耐药(YIDDYVDD),在HBVDNA小于10pgml(106拷贝ml)的病人中YMDD耐药株与野生株共存。加大口服拉米夫定剂量,绝大多数YMDD耐药株仍不能转变为YMDD野生株。提示中国乙肝患者YMDD耐药后不适合加大剂量继续使用拉米夫定治疗 。     

Comparison of the Efficacies and Safety of Combined Therapy between Telbivudine Plus Adefovir and Lamivudine Plus Adefovir in Patients with Hepatitis B Virus Infection in Real-World Practice

MethodsThis study enrolled a total of 171 patients (110 patients received LAM+ADV and 60 patients received LdT+ADV). We analyzed the changes in renal function using the estimated glomerular filtration rate (eGFR). The DNA undetectable rate, hepatitis B e antigen (HBeAg) seroconversion rate, and alanine aminotransferase (ALT) normalization rate were analyzed. We checked the serum uric acid, phosphate and creatine kinase, and lactic acid levels to analyze safety. We observed these patients for 48 to 240 weeks and checked their serum profile every 6 months.ResultsThere was no statistically significant difference between the two groups in anti-hepatitis B virus (HBV) efficacy in terms of DNA undetectable rate, ALT normalization rate, and HBeAg seroconversion rate. Both the LAM+ADV and LdT+ADV groups had stable or improved renal function. However, a higher eGFR was found in the LdT+ADV group with continuous serum fluctuation during 3 years of combined therapy as well as a higher serum creatine kinase level.ConclusionsLong-term LdT+ADV combined therapy and LAM+ADV combined therapy were both associated with stable or improved renal function. The clinical efficacy was similar between the two groups, but the LdT group had a higher serum creatine kinase level. We need to monitor the data regularly in clinical practice.     

Levels of hepatitis B virus replicative intermediate in serum samples of chronic hepatitis B patients

Hepatitis B virus (HBV) cccDNA levels is an absolute marker of HBV replication in the liver of HBV infected patients. This study aimed to quantify the HBV cccDNA levels in sera and liver tissue samples of treatment naïve patients with chronic hepatitis B. Eighty one chronic hepatitis B (CHB) treatment naïve patients were enrolled from January 2009 to June 2011. Total HBV DNA and HBV cccDNA levels were quantified using sensitive real time PCR assay. The mean age of recruited patients was 34 ± 11.5 years. Fifty four (66.7 %) patients were HBeAg negative. Liver tissue samples were available from 2 HBeAg positive and 21 HBeAg negative CHB patients. The amount of total intrahepatic HBV DNA ranged from 0.09 to 1508.92 copies/cell. The median intrahepatic HBV cccDNA was 0.31 and 0.20 copies/cell in HBeAg positive and HBeAg negative cases, respectively. Serum HBV cccDNA was detectable in 85.2 % HBeAg positive and 48.1 % HBeAg negative CHB patients. Median serum HBV cccDNA was 46,000 and 26,350 copies/mL in HBeAg positive and HBeAg negative subjects, respectively. There was a significant positive correlation between the levels of intrahepatic total HBV DNA and intrahepatic HBV cccDNA (r = 0.533, p = 0.009). A positive correlation was also seen between serum HBV cccDNA levels and serum HBV DNA levels (r = 0.871, p < 0.001). It was concluded that serum HBV cccDNA could be detectable in higher proportion of HBeAg positive patients compared to HBeAg negative patients. Moreover, the median level of serum HBV cccDNA was significantly higher in HBeAg positive patients in contrast to HBeAg negative subjects.     

