Determinants of early mortality and benefits of lamivudine therapy in patients with hepatitis B virus-related decompensated liver cirrhosis

Chronic hepatitis B infection (HBV) is a major health problem worldwide. The prognosis is grave for patients with HBV-related decompensated liver cirrhosis (LC). We evaluated the effectiveness and the determinants of early mortality of lamivudine treatment in patients with HBV-related decompensated LC. Thirty patients with HBV-related decompensated LC and active viral replication were treated with lamivudine 100 mg daily for a median duration of 9 months. Among these patients, five patients died within 3 months. Two patients were lost to follow-up at week 8 and 9. One patient was treated for <6 months. Twenty-two patients were treated over 6 months. Univariate analysis revealed that the total bilirubin (P = 0.008), prothrombin time (P = 0.004), Child-Turcotte-Pugh score (P = 0.005), the model of efd-stage liver disease score (P = 0.004) and stage III hepatic encephalopathy (P = 0.001) were predictive factors of early mortality. Multivariate analysis revealed that the independent factor associated with early mortality was stage III encephalopathy. Among 22 patients, liver function improved markedly after lamivudine therapy. Of the nine hepatitis B e antigen (HBeAg)-positive patients, three had HBeAg seroconversion. Two patients had YMDD mutant and virological breakthrough at 41 and 46 weeks. One of the two had hepatocellular carcinoma and died of hepatic failure at week 125; the other received adefovir and is doing well. Lamivudine appeared to have benefits in viral suppression and significant improvement in liver function in patients with HBV-related decompensated LC. As noted in prior studies, poor baseline liver function is associated with a poor prognosis in Asian patients with decompensated HBV cirrhosis treated with lamivudine.     

The prevalence of occult hepatitis B in chronic hepatitis C patients treated with interferon-based antiviral therapy

Background and study aims

Occult hepatitis B infection (OBI) is known to be mostly prevalent in chronic hepatitis C (CHC) patients and OBI reactivation might be life-threatening in patients undergoing interferon (IFN)-free direct acting antiviral (DAA) therapy. As previous studies have revealed a relationship between OBI and non-response to IFN-based antiviral therapy, the aim of the current study was to determine if there was a higher prevalence of OBI in IFN non-responders than responders.

Long term outcome of antiviral therapy in patients with hepatitis B associated decompensated cirrhosis

AIM To investigate survival rate and incidence of hepatocellular carcinoma(HCC) in patients with decompensated cirrhosis in the antiviral era.METHODS We used the Korean Health Insurance Review and Assessment. Korea's health insurance system is a public single-payer system. The study population consisted of 286871 patients who were prescribed hepatitis B antiviral therapy for the first time between 2007 and 2014 in accordance with the insurance guidelines.Overall, 48365 antiviral treatment-na?ve patients treated between 2008 and 2009 were included, and each had a follow-up period ≥ 5 years. Data were analyzed for the 1 st decompensated chronic hepatitis B(CHB) and treatment-na?ve patients(n = 7166). RESULTS The mean patient age was 43.5 years. The annual mortality rates were 2.4%-19.1%, and 5-year cumulative mortality rate was 32.6% in 1~(st) decompensated CHB treatment-na?ve subjects. But the annual mortality rates sharply decreased to 3.4%(2.4%-4.9%, 2-5 year) after one year of antiviral treatment. Incidence of HCC at first year was 14.3%, the annual incidence of HCC decreased to 2.5%(1.8%-3.7%, 2-5 year) after one year. 5-year cumulative incidence of HCC was 24.1%. Recurrence rate of decompensated event was 46.9% at first year, but the annual incidence of second decompensation events in decompensated CHB treatment-na?ve patients was 3.4%(2.1%-5.4%, 2-5 year) after one year antiviral treatment. 5-year cumulative recurrence rate of decompensated events was 60.6%. Meanwhile, 5-year cumulative mortality rate was 3.1%, and 5-year cumulative incidence of HCC was 11.5% in compensated CHB treatment-na?ve patients.CONCLUSION Long term outcome of decompensated cirrhosis treated with antiviral agent improved much, and incidence of hepatocellular carcinoma and mortality sharply decreased after one year treatment.     

