应用Cox比例风险模型分析抗病毒治疗对慢性乙型重型肝炎预后的影响

目的应用Cox比例风险模型分析核苷（酸）类似物抗病毒治疗对慢性乙型重型肝炎预后的影响。方法选择219例慢性乙型重型肝炎患者,采用Cox比例风险模型对可能影响其预后的因素进行单变量和多变量回归分析。重点分析核苷（酸）类似物抗病毒治疗对慢性乙型重型肝炎预后的影响。结果多变量回归分析结果显示：年龄、肝性脑病、总胆红素、白蛋白、凝血酶原活动度、血尿素氮、核苷（酸）类似物抗病毒治疗具有独立的预后意义（P〈0．05）。纠正混杂因素后,在多变量Cox比例风险模型中比较拉米夫定与恩替卡韦两种药物对慢性乙型重型肝炎预后的影响程度,两者无显著性差异（P〉0．05）;比较在慢性乙型重型肝炎的早期、中期和晚期抗病毒治疗对预后的影响程度,结果在早期和中期抗与不抗病毒治疗有显著性差异（P〈0．05）,但晚期抗与不抗病毒治疗已无显著性差异（P〉0．05）。结论核苷（酸）类似物抗病毒治疗是影响慢性乙型重型肝炎预后的独立因素。较早开始抗病毒治疗可以改善预后。拉米夫定和恩替卡韦均可选用于对这种患者的治疗。     

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。     

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.     

中西医结合治疗早中期慢性乙型重型肝炎的临床疗效及预后分析

目的通过对214例早中期慢性乙型重型肝炎患者中西医结合治疗的临床研究,探讨中西医结合治疗方案疗效以及相关因素对预后的影响。方法所有病例均采用常规中西医结合治疗措施,包括保肝、退黄、抗病毒、对症支持及中医辩证治疗,对其治疗前后相关指标及预后进行统计分析。结果 214例早中期慢性乙型重型肝炎患者治疗总有效率63.1%,无效率36.9%;治疗前后自身对比,TBil、DBil、ALT、AST、PAT、Chol、TG、HBV DNA等指标均有明显改善（P〈0.05）。抗病毒药物使用、电解质紊乱、肝肾综合征和治疗后重型肝炎分期为预后的强影响因素（P〈0.05）。抗病毒药物中恩替卡韦组及拉米夫定组有效率较高（P〈0.05）。结论中西医结合治疗慢性乙型重型肝炎早、中期患者可以取得良好的治疗效果,合并电解质紊乱、肝肾综合征的患者预后较差,选择恩替卡韦或拉米夫定可能会提高有效率。     

核苷类似物治疗乙型肝炎病毒感染相关肝衰竭患者的临床研究进展

乙型肝炎病毒感染是我国肝功能衰竭的常见原因,乙型重型肝炎病死率高达70%以上.与其他原因所致肝功能衰竭不同,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.由于乙型肝炎病毒的复制在乙型重型肝炎的发生发展中起着始动或主导作用,因此,通过抗病毒治疗降低病毒载量,缓解过强的免疫反应,从而缓解病情,是乙型重型肝炎治疗...     

恩替卡韦联合血浆置换治疗慢性乙型重型肝炎10例

HBV高复制状态是引起重型肝炎患者病情持续活动、发展和加重的重要原因之一,因此慢性乙型重型肝炎的抗病毒治疗日益受到重视.恩替卡韦作为新的抗病毒药,具有起效快、变异率低的特点,我们回顾性分析恩替卡韦联合血浆置换(PE)治疗慢性乙型重型肝炎的疗效,现报道如下.     

