苦参素合用拉米夫定治疗慢性乙型肝炎观察

目的观察苦参素联合拉米夫定治疗慢性乙型肝炎的疗效。方法83例慢性乙型肝炎患者,随机分为两组,治疗组45例苦参素静脉滴注,同时口服拉米夫定,对照组38例干扰素肌肉注射,同时口服拉米夫定,疗程均为6个月,随访半年,治疗各阶段测血清HBVDNA、乙肝标志物、ALT做为疗效观察指标。结果治疗结束时,治疗组血清HBVDNA阴转率88.9%、HBeAg阴转率57.8%,HBeAb血清转换率46.7%与对照组血清HBVDNA阴转率86.8%,HBeAb阴转率60.5%、HBeAb血清转换率47.4%相比无显著差别(P>0.05),半年随访治疗组HBVDNA阴转率77.8%、HBeAg阴转率53.3%、HBeAb血清转换率40.0%与对照组HBVDNA阴转率71.1%、HBeAg阴转率50%,HBeAb血清转换率39.5%相比(P>0.05),而ALT复常率明显高于对照组(P<0.05)。结论苦参素联合拉米夫定治疗慢性乙型肝炎协同作用好,特别是恢复肝功能效果显著。     

干扰素α-2b联合苦参素治疗慢性乙型肝炎的疗效观察

目的探讨干扰素α-2b和苦参素联合治疗慢性乙型肝炎疗效。方法将60例慢性乙型肝炎随机分为两组，Ⅰ组30例，干扰素α-2b联合苦参治疗；Ⅱ组30例，单用苦参素治疗，疗程3～6个月。治疗前后定期检测肝功能、HBeAg、抗-HBe、HBV DNA。结果Ⅰ组治疗6个月HBeAg／抗-HBe转换率63．3％、HBV DNA阴转率70％，Ⅱ组治疗6个月HBeAg／抗-HBe转换率13．3％、HBV DNA阴转率13．3％，两组比较差异有统计学意义（P〈0．05）。结论干扰素α-2b和苦参素联合治疗慢性乙型肝炎在HBeAg、HBV DNA阴转方面有较好疗效，并对使用干扰素所致WBC降低有一定保护作用。     

干扰素α-2b与恩替卡韦联合治疗慢性乙型肝炎患者疗效观察

目的观察干扰素α-2b、恩替卡韦单药治疗及两药联合治疗慢性乙型肝炎的疗效。方法采用病例对照,将60例HBsAg阳性慢性乙型肝炎患者随机分为干扰素α-2b组20例(A组),恩替卡韦组20例(B组)和干扰素联合恩替卡韦组20例(C组),监测3组患者治疗12、24及48周的ALT变化、HBeAg,抗-HBe,及血HBVDNA水平。结果 3组治疗12周时ALT复常率,HBVDNA阴转率及HBeAg血清转换率3组之间差异均无统计学意义(P>0.05)。3组患者在治疗24周时ALT复常率,HBVDNA阴转率及HBeAg血清转换率C组明显高于A组,B组,且3组之间差异有统计学意义(P<0.05)。治疗48周时ALT复常率,HBeAg血清转换率,HBVDNA阴转率联合组均高于单药组,且差异有统计学意义(P<0.05)。结论干扰素α-2b与恩替卡韦联合治疗,疗程24及48周时的病毒学应答均优于两药单独治疗时的效果。     

乙型肝炎病毒基因类型与干扰素治疗效果关系

目的观察干扰素治疗B、C基因型慢性乙型肝炎患者的临床疗效。方法20例B基因型慢性乙型肝炎患者（B组）及23例C基因型慢性乙型肝炎患者（C组）均给予干扰素α-1b500万u,肌内注射,隔日一次,疗程1年,观察两组患者血清病毒学指标、肝功能变化及药物不良反应等情况。结果治疗后B组、C组在HBV-DNA阴转率（60．0％、39．1％）、HBeAg阴转率（42．9％、30．8％）、抗HBe阳转率（35．7％、23．1％）、ALT复常率（85．0％、73．9％）等方面比较,差异均无统计学差异（t=1．86、0．69、0．68、0．79,均P〉0．05）。结论干扰素α-1b抗病毒疗效在B、C基因型间无明显差异。     

