HBsAg clearance by Peg-interferon addition to a long-term nucleos(t)ide analogue therapy

The ideal endpoint of hepatitis B virus (HBV) antiviral therapy is HBsAg loss, a difficult goal to obtain, especially in HBeAg negative patients. Herein, we report the results obtained by the addition of peg-interferon α-2a to a long-lasting nucleos(t)ide analogue therapy in a HBeAg negative, genotype D patient with steadily HBV-DNA negative/HBsAg positive values. In 2002, our Caucasian 44-year-old male patient received lamivudine and, 4 years later, added adefovir because of a virological breakthrough. In 2011, considering his young age, liver stiffness (4.3 kPa) and HBsAg levels (3533 IU/mL), we added Peg-interferon α-2a for six months (3 in combination with nucleos(t)ide analogues followed by 3 mo of Peg-interferon α-2a monotherapy). A decrease of HBsAg levels was observed after 1 mo (1.21 log) of Peg-interferon and 3 mo (1.88 log) after the discontinuation of all drugs. Later, a complete clearance of HBsAg was obtained with steadily undetectable HBV-DNA serum levels (< 9 IU/mL). HBsAg clearance by the addition of a short course of Peg-interferon α-2a represents an important result with clinical and pharmaco-economic implications, considering that nucleos(t)ide analogues therapy in HBeAg negative chronic hepatitis B patients is considered a long-lasting/life-long treatment.     

Lamivudine therapy for korean children with chronic hepatitis B

PURPOSE: Lamivudine is known to be very effective in suppressing hepatitis B virus replication and virus induced necroinflammation. The aim of this study was to evaluate lamivudine therapy efficacy, predictive factors, breakthrough, prevalence of YMDD mutation, and relapse rate in Korean children with chronic hepatitis B. MATERIALS AND METHODS: Between August 1999 and February 2005, 60 children on lamivudine therapy for chronic hepatitis B were enrolled. Treatment response was defined as alanine aminotransferase (ALT) normalization, and HBeAg and HBV-DNA disappearance. RESULTS: Seroconversion rates of HBeAg and HBV- DNA were 42% and 53%, respectively, and ALT normalization rate was 88%. Seroconversion rates of HBeAg (60.0%) and anti-HBe (60.0%) were higher in patients younger than 6 years. Seroconversion rate of HBV-DNA (68.4%) and normalization rate of serum ALT (94.7%) were highest in patients between 6 and 12 years. Seroconversion rates of all HBV markers were lowest in patients older than 12 years. Predicted 3 year cumulative seroconversion rates, were 70%, 68% for HBeAg, HBV-DNA, respectively. These were calculated by Kaplan-Meier method. Cox proportional hazard regression model showed that pre-treatment ALT was a positive predictive factor for seroconversion of HBeAg and HBV-DNA. Breakthrough phenomenon was noted in 6 patients, and 3 had a YMDD mutation. CONCLUSION: Lamivudine therapy had a significant effect on HBeAg seroconversion and HBV-DNA disappearance, and ALT normalization for Korean children with chronic hepatitis B.     

前列地尔联合复方鳖甲软肝片治疗慢性乙型肝炎肝硬化的疗效观察

目的探讨复方鳖甲软肝片联合前列地尔治疗慢性乙型肝炎肝硬化的临床疗效。方法选取2013年4月—2016年6月在雅安市人民医院接受治疗的126例慢性乙型肝炎肝硬化患者作为研究对象,随机分为对照组和治疗组,两组各63例。对照组患者口服复方鳖甲软肝片,4片/次,3次/d;治疗组患者在对照组的基础上静脉注射前列地尔注射液,5μg加入到10mL生理盐水中,1次/d。两组患者均治疗6周。观察两组的乙肝病毒的脱氧核糖核酸(HBV-DNA)转阴率、乙肝E抗原(HBeAg)转阴率及HBeAg转换率,比较治疗前后两组患者的Child-Pugh评分、肝功能指标以及肝纤维化指标的变化。结果治疗组的HBV-DNA转阴率、HBeAg转阴率和HBeAg转换率分别为77.8%、54.0%、44.4%,均显著高于对照组的55.6%、30.2%、27.0%,两组比较差异具有统计学意义(P0.05);两组患者的Child-Pugh评分均降低,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后治疗组的Child-Pugh评分明显低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者的丙氨酸氨基转移酶(ALT)和总胆红素(TBIL)显著降低,凝血酶原活动度(PTA)升高,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后治疗组的肝功能指标明显优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者的透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、IV型胶原(Ⅳ-C)、层黏连蛋白(LN)均显著降低,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后治疗组的肝纤维化指标明显低于对照组,两组比较差异具有统计学意义(P0.05)。结论复方鳖甲软肝片联合前列地尔治疗慢性乙型肝炎肝硬化疗效显著,可有效改善肝功能和肝纤维化,具有一定的临床推广应用价值。     