抗结核病史对乙型重型肝炎临床特点及预后影响

目的 探讨抗结核治疗病史对乙型重型肝炎临床特点及预后的影响.方法 通过对比有抗结核治疗病史的乙型重型肝炎85例患者与无抗结核病史的乙型重型肝炎123例患者,了解抗结核治疗病史对乙型重型肝炎的影响.结果 与无抗结核病史的乙型重型肝炎比较,有抗结核治疗病史的乙型重型肝炎死亡率高(P=0.0062),住院天数延长(P=0.04),并发症(脾大、腹水、肝硬化、自发性腹膜炎)发生频率较高(P＜0.05);凝血酶原时间、凝血酶原活动度、白蛋白、总胆红素、肌酐与无抗结核治疗病史的乙型重型肝炎比较差异有统计学意义(P＜0.05).结论 抗结核治疗病史可以显著影响乙型重型肝炎的临床表现及预后.     

第十讲重型乙型肝炎的抗病毒治疗新进展

重型乙型病毒性肝炎是临床常见的危重和疑难病，治疗比较困难，治疗时间长，病情凶险，病死率高，其治疗是一个亟待解决的问题。除了保肝、退黄，支持疗法等综合治疗措施外，抗病毒疗法日益得到重视。有关乙型重型肝炎的抗病毒疗法，一种观点认为，肝细胞的严重损伤并非由HBV引起，至少HBV不是直接导致肝细胞损伤的主要原因，故无需抗病毒治疗。但HBV     

恩替卡韦治疗慢性乙型重型肝炎近期疗效观察

目的观察恩替卡韦抗病毒治疗对慢性乙型重型肝炎存活率的影响。方法对20例慢性乙型重型肝炎患者临床资料进行分析,治疗组11例,对照组9例,对照组接受综合治疗,治疗组在综合治疗的基础上加用恩替卡韦0.5mg,口服,每日1次,平均治疗41天。结果治疗组存活9例(81.8%),对照组存活2例(22.2%)。结论恩替卡韦治疗慢性乙型重型肝炎,可提高存活率。     

中晚期慢性乙型重型肝炎预后影响因素分析

目的探讨中晚期慢性乙型重型肝炎的预后影响因素,为制定中西医结合治疗方案提供依据。方法对2005年7月-2009年7月我院收治的578例中晚期慢性乙型重型肝炎患者给予常规中西医结合保肝、退黄、抗病毒、支持和对症等治疗,部分患者接受人工肝治疗。分析影响中晚期慢性乙型重型肝炎预后的因素。结果578例慢性乙型重型肝炎患者治疗有效率为37．7％,无效率为62．3％;影响预后的高危因素包括肝肾综合征、肝性脑病和消化道出血。结论慢性乙型重型肝炎中晚期患者预后差,影响预后的因素包括肝肾综合征、肝性脑病和消化道出血等严重并发症,而并发症之间又相互影响,有效控制并发症是提高中晚期慢性乙型重型肝炎疗效的途径之一。     

Efficacy of combination therapy of antiviral and immunosuppressive drugs for the treatment of severe acute exacerbation of chronic hepatitis B

BACKGROUND: Patients with severe exacerbation of chronic hepatitis B, sometimes developing into fulminant liver failure, are at high risk for mortality even with antiviral therapy. The efficacy of immunosuppressive therapy in clinically severe exacerbation of chronic hepatitis B has not been well demonstrated. In this study, we evaluated the efficacy of the early introduction of immunosuppressive therapy in combination with antiviral therapy in such patients. METHODS: Forty-two patients, 29 men and 13 women, were defined as having severe exacerbation of chronic hepatitis B based on our uniform criteria, and were enrolled in this study. Sixteen patients between 1982 and 1996 were analyzed retrospectively. We defined the criteria of severe disease in 1997, and then began to introduce sufficient doses of corticosteroids prospectively. Nucleoside analogs were administered in combination with corticosteroids after 1999. Twenty-six patients between 1997 and 2007 were analyzed prospectively. RESULTS: In the retrospective study between 1982 and 1996, four of 16 (25%) patients recovered. In the prospective study between 1997 and 2007, 17 of 26 (65%) patients recovered; 15 of 17 patients treated with corticosteroids with or without antiviral drugs within 10 days after the diagnosis of severe disease recovered, none of five treated similarly but later than 10 days after the diagnosis recovered, and two of three treated with antiviral drugs recovered. CONCLUSIONS: The early introduction of sufficient doses of corticosteroids and nucleoside analogs could be one option for reversing the potential deterioration of patients with clinically severe, life-threatening exacerbation of chronic hepatitis B.     