恩替卡韦联合胸腺肽α1治疗慢性乙型肝炎的临床效果分析

目的探讨恩替卡韦联合胸腺肽α1治疗慢性乙型肝炎的效果。方法将本院63例慢性乙型肝炎患者随机分为治疗组31例和对照组32例,治疗组采用恩替卡韦联合胸腺肽Ot．治疗,对照组采用恩替卡韦治疗,治疗48周对其疗效进行评价,评价标准包括HBeAg阴转率、HBeAg／HBeAb血清转换率、HBVDNA阴转率、血清丙氨酸氨基转移酶（ALT）复常率及不良反应。结果两组患者的HBeAg阴转率、HBeAg／HBeAb转换率差异有统计学意义（P〈0．05）,HBVDNA、ALT复常率、不良反应差异无统计学意义（P〉O．05）。结论恩替卡韦联合胸腺肽仪。治疗慢性乙型肝炎既起抗病毒的功效,又起免疫调节的作用,临床效果显著,值得临床推广应用。     

苦参素联合干扰素治疗慢性乙型肝炎疗效观察

目的观察苦参素与α-2b干扰素治疗慢性乙型肝炎疗效;方法对53例慢性乙型肝炎患者随机分为联合用药组和单用干扰素组,用ELISA法检测HBeAg,用PCR法检测HBV-DNA,观察两组中HBeAg、HBV—DNA阴转情况;结果联合用药组比单用干扰素组在HBeAg、HBV—DNA阴转率高;结论苦参素联合α-2b干扰素对慢性乙型肝炎确有良好的治疗作用。     

干扰素、苦参素联合治疗HBeAg阳性慢性乙型肝炎疗效观察

目的α干扰素和苦参素联合治疗慢性乙型肝炎。方法将90例慢性乙型肝炎随机分为3组,1组30例α干扰素联合苦参素治疗;两组30例单用α干扰素治疗;3组30例单用苦参素治疗,疗程3～6个月。治疗前后定期检测肝功能、HBeAg、抗-HBe、HBV-DNA。结果联合治疗组HBeAg/抗-HBe转换率、HBV-DNA阴转率均显著高于单一药物组,差异有统计学意义(P<0.05)。结论α干扰素和苦参素联合治疗慢性乙型肝炎有显著疗效,值得临床推广。     

苦参素胶囊联合干扰素-α1 b治疗HBeAg阳性慢性乙型肝炎疗效观察

目的观察苦参素胶囊联合干扰素-α1b治疗HBeAg阳性慢性乙型肝炎的疗效。方法40例HBeAg阳性慢性乙型肝炎患者随机分为2组,每组20例,2组患者均以干扰素-α1b作为基础抗病毒治疗。治疗组加用苦参素胶囊,对照组加用甘草酸二铵胶囊。疗程均24周。观察临床症状、肝功能、病毒指标及HBV-DNA阴转率。结果2组患者的临床表现均有改善,治疗组血清HBV-DNA阴转率明显高于对照组（P〈0.05）。结论苦参素胶囊联合干扰素-α1b能较好地改善肝内炎症,保护肝细胞,提高干扰素抗病毒效果。     

苦参素联合干扰素治疗慢性乙型肝炎36例疗效观察

目的观察苦参素联合干扰素治疗慢性乙型肝炎的临床效果。方法用苦参素联合干：扰素治疗慢性乙型肝炎36例，与单用苦参素和单用于扰素治疗慢性乙型肝炎比较。结果联合治疗组肝：叻复常率达94.4％，单用苦参素组达80．6％，单用干扰素组达83．3％，联合治疗组优于单用对照组（P〈0．01）：联合治疗组HBeAg阴转率达58．3％，HBV—DNA阴转率达61％；单用苦参素组HBeAg阴转率达38．9％，HBV—DNA阴转率达41．7％；单用干扰素组HBeAg阴转率达41．7％．HBV—DNA阴转率达44％．联合治疗组优于单用对照组（P〈0．01）。应用干扰素者有不同程度的发热，头痛．肌肉关节痛．白细胞及血小板减少。结论苦参素联合干扰素治疗慢性乙型肝炎疗效比单用好．达到药物协同和增强作用。     

