慢性乙型重型肝炎患者外周血IL-18IL-4、TFNγ变化的研究

分析IL-18、IL-4、IFNγ在慢性乙型重型肝炎中的作用。采用固相夹心法酶联免疫吸附试验检测25例正常人,35例慢性乙型肝炎,45例慢性乙型重型肝炎患者血清IL-18、IL-4、IFNγ的水平。结果发现1.IL-18、IL-4三组间均有显著性差异,IFNγ慢性肝炎与慢重肝无显著性差异,但均显著高于正常对照组;2．IL-18、IL-4生存组显著低于死亡组（P〈0．05）,IFNγ两组间无显著性差异;3．重型肝炎重症期与康复期比较,IL-18、IFNγ康复后均显著性下降（P〈0．05）;4．慢重肝组IL-4与IL-18呈正相关（r=0．6,P〈0．01）;IL-4与IFNγ呈正相关（r=0．54,P〈0．01）,TL—18、IL-4、IFNγ参与了重型肝炎的发病及转归过程,在慢性重型肝炎的免疫病理中有重要作用。     

替比夫定治疗慢性乙型重型肝炎的近期疗效观察

目的观察替比夫定治疗慢性乙型重型肝炎的临床疗效。方法随机将60例慢性乙型重型肝炎患者分为2组,对照组30例采用常规综合治疗,治疗组30例常规综合治疗的基础上加用替比夫定600mg,每日一次口服。观察两组在治疗前及后在2周、4周、12周的HBVDNA,治疗前后肝功能,PTA,评估临床疗效。结果治疗组HBVDNA阴转率2,4,12周分别为33.0%,80.0%,83.3%,对照组分别为0%,3.3%,10.0%两组比较差异有统计学意义（P均〈0.01）。治疗4周后,与对照组比较在TBil降低（P〈0.01）、PTA升高（P〈0.01）方面有统计学意义,治疗组总有效率67.7%,对照组40.0%（P〈0.05）。结论替比夫定有较强的抗HBVDNA活性,且起效快,能显著改善肝功能,适合重型肝炎患者使用。     

恩替卡韦联合川芎嗪治疗慢性乙型重型肝炎疗效观察

目的观察恩替卡韦联合川芎嗪治疗慢性乙型重型肝炎的疗效。方法将72例慢性乙型重型肝炎患者,随机分为治疗组40例和对照组32例。对照组应用综合护肝治疗,治疗组在综合护肝治疗的基础上加用恩替卡韦和川芎嗪治疗。结果治疗6周后,治疗组血清总胆红素、丙氨酸氨基转移酶、天冬氨酸氨基转移酶、白蛋白和凝血酶原时间明显改善,而对照组疗效不如治疗组好;治疗组HBVDNA为2．38±1．23 lgcopies／ml,而对照组血清总胆红素、丙氨酸氨基转移酶、天冬氨酸氨基转移酶、白蛋白和凝血酶原时间为4．87±1．79 lgcopies／ml（P〈0．01）;治疗组住院时间为46．5±12．4天,而对照组为59．3±17．2天（P〈0．01）;治疗组死亡2例（5．0％）,而对照组死亡5例（15．6％）。结论恩替卡韦联合川芎嗪治疗慢性乙型重型肝炎可明显改善肝功能,降低HBVDNA载量。     

拉米夫定治疗慢性乙型重型肝炎近期疗效的观察

目的观察拉米夫定治疗慢性乙型重型肝炎的疗效。方法对25例慢性乙型重型肝炎患者临床资料进行回顾性分析。治疗组11例，对照组14例。对照组接受综合治疗，治疗组在综合治疗的基础上加用拉米夫定100mg口服，每日一次。结果治疗组存活9例(81．8％)，对照组存活4例(28．6％)。结论拉米夫定治疗伴有乙型肝炎病毒复制的慢性重型肝炎患者，可提高成活率。     

