慢性乙型肝炎e抗原阳性及阴性患者临床特点分析

目的分析HBeAg阴性及阳性CHB患者临床及病毒学特点。方法对209例CHB患者的临床资料、肝功能和HBVDNA进行分析。结果209例CHB患者中男143例,女66例。HBeAg阴性患者121例,占57.9%(121/209),平均年龄(42.9±10.7)岁,病程(16.7±8.2)年。HBeAg阳性患者88例,占42.1%(88/209),平均年龄(37.1±11.3)岁,病程(12.2±8.3)年。HBeAg阴性患者平均年龄及病程均高于HBeAg阳性患者,差异有统计学意义(t值分别为-6.21和-5.42,P值均<0.01)。HBeAg阴性及阳性患者ALT分别为(37.6±32.8)U/L和(82.2±107.5)U/L,差异有统计学意义(t=5.31,P<0.01),两组患者的ALT分布差异也有统计学意义(χ2=40.20,P<0.01)。HBVDNA大于105拷贝/ml的患者,HBeAg阴性组46例,占38.0%(46/121),HBeAg阳性组83例,占94.3%(83/88),HBeAg阴性组低于阳性组(χ2=180.32,P<0.01)。结论应重视对HBVDNA低复制的HBeAg阴性的CHB患者的随访和治疗。     

Interferon-alpha therapy in HBeAg-negative chronic hepatitis B: a long-term prospective study from north-western Greece

AIMS: To determine the long-term response to interferon-alpha therapy in patients with hepatitis B e antigen-negative chronic hepatitis B, and the factors independently associated with response and survival. METHODS: Sixty-three patients with documented hepatitis B e antigen-negative chronic hepatitis B treated with interferon-alpha for a year were followed-up for a period of 6 years. RESULTS: Sustained biochemical and virological response was seen in 34.91% and 33.33% of patients at 6 and 12 months of follow-up, respectively, and histological improvement in 54.5% of sustained responders compared with non-responders (7.1%, P = 0.004, chi-squared test), at 6 months of follow-up. Multivariate analysis showed that patients with hepatitis B virus-DNA levels at 6 months of treatment <10,000 copies/mL had a low probability of relapse, compared with those with levels >10 000 copies/mL (P = 0.032). Age (>65 years) and hepatitis B virus-DNA level at 6 months of treatment (>10,000 copies/mL) were the independent factors for disease progression and survival (P = 0.041 and P = 0.044 respectively). At 6 years, a sustained response was still present in 19.04% of patients and 4.8% of them had developed anti-HBs. CONCLUSION: Hepatitis B virus-DNA monitoring by quantitative polymerase chain reaction at 6 months of treatment may allow for early prediction of response to interferon-alpha, and may serve as an indicator of disease progression in the future.     

Lamivudine for the treatment of chronic hepatitis B

Lamivudine (Zeffix, Epivir, GlaxoSmithKline) is the most important recent advance in the treatment of chronic hepatitis B in both adults and children. It is the only available oral treatment and has an excellent safety profile, which makes it even more attractive. It increases the rate of hepatitis B e antigen (HBeAg) loss and seroconversion in compensated chronic HBeAg-positive carriers, with subsequent improvement of histology at a similar rate as IFN-alpha. Lamivudine is mostly active in patients with elevated transaminases and is not effective in compensated patients with quiescent disease. Long-term follow-up studies are still required to evaluate long-term benefits, including those on hepatitis B surface antigen (HBsAg) seroconversion rate and disease evolution control. In decompensated patients, the drug can stabilise and improve liver function, allowing the patient to wait safely for transplantation. Patients may improve to such an extent that transplantation can be postponed. Combined with hepatitis B immunoglobulin (HBIG), lamivudine considerably decreases the risk of graft re-infection after transplantation. It is also active in chronic HBeAg-negative hepatitis patients, for whom IFN is less efficient. The major drawback is the emergence of the tyrosine-methionine-aspartate-aspartate (YMDD) mutation, which prevents further efficacy of the drug and may lead to flares of hepatitis. Due to the questions the YMDD mutation raises and because hepatitis B is a complex disease, indications for treatment must be established with care and only by physicians with expert knowledge of the disease, the drug and YMDD mutation-related issues.     