抗病毒治疗对失代偿期乙型肝炎肝硬化患者远期预后的影响

目的探讨抗病毒治疗对失代偿期乙型肝炎肝硬化患者远期预后的影响。方法收集2009年5月-2012年5月于资阳市乐至县人民医院住院次数≥3次的失代偿期乙型肝炎肝硬化患者132例。根据治疗方法不同分为对照组(n=51)和观察组(n=81),门诊和电话随访5年,均行Child-Pugh评分和MELD评分,观察HBV DNA下降、阴转情况及肝功能指标,随访结束时对比两组临床结局。计量资料组间比较采用t检验,计数资料组间比较采用χ2检验。结果观察组肝癌、肝移植发生率及病死率均显著低于对照组(χ2值分别为4.32、4.33、4.71,P值均0.001);观察组治疗后HBV DNA载量显著低于同组治疗前(t=20.60,P0.001);观察组治疗后HBV DNA载量显著低于对照组治疗后(t=16.40,P0.05);观察组治疗后HBV DNA累积转阴率显著高于对照组(88.89%vs 6.67%,P0.05);观察组治疗后血清白蛋白水平显著高于对照组,TBil、ALT水平显著低于对照组(t值分别为6.77、16.60、11.67,P值均0.001);与治疗前比较,两组治疗后TBil、ALT水平显著下降(观察组:t值分别为25.18、23.33,P值均0.001;对照组:t值分别为6.15、7.20,P值均0.001);观察组治疗后白蛋白水平显著上升(t=10.08,P0.001);观察组治疗后Child-Pugh评分和MELD评分均显著低于对照组(t值分别为2.27、2.24,P值均0.05);与治疗前比较,两组治疗后Child-Pugh评分和MELD评分均显著下降(观察组:t值分别为9.18、8.17,P值分别为0.001、0.03;对照组:t值分别为2.93、3.12,P值分别为0.01、0.04)。结论长期抗病毒治疗能够改善失代偿期乙型肝炎肝硬化患者远期预后,提高5年存活率。     

慢性乙型肝炎特殊患者抗病毒治疗专家共识

<正>近年来,慢性乙型肝炎(chronic hepatitis B,CHB)患者抗病毒治疗不断进展,一般患者的治疗逐渐趋于规范,而特殊人群患者由于循证医学证据相对不足、相关指南无统一的推荐意见等原因成为临床治疗的难点。     

乙型肝炎肝硬化失代偿期抗病毒治疗的研究进展

乙型肝炎肝硬化失代偿期是慢性乙型肝炎、肝纤维化发展的最终结局之一。大量的研究证明抗病毒治疗可以延缓病情进展,明显改善临床结局,减少并发症的发生,延缓失代偿肝硬化进程,最终提高生存期。核苷和核苷酸类药物是目前失代偿期乙型肝炎肝硬化的主要抗病毒药物。介绍了适用于乙型肝炎肝硬化失代偿期的抗病毒药物,针对治疗中的一些问题进行探讨,指出在临床工作中,在规范化抗病毒的前提下应遵循个体化治疗的原则。     