凯因益生伴侣颗粒联合干扰素治疗慢性乙型肝炎的临床疗效研究

目的：探讨凯因益生伴侣颗粒联合干扰素α-2b治疗慢性乙型肝炎的临床疗效。方法选取2012年2月—2013年2月在邯郸市传染病医院接受治疗的慢性乙型肝炎患者120例,随机分为干预组和对照组,各60例。对照组在基础保肝、降酶支持对症治疗的基础上给予重组人α-2b干扰素治疗,干预组在对照组基础上给予凯因益生伴侣颗粒治疗,检测并比较两组患者的肝功能指标、血清HBsAg水平、血清HBV-DNA水平、血清HBeAg/HBeAb转换率。结果治疗12周后干预组的谷氨酸氨基转移酶（ ALT）、天冬氨酸氨基转移酶（ AST）、总胆红素（ TBiL）低于对照组,差异有统计学意义（ P<0.05）。治疗后4周、8周、12周干预组血清HBsAg水平、血清HBV-DNA水平低于对照组,差异有统计学意义（ P<0.05）。治疗后两组不同血清HBsAg水平的患者血清HBeAg/HBeAb转换率比较,差异无统计学意义（ P>0.05）;治疗后12周,干预组血清HBeAg/HBeAb转换率高于对照组,差异有统计学意义（P<0.05）。结论凯因益生伴侣颗粒联合干扰素是慢性乙型肝炎抗病毒治疗的有效药物,与单纯干扰素用药相比,具有明显的改善患者肝功能、降低血清HBsAg水平及血清DNA水平、降低血清HBeAg/HBeAb转换率的效果。     

干扰素联合微卡治疗慢性乙型肝炎

目的：探讨干扰素联合微卡治疗慢性乙型肝炎的作用机制及疗效。方法：按诊断标准选择慢性乙型肝炎患者80例，随机分为干扰素联合微卡为治疗组(40例)和干扰素为对照组(40例)，观察比较两组患者肝功能、HBeAg及HBVDNA的变化。结果：治疗组的肝功复常率、HBeAg及HBVDNA阴转率均明显高于对照组(P＜0.05)。结论：干扰素联合微卡治疗慢性乙型肝炎有协同作用，它能提高细胞免疫应答能力、促进HBeAg及HBVDNA的阴转，减少病毒的变异，延迟耐药性的发生。     

Long-term outcomes of thymosin-alpha 1 and interferon alpha-2b combination therapy in patients with hepatitis B e antigen (HBeAg) negative chronic hepatitis B

Hepatitis B e antibody (HbeAb) and hepatitis B virus (HBV) DNA positive chronic hepatitis is a clinical entity, distinct from classical hepatitis B e antigen (HbeAg) positive chronic hepatitis B. Our aim was to evaluate the long-term therapeutic efficacy of the combination of interferon alpha-2b and thymosin-alpha1 compared with lamivudine plus interferon alpha-2b and interferon alpha-2b alone. Fifty-two patients with HbeAg-negative chronic hepatitis B were assigned to three different groups in a nonrandomized manner. Group 1 (n = 27) received thymosin-alpha1 [1.6 mg subcutaneously (sc), twice a week] and interferon alpha-2b (10 MIU sc, three times per week) for 26 weeks, subsequently followed by interferon alpha-2b monotherapy at the same dosage for an additional 26 weeks. Group 2 (n = 10) received interferon alpha-2b (10 MIU sc, three times per week) for 52 weeks. Group 3 (n = 15) received interferon alpha-2b (10 MIU sc, three times per week) and lamivudine [100 mg orally (po), q.d.] for 52 weeks, followed by continuous lamivudine (100 mg po, q.d.) therapy. By the end of 78 weeks, a sustained response (SR-6 mo) was seen in 74% (20/27) of the patients within Group 1. On the contrary, Groups 2 and 3 had sustained response rates of 40 (4/10) and 53.3% (8/15), respectively (p = 0.13). At the end of 12 months post-treatment in Group 1, a virological and biochemical response rate was seen in 70.3% of patients (19/27); in contrast, Groups 2 and 3 had response rates of 20 (2/10) and 26.6% (4/15), respectively (p = 0036). At the end of the 18-month post-treatment follow-up period, 71.4% (19/27) of patients in Group 1, 10% of patients in Group 2 (1/10), and 20% of patients in Group 3(3/15) preserved their sustained response (p = 0.0003). Interferon alpha-2b and thymosin-alpha1 combination therapy results in significant virological and biochemical response rates compared with standard therapeutic regimens and is well tolerated.     