Lamivudine for the treatment of chronic hepatitis B

Lamivudine (Zeffix^®, Epivir^®, GlaxoSmithKline) is the most important recent advance in the treatment of chronic hepatitis B in both adults and children. It is the only available oral treatment and has an excellent safety profile, which makes it even more attractive. It increases the rate of hepatitis B e antigen (HBeAg) loss and seroconversion in compensated chronic HBeAg-positive carriers, with subsequent improvement of histology at a similar rate as IFN-α. Lamivudine is mostly active in patients with elevated transaminases and is not effective in compensated patients with quiescent disease. Long-term follow-up studies are still required to evaluate long-term benefits, including those on hepatitis B surface antigen (HBsAg) seroconversion rate and disease evolution control. In decompensated patients, the drug can stabilise and improve liver function, allowing the patient to wait safely for transplantation. Patients may improve to such an extent that transplantation can be postponed. Combined with hepatitis B immunoglobulin (HBIG), lamivudine considerably decreases the risk of graft re-infection after transplantation. It is also active in chronic HBeAg-negative hepatitis patients, for whom IFN is less efficient. The major drawback is the emergence of the tyrosine-methionine-aspartate-aspartate (YMDD) mutation, which prevents further efficacy of the drug and may lead to flares of hepatitis. Due to the questions the YMDD mutation raises and because hepatitis B is a complex disease, indications for treatment must be established with care and only by physicians with expert knowledge of the disease, the drug and YMDD mutation-related issues.     

Lamivudine resistance in hepatitis B: mechanisms and clinical implications.

Lamivudine (beta-L-(-)-2',3'-dideoxy-3'-thiacytidine) has been a major breakthrough in the care of patients with hepatitis B. With prolonged monotherapy the development of resistance is an increasingly recognized problem that limits the long term efficacy of this nucleoside analogue. The most common mutations associated with lamivudine resistance occur within the highly conserved YMDD motif in the C domain of the viral polymerase and are often associated with a compensatory mutation in the proximal B domain. The structural and functional relationship of resistance mutations is reflected in different in vitro sensitivities to lamivudine and changes in replication capacities. During prolonged lamivudine treatment there can be successive changes of different resistant mutants (genotypic succession) or a single mutant can remain the dominant viral species. In patients treated for chronic hepatitis B infection the cumulative incidence of viral resistance reaches over 50% after 3 years. Most patients will have lower serum HBV DNA levels after the emergence of resistance which is ascribed to the decreased replication capacity of these mutants. Although severe flares and ongoing HBe antigen seroconversion can occur in these patients with lamivudine-resistant HBV, the impact of continued therapy on the long-term outcome is still insufficiently studied. In the setting of liver transplantation for HBV-associated disease the clinical course after the emergence of viral resistance is variable but still may lead to disease progression and graft failure. Analogous to the success of combination therapies to delay the emergence of antiviral-resistant HIV, it will be important to combine anti-HBV agents with additive or synergistic antiviral properties and different resistance profiles for future de novo combination therapies for hepatitis B infection.     

拉米夫定治疗慢性乙型肝炎的临床研究

为探讨拉米夫定对慢性乙型肝炎的临床治疗效果 ,将 114例慢性乙型肝炎患者随机分为治疗组及对照组 ,两组均使用保肝及对症综合治疗 ,治疗组同时给予拉米夫定片剂 ,10 0 mg.d- 1 ,疗程 1年。 HBV-DNA阴转、HBe Ag/HBe Ab转换和 ALT正常为有效指标。结果显示 ,拉米夫定能抑制 HBV-DNA的复制 ,对慢性乙型肝炎及重症慢肝是安全有效的抗病毒治疗药物     

拉米夫定联合泛昔洛韦治疗慢性乙型肝炎

目的　研究拉米夫定和泛昔洛韦联合疗法对慢性乙型肝炎感染的疗效。方法　联合治疗组用拉米夫定每日口服 10 0 mg,疗程 12个月 ,拉米夫定治疗开始时给予泛昔洛韦 5 0 0 mg tid口服 4个月。拉米夫定组仅给予拉米夫定每日口服 10 0 mg,疗程 12个月。结果　治疗开始后第 6个月、12个月、随访 6个月、12个月时AL T复常率、联合治疗组分别为 89.7% (2 6 / 2 9例 )、93.1% (2 7/ 2 9例 )和 93.1%、86 .2 % (2 5 / 2 9例 ) ;拉米夫定组分别为 6 4 .5 % (2 0 / 31例 )、71.0 % (2 2 / 31例 )和 6 1.3% (19/ 31例 )、5 1.6 % (16 / 31例 ) ,AL T复常率各时间段联合治疗组均高于拉米夫定组。χ2值分别为 5 .2 9、4 .90和 8.4 8、8.2 9,P<0 .0 5和 P<0 .0 1,有显著差异和非常显著意义。治疗后第 6个月、12个月和随访 6个月、12个月时血清 HBV DNA转阴率 ,联合治疗组分别为 96 .6 % (2 8/ 2 9例 )、89.7% (2 6 / 2 9例 )和 82 .8% (2 4 / 2 9例 ) ;拉米夫定组分别为 93.5 % (2 9/ 31例 )、80 .6 %(2 5 / 31例 )和 77.4 % (2 4 / 31例 )、6 7.7% (2 1/ 31例 )。各时间段 HBV DNA复常率两组比较无显著差异。2 0例接受肝活检复查的患者中 ,分别有 16例 (80 % )和 8例 (40 % )肝脏炎症活动度和纤维化程度得到改善 (P<0 .     

