抗病毒治疗慢性重型乙型肝炎165例临床分析

目的 探讨慢性重型乙型肝炎抗病毒治疗转归的影响因素及抗病毒治疗对其转归的影响.方法 应用回顾性分析的方法,分析165例慢性重型乙型肝炎患者的年龄、凝血酶原活动度(VIA)、血清中HBeAg、抗.HBe滴度,HBVDNA定量,有无并发症,抗病毒治疗等因素与治疗转归的关系.结果 慢性乙型重型肝炎患者随年龄的增加、PTA降低、并发症增多,其死亡率明显增高;慢性乙型重型肝炎患者血清HBVDNA定量＞1×103 copies/ml者其死亡率(52.3%)比HBVDNA＜1×10'copies/ml的死亡率(32.4%)明显升高;HBeAg,抗-HBe的表达对死亡率无影响;2006年应用拉米夫定抗病毒治疗后慢性乙型重型肝炎HBVDNA定量＞1×105 copies/ml的患者其死亡率(30.38%)比2002年未使用抗病毒治疗者(54.64%)明显下降.结论 影响慢性乙型重型肝炎预后的因素除年龄、PTA和有较多并发症外,患者血清中高病毒载量是影响其死亡率的关键因素,及时抗病毒治疗可以降低死亡率.     

人工肝血浆置换联合恩替卡韦治疗慢性乙型重型肝炎45例

慢性乙型重型肝炎导致的肝功能衰竭,病情凶险,预后差,死亡率超过70%,目前尚无特效治疗方法,内科综合治疗仍是主要的治疗措施。非生物型人工肝-血浆置换广泛应用于临床,是治疗重型肝炎临床常用的可靠技术[1]。随着核苷（酸）类抗病毒药物的广泛应用,给慢性乙型重型肝炎提供了一种有效的治疗手段。近年来,我们以血浆置换联合恩替卡韦治疗慢性乙型重型肝炎取得了较好的疗效。     

重型肝炎死因及主要并发症探讨

探讨重型肝炎的死亡原因及主要并发症 ,进一步提高存活率。对 154例重型肝炎的死亡原因及主要并发症进行分析。重型肝炎的病死率仍以慢性乙型为主。直接死亡原因以肝肾综合症最高 ( 36.4 % ) ,其次为严重感染 ( 2 8.6% )、上消化道大出血 ( 2 2 .1% )、肝功能衰竭伴肝性脑病和脑水肿。降低重型肝炎的病死率应从源头抓起 ,做好乙型肝炎的预防 ,减少乙型肝炎的发病率。早期阻止免疫病理损伤和肠源性内毒素的继发性损伤 ,积极预防和治疗各种并发症 ,是减少重型肝炎病死率的关键。重型肝炎死因及主要并发症探讨@隋云华!210002$南京解放军第八一…     

799例重型肝炎患者的临床病原学与实验室分析

目的探讨乙型重型肝炎患者乙型肝炎病毒(HBV)DNA定量、e抗原表达与病死率的相关性,为重型肝炎临床治疗提供参考。方法统计我院2000-2004年各型重型肝炎的发病率,进一步应用荧光定量多聚酶链反应方法检测乙型重型肝炎患者血清HBV DNA,应用微粒子方法检测乙型肝炎e抗原表达情况,并分析其与病死率及抗病毒治疗的临床疗效间的关系。结果(1)重型肝炎中乙型肝炎占83．50％,慢性重型肝炎中乙型肝炎占96．77％;(2)5年间慢性乙型重型肝炎患者HBV DNA定量大于1×10,拷贝／ml组,总病死率为53．25%,小于1×105拷贝／ml组,病死率为34．50％,差异有统计学意义(P<0．01);e抗原表达对病死率无影响;(3)2004年,慢性乙型重型肝炎患者HBV DNA定量大于1×105拷贝／ml病例加用拉米夫定抗病毒治疗,病死率由2000年的54．64%下降至2004年的30．38%,差异有统计学意义(P<0．01)。结论重型肝炎以慢性乙型重型肝炎为主,病毒载量高是高病死率关键因素之一,抗病毒治疗可以降低患者的病死率。     

替比夫定治疗乙型肝炎肝硬化96周疗效观察

在我国,乙型肝炎病毒（HBV）是导致肝炎后肝硬化最常见的原因,有研究表明,HBV复制活跃的乙型肝炎肝硬化患者,更易发生肝功能衰竭或肝细胞癌,而抗病毒治疗抑制HBV复制,是控制病情进展的关键。替比夫定对HBV有抑制作用,本研究通过口服替比夫定治疗92例乙型肝炎肝硬化初治患者,观察其临床疗效及肝纤维化指标改变情况。     