长期恩替卡韦经治慢性乙型肝炎患者低病毒血症的相关影响因素

目的探讨长期接受恩替卡韦治疗的慢性乙型肝炎(CHB)患者仍维持低水平病毒复制的相关影响因素。方法选取2018年11月—2020年6月于徐州医科大学附属医院门诊接受恩替卡韦抗病毒治疗至少1年的CHB患者,根据至观察期结束患者HBV DNA载量分为低病毒血症(LLV)组和持续病毒学应答(SVR)组。观察患者人口学特征参数和实验室检测指标。计量资料两组间比较采用独立样本t检验或Mann-Whitney U检验;计数资料两组间比较采用χ2检验。采用多因素logistic回归分析长期恩替卡韦经治患者出现LLV的影响因素。结果共纳入560例CHB患者,其中LLV组204例,SVR组356例。两组患者比较,年龄(Z=-3.530,P<0.001)、性别(χ2=4.270,P=0.039)、是否存在肝硬化(χ2=53.879,P<0.001)、服药依从性(χ2=5.326,P=0.021)、HBeAg阳性率(χ2=90.681,P<0.001)、治疗前基线HBV DNA载量(Z=-8.337,P<0.001)、基线HBsAg定量(Z=-10.472,P<0.001)以及用药类型(χ2=7.558,P=0.006)差异均有统计学意义。多因素logistic回归分析显示,治疗前基线HBeAg状态(OR=3.381,95%CI:1.985~5.756,P<0.001)、HBV DNA载量(OR=1.223,95%CI:1.050~1.424,P=0.010)和HBsAg定量(OR=2.448,95%CI:1.743~3.438,P<0.001)是长期恩替卡韦抗病毒治疗出现LLV的危险因素。结论在临床实践中,基线高载量HBV DNA水平、高HBsAg定量和HBeAg阳性的CHB患者即使长期坚持服用恩替卡韦抗病毒治疗,也存在较高的LLV风险。因此,对于此类人群应予以重视,需动态监测HBsAg定量、HBV DNA载量、HBeAg状态。     

慢性乙型肝炎抗病毒治疗的药物选择

近年来慢性乙型肝炎(乙肝)的治疗进展迅速,治疗方法和治疗药物增多,可供临床选择的机会增多,抗病毒治疗的药物选择成为临床面临的新热点     

Effects of antiviral therapy in patients with chronic hepatitis B and cirrhosis

Introduction: Hepatitis B virus (HBV) infection is the major cause of cirrhosis worldwide. The ultimate goal of current antiviral treatments for chronic hepatitis B (nucleos(t)ide analogs and interferon-α) is to prevent the development of end-stage liver diseases.

Areas covered: We present a review of the current literature on antiviral therapy in patients with chronic hepatitis B and cirrhosis. Medline search was performed to identify relevant literature from 1993 through January of 2017.

Expert commentary: One randomized controlled trial and a number of observational studies have shown that nucleos(t)ide analogs can decrease the incidence of hepatocellular carcinoma (HCC) in chronic hepatitis B patients with advanced fibrosis. Data from clinical trials of entecavir and tenofovir have shown that histological improvement and regression of fibrosis can be achieved in the majority of patients with chronic hepatitis B by successful viral suppression. Entecavir and tenofovir are the preferred antiviral agents for treatment of chronic hepatitis B in patients with cirrhosis due to their high antiviral potency and high genetic barrier to resistance. Pegylated interferon-α is another therapeutic option for chronic hepatitis B patients with well-compensated cirrhosis. However, interferon therapy is contraindicated in patients with decompensated cirrhosis, and evidence for reduced HCC is currently insufficient.     

长期抗病毒治疗对失代偿期乙型肝炎肝硬化患者预后的影响

目的观察失代偿期乙型肝炎肝硬化患者长期抗病毒治疗疗效。方法将78例乙型肝炎肝硬化失代偿期患者随机分为治疗组46例、对照组32例,治疗组给予拉米夫定(100 mg/d)、阿德福韦酯(10 mg/d)、替比夫定(600 mg/d)或恩替卡韦(0.5 mg/d)口服,同时予以保肝、支持及对症治疗;对照组仅给予常规保肝、对症及支持治疗。随访结束时比较2组治疗前后Child-Pugh分级的变化、血清肝功能指标、肝纤维化指标及临床结局。结果治疗组丙氨酸转氨酶、天冬氨酸转氨酶和总胆红素均较治疗前下降,白蛋白及胆碱酯酶(CHE)较治疗前升高,对照组治疗后CHE水平下降(P均<0.05)。治疗组治疗后39例(84.78%)Child-Pugh分级下降,肝纤维化指标较治疗前下降(P均<0.05)。两组发生肝癌比例分别为2.17%和21.88%,比较差异有统计学意义(P<0.05)。结论失代偿期乙型肝炎肝硬化患者通过长期抗病毒治疗可以改善肝功能,改善预后,降低肝癌发生机会,延缓肝移植需求。     