慢性乙型肝炎病情与乙型肝炎病毒标志物表达模式的关系

目的观察乙型肝炎病毒(HBV)标志物(HBsAg、HBsAb、HBeAg、HBeAb、HBcAb)表达模式与慢性乙型肝炎病情的关系。方法对582例5组慢性乙型肝炎和乙型肝炎后肝硬化患者,用酶联免疫吸附试验(ELISA)检测HBV标志物,用OlympusAU2700全自动生化分析仪检测血清总胆红素(TBIL)、白蛋白(ALB)、丙氨酸氨基转移酶(ALT)、前白蛋白(PA)。依据HBV标志物阳性情况分为6组:A组173例,为HBsAg、HBeAg、HBcAb阳性;B组218例,为HBsAg、HBeAb、HBcAb阳性;C组161例,为HBsAg、HBcAb阳性;D组13例,为HBeAb、HBcAb阳性;E组6例,为HBsAb、HBeAb、HBcAb阳性;F组11例,为HBsAb、HBcAb阳性。结果582例中,A组阳性率为29.7%;B组为37.4%;C组为27.7%;D组为2.2%;E组为1.0%;F组为1.9%。A、B、C模式组间阳性率有显著性差异(χ2=14.75,P<0.01),以B模式组的阳性率最高。5组慢性肝病间比较,A组阳性率有显著性差异(χ2=23.17,P<0.01),B组阳性率无显著性差异(χ2=3.72,P>0.05),C组阳性率有显著性差异(χ2=25.74,P<0.01)。HBeAg阳性的A组与HBeAg阴性的B、C组比较,TBIL、ALB、ALT、PA水平及其异常率均无显著性差异(F=1.91、2.48、0.58、1.37,P>0.05;χ2=2.09、5.97、2.35、2.26,P>0.05)。结论HBV标志物的表达模式与慢性乙型肝炎的病情无明显相关,临床上不能根据HBV标志物的表达模式来预测判断病情轻重和预后情况。     

替比夫定联合阿德福韦酯对 HBeAg 阳性慢性乙型肝炎的疗效观察

目的：探讨替比夫定联合阿德福韦酯对HBeAg阳性慢性乙型肝炎患者的疗效。方法将76例慢性乙型肝炎患者分为干扰素组和替比夫定组,干扰素组应用聚乙二醇干扰素α-2a联合阿德福韦酯,替比夫定组给予替比夫定联合阿德福韦酯,治疗48周,观察血清谷氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）的含量和正常化率及血清HBsAg、HBeAg和乙肝病毒（HBV） DNA的含量及HBeAg阴转率和血清转换率及HBV DNA低于检测下限值率变化。结果2组治疗后24周和48周ALT和AST的含量及血清HBsAg、 HBeAg和HBV DNA的含量均明显降低（ P ＜0．01）,而替比夫定组治疗后降低量更显著;ALT和AST正常化率,HBeAg阴转率和血清转换率及HBV DNA低于检测下限值率显著增加（ P ＜0．01）,而替比夫定组治疗后的增加量更显著。结论替比夫定联合阿德福韦酯的治疗效果比干扰素联合阿德福韦酯的治疗更加显著。     