拉米夫定治疗慢性乙型重型肝炎近期疗效观察

目的　观察拉米夫定治疗慢性乙型重型肝炎的近期疗效。方法　选择慢性乙型重型肝炎病人 2 3例 ,随机分成两组 ,拉米夫定组口服拉米夫定 ( 10 0mg/d) ,其它综合治疗措施与对照组相同 ,两组疗程均为 12周 ,观察其临床、生物化学、病毒学指标变化。结果　 ( 1)拉米夫定组TBIL、PTA、Child Pugh计分较对照组下降更显著 (P <0 .0 5 ) ,而ALT、AST、ALB下降和对照组无显著差异。 ( 2 )拉米夫定组HBVDNA阴转率显著高于对照组 ( 88.9%对 3 7.5 % ,P <0 .0 5 )。( 3 )拉米夫定组病死率与对照组无显著差异 ( 18.2 %对 3 3 .3 % ,P >0 .0 5 )。结论　拉米夫定治疗慢性乙型重型肝炎 ,可缓解病情 ,改善肝功能 ,抑制HBV复制 ,但对病死率无显著影响     

乙型肝炎病毒e抗原及DNA载量对慢性乙型重型肝炎预后的影响

目的探讨乙型肝炎病毒e抗原(HBeAg)阳性、阴性及乙型肝炎病毒(HBV)DNA载量对慢性乙型重型肝炎预后的影响。方法回顾性分析2002年7月至2004年12月在北京地坛医院住院的慢性乙型重型肝炎患者206例,以HBeAg阳性、阴性及HBV DNA载量和其他可能影响预后的因素做单因素分析和多因素分析。结果 x2单因素分析显示HBeAg阳性、阴性对慢性乙型重型肝炎预后无影响(x2=0．440,OR=0．777,95％ CI 0．424～1．425,P=0．50),HBV DNA载量对预后影响显著,HBV DNA低载量组和高载量组,好转率分别为53．1％和27．O％(x2=9．806,OR=3．055,95％ CI 1．554～6．007,P=0．002)。经Logistic多元回归分析筛选出肝硬化,肝肾综合征,肝性脑病,凝血酶原时间活动度<20％,总胆红素>513μmol／L,白蛋白<30 g／L, 总胆固醇<1．6 mmol／L,血小板<5×109／L和较高载量HBV DNA(HBeAg阴性者>3×104拷贝／ml,HBeAg 阳性者>1×105拷贝／ml)等9个因子对慢性乙型重型肝炎预后有重大影响,回归系数分别是1．539、21．356、 1．398、1．650、2．440、2．266、1．738、2．631和2．656。其中HBV DNA载量对预后影响的回归系数为2．656, Wald值为7．768,P=0．005,回归系数期望值为14．235,期望值95．O％ CI为2．199～92．133。提示HBV DNA 载量在其他重要因子存在时仍是影响慢性乙型重型肝炎预后的重要因子,其重要程度仅次于肝肾综合征及Ⅱ度以上肝性脑病。结论HBeAg阳性、阴性对慢性乙型重型肝炎预后无影响,HBV DNA载量为预测慢性乙型重型肝炎预后的重要因子,HBV DNA低载量者预后较好。     

重型病毒性肝炎病原学特点及转归

探讨重型病毒尾肝炎的病原学特点。收集各型重型病毒性肝炎418例，分析其病原学分型及乙型肝炎病毒不同病原学模式与重型肝炎预后的关系。急性重型肝炎以甲型、戊型及乙型病毒性肝炎为主，乙型肝炎病毒感染治愈后病毒阴转率较高。亚急性有慢性重型肝炎以乙型肝炎病毒毒感染居首，占92．8％。在乙型肝炎病毒感染的病原学模式中，以HBsAgHBeAbHBcAb阳性的重型肝炎发病及死亡率最高。乙型肝炎病毒与其他肝炎病毒重叠感染与单独感染比较，死亡率无显著差异。单纯TTV感染可导致重型肝炎。重型肝炎发病后HBVDNA可自然阴转，阴转率可达53．6％。重型肝炎仍以乙型肝炎病毒病毒感染为主。乙型肝炎病毒前C区发生基因突变可能较易发生重型肝炎。     