抗乙型肝炎病毒治疗在乙型重型肝炎抢救治疗中的作用探讨

目的探讨抗乙型肝炎病毒治疗在乙型重型肝炎抢救治疗中的作用。方法急性重型乙型肝炎为Ⅰ组,亚急性重型乙型肝炎为Ⅱ组,慢加急(亚急)性重型乙型肝炎为Ⅲ组。比较Ⅰ、Ⅱ组间抗病毒治疗与未抗病毒治疗患者的临床转归。结果急性重型乙型肝炎患者未抗病毒治疗者抢救成功率55.56%(5/9),抗病毒治疗者均死亡,抢救成功率0%(0/2),P0.05,差异有明显统计学意义。急性重型乙型肝炎患者均发生HBV DNA自然转阴,并出现HBsAg及HBsAb自然血清学转换。亚急性重型乙型肝炎患者抗病毒治疗抢救成功率83.33%,高于未抗病毒治疗者61.54%,P0.05,差异有统计学意义。亚急性重型乙型肝炎患者中未抗病毒治疗者61.54%(8/13)发生HBsAg及HBsAb的血清学转换,抗病毒治疗者有83.33%(5/6)未发生HBsAg及HBsAb的血清学转换。慢加急(亚急)性重型肝炎患者抗病毒治疗后抢救成功率69.70%。结论急性重型乙型肝炎患者不需要积极抗病毒治疗。亚急性重型乙型肝炎患者确诊后HBV DNA仍大量复制且3 d后仍未转阴者,应及早予抗病毒治疗,以提高亚急性重型乙型肝炎患者抢救成功率。     

重型肝炎综合治疗进展的临床教学实践及体会

对于临床肝病工作者而言,慢性病毒性肝炎的抗病毒疗法、重型肝炎的综合治疗以及抗肝纤维化的有效措施仍为今日和未来研究的三大热点。重型肝炎其病理基础为肝功能衰竭及多脏器衰竭引起的一系列临床重症,属危重病急救医学领域之一。也是传染病科、消化内科、普通外科、急诊科和I     

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。     

重型病毒性肝炎病原学与预后的关系探讨

目的探讨重型病毒性肝炎的病原学特点。方法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。结果急性重型肝炎以甲型和戊型病毒性肝炎为主,乙型肝炎病毒感染治愈后病毒阴转率较高。亚急性及慢性重型肝炎以乙型肝炎病毒感染居首位,占92.8％。在乙型肝炎病毒感染的病原学模式中,以HBsAg、HBeAb、HBcAb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纯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HBV DNA可自然阴转,阴转率可达53.6％。结论重型肝炎仍以乙型肝炎病毒感染为主。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。     

拉米夫定治疗慢性乙型肝炎病毒感染的近期疗效

目的评价拉米夫定治疗不同临床类型慢性乙型肝炎病毒（HBV）感染的近期疗效。方法口服拉米夫定150mg,每日1次,连服6个月,治疗慢性乙型肝炎病人40例,肝炎肝硬化18例,慢性重型肝炎10例。观察其临床、生物化学、血清学和病毒学改变。结果（1）慢性乙型肝炎病情缓解。对照组病毒血症持续,27．5％病人于随访期内肝炎复发（P＜0．001）。同时观察拉米夫定联用干扰素治疗病人20例,未见提高疗效。（2）肝炎肝硬化病情渐趋稳定,肝功能好转,Child—Pugh积分下降。（3）慢性重型肝炎除2例服药不足3个月死亡外,余8例病情缓解,随着肝功能改善,生活质量显著好转。结论拉米夫定适用于治疗慢性乙型肝炎,对处于HBV复制状态的肝硬化和重型肝炎也有效。     

核苷(酸)类似物治疗慢加急性肝衰竭研究进展

乙型肝炎是威胁全球的健康问题,每年约有60万人死于HBV感染所致的各种疾病,如肝炎、肝硬化和原发性肝癌等.乙型肝炎相关性慢加急性肝衰竭是我国肝衰竭主要类型,在治疗上除综合治疗外,是否进行抗病毒治疗是近年研究的热点.本文就该领域的研究现状作一综述.     

Combined glucocorticoid and antiviral therapy of hepatitis B virus-related liver failure

Acute hepatic failure due to hepatitis B virus(HBV)can occur both during primary infection as well as after reactivation of chronic infection.Guidelines recommend considering antiviral therapy in both situations,although evidence supporting this recommendation is weak.Since HBV is not directly cytopathic,the mechanism leading to fulminant hepatitis B is thought to be primarily immunemediated.Therefore,immunosuppression combined with antiviral therapy might be a preferred therapeutic intervention in acute liver failure in hepatitis B.Here wereport our favourable experience in three hepatitis B patients with fulminant hepatic failure who were treated by combining high-dose steroid therapy with standard antiviral treatment,which resulted in a rapid improvement of clinical and liver parameters.     