阿德福韦酯优化治疗HBeAg阴性慢性乙型肝炎疗效观察

目的 优化阿德福韦酯抗乙肝病毒治疗策略,提高治疗效果.方法 将42例HBeAg阴性慢性乙型肝炎患者依照HBV DNA载量分为2组,高病毒载量组22例,拉米夫定联合阿德福韦酯治疗;低病毒载量组20例,阿德福韦酯单药治疗,定期检测HBV DNA、肝功能和乙肝病毒血清标志物(HBV-M).结果 联合治疗组HBV DNA下降速度快,12周有效抑制率为72.7%,显著高于单药治疗组(x2=23.49,P＜0.001);治疗48周后两组患者均获得较高的病毒学应答,HBV DNA有效抑制率(95.45%vs 95%)和测不到率(77.27%vs 80.90%)无统计学差异(P＞0.05);治疗12周及48周两组ALT复常率无差异(P＞0.05),分别为40%、36.36%,90%、86.36%;两组患者均未出现严重不良反应.结论 对于HBV DNA载量较低的初治HBeAg阴性慢性乙型肝炎患者,阿德福韦酯单药治疗可获得较好的疗效,而HBV DNA≥6log拷贝/mL的高病毒载量患者则需要联合拉米夫定才能获得较高的病毒及生化学应答率.     

拉米夫定联合泛昔洛韦治疗慢性乙型肝炎

目的 研究LMD和FCV联合疗法对慢性乙型肝炎感染的疗效。方法 联合治疗组用拉米夫定100 mg·d-1口服,疗程12个月,拉米夫定治疗开始时给予泛昔洛韦500 mg,tid口服12个月。拉米夫定组仅给予拉米夫定100 mg·d-1口服,疗程12个月。于治疗开始后第1,3,6,9,12及治疗结束后第3,6,12个月进行临床评估及实验室检查。结果 治疗后6个月、12个月、随访6个月、12个月时ALT复常率各时间段联合治疗组均高于拉米夫定组。差异有显著和非常显著意义。治疗后6个月、12个月和随访6个月、12个月时血清HBV DNA转阴率:联合治疗组各时段均高于拉米夫定组,但2组比较差异无显著意义。结论 LMD和FCV有协同或相加性抗HBV作用,且停药后DHBV DNA无明显“反跳”,两者用药有协同作用。可作为慢性乙型肝炎可供选择的治疗方法。     

拉米夫定治疗HBeAg阴性的慢性乙型肝炎52例疗效观察

目的:观察和评价拉米夫定治疗HBeAg(-)、HBV-DNA(+)的慢性乙型肝炎的近期及远期疗效。方法:HBeAg(-)、HBV-DNA(+)的慢性乙型肝炎52例,HBeAg(+)、HBV-DNA(+)的慢性乙型肝炎60例,均服用拉米夫定100 mg,每日一次,在治疗2 a时进行疗效评价。对治疗2 a时达完全应答者予以停药,并随访观察1 a。将两组病例在治疗3 mo、2 a及停药la时的ALT、HBV DNA及治疗2 a时的完全应答率和停药1 a时的持续应答率进行比较。结果:治疗3 mo、2 a及停药1 a时HBeAg(-)组、HBeAg(+)组的ALT复常率分别为84.6％、75％、38.2％和81.7％、73.3％、82.4％;HBV DNA复常率分别为78.8％、65.4％、29.4％和73.3％、60％、70.6％。治疗2 a的完全应答率分别为65.4％和28.3％(P<0.05=停药1 a时的持续应答率为29.4％和70.6％(P<0.01)。结论:拉米夫定治疗HBeAg(-)的慢性乙型肝炎在降低ALT、HBV-DNA方面同HBeAg(+)的慢性乙型肝炎一样有较好的近期疗效,但其远期疗效欠佳,停药1 a时的持续应答率仅29.4％,明显低于HBeAg(+)的慢性乙型肝炎的70.6％(P<0.05),其停药后反跳率高。     