镇江地区B、C基因型慢性乙型肝炎临床因素分析

目的：比较B、C基因型慢性乙型肝炎患者（慢乙肝）在临床特征上的差异，总结与C基因型乙型肝炎有关的临床因素。方法：选择经肝穿刺行肝组织病理检查、并经基因型检测确定为B、C基因型的患者共78例，检测血清HBV DNA载量，统计重型肝炎、肝硬化、肝细胞癌和HBeAg阳性发生率，确定肝组织病理炎症分级及纤维化分期。通过x^2检验和多分类Logistic多元回归，分析B、C基因型患者间上述指标的差异，总结与HBVC基因型有关的临床因素。结果：HBVC基因型慢乙肝患者血Alb、前白蛋白均低于B基因型，而ALT、TBil及凝血酶原时间（PT）均高于B基因型，差异有统计学意义。HBVC基因型慢乙肝患者比率随肝组织炎症分级G0～G4（1．8％、11、1％、20．4％、33．3％、33．3％）及纤维分期S0～S4（5．6％、5．6％、14．8％、33．3％、40．7％）进展均明显增加，而B基因型患者随炎症分级（16、7％、25、0％、25、0％、20．8％、12．5％）及纤维分期（16．7％、29．2％、20、8％、16、7％、16．7％）进展变化不大，两种基因型分布与炎症分级（x^2=11．49，P=0．022）及纤维分期（x^2=13.56，P=0．006）差异均有统计学意义。在HBV DNA〉1．0×10^6拷贝／mL时，C基因型患者比率明显高于B基因型（51．8％比12、5％），5．0×10^2～1．0×10^6拷贝／mL时差异不大（35.2％比45．8％），〈5．0×10^2拷贝／mL时明显低于B基因型（13．0％比41．7％），两种基因型分布与DNA载量差异有统计学意义（x^2=13．25，P=0．001）；C基因型慢乙肝患者HBeAg阳性率明显高于B基因型（61．1％比25．0％），差异有统计学意义（x^2=8、67，P=0、003）；C基因型患者发生失代偿期肝硬化比率明显高于B基因型（40．7％比4．2％），未发生肝硬化比率明显低于B基因型者（37.0％比75．0％），两种基因型患者发生肝硬化比率差异有统计学意义（x^2=12.47，P=0．002）。结论：C基因型慢乙肝患者与肝纤维化、炎症损伤程度、HBV标志物、肝硬化发生率及程度等均有较高的相关性。     

血浆置换治疗慢性乙型重型肝炎临床疗效观察

目的 探讨血浆置换治疗慢性乙型重型肝炎的疗效。方法 47例慢性乙型重型肝炎患者分成治疗组和对照组，在综合治疗的基础上，治疗组同时给予血浆置换治疗，观察两组治疗效果。结果 血浆置换后，患者临床症状有不同程度的改善；血浆总胆红素、丙氨酸氨基转氨酶、天门冬氨酸氨基转氨酶、凝血酶原时间较治疗前明显降低。血浆置换的不良反应发生率为17．1％。治疗组成活率61．11％，高于对照组的31．03％（P〈0.05）。结论 血浆置换治疗重型肝炎安全、有效。     

恩替卡韦联合血浆置换治疗慢性乙型重型肝炎临床观察

目的观察恩替卡韦联合血浆置换（PE）治疗慢性乙型重型肝炎的临床疗效。方法选择观察70例慢性乙型重型肝炎患者,35例给予综合治疗基础上加用恩替卡韦和PE治疗;另35例给予基础护肝治疗。结果接受恩替卡韦治疗的患者,血清总胆红素、谷丙转氨酶、HBVDNA定量分别由治疗前的286．6±127．81μmol／L、1105．8±270．3U／L、6．5±1．7log10copies／ml降至119．1±44．2μmol／L、63．7±49．1U／L和3．3±0．6log 10 copieshnl,均较对照组改善更明显（P〈0．05或P〈0．01）;治疗死亡12例（34．3％）,显著低于对照组的57．1％（20／35）。结论恩替卡韦联合PE可以有效地改善慢性乙型重型患者的肝功能,降低病死率。     

乙型肝炎e抗原阴性慢性乙型肝炎和肝硬化患者病毒基因型及丙氨酸氨基转移酶水平分析

目的观察乙型肝炎e抗原(HBeAg)阴性慢性乙型肝炎(CHB)及肝硬化患者的乙型肝炎病毒(HBV)基因型及丙氨酸氨基转移酶(ALT)水平。方法采用酶联免疫吸附法检测62例CHB和41例肝硬化患者HBV标志物和血清ALT水平,用聚合酶链反应法检测其HBV基因型。结果CHB患者中,21 例(33.9%)为HBeAg阴性,41例(66.1%)为HBeAg阳性;肝硬化患者中,28例(68.3%)为HBeAg阴性,13例(31.7%)为HBeAg阳性。CHB患者中,53例(85.5%)为C基因型,9例(14.5%)为B基因型; 肝硬化患者中39例(95.1%)为C基因型,2例(4.9%)为B基因型。HBeAg阴性CHB患者ALT>40 U/L 者的比例低于HBeAg阳性组(分别为47.6%和85.4%),差异有统计学意义(P<0.01)。HBeAg阴性肝硬化患者ALT>40 U/L者的比例低于HBeAg阳性组(分别为64.3%和92.3%)但差异无统计学意义。结论CHB 和肝硬化患者中,HBeAg阴性者的比例较高,此类患者的ALT水平较低,以C基因型占优势。     