Management of chronic hepatitis B in severe liver disease

In the past few decades,chronic hepatitis B(CHB)has evolved from a disease that was untreatable and progressive,to one that can be easily controlled with antiviral therapy.However,patients with severe liver disease still remain difficult to treat despite the availability of highly potent nucleos(t)ide analogs.These include those with underlying cirrhosis,severe flares of CHB,hepatocellular carcinoma(HCC),and for those undergoing liver transplantation.For those with established cirrhosis,antiviral therapy should be considered for all,as unpredictable flares can still occur,which can be fatal for those with advanced chronic liver disease.However,even with effective viral suppression,the development of HCC can still occur.For patients with severe flares of CHB,although the use of antiviral can improve long term outcomes,a significant proportion may still die without liver transplantation.The short term prognosis of these patients is dependent on both the severity of flare and underlying pre-existing liver disease.In patients with decompensated cirrhosis,liver failure secondary to severe flares,or those with HCC,liver transplantation may be curative.After liver transplantation,long term antiviral therapy is required to prevent graft loss from recurrent hepatitis B infection.The use of hepatitis B immune globulin(HBIG)in combination with an oral antiviral agent has been the mainstay of post-transplant antiviral regimen for over adecade.With newer and more potent antiviral agents such as tenofovir and entecavir,use of these agents along with HBIG have demonstrated to be effective in preventing significant recurrence in the long term.     

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.     

Future aspects of therapy for hepatitis B virus infection: value of surrogate markers,innovative therapy,and global collaboration

Both optimism and frustration exist regarding therapy for patients with chronic hepatitis B virus infection. Due to the recent advent of several drugs with potent antiviral capacities and comparatively low rates of adverse effects, considerable optimism has developed regarding the treatment of these patients. Chronic hepatitis B is now a treatable disease, and suppression of hepatitis B virus replication, normalization of alanine aminotransferase levels, seronegativity/seroconversion of hepatitis B e antigen and hepatitis B surface antigen, and decreased hepatic inflammation and liver fibrosis have been documented in chronic hepatitis B virus-infected patients treated with antiviral therapy. In contrast, many frustrations regarding antiviral therapy for chronic hepatitis B have arisen, because the disease, although treatable, is not curable. The present regimens of antiviral therapy modulate some intermediate parameters or so-called surrogate markers in chronic hepatitis B virus-infected patients, but usually fail to improve all intermediate parameters or ultimate clinical outcomes. In addition, major concerns remain about the applicability and use of antiviral drugs in developing and resource-constrained countries in which healthcare delivery systems do not support the proper use of antiviral therapy. New and more effective therapeutic regimens for chronic hepatitis B patients are needed that take into account potential surrogate markers of treatment outcomes and allow for effective collaboration between resource-constrained and advanced countries.     

慢性乙型肝炎抗病毒治疗的困境和进展

慢性乙型肝炎(CHB)由乙型肝炎病毒(HBV)感染引起,易反复发作引起肝脏损伤,严重威胁人类健康。CHB治疗最根本、最关键的是抗HBV治疗,抗HBV治疗在近年来取得了很大的进展,基因治疗、免疫治疗等新技术为抗HBV治疗提供了新的发展方向,但抗HBV治疗仍面临难以突破的困境。本文就抗HBV治疗的困境和进展进行综述。     