The use of lamivudine for patients with acute hepatitis B (a series of cases)

There are limited data on the use of lamivudine for patients with severe forms of acute hepatitis B. We report our experience with the use of lamivudine in six patients with acute HBV infection. Lamivudine was justified by disease severity for four patients and by concerns about risk of chronicity for two patients. The diagnoses of the treated patients were: fulminant liver failure (two patients), severe acute hepatitis B, protracted acute hepatitis B, and new HBV infection in the renal dialysis setting (two patients, one with severe liver injury). Serum HBV DNA titres ranged from 10(5) to 10(7) copies/mL prior to commencement of lamivudine. Lamivudine treatment was associated with a decline in serum HBV DNA and serum transaminases in all patients. All but one patient survived. A 58-year-old man with fulminant hepatitis and multiple organ failure died despite antiviral treatment. When possible, HBeAg and HBsAg seroconversion was documented during follow-up. In the absence of a randomized, prospective study of lamivudine in patients with severe acute hepatitis B, our data encourage the use of this safe and well tolerated drug.     

Epidemic of hepatitis B with high mortality in India: association of fulminant disease with lack of CCL4 and natural killer T cells

An explosive outbreak of Hepatitis B with high mortality was reported in 2009, in Modasa, Gujarat, India. Mortality was associated with basal core promoter and precore mutant hepatitis B virus (HBV). The current study addresses the role of immunological parameters in the progression to fulminant hepatitis. The study population comprised of 22 acute HBV patients, 13 fulminant HBV liver failure patients and 54 healthy controls. Hepatitis B surface antigen-induced CTL responses by enzyme-linked immunosorbent spot (ELISPOT), cytokine and chemokine quantitation by Bioplex assay, peripheral NK, natural killer T (NKT), CD4 and CD8 T-cell frequencies by flow cytometry were carried out. The median percentage of NK cells in the lymphocytes of the acute and fulminant liver failure patients were significantly lower compared to controls. Acute and fulminant liver failure patients had significantly high and comparable NKT cells compared to controls, respectively. Importantly, NKT cells were significantly lower in fulminant HBV liver failure than acute HBV patients. Circulating peripheral CD4/CD8 T-cell subsets among the patient categories and controls were comparable. In acute HBV patients, a significant increase in IFN-γ release was recorded (ELISPOT) by the unstimulated, antigen-stimulated and mitogen-stimulated cells when compared to controls. Comparisons of cytokines and chemokines among the disease categories revealed significantly lower levels of CCL4 in fulminant liver failure patients. NKT cells and CCL4 might be playing a pivotal role in limiting HBV infection among the patients investigated.     

Acute fulminant hepatitis B in a patient with diabetic nephropathy treated successfully with concomitant lamivudine and molecular adsorbents recirculating system

A 36-year-old man with type 2 diabetes and diabetic nephropathy treated with hemodialysis developed hepatitis B virus (HBV)-induced acute fulminant hepatic failure (FHF). Despite supportive treatment, the condition rapidly progressed as manifested by severe jaundice, coagulopathy and hepatic coma. He was placed on the waiting list for liver transplantation and was treated with lamivudine and extracoporeal liver support with the molecular adsorbent recirculating system (MARS). After three 8-h sessions of MARS treatment in 1 week, he had remarkable improvement in clinical symptoms and serum biochemistry. On the 14th hospital day, surface antigen seroconversion was noted with undetectable hepatitis B virus surface antigen (HBs Ag) and low titre of anti-HBs antibody, indicating a complete recovery from acute fulminant hepatitis B. MARS treatment has been reported to benefit patients with liver failure from different causes including acute exacerbation of chronic hepatitis B, poisoning, post transplantation and Wilson's disease. The present case suggests its potential benefit when combined with lamivudine in treating uremic patients with acute fulminant hepatitis B.     