Hepatocellular carcinoma in chronic hepatitis B patients under antiviral therapy

Patients with chronic hepatitis B are at increased risk of hepatocellular carcinoma(HCC),while the inhibition of viral replication can represent a reasonable target for HCC prevention.Interferon-αtherapy results in decreased HCC risk,which is more evident in patients with high baseline HCC risk.The majority of chronic hepatitis B patients are treated with a nucleos(t)ide analogue(NA)for several reasons including the nonsustained response after interferon-α.The effect of the first licensed and low genetic barrier NA,lamivudine,on HCC incidence,has been repeatedly evaluated.Lamivudine,compared to no treatment,reduces the HCC incidence,which may increase again in cases with lamivudine resistance.Emerging data with the currently first-line NAs,entecavir and tenofovir,suggest that they also reduce the HCC incidence.The treatment benefit in reduction of the HCC incidence is always greater in patients with high baseline HCC risk,particularly cirrhotics,and without virological remission under entecavir/tenofovir.However,the HCC risk is not eliminated even in the vast majority of patients who remain in virological remission under entecavir/tenofovir.Therefore,patients at increased baseline HCC risk should continue to undergo HCC surveillance even if they have achieved complete long-term inhibition of viral replication and improvements in liver histology.     

丙型肝炎失代偿期肝硬化的抗病毒治疗

丙型肝炎肝硬化代偿期患者每年发展为失代偿期的比例为3.6％ ～ 6.0％,目前惟一有效的治疗方法是肝移植.由于肝移植费用高、供肝短缺以及肝移植后复发率高,因此,国内外研究者对失代偿期肝硬化患者尝试着进行抗病毒治疗.通过清除HCV可改善患者的肝功能,延缓疾病进展,减少肝脏失代偿,部分患者甚至免于肝移植,延长患者的生存期.但是抗病毒治疗的时机、剂量和疗程、疗效尚不是很明确.     

慢性乙型肝炎的抗病毒治疗

自1965年Blumberg发现HBsAg以来,乙型病毒性肝炎(HBV)在分子病毒学、组织病理学、免疫学、流行病学及临床诊断治疗学等方面已取得了长足的发展,一些问题得到阐明达成了共识,但仍存在许多问题,我国是乙型肝炎的高流行区,全世界的慢性乙型肝炎患者我国占50％以上,而我国的乙型肝炎防治工作存在一些国外不曾有过的问题,这些问题需要我们自己来研究解决,可以说,在乙型肝炎临床与科研过程中充满了艰辛,我国的临床医师及基础科研工作者尽管在治疗中做了大量工作,遗憾的是至今尚未有重大性突破,这使我们喜忧参半、任重而道远。在临床研究中我国与欧美存在较大的差距,除外经济、政治和学风中的一些问题外,主要存在以下一些问题:(1)临床治疗试验不规范,难以严格的按照随机、双盲、对照和多中心原则实施临床科研方案;(2)临床科研与基础实验研究结合不够,重基础研究,轻临床科研;(3)存在多经验,少证据的现象;(4)肝活体组织检查较少,尤其是治疗前、后自身对照的肝活体组织标本甚少;(5)缺乏长期随访资料,医学资料保管不善,丢失现象较为普遍;(6)国内诊断试剂质量不稳定,缺乏统一标准,大多不能通过国际质检要求,实验数据难以得到国际权威性杂志的认可;(7)临床研究及经典流行病学调研难以获得基金资助等。慢性乙型肝炎已成为相关临床医生面临的重要问题,为了更好地解决这些临床问题,我们组织国内部分专家结合个人的临床经验及科研体会,对"慢性乙型病毒性肝炎的诊断与治疗"进行讨论,目的是引导临床医生科学、准确地处理这些问题,同时进一步深入开展慢性乙型肝炎的临床实用性研究,为提高我国慢性乙型肝炎诊治水平做出应有的贡献,造福于人类,这也是本期"焦点论坛"主办者的心愿。     