Treatment of HBe antigen-positive chronic hepatitis B

Spontaneous loss of hepatitis B e antigen (HBeAg) followed by seroconversion to anti-HBe usually coincides with normalization of serum alanine aminotransferase (ALT) levels, reduction in HBV DNA in serum (< 1 x 10(6) copies/mL), and a marked reduction in hepatic inflammation. Licensed antiviral therapies are the interferon (IFN) alphas and the nucleoside analogue lamivudine. Both drugs enhance the rate at which HBeAg seroconversion takes place and thus reduce progression of disease. These therapeutic agents are ineffective if given when there is no ongoing hepatitis (i.e., normal ALT), and their efficacy is greatest in individuals with the most active disease. The effectiveness of these two classes of drugs is similar, and it is possible that the two therapies combined are more effective than monotherapy with either drug. A high side-effect profile and the high risk of further morbidity when given to patients with decompensated disease limit the use of IFN-alpha. When prescribing lamivudine, drug resistance that increases with duration of therapy and the potential risk of a severe flare of hepatitis with sudden cessation of therapy, probably greatest in patients with cirrhosis, are realistic concerns. Both patient and physician need to recognize the need for close monitoring both during and after cessation of any antiviral therapy for hepatitis B.     

Does antiviral therapy for hepatitis B and C prevent hepatocellular carcinoma?

Approximately 75% to 80% of hepatocellular carcinomas (HCC) worldwide are attributed to chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) infection. Thus, effective prevention of HBV and HCV infection and progression from acute HBV and HCV infection to chronic hepatitis, cirrhosis and HCC might prevent as many as 450,000 deaths from HCC each year. The most effective approach to preventing HCC is to prevent HBV and HCV infection through vaccination. Indeed HBV vaccine is the first vaccine demonstrated to prevent cancers. However, a vaccine for HCV is not available and for persons who are chronically infected with HBV or HCV, antiviral therapy is the only option for preventing HCC. Direct evidence supporting a benefit of antiviral therapy on the prevention of HCC has been shown in a few randomized controlled trials. There is abundant evidence that antiviral therapy, in patients with long-term virological response, can improve liver histology, providing indirect support that antiviral therapy may prevent HCC by slowing progression of liver disease and possibly even reversing liver damage. Nevertheless, the risk of HCC remains in patients with chronic HBV or chronic HCV infection if treatment is initiated after cirrhosis is established. These data indicate that treatment might be of greater benefit if instituted earlier in the course of chronic hepatitis B or C. Safer, more effective, and more affordable antiviral therapies are needed for both hepatitis B and hepatitis C so more patients can benefit from treatment and more HCCs can be prevented.     

慢性乙型肝炎血清HBVDNA临床诊断与病理分度的关系

为探讨慢性乙型肝炎时血清ＨＢＶＤＮＡ与病理分度，临床诊断便分度的关系，对１４０例慢性乙型肝炎患者进行ＨＢＶＤＮＡ检测，肝活检，行临床诊断与病理分度对照，ＨＢＶＤＮＡ阴，阳组间比较。结果显示临床诊断与病理分度符合率，慢轻肝７５．８％，慢中肝４３．２８％，慢重肝不符合，ＨＢＶＤＮＡ阳性组病例程度明显加重，差异显著。随炎症活动度增加，ＡＬＴ值升高愈明显，结论提示慢性中重度患者应行病理检查，ＡＬＴ仍然观察     

慢性重型乙型肝炎预后影响因素分析及拉米夫定抗病毒治疗对患者生存的影响

目的探讨慢性重型乙型肝炎预后影响因素及应用拉米夫定（LAM）抗病毒治疗对患者生存的影响。方法选择经LAM治疗的810例慢性巫型乙型肝炎患者临床指标和随访资料,用Cox比例风险模型对预后因素进行分析,并比较抗病毒治疗对患者近期临床指标和远期生存的影响。结果除年龄、总胆红素、凝血酶原时间、国际标准化比率（INR）、白细胞和肌酐外,血清HBVDNA和钠水平是影响患者预后的重要因素,其风险比（RR）分别为2．347和0．023。早期和晚期抗病毒治疗组患者中位生存时间分别54d和36d,3个月的中位生存率分别为41．6％和18．3％（X^2=153．230,P〈0．001）。结论血清HBVDNA和钠水平是影响生存的重要因素;尽早抗病毒治疗和纠正低钠血症可能改善慢性重型乙型肝炎患者的生存。     

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.