Pegylated interferon alpha-2a (40 kDa) in the treatment of chronic hepatitis B

Chronic hepatitis B virus (HBV) is a serious and life-threatening disease afflicting 350 million of the world's population. So far, current monotherapy with conventional interferon-alpha, lamivudine, and adefovir dipivoxil remains unsatisfactory. In addition, the use of conventional interferon-alpha needs to be administered subcutaneously daily or thrice weekly and is associated with frequent adverse events. Although nucleoside-nucleotide analogs such as lamivudine and adefovir dipivoxil are well tolerated and can normalize serum alanine aminotransaminase rapidly, 1-year therapy with either lamivudine or adefovir dipivoxil results in low hepatitis B e antigen (HBeAg) seroconversion rates. In HBeAg negative patients, most of the patients would relapse after lamivudine has been discontinued. Pegylated interferon alpha-2a, an immunomodulatory agent, is a new drug that has just completed phase III clinical trials for the treatment of both HBeAg positive and HBeAg negative chronic HBV infection. The advantage of pegylated interferon alpha-2a in achieving sustained virological response over nucleoside-nucleotide analogs is particularly obvious in the HBeAg negative group. In both of these phase III studies, sustained off-treatment response is superior to the use of lamivudine. These recent data put pegylated interferon alpha-2a as the first choice of anti-HBV therapy, especially in young and motivated patients with chronic HBV infection.     

新疆维吾尔族与汉族乙型肝炎患者HBVDNA 及肝功能检测结果的比较

目的:探讨新疆乌鲁木齐地区伴有肝功能指标:丙氨酸氨基转移酶(ALT)浓度异常的维吾尔族(维族)及汉族HBeAg阳性乙型肝炎初次就诊患者,乙型肝炎病毒DNA复制载量及ALT浓度是否存在差异及其对患者诊断、预后的意义。方法:回顾性选取门诊伴有ALT浓度异常的汉族、维族初次就诊患者并筛选出HBeAg阳性患者汉族、维族共373例。采用实时荧光定量聚合酶链反应、生化测定及酶联免疫吸附试验法分别测定HBV DNA、ALT浓度及乙肝HBeAg。结果:(1)汉族HBV DNA组秩和8869,维族HBV DNA组秩和10359.36,经Mann-Whitney Test检验两组间尚不能肯定HBVDNA分布有统计学意义,即伴有肝功能损害的汉族、维族初次就诊HBeAg阳性患者HBV DNA复制程度没有差异。(2)汉族ALT组秩和26818.50,维族ALT组秩和22009.50,经Mann-Whitney Test检验两组间ALT分布有统计学意义,即伴有肝功能损害的初次就诊HBeAg阳性患者汉族肝功能损害程度高于维族。(3)HBVDNA低复制组(103-104copy/mL):汉族秩和3771.46,维族秩和4993.2;中复制组(104-106copy/mL):汉族秩和6412.4,维族秩和5088.2;高复制组(>106copy/mL):汉族秩和929.04,维族秩和666.96,经Mann-Whitney Test检验在低复制组两民族间ALT分布无统计学意义,在中、高复制组两民族间ALT具有统计学意义。即:伴有肝功能损害的初次就诊HBeAg阳性患者在HBV DNA低复制组两民族间肝功能损害程度无差异,但在中、高复制组汉族肝功能损害程度高于维族。结论:新疆乌鲁木齐地区伴有肝功能损害的初次就诊的HBeAg阳性的汉族与维族之间HBV DNA的病毒复制无统计学意义(P>0.05),但两民族间的ALT具有统计学意义,可能跟维族的民俗、饮食习惯及生存环境、免疫相关基因HLA基因频率分布差异等因素有关。     

