脱氧核苷酸联合聚乙二醇化干扰素α-2a治疗慢性乙型病毒性肝炎合并肝功能异常的临床研究

目的探讨脱氧核苷酸联合聚乙二醇化干扰素α-2a治疗慢性乙型病毒性肝炎合并肝功能异常的临床效果。方法将慢性乙型病毒性肝炎合并肝功能异常患者78例随机分为两组,对照组39例采用聚乙二醇化干扰素α-2a治疗,观察组39例采用脱氧核苷酸联合聚乙二醇化干扰素α-2a治疗,比较两组治疗效果。结果治疗后,两组丙氨酸氨基转移酶、天门冬氨酸氨基转移酶、总胆红素、碱性磷酸酶、白蛋白、总蛋白、白细胞计数、血小板计数降低(P0.05),肝组织炎性程度、纤维化程度改善(P0.05)。观察组丙氨酸氨基转移酶、天门冬氨酸氨基转移酶、总胆红素、碱性磷酸酶低于对照组(P0.05),白蛋白、总蛋白、白细胞计数、血小板计数、HBe Ag阴转率、HBVDNA阴转率、HBs Ag阴转率高于对照组(P0.05),肝组织炎性程度、纤维化程度好于对照组(P0.05)。结论脱氧核苷酸联合聚乙二醇化干扰素α-2a治疗慢性乙型病毒性肝炎合并肝功能异常的疗效显著,可明显改善临床指标,减轻肝组织炎性程度与纤维化程度。     

阿德福韦酯联合聚乙二醇干扰素α-2a治疗慢性乙型肝炎的疗效观察

目的：探讨阿德福韦酯联合聚乙二醇干扰素α-2a治疗慢性乙型肝炎的临床疗效。方法选取2012年1月至2014年1月门诊收治的慢性乙型肝炎患者80例,随机分为对照组和观察组各40例。对照组患者每周1次皮下注射180μg聚乙二醇干扰素α-2a;观察组在对照组基础上口服阿德福韦酯,10 mg/d。比较两组患者治疗后丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）以及乙型肝炎病毒（HBV）DNA、乙型肝炎e抗原（HBeAg）转阴率和HBeAg血清转换率。结果治疗后观察组患者ALT和AST显著低于对照组,差异有统计学意义（P〈0.01）,且观察组患者HBV DNA、HBeAg转阴率和HBeAg血清转换率均显著高于对照组,差异均有统计学意义（P＜0.05）。结论阿德福韦酯联合聚乙二醇干扰素α-2a治疗慢性乙型肝炎疗效显著,值得在临床推广应用。     

聚乙二醇干扰素α-2a联合阿德福韦酯治疗慢性乙型肝炎的疗效观察

目的探讨聚乙二醇干扰素α-2a与阿德福韦酯联合治疗慢性乙型肝炎的临床疗效,为临床推广做出指导。方法选择医院自2010年1月-2013年1月收治的HBeAg阳性的慢性乙型肝炎患者123例为研究对象,随机分为甲、乙、丙组各41例,甲组给予聚乙二醇干扰素α-2a治疗,乙组给予阿德福韦酯治疗,丙组则给予聚乙二醇干扰素α-2a与阿德福韦酯联合治疗,对比观察3组患者的临床治疗效果以及不良反应情况。结果治疗后丙组患者丙氨酸氨基转移酶（ALT）复常率、HBV-DNA转阴率以及HBeAg血清转换率均明显高于甲组和乙组,差异有统计学意义（P〈0.05）;所有患者均未出现严重不良反应,仅部分患者用药后出现低热、头痛以及外周血白细胞减少等不良反应,经过相应处理后恢复。结论聚乙二醇干扰素α-2a与阿德福韦酯联合治疗慢性乙型肝炎的临床疗效显著,且安全可靠,值得临床广泛推广。     

聚乙二醇干扰素α-2a联合脱氧核苷酸钠治疗慢性乙型肝炎的临床研究

目的探讨聚乙二醇干扰素α-2a(PEG-IFNα-2a)联合脱氧核苷酸钠注射液治疗慢性乙型病毒性肝炎的临床疗效。方法将113例患者随机分为两组,治疗组57例给予PEG-IFNα-2a联合脱氧核苷酸钠注射液治疗,对照组56例单用PEG-IFNα-2a,对治疗前后肝组织学、血清病毒学等指标的变化进行观察。结果与对照组比较,治疗组患者6个月时的血清丙氨酸氨基转移酶(ALT)、天门冬酸氨基转移酶(AST)复常率显著增高(P<0.05),治疗6,9,12个月时乙型肝炎表面抗原(HBsAg)、e抗原(HBeAg)及HBV-DNA转阴率均降低(P<0.05)。两组患者肝组织病理肝细胞炎症及纤维化程度均较治疗前明显减轻(P<0.05)。结论 PEG-IFNα-2a联合脱氧核苷酸钠注射液治疗慢性乙型病毒性肝炎的疗效优于单用PEG-IFNα-2a。     