复合α干扰素治疗HBeAg阳性的慢性乙型肝炎多中心临床研究

目的：观察复合α干扰素（CIFN）在治疗HBeAg阳性的慢性乙型肝炎中的疗效及其安全性。方法：采用多中心、随机、双盲、平行阳性药物对照的研究设计。选择260例慢性乙型肝炎患者随机分为试验组和对照组，试验组给予CIFN9μg，前4周每天1次，后20周每周3次，共治疗24周，停药后随访24周；对照组给予干扰素-α2b，300万IU，疗程同试验组。观测治疗前、治疗结束时以及随访24周时患者的肝脏功能、乙型肝炎病毒血清学标志物（ELISA法）和HBVDNA含量（PCR法）以及其他不良反应。结果：治疗结束及随访后24周，试验组病毒学部分应答率及总应答率均高于对照组（44．1％V825．7％；65．7％vs45．5％），完全应答率两组相似；试验组血清学完全应答率明显高于对照组（23．4％V812．9％；25．7％V812．2％）；生化学应答无显著差异。两组不良反应的发生无显著差异。结论：CIFN在抑制乙肝病毒复制、降低病毒载量和促进机体产生持续应答方面优于干扰素-α2b。     

乙型肝炎病毒基因型分布及临床意义

目的 了解珠海地区乙型肝炎病毒(HBV)基因型流行病学分布特征,并分析不同基因型与HBV感染谱的相关性.方法 采用聚合酶链反应-限制片段长度多态性(PCR-RFLP)的基因型分型方法对62例HBV携带者及63例慢性乙型肝炎、7例慢性重症乙型肝炎、5例肝硬化患者感染的HBV进行分型,并分析不间感染谱中HBV基因型的分布.结果 137例感染者HBV基因型B型72例(52.6%),C型65例(47.4%),慢性肝炎患者、重症肝炎、肝硬化患者的C基因型比例[45例(69.2%)、5例(7.7%)、4例(6.2%)]明显高于B基因型[18例(25.0%)、2例(2.8%)、1例(1.4%)],差异均有统计学意义(均P＜0.05);HBV携带者B基因型比例[51例(70.8%)]明显高于C基因型[11例(16.9%)],差异有统计学意义(P＜0.05).C基因型慢性肝炎患者的HBV-DNA、平均ALT水平高于B基因型慢性肝炎患者,但差异均无统计学意义(P＞0.05).结论 珠海地区HBV感染者以B型和C型为优势基因型,C基因型可能是乙型肝炎病情进展的相关因素.

Abstract：

Objective To understand the distribution of hepatitis B virus (HBV) genotypes in Zhuhai area and to analyze the relationship between HBV genotypes and patients with hepatitis B. Methods A polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis assay amplifying S-segment sequences of HBV-DNA were used for analyzing the distribution of HBV genotypes among 62 HBV carriers (ASC group),63 patients with chronic hepatitis B (CHB group),7 patients with severe chronic hepatitis B (CSH group)and 5 cases liver cirrhosis (LC group). Results The proportion of HBV genotyjpes B and C was 52.6% and 47.4%. There were no significant differences of indexes related to liver function damage (ALT) or serum HBV DNA levels between subtype B and subtype C infected patients. Conclusion The genotypes B and C are two predominant genotypes in Zhuhai area;genotype C may be associated with the development of hepatitis.     

Antiviral therapy for chronic hepatitis B: a review

Chronic hepatitis B virus (HBV) infection is a well-recognized risk factor for the development of hepatocellular carcinoma (HCC), which is becoming a more prevalent clinical problem, especially in HBV-endemic areas. It is estimated that 1.25 million people in the United States and more than 300 million people worldwide are chronically infected with HBV. Despite the introduction of universal vaccination against hepatitis B in over 100 countries, persistent HBV infection is still a serious problem worldwide, causing an estimated annual death rate of one million. It may take several decades until the effect of vaccination will be translated into reduced transmission and morbidity. Meanwhile, patients with persistent HBV infection require better antiviral therapeutic modalities than are currently available. It is well accepted that antiviral therapy for chronic hepatitis B is effective to improve prognosis of patients with HBV by preventing development of hepatitis state and HCC. The therapeutic endpoints for hepatitis B treatment are: 1) sustained suppression of HBV replication, as indicated by HBsAg and HBeAg loss, 2) decrease of serum HBV DNA of an undetectable level by a non-PCR method, 3) remission of disease, as shown by normalization of ALT, 4) improvement in liver histology, and 5) reduction of the acute exacerbation, cirrhosis, and HCC. In the present, the antiviral treatment of hepatitis B consists of either interferon alpha or oral lamivudine alone or in combination with existing therapy. Each major antiviral drug of interferon alpha and lamivudine has pros and cons, and effect of combination therapy of both drugs is also still limited. More powerful and safe new antiviral therapies are required to achieve final goal of these therapeutic endpoints. Management of chronic hepatitis B requires significant knowledge of approved pharmacotherapeutic agents and their limitations. Therapeutic options for managing hepatitis infection after liver transplantation (LT) are also evolving.     