HBV感染与慢性胆囊炎的相关性研究

目的研究HBVDNA、HBV基因型与慢性胆囊炎发病之间的关系。方法对566例乙型肝炎患者采用荧光定量PCR方法检测血清HBVDNA、HBV基因型及肝胆B超检查等。（检测HBVDNA及基因型应用的均为实时定量PCR方法,只是试剂盒不同）结果不同HBV基因型患者的慢性胆囊炎患病率存在统计学差异,HBV基因C型患者慢性胆囊炎的患病率明显高于非HBV基因C型（72.5%vs54.4%,x2=9.369,P〈0.01）;血清HBVDNA定量水平与慢性胆囊炎的患病无统计学意义（x2=1.171,P〉0.05）。结论HBV基因C型可能与慢性乙型肝炎患者中慢性胆囊炎的患病相关。     

Hepatitis B genotypes： Relation to clinical outcome in patients with chronic hepatitis B in Saudi Arabia

INTRODUCTION Hepatitis B virus (HBV) infection is a global health problem with over 350 million chronic carriers of the virus with the risk of developing chronic hepatitis, cirrhosis or hepatocellular carcinoma (HCC). HBV is a circular, partially double-s…     

抗核抗体在乙肝患者中的表现及意义

目的观察不同病程的乙肝患者血清中ANA的表达及其与肝功能、HBVDNA的关系。方法对35例乙肝携带1患者、192例慢性乙肝患者,35例乙肝肝硬化患者检测血清中的ANA、肝功能、HBVDNA,并进行统计学分析。结果1.ANA在乙肝携带、慢性乙肝及乙肝肝硬化患者的血清中呈进行性升高趋势。2.192例患者中ANA阳性者共29例占15.10%,29例ANA阳性患者的ALT、TBil、ALB及HBVDNA较163例ANA阴性患者的均有升高,两者间差异有统计学意义（P〈0.05）。结论ANA与乙肝患者的病程相关,并与HBVDNA复制水平及肝功能损伤的程度相关。     

血清cccDNA与HBVDNA、YMDD变异及肝炎复发的临床关系

目的探讨cccDNA与病毒复制及拉米夫定耐药突变(YMDD)及肝脏病变的关系。方法采用分子信标PCR技术检测HBV携带者(ASC)、慢性乙型肝炎(CHB)、乙型肝炎肝硬化(LC)、肝癌(HCC)患者血清中cccD-NA与HBVDNA及YMDD突变。结果在283例HBV感染者血清中,cccDNA阳性123例(43.46%),均为HBVD-NA阳性标本;cccDNA与血清HBVDNA相关(x2=28.27,P<0.01)及ALT相关(x2=48.46,P<0.01)。60例接受拉米夫定治疗半年患者复查血清ALT、HBVDNA、YMDD及ccDNA,显示ALT异常32例(与cccDNA相关x2=48.46,P<0.01),HBVDNA阳性24例(与cccDNA相关x2=28.27,P<0.01),其中包括YMDD阳性18例与cccD-NA阳性16例(P=0.046)。结论血清cccDNA,是反映HBV复制及肝脏细胞损伤的血清标志。监测YMDD与血清cccDNA可以提示抗病毒治疗中HBV复制状态及病变进展情况。     

Influence of hepatitis B virus genotype on the long-term outcome of chronic hepatitis B in western patients