抗病毒治疗对慢性乙型肝炎患者肝脏组织学的影响

目的分析慢性乙型肝炎患者的不同抗病毒治疗方式与疗程对肝组织学的影响,探讨临床用药的最佳方案。方法回顾性总结142例慢性乙型肝炎患者,分析其用药方式、疗程、肝脏生化学、病毒学、血清学、肝组织学等相关指标。结果病毒学完全应答:干扰素组58.93%(33/56),核苷(酸)类似物组90.20%(46/51),未抗病毒组0;HBeAg转阴率:干扰素组39.29%(22/56),核苷(酸)类似物组15.68%(7/51),未抗病毒组6%(2/35);HBsAg转阴率:干扰素组21.43%(12/56),核苷(酸)类似物组1.96%(1/51),未抗病毒组0;组织学应答:炎症改善方面,疗程≤1年者为干扰素组核苷(酸)类似物组未抗病毒组,疗程1年者为核苷(酸)类似物组干扰素组未抗病毒组,而肝组织纤维化改善方面,不论疗程长短均为核苷(酸)类似物组干扰素组未抗病毒组。结论抗病毒治疗获得病毒学应答者肝脏组织学均能得到不同程度的改善;核苷(酸)类似物抗病毒治疗2年以上者肝组织学改善程度优于干扰素。     

慢性乙型肝炎患者抗病毒治疗过程中的免疫应答特点

宿主的免疫应答是一把双刃剑,参与慢性HBV感染的肝损伤和病毒控制,核苷和核苷酸类药物及干扰素抗病毒治疗可以通过调节宿主免疫应答影响预后。简要论述了宿主免疫应答在慢性HBV感染中的作用及其在抗病毒治疗过程中的特点,指出宿主免疫功能重建在持久HBV感染控制中的重要性。     

慢性乙型肝炎抗病毒治疗的进展

全球约有3．5亿乙肝病毒携带者，亚太地区占1／3，而我国是乙肝感染高发区。据全国最新流行病学调查显示，我国HBV携带者占总人数的10％，约有1．3亿ASC，其中1／4为慢性乙型肝炎(CHB)，其中又有15％～25％可发展成肝硬化或肝癌。要阻断慢性乙肝向肝硬化、肝癌发展，则进行抗病毒治疗是关键。     

抗病毒经治慢性乙型肝炎患者的再治疗

随着抗病毒药物,包括聚乙二醇干扰素(Peg-IFN)和核苷(酸)类似物(NAs)在临床上的长期和广泛应用,加之我国慢性乙型肝炎防治指南的颁布和不断更新,同时,中华医学会肝病学分会和感染病学分会的专家对慢性乙型肝炎防治指南的广泛巡讲、解读,使包括基层医院在内的广大肝病工作者对慢性乙型肝炎抗病毒治疗的认识不断提高,越来越多的患者接受了抗病毒治疗.然而,由于HBV本身的特点、机体对HBV的免疫耐受或免疫功能低下,不能自发地清除病毒,以及所用药物抗病毒作用的局限性,即不能彻底清除肝组织内病毒复制的模板cccDNA等因素,同时评价抗病毒治疗疗效的指标均为病毒学或血清学的替代指标,因此,不能确定哪些患者停药后疾病不复发.所以在接受抗病     

慢性乙型肝炎患者抗病毒治疗依从性的研究现状

为了持续抑制HBV复制,慢性乙型肝炎(CHB)患者需要长期甚至终生抗病毒治疗,而依从性是影响治疗效果的关键因素之一。回顾了目前CHB患者抗病毒治疗依从性相关研究,包括依从性水平、依从性对治疗效果的影响,总结了影响治疗依从性的因素,分析了目前CHB依从性研究中存在的问题,指出今后研究中应该更加关注如何提高依从性从而改善预后。     

慢性乙型肝炎治愈新药研究进展

正据2016年世界卫生组织报道,全球约有2.4亿慢性HBV感染者,每年约有65万人死于慢性HBV感染导致的肝硬化或肝癌[1]。2017年欧洲肝病研究学会对乙型肝炎治愈作出定义:(1)完全治愈(complete sterilizing cure),即血清HBsAg完全检测不到,HBV DNA彻底清除,包括共价闭合环状DNA(cccDNA)和整合的HBV DNA;(2)功能性治愈