慢性HBV感染患者HBV DNA前C区变异的临床意义

目的:探讨慢性HBV感染患者HBVDNA前C区变异的临床意义。方法:采用ELISA测定99例HBV感染患者血清肝炎病毒标志物,并采用RT-PCR检测HBVDNA前C区变异。结果:99例HBV感染患者中,乙型肝炎病毒携带26例,慢性乙型病毒性肝炎61例,慢性重型病毒性肝炎(乙型)11例和急性乙型病毒性肝炎1例。乙型肝炎病毒携带,慢性乙型病毒性肝炎和慢性重型病毒性肝炎中,变异株组HBVDNA前C区变异发生率与混合株组、野生株组相比,差异均无显著性(P>0.05)。与混合株和野生株两组相比,HBVDNA变异株组肝功能变化差异均无显著性(P>0.05)。结论:HBVDNA前C区变异可发生于HBV感染的不同临床状态。HBVDNA前C区变异可能与肝炎程度和病情进展无明显关系。     

干扰素α2b抗慢性乙型肝炎病毒复制长短程疗法随访观察

目的评价干扰素α2b(anferon,安福隆)的长短程疗法抗慢性乙型肝炎(CHB)病毒疗效。方法治疗短疗程组21例,长疗程组32例慢性乙型肝炎患者。治疗前、治疗后3个月、6个月、1年检测血清HBVDNA、HBV血清学标志、血常规及丙氨酸转氨酶(ALT)。结果安福隆治疗慢性乙型肝炎疗效显著。长疗程组HBVDNA明显高于短疗程组,差异有统计学意义(P<0.01),ALT复常率明显高于短疗程组(P<0.05)。结论安福隆在慢性乙型肝炎抗病毒治疗中,长疗程的远期疗效明显优于短疗程组,可作为慢性乙型肝炎抗病毒治疗的首选药物之一。     

High prevalence of the B2+C2 subgenotype mixture in patients with chronic hepatitis B in Eastern China

Aim:

To investigate the prevalence of hepatitis B virus (HBV) genotype mixtures among patients with chronic hepatitis B (CHB) in Eastern China.

Methods:

A total of 4908 chronic HBV patients from Eastern China were enrolled. HBV genotypes and subgenotypes were determined using a multiplex PCR technique. Serum viral loads and hepatitis B e antigen (HBeAg) levels detected using real-time fluorescent quantitative PCR and ELISA assay, respectively. The presence of precore/basic core promoter (PC/BCP) mutations was examined with PCR and direct sequencing of the amplified products.

Results:

HBV genotypes B, C, D, B+C, and B+D were found in 19.21%, 64.75%, 1.49%, 13.63%, and 0.92% of the patients, respectively. In 669 patients with the genotype mixture B+C, the subgenotypes B2+C2 and B2+C1 accounted for 68.13% and 31.87%, respectively, no other subgenotypes were identified. HBV B+C was more frequent in the patients with moderate CHB than in patients with mild CHB. In patients with moderate CHB, the subgenotype mixture B2+C2 was lower than B2+C1 (51.97% vs 63.38%), while the opposite situation was found in patients with severe CHB (22.15% vs 15.49%). The highest average viral load was found in patients with the genotype B+C mixture. The prevalence of HBV B2+C2 increased in patients from 50 to 59 years of age and was significantly different from the proportion of patients in the same age group with genotype B (23.2% vs 15.2%). A double mutation (G1896A) in the PC was significantly more common in subgenotype B2+C2 than in subgenotype B2+C1.

Conclusion:

The HBV B2+C2 subgenotype was prevalent in CH patients with a high HBV replication status and correlated with a more severe course of the disease.