聚乙二醇化干扰素α-2a治疗HBeAg阴性的慢性乙肝药物经济学分析

目的：探讨聚乙二醇化干扰素α-2a治疗HBeAg阴性的慢性乙型肝炎的临床效果和经济效果。方法：运用成本-效果分析法对48例HBeAg阴性的慢性乙型肝炎患者分别用聚乙二醇化干扰素α-2a和干扰素两种方案治疗的结果进行比较。结果：聚乙二醇化干扰素组疗效对比干扰素组有显著差异，且成本-效果比较低。结论聚乙二醇化干扰素α-2α作为一种新型抗病毒药物，治疗HBeAg阴性的慢性乙型肝炎具有较好的成本-效果比，有着良好的发展前景。     

聚乙二醇干扰素α-2a联合复方阿嗪米特肠溶片对慢性乙型肝炎纤维化疗效及血清Th1/Th2水平的影响

目的 回顾性分析聚乙二醇干扰素α-2a联合复方阿嗪米特肠溶片对慢性乙型肝炎纤维化的疗效及血清Th1/Th2细胞因子水平的影响.方法 选择2018年1月—2019年6月收治的慢性乙型肝炎纤维化120例,按治疗方法分为观察组和对照组,每组60例.对照组采用聚乙二醇干扰素α-2a,观察组采用聚乙二醇干扰素α-2a联合复方阿嗪...     

聚乙二醇干扰素α-2a与阿德福韦酯联用对患者拉米夫定停用后复发慢性乙型肝炎的临床疗效评价

目的:评价聚乙二醇干扰素α-2a与阿德福韦酯联用对患者停用拉米夫定后复发慢性乙型肝炎(CHB)的临床疗效。方法:选取2011年1月—2013年12月间收治的拉米夫定经治患者规范停药后复发CHB患者78例,将其分为治疗组与对照组各39例;治疗组患者均给予聚乙二醇干扰素α-2a与阿德福韦酯联用治疗,对照组患者均给予单用聚乙二醇干扰素α-2a治疗,评价两组患者分别在治疗24周和48周时ALT、HBs Ag、HBe Ag和HBV-DNA及用药期间不良的发生率。结果:两组患者治疗后ALT均明显下降,治疗组患者HBs Ag、HBe Ag转阴率、HBVDNA转阴率均高于对照组(P<0.05)。结论:采用聚乙二醇干扰素α-2a与阿德福韦酯联用治疗拉米夫定停药后复发CHB患者,临床疗效优于单用聚乙二醇干扰素α-2a的疗效。     

聚乙二醇干扰素α-2a治疗对拉米夫定耐药的慢性乙型肝炎的临床观察

目的:观察聚乙二醇干扰素α-2a治疗对拉米夫定耐药的慢性乙型肝炎的临床效果。方法:采用随机分组法将112例对拉米夫定耐药的慢性乙型肝炎患者分为3组:长效干扰素治疗组(40例)皮下注射聚乙二醇干扰素α-2a注射液,每次180μg,每周1次;阿德福韦酯组(36例)服用阿德福韦酯片,每次10mg,qd;对照组(26例)继续服用拉米夫定片治疗。3组疗程均为6个月,且均积极给予护肝治疗。比较3组治疗前后肝功能、乙肝标志物和乙型肝炎病毒(HBV)DNA、肝纤维化指标以及不良反应。结果:治疗3个月时,长效干扰素治疗组与阿德福韦酯组丙氨酸氨基转移酶(ALT)复常率均显著高于对照组(P<0.05),但2组间无显著性差异(P>0.05);治疗6个月时,长效干扰素治疗组ALT复常率较对照组和阿德福韦酯组均有显著升高(P<0.01或P<0.05)。长效干扰素治疗组较阿德福韦酯组能更好地抑制HBVDNA复制,促进HBeAg/HBeAb转换,2组比较差异有统计学意义(P<0.05)。对照组治疗前、后肝纤维化指标无显著变化,而阿德福韦酯组和长效干扰素治疗组治疗前后玻璃酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(Ⅳ-C)均有显著差异(P<0.01),且治疗后长效干扰素治疗组HA、LN、PCⅢ较阿德福韦酯组显著降低(P<0.01)。长效干扰素治疗组虽不良反应发生率较高,但不严重,均未影响治疗。结论:聚乙二醇干扰素α-2a治疗拉米夫定耐药的慢性乙型肝炎疗效确切,不良反应可耐受。     