Fulminant hepatitis after allogenic bone marrow transplantation caused by reactivation of hepatitis B virus with gene mutations in the core promotor region

Under immunosuppressive conditions after hematopoietic stem cell transplantation (HSCT), even if hepatitis B virus (HBV) antigen is negative but hepatitis B surface antibody (HBsAb) or hepatitis B core antibody (HBcAb) is presented, HBV reactivates and sometimes causes fulminant hepatitis. However, it remains unclear which patients will develop fulminant hepatitis, or whether fulminant hepatitis is caused by host-related factors or by virus-related factors. A 30-yr-old man with a history of aplastic anemia since 3 yr of age underwent allogenic BMT, when HBsAb and HBcAb were positive but HBs antigen (HBsAg) was negative. The donor was negative for HBsAg, HBsAb and HBcAb. After transplantation, the patient was complicated by acute graft-vs.-host disease (GVHD), cytomegalovirus infection, intestinal thrombotic microangiopathy and aspergillus colitis. Chronic GVHD was well controlled by FK506 and prednisolone. Twenty months after transplantation, the patient was admitted with general fatigue and liver dysfunction and was found to be positive for HBsAg and HBeAg. His serum HBV-DNA level was >8.8 log of the genome equivalent (LGE)/mL. Therefore, he was diagnosed as having hepatitis B caused by HBV reactivation and 100 mg/d lamivudine treatment was started. However, jaundice and hepatic failure deteriorated and became fatal. On analysis of the HBV-DNA, two adjacent gene mutations in the core promoter region (T1762/A1764) were detected. Increased replication of the mutated HBV might have caused HBV reactivation which progressed to fulminant hepatitis.     

Management of severe acute to fulminant hepatitis B: to treat or not to treat or when to treat?

Despite a decline in cases of acute hepatitis B and the low hepatitis B virus (HBV) chronicity rates in adults, still some patients progress to HBV-related fulminant liver failure. In this review, we discuss treatment options that may prevent the progression of severe acute hepatitis B to fulminant liver failure and death. In severe acute HBV with prolonged prothrombin time and increased bilirubin, interferon failed to be effective while antiviral treatment, particularly with lamivudine, appears to improve survival (mean survival almost 80%). Outcome without antiviral therapy has remained considerably poor, whereas there is no convincing evidence of amelioration of HBV-targeted immunity. Of note, most patients who died or required transplantation despite lamivudine therapy, were started on lamivudine at advanced stages compared with those survived. This suggests that prompt and timely antiviral therapy is crucial. Owing to the abovementioned results the design of randomized placebo-control trials in the setting of severe acute hepatitis B seems unethical. On the contrary, the design of multicentre double-blind randomized trials to compare the efficacy between lamivudine and entecavir or even tenofovir in acute severe HBV cases is ideally needed, but these studies appear to be very difficult to perform considering that these cases are not frequent and therefore, it is almost impossible to have two arms adequately numerous and homogenous for statistical evaluation. Thus, in the absence of solid evidence based data, the hepatologists could treat their patients with severe acute hepatitis B with lamivudine or the most potent antivirals entecavir or tenofovir.     

Hepatitis B vaccination in liver transplant candidates

Liver transplantation has become the treatment of choice for patients with end-stage liver disease. De novo hepatitis B infection after liver transplantation is a rare event and usually runs a mild clinical and histological course. Despite the favourable outcome, a wide spectrum of hepatitis B virus (HBV)-associated liver disease may develop, ranging from asymptomatic carriage to severe chronic active hepatitis or cirrhosis and even fulminant hepatic failure. The achievement of protective titres of anti-HBs through vaccination has been suggested to be protective against the development of de novo HBV infection. The results of vaccination in cirrhotic patients awaiting for liver transplant have been very disappointing. High-dose/short-term schedules have been tried in transplant candidates in order to increase the response rate. New and more immunogenic formulations (containing new adjuvants or additional pre-S1/pre-S2 recombinant antigens), and, more importantly, early vaccination of potential transplant candidates at earlier stages of their liver disease should further prevent de novo hepatitis B in transplant recipients.     

Impact of determination of hepatitis B virus subgenotype and pre-core/core-promoter mutation for the prediction of acute exacerbation of asymptomatic carriers

Aim:  A large cohort study in Japan revealed that the specific viral profile may influence the fulminant outcome in acute hepatitis B virus (HBV) infections, while the genetic influence on outcome has not been clarified in patients with acute exacerbation of chronic liver disease caused by HBV. We experienced a case of fatal liver failure that developed as the result of chronic HBV infection. To determine possible genetic factor involving acute exacerbation, genetic analysis of serum from the patient and his siblings was performed.
Methods:  HBV subgenotype as well as pre-core/core-promoter mutations of samples mentioned above were determined.
Results:  Patient had HBV-Bj with pre-core (1896/1899) and core-promoter (1762/1764) mutations, the genomic profile frequently seen in fulminant hepatitis caused by acute HBV infection.
Conclusion:  This result suggests that determination of the HBV subgenotype and pre-core/core promoter mutations could provide a rationale for development of a treatment strategy in asymptomatic HBV carriers.