BACKGROUND & AIMS: The aim of this study was to investigate if the variable outcome of chronic hepatitis B may be related to hepatitis B virus (HBV) genotype. METHODS: The clinical and virologic events observed over prolonged follow-up in 258 Spanish patients with chronic hepatitis B infected with different genotypes of HBV were compared. RESULTS: The prevalence of genotype A, D, and F was 52%, 35%, and 7%, respectively. Concomitant sustained biochemical remission and clearance of HBV DNA occurred at a higher rate in genotype A- than in genotype D- (log-rank, 14.2; P = 0.002) or genotype F-infected patients (log-rank, 4.2; P = 0.03). The rate of hepatitis B surface antigen (HBsAg) clearance was higher in genotype A than in genotype D hepatitis (log-rank, 4.6; P = 0.03). Sustained remission and clearance of HBsAg were associated with infection with genotype A by Cox regression analysis. Seroconversion to antibody to hepatitis B e antigen (anti-HBe) was unrelated to HBV genotype, but the rate of sustained remission after seroconversion was higher in genotype A than in genotype D hepatitis both in patients who seroconverted to anti-HBe during follow-up (log-rank, 4.5; P = 0.03) and in patients with positive anti-HBe at baseline (log-rank, 6.66; P = 0.009). Death related to liver disease was more frequent in genotype F than in genotype A (P = 0.02) or genotype D (P = 0.002) hepatitis. CONCLUSIONS: The long-term outcome of chronic hepatitis B is different in patients infected with HBV genotype A, D, or F.     

ICAM-1基因多态性与HBV感染不同临床结局之间的关系

目的探讨细胞间黏附分子l（ICAM-1）基因多态性与HBV感染不同临床结局之间的相关性。方法应用病例．对照研究和聚合酶链反应-序列特异性引物法（PCR-SSP）检测118例慢性持续性HBV感染患者（包括无症状HBV携带者、慢性乙型肝炎、乙肝后肝硬化患者）和60例HBV急性自限性感染者的ICAM-1基因G241R（G／A）、K469E（A／G）两个位点的多态性，比较各组间基因型和等位基因频率，并对数据进行统计分析。结果①ICAM-l G241R（G／A）位点总GG基因型频率在HBV慢性持续性感染组高于急性自限性感染组，但差异无统计学意义（X^2=1．38，P〉0．05）。②ICAM-1 K469E（A／G）位点，进展性肝病组（慢性乙型肝炎和肝硬化）总KK基因型和总K等位基因的频率与无症状携带者组和自限性感染组相比显著增高（X^2=8．60，P〈0．05；X^2=5．07，P〈0、05），而在自限性感染和无症状携带者之间却无显著差异。结论携带ICAM-1 K469E KK基因型和K等位基因的患者容易进展成慢性乙型肝炎甚至肝硬化，可致慢性HBV感染患者病情进展。     

Hepatitis B virus genotype A is more often associated with severe liver disease in northern India than is genotype D.

BACKGROUND: The clinical outcome of chronic hepatitis B may depend on hepatitis B virus (HBV) genotype. Data from India on this aspect are limited and contradictory. We studied the frequency of HBV genotypes and their clinical significance. METHODS: Stored sera from patients with chronic HBV infection were tested for HBV genotype using PCR-RFLP. Clinical data, and biochemical and serological parameters were retrieved from medical records; patients were classified as having chronic hepatitis or cirrhosis. RESULTS: Of 70 patients studied (mean age [SD] 38.4 [17.0] years; 63 men; ALT 140 [177] U/L), 32 had chronic hepatitis and 38 had cirrhosis. HBeAg was positive in 50/67 (75%), and anti-HBe in 12/66 (18%). Genotype A was the commonest (37; 53%), followed by D (32; 46%) and C (1; 1%). Patients with genotype A more often had ALT elevation exceeding 1.5 times normal (30/37 [81%] than those with genotype D (18/31 [58%]; p< 0.05). They also more often had positive HBeAg (32/37; 86%) and negative anti-HBe (33/36; 92%) than those with genotype D (18/29 [62%] and 21/29 [72%], respectively; p< 0.05 each). Of 37 patients with genotype A, 23 (62%) had cirrhosis and 14 (38%) had chronic hepatitis; of 32 patients with genotype D, 15 (47%) had cirrhosis and 17 (53%) had chronic hepatitis (p=ns). In the subgroup aged> 25 years, genotype A patients more often had cirrhosis than those with genotype D (23/28 [82%] vs 13/23 [57%]; p < 0.05). CONCLUSION: HBV genotypes A and D were the commonest in our population. Genotype A was more often associated with ALT elevation, HBeAg positivity, absence of anti-HBe and, among those aged 25 years and above, cirrhosis of liver, than was genotype D.     

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.     

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…