替诺福韦酯治疗HBeAg阳性慢性乙型肝炎患者的疗效及对肝功能指标的影响

目的探讨替诺福韦酯治疗HBeAg阳性慢性乙型肝炎患者的疗效及对肝功能指标的影响。方法选取2017年2月至2018年3月本院收治的126例HBeAg阳性慢性乙型肝炎患者,按照年龄、性别组间具有可比性原则分为对照组与观察组,各63例。对照组予以恩替卡韦治疗,观察组予以替诺福韦酯治疗,比较两组治疗前后肝功能指标及ALT复常率、HBV DNA转阴率、HBeAg转阴率。结果治疗后,两组AST、ALT、TBiI均低于治疗前,且观察组低于对照组,ALB高于治疗前,且观察组高于对照组,差异有统计学意义(P<0.05);观察组ALT复常率、HBV DNA阴转率、HBeAg转阴率均高于对照组,差异有统计学意义(P<0.05)。结论相比恩替卡韦治疗,替诺福韦酯治疗HBeAg阳性慢性乙型肝炎患者,可有效改善肝功能,提高HBV DNA阴转率及HBeAg阴转率。     

慢肝患者HBeAg不同状态HBsAg水平与HBV-DNA载量相关性

目的探讨慢肝患者HBe Ag不同状态下HBs Ag水平与HBV-DNA载量关系。方法选择2013年7月至2014年5月在我院肝病门诊就诊的239例CHB患者,运用化学发光法、FQ-PCR法对患者HBs Ag水平及HBV-DNA载量进行监测分析,并将各指标进行有效性讨论。结果 239例患者中,HBe Ag阳性患者的HBs Ag含量和HBV DNA载量均数分别为38089.34 IU/m L和2.88×107 Copy/m L,HBe Ag阴性患者的HBs Ag含量和HBV DNA载量均数分别为4122.51 IU/m L和3.93×106 Copy/m L,统计学分析表明,两组差异具有统计学意义(P<0.001)。高复制水平(HBV-DNA≥105)组的HBV-DNA及HBs Ag定量均值高于低复制水平(HBV-DNA<105)组,两组差异具有统计学意义(P<0.001),从相关性表明,高复制组的HBV-DNA载量与HBs Ag含量具有显著相关性。结论 HBe Ag阳性患者HBV-DNA载量及HBs Ag水平明显高于HBe Ag阴性患者,HBV-DNA载量越高,HBs Ag水平亦高。HBe Ag阴性患者乙型肝炎病毒虽然处于一个相对较低水平,但仍然存在病毒在体内复制的可能,因此,CHB患者应定期进行相关标志物及HBV-DNA检测,以了解患者个体治疗情况,对患者病情、疗效、预后有良好的判断作用。     

HBV-M在慢乙肝、肝硬化及肝癌中的表达及意义

目的 比较HBsAg、HBeAg滴度与HBV DNA水平在慢性乙型肝炎、乙型肝炎肝硬化及HBsAg 阳性的原发性肝癌患者中的变化,并探讨其对病情进展的影响。方法 在149例慢性乙型肝炎患者,115例乙型肝炎肝硬化患者及146 例肝癌患者中,采用荧光PCR定量法和Abbott化学发光微粒子免疫分析技术分别测定HBV DNA定量水平及HBsAg和HBeAg的滴度, 分析它们在这三组患者中的变化。结果1.HBeAg定量值在三组患者中比较有统计学意义(F=9.944,P=0.007);乙型肝炎组与肝硬化组、肝癌组比较均有统计学意义(x2=4.147,P=0.042; x2=9.499,P=0.002);肝硬化组与肝癌组比较无统计学意义(x2=0.747,P=0.387)。2.在不同HBeAg状态下,HBsAg定量值在乙型肝炎组与肝硬化组患者中比较均有统计学意义(t=2.549,P=0.012;t=2.428,P=0.017);HBsAg定量值在肝癌组中无统计学意义(t=1.375,P=0.171);HBVDNA定量值在三组患者中比较,差异均有统计学意义(Z分别为3.148、6.544、4.520,P<0.05)。 结论 定量检测慢性乙型肝炎、肝硬化及肝癌患者血清中的HBsAg、HBeAg及HBV DNA的变化有一定的临床意义,将三者结合能更好地为临床提供准确可靠的诊断和治疗数据。     

聚乙二醇干扰素α-2a联合阿德福韦酯治疗HBeAg阴性慢性乙型肝炎的临床观察

目的：观察聚乙二醇干扰素α-2a联合阿德福韦酯治疗HBeAg阴性慢性乙型肝炎的临床疗效。方法沭阳县中心医院2011年1月—2013年1月收治的HBeAg阴性慢性乙型肝炎130例,随机分为干扰素组（43例）,阿德福韦酯组（39例）和联合治疗组（48例）。干扰素组皮下注射聚乙二醇干扰素α-2a注射液180μg,每周1次。阿德福韦酯组口服阿德福韦酯片10 mg/次,1次/d。联合治疗组同时给予聚乙二醇干扰素α-2a注射液和阿德福韦酯片,用法用量同以上两组。3组患者均连续治疗48周。观察3组患者丙氨酸氨基转移酶（ALT）复常情况、HBsAg清除情况、HBV DNA转阴情况。结果治疗24、48、72周,干扰素组、阿德福韦酯组的HBsAg清除率、HBV DNA转阴率均显著低于联合治疗组,差异有统计学意义（P＜0.05）。3组治疗后ALT、HBV DNA拷贝