聚乙二醇干扰素α-2a治疗HBeAg阳性慢性乙型肝炎疗效分析

目的观察聚乙二醇干扰素α-2a治疗HBeAg阳性慢性乙型肝炎的临床疗效及安全性。方法共收集我院68例HBeAg阳性慢性乙型肝炎患者,随机分为A、B两组各34例分别给予聚乙二醇干扰素α-2a和普通干扰素α-2a治疗,于治疗24周和48周时,检测两组HBV血清学标志物及血清ALT变化,并记录不良反应。结果治疗24周、48周时,A组血清HBeAg阴转率、ALT复常率均明显高于B组,差异有统计学意义(P<0.05)。结论聚乙二醇干扰素α-2a治疗慢性乙型肝炎疗效优于普通干扰素,且用药简单、方便,从而改善患者的依从性,以确保其疗效。     

乙型肝炎病毒基因型用干扰素α-2b联合苦参素治疗的临床研究

目的：研究乙型肝炎病毒基因型用干扰素α-2b联合苦参素治疗慢性乙型肝炎疗效的关系。方法：应用免疫荧光定量方法检测60例慢性乙型肝炎（慢乙肝）的乙肝病毒基因型，患者均在常规保肝治疗基础上应用干扰素α-2b和苦参素联合抗病毒治疗，疗程6个月。随访6个月。结果：治疗结束及随访6个月时血清HBeAg／HBeAb转换率、HBVDNA阴转率、HBVDNA降低2—5logL率为B基因型组分别为83.3％、83.3％、16．67％；66．67％、75．00％、25．00％；C基因型组分别为45．83％、47．92％、45．65％；35．42％、39．58％、41．67％。B基因型组与C基因型组比较．血清HBeAg／HBeAb转换率、HBVDNA阴转率、血清转氨酶及肝纤维化指标下降均有统计学意义（P〈0．05）。结论：干扰素α-2b联合苦参素治疗慢性乙型肝炎疗效及随访观察疗效B基因型优于C基因型。     

Genetic polymorphisms of interleukin-1-beta in association with sustained response to anti-viral treatment in chronic hepatitis B in Chinese

BACKGROUND: Interleukin-1beta is a pro-inflammatory cytokine that may influence host defence against viral infection. AIM: To investigate the impact of interleukin-1beta gene polymorphism on the response to anti-viral treatment. METHOD: Hepatitis B e antigen-positive chronic hepatitis B patients who have completed a randomized study of peginterferon alpha-2b and lamivudine combination vs. lamivudine monotherapy were included. Sustained responders were patients who had persistent hepatitis B e antigen loss and less than two occasions with hepatitis B virus DNA >100 000 copies/mL at any time up to week 76 post-treatment. Polymorphisms at interleukin-1beta-511, -31 and -3954 and interleukin-1 receptor antagonist (RN) were studied. RESULTS: Eighty-eight patients were studied and 18 (20%) patients developed sustained response. Near complete linkage disequilibrium was observed between interleukin-1beta-511 and -31 loci. After adjustment for the potential confounding effects of treatment allocation, hepatitis B virus genotype, pre-treatment alanine aminotransferase and hepatitis B virus DNA levels, genotype C/T at interleukin-1beta-511 was found to be associated with higher sustained response than genotype C/C (adjusted odds ratio 10.4, 95% CI 1.1, 96.9, P = 0.040). The proportion of sustained responders tend to be higher among patients with allele T at interleukin-1beta-511 (83%) than those without (70%) (P = 0.058). CONCLUSION: High interleukin-1beta production genotype at position -511 has a favourable response to anti-viral treatments.     