Evaluating anti-viral drug selection and treatment duration in HBeAg-negative chronic hepatitis B: a cost-effectiveness analysis

Background  Several anti-viral treatments are now available for HBeAg-negative chronic hepatitis B (CHB), but the clinical and economic outcomes of potential treatment strategies and durations are unclear.
Aim  To examine the clinical and economic outcomes of potential treatment strategies and durations for HBeAg-negative CHB.
Methods  We conducted a cost-utility analysis from a payer perspective over a lifetime time horizon. Disease progression probabilities, costs and quality of life data were derived from the literature. We evaluated 5-year, 10-year, lifetime and 5 on–1 off treatment durations. For each of these treatment durations, we evaluated initial therapy with entecavir, lamivudine or adefovir, with addition of adefovir or entecavir for patients who developed virological breakthrough because of resistance (12 strategies total).
Results  Increasing treatment duration improved quality-adjusted life-years (QALYs) and was generally cost-effective for all three drugs. However, a 5 on–1 off strategy was the most cost-effective: lifetime vs. 5 on–1 off entecavir had an ICER of $148 200/QALY. In probabilistic sensitivity analyses, entecavir 5 on–1 off was the preferred strategy over the range of commonly reimbursed cost-effectiveness thresholds. Lifetime treatment was preferred to a 5 on–1 off strategy, if treatment durability was <10%.
Conclusion  The results of our analysis suggest that in HBeAg-negative CHB infection, a 5 on–1 off treatment strategy with entecavir improves health outcomes in a cost-effective manner compared to alternative strategies.     

HBeAg阳性与HBeAg阴性慢性重型乙型肝炎死亡患者的临床特征比较

目的探讨HBeAg阳性与HBeAg阴性慢性重型乙型肝炎患者的临床特征。方法对95例慢性重型乙型肝炎患者的临床资料、肝功能、肝纤维化指标、HBVDNA载量及并发症发生率进行回顾性分析。结果95例患者中,HBeAg阳性41例（43％）,HBeAg阴性54例（57％）。HBeAg阳性组与HBeAg阴性组平均发病年龄,ALB、TB、CHE、肝纤维化指标及肝衰竭并发症发生率差异无统计学意义（P〉0．05）。HBeAg阴性患者的ALT、AST分别为（400．37±413．59）U／L和（578．14±600．23）U／L,高于阳性患者的（198．25±215．37）u／L和（254．78±269．16）U／L（P〈0．05）。HBeAg阳性患者的HBVDNA载量为（6．17×10^6±8．24×10^1）copies／ml高于阴性患者的（2．39×10^5±6．75×10^1）copies／ml,两组间具有显著差异（P〈0．05）。另外HBeAg阳性患者的左肝前后径及右肝厚度分别为（65．12±12．43）mm及（95．37±12．69）mm,均高于阴性患者的（56．78±11．04）mm和（89．34±9．23）mm（P〈0．05）。结论HBeAg阴性慢性重型乙型肝炎患者与HBeAg阳性患者相比在较低的HBVDNA载量下,仍引起较高的肝损伤和较大幅度的肝脏萎缩。     

慢性乙型肝炎患者拉米夫定耐药的药物选择

近年来慢性乙型肝炎的抗病毒治疗进展迅速，尤其是核苷（酸）类似物的研究开发和临床应用使治疗慢性乙型肝炎进入一个新时代。随着接受核苷（酸）类似物治疗患者的增多和治疗时间延长，临床耐药及其处理日益成为突出的问题。现就临床最常见的拉米夫定耐药患者使用核苷（酸）类似物治疗中如何进行药物选择．谈谈个人看法。     

421例乙肝病毒e抗原阴性及阳性慢性乙型肝炎及相关肝病临床和病毒学特点比较分析

目的:了解乙肝病毒e抗原(HBeAg)阴性和阳性慢性乙型肝炎及相关肝病患者临床和病毒学特点。方法:对421例慢性乙型肝炎及相关肝病患者进行回顾性调查,分析HBeAg阴性和阳性的乙肝患者流行病学、病例构成、肝功能、HBV-DNA载量及乙肝前S1抗体(PreS1Ag)等指标的差异。结果:HBeAg阴性组发病率高,占57.96%,高于HBeAg阳性组,其重型肝炎、肝硬化、肝癌构成及肝功能损害指标高于HBeAg阳性组,HBV-DNA载量、PreS1Ag阳性率低于HBeAg阳性组。结论:HBeAg阴性的慢性乙型肝炎及相关肝病发病率高,进展快,预后差,是今后防治慢性乙型肝炎的重点。