内蒙古地区乙型肝炎病毒的基因分型及临床意义

为了探讨乙型肝炎病毒在内蒙古地区的基因分型,为本地区乙型肝炎的临床治疗、病情进展和发病机制等方面研究提供有益的实验依据。2013年7月至2014年7月本研究在内蒙古自治区人民医院、内蒙古医科大学第一附属医院、通辽市医院的门诊及住院病例中随机选取已感染乙型肝炎病毒的253例。以荧光定量PCR法检测HBV基因分型和HBV病毒基因载量,Elisa法检测血清标志物HBeAg,全自动生化分析仪检测ALT、AST、TBA、TBIL和ALB。实验发现,内蒙古地区253例患者HBV基因分型结果以B型(49例,19.37%)、C型(188例,74.31%)为主,且C基因型显著多于B基因型(p<0.05);HBeAg阳性率为67.59%,且C基因型HBeAg阳性率高于B基因型;高载量病例中B型占31例(63.27%),而C型占162例(86.17%),C基因型组中HBV DNA载量显著高于B基因型组(p<0.01);B基因型与C基因型TBA、TBIL和ALB结果比较差异无统计学意义(p>0.05),但C基因型的ALT和AST这两项生化指标均显著高于B基因型组(p<0.05)。本研究结果初步说明,内蒙古地区HBV感染以B型和C型为主,尤以C型居多;且C型病毒的复制较活跃,致病力较强,HBV感染者更易转成严重肝病。     

利用基因芯片分析拉米夫定治疗过程中HBV DNA的基因变异

依据乙型肝炎病毒(Hepatitis B virus;HBV)聚合酶基因序列研制HBV基因芯片,此芯片可分析HBV的7个基因型、4种血清型和HBV聚合酶基因rtV173、rtL180、rtM204和rtV207位点的突变。利用此芯片对A、B两组共计45例拉米夫定治疗12个月的患者进行服药前和服药后3、6、9、12个月的动态检测,其中C基因型39例,且血清型均为adr;B基因型6例,其血清型均为adw。在完成全程检测的38例患者中,17例ALT升高的A组出现1例拉米夫定耐药变异株,而21例ALT正常的B组出现4例变异株,且所有变异株均为rtM204 V／rtL180M,其中2例野生株和变异株共存。rtM204V变异最早在服药6个月时出现,随后出现rtL180M变异。10份PCR产物测序分析表明,芯片检测结果与测序结果基本一致,仅在rtL173位点出现1例差异。进一步分析HBV DNA变异与HBV DNA含量、ALT水平和HBeAg血清转换率的相关性,初步结果表明变异株的出现与治疗过程中的DNA反弹呈正相关,而与起始HBVDNA水平、ALT值无关联。HBV基因芯片可初步用于HBV DNA检测,可能是临床追踪评价抗病毒治疗效果的较好方法之一。     

内江地区慢性乙型肝炎患者的基因型及拉米夫定联合阿德福韦酯抗病毒治疗效果

目的探讨内江地区慢性乙型肝炎患者的基因型及拉米夫定联合阿德福韦酯抗病毒的治疗效果。方法将201例慢性乙型肝炎患者进行HBV基因型的测定,其中120例HBeAg(+)慢性乙型肝炎患者随机分为三组:A组、B组和C组,每组40例。A组给予拉米夫定(LAM)治疗;B组给予恩替卡韦(ETV)治疗;C组给予LAM联合阿德福韦酯(ADV)治疗,比较治疗情况。结果 201例慢性乙型肝炎患者中B型119例(59.2%),C型68例(33.8%),B/C混合型10例(5.0%),未知型4例(2.0%),各分型之间的性别、年龄差异无统计学意义(P0.05)。C型感染者HBeAg阳性率为86.8%,显著高于B型的51.3%(P0.05)。HBeAg(+)的3组患者治疗12、24和48周时,B组和C组患者的ALT复常率、HBV DNA阴转率及48周时的HBeAg血清转换率均显著高于A组(P0.05);C组患者与B组比较差异无统计学意义(P0.05)。治疗期间均未见不良反应发生。C组患者(包括B型19例、C型21例)中B型的HBV DNA阴转率及HBeAg血清转换率显著高于C型(P0.05)。结论地处西南方的内江地区慢性乙型肝炎患者主要以B型为主,C型次之,B型和C型共占93.0%,其他型别仅占较少部分。ETV方案或LAM联合ADV方案治疗HBeAg(+)慢性乙肝疗效优于LAM治疗。初始LAM联合ADV治疗基因B型HBeAg(+)慢性乙型肝炎疗效优于C型。