Systematic review: treatment of chronic hepatitis B virus infection by pegylated interferon

BACKGROUND: Pegylated interferon-alpha has been shown to be more efficacious than conventional interferon in treating chronic hepatitis C. The use of peginterferon in chronic hepatitis B virus infection with positive hepatitis B e antigen has also been tested in a number of trials since 2003. AIM: To systematically summarize and compare the results of these studies. METHODS: Four studies were identified from PubMed, Medline and reference lists. Data from the trials were extracted and analysed. Where appropriate, combined odds ratio of different trials was calculated. Safety data including serious adverse events and emergence of drug-resistant mutants were recorded. RESULTS: Three of the four trials contained predominantly Asian patients. Peginterferon is found to be superior to lamivudine monotherapy and induced sustained biochemical and virological responses in about one-thirds of patients after 12 months of therapy. Coadministration of lamivudine did not result in improvement in viral suppression. Peginterferon appears to reduce the emergence of YMDD mutation in the combination treatment groups. It was well tolerated with serious adverse events reported in <10% of patients in most trials. CONCLUSIONS: Peginterferon-alpha treatment of at least 6 months should be considered as one of the first-line therapeutic options for hepatitis B virus infection.     

A histological and serological study of persistent hepatitis B antigenaemia

A population of persistent hepatitis B antigen positive persons was investigated in north Taranaki. Over a period of three years, 0.17 percent of blood donors and 7.7 percent of patients investigated for acute infection, possibly hepatitis, had a positive test for hepatitis B surface antigen (HBsAg). Repeat testing was performed at approximately four months in 65 persons and 18 (28 percent) remained positive and of these 15 were males. Liver biopsy in 17 of these patients revealed chronic persistent hepatitis in 30 percent, non-specific changes in 11 percent and in the remainder no significant abnormalities were found. There was no correlation of histology with a wide variety of hepatitis B serological markers. Forty-seven percent of the persistent carriers were Maoris and this group may be more susceptible to chronic hepatitis B infection. Long term follow up of HBsAg carriers is recommended to ascertain the prognosis of this condition.     

Recent advances in the treatment of chronic hepatitis B

Introduction: At present, two strategies exist for the treatment of chronic hepatitis B (CHB): i) standard or pegylated interferon alpha (IFN) with mainly immune modulatory effects; and ii) nucleos(t)ide analogues (NA) with direct antiviral effects. The optimal treatment for an individual patient remains controversial. Areas covered: The treatment efficacy and prediction of response to antiviral agents for chronic hepatitis B are reviewed and discussed. Expert opinion: The rates of hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) loss or seroconversion are continuously increasing in CHB patients after stopping a finite course of IFN, whereas long-term NA therapy is usually required to improve the adverse outcomes of CHB. Lower baseline HBV DNA level is a strong predictor for both sustained viral suppression and HBeAg seroconversion in patients receiving IFN-based as well as NAs therapy. In addition, HBeAg-positive patients with genotype A or B infection have better responses to IFN-based therapy than those with genotypes C or D infection. Furthermore, on-treatment predictors such as declines of serum HBV DNA, HBsAg and HBeAg levels may be helpful in making decisions of subsequent therapy. Regarding the association of host genetic factors with responses to antiviral therapy, current evidence is limited.     

拉米夫定联合香菇多糖治疗慢性乙型肝炎疗效分析

目的:观察拉米夫定联合香菇多糖治疗慢性乙型肝炎(简称慢性乙肝)疗效。方法:对64例慢性乙肝患者随机分为拉米夫定联合香菇多糖组与拉米夫定单用组,每组32例,每组口服用药1年即停药,停药后继续观察6个月。结果:拉米夫定联合香菇多糖组与单用拉米夫定组比较差异无显著性(P>0.05)。结论:拉米夫定联合香菇多糖治疗慢性乙肝疗效相对于单用拉米夫定治疗慢性乙肝疗效无更多的临床价值。     

阿德福韦治疗HBeAg阳性慢性乙型肝炎的疗效与安全性--随机双盲对照研究

目的观察阿德福韦治疗HBeAg阳性慢性乙型肝炎的临床疗效和安全性.方法研究设计为随机、双盲、安慰剂对照临床试验,入选患者40例,阿德福韦口服剂量为每日10 mg.观察阿德福韦对HBV DNA、ALT以及e抗原/e抗体血清转换率的影响,并对不良反应进行监测.结果37例患者完成132周的治疗观察.结果显示ADV可明显降低血清HBV DNA水平,使ALT复常;e抗原/e抗体血清转换率随药物的持续应用而逐渐增高.对达到完全应答半年以上停药者(6例)随访36周,未发现复发者.治疗期间患者生活质量改善,且不良反应轻微.结论阿德福韦为治疗HBeAg阳性慢性乙型肝炎的安全有效药物.     

Clinical features, biochemical parameters, and virological profiles of patients with hepatocellular carcinoma in Hong Kong

BACKGROUND: Clinical features of hepatocellular carcinoma patients are changing because of screening. AIM: To examine the clinical features of hepatocellular carcinoma patients in Hong Kong and validity of different staging systems. METHODS: A total of 223 Chinese patients with hepatocellular carcinoma were studied. RESULTS: Seventy-eight percent of hepatocellular carcinoma patients had chronic hepatitis B (43% diagnosed by screening). Hepatitis B positivity, weight loss, jaundice, encephalopathy, alpha-fetoprotein level, portal vein thrombosis, extrahepatic metastasis, and treatment were shown to be independent factors affecting survival. Of chronic hepatitis B patients, hepatitis B virus DNA levels (P = 0.001) and portal vein thrombosis (P = 0.008) were independent factors affecting survival. Seventy-six percent of chronic hepatitis B patients with hepatocellular carcinoma were hepatitis B e antigen negative. Screening patients had hepatocellular carcinoma detected at an earlier stage and better survival (median survival: 21 vs. 4 months, P < 0.0001). All staging systems had good stratification of survival. Prognosis and median survival generated were different when compared with the US data. CONCLUSIONS: Chronic hepatitis B was the most common cause of hepatocellular carcinoma in Hong Kong. High-risk chronic hepatitis B patients should be followed irrespective of the hepatitis B e antigen status. Hepatitis B virus DNA levels at the time of diagnosis are an important survival predictor. Screening detected hepatocellular carcinoma at an earlier stage and prolonged survival. Staging systems should be validated in different populations.     

Comparative efficacy and overall safety of different doses of consensus interferon for treatment of chronic HCV infection: a systematic review and meta-analysis

Background  

About one-half of patients with hepatitis C genotype 1 and one-third with genotype 2/3 have treatment failure with peginterferon alpha and ribavirin. Consensus interferon (CIFN) is an option for retreatment of these patients.     

Poor response to 18-month lamivudine monotherapy in chronic hepatitis B patients with IgM anti-HBc and acute exacerbation

BACKGROUND: Appearance of immunoglobulin class M antibody against hepatitis B core antigen is a predictor of beneficial response to interferon-alpha therapy in chronic hepatitis B patients, but its relationship with the efficacy of lamivudine therapy remains unclear. AIM: To investigate the outcome of lamivudine therapy in chronic hepatitis B patients with immunoglobulin class M antibody against hepatitis B core antigen and acute exacerbation. METHODS: Chronic hepatitis B patients with acute exacerbation receiving a national-wide therapeutic trial of 18-month lamivudine monotherapy were enrolled for the analysis. Four consecutive seronegative patients were recruited as individual matching controls of one positive subject. Immunoglobulin class M antibody against hepatitis B core antigen in serum was assayed monthly by an automated microparticle enzyme immunoassay. RESULTS: Fifteen (8.9%) of 167 chronic hepatitis B patients with acute exacerbation were seropositive for IgM anti-HBc. Thus 60 seronegative patients were consecutively recruited as control group. At the end of therapy, two (13.3%) of the 15 seropositive patients achieved a sustained response, significantly lower than 26 (43.3%) of the control group. CONCLUSIONS: Appearance of immunoglobulin class M antibody against hepatitis B core antigen in chronic hepatitis B patients with acute exacerbation is a predictor of poor response to lamivudine monotherapy. This is clinically relevant to the decision-making in treating chronic hepatitis B patients with acute exacerbation.     

Pegylated interferons for chronic hepatitis B

Conventional interferon therapy has been used for the treatment of chronic hepatitis B (CHB) for many decades. However, the use of interferon has been limited by its short half-life and high incidence of dose-related side effects. A meta-analysis investigating the short- and long-term consequences of interferon therapy showed that, whilst interferon therapy was beneficial in the short term, resulting in normalization of alanine aminotransferase (ALT) levels, loss of HBeAg, 'e' seroconversion and suppression of hepatitis B virus (HBV) DNA, the long-term benefits were less substantial. Pegylation of interferon (peginterferon alpha-2a [40 kDa]) led to improved pharmacokinetic and pharmacodynamic profiles, which translated to superior efficacy compared with conventional, nonpegylated interferon, in the treatment of chronic hepatitis C. A phase II study investigated the safety and efficacy of peginterferon alpha-2a (40 kDa) in the treatment of chronic hepatitis B. The results demonstrated a rapid and dramatic reduction in HBV DNA levels, HBeAg clearance and normalization of ALT with peginterferon alpha-2a (40 kDa) compared with conventional interferon. Furthermore, peginterferon alpha-2a (40 kDa) conferred a notably improved treatment response in patients with 'difficult-to-treat' hepatitis B infection. In conclusion, peginterferon alpha-2a (40 kDa) is a promising emerging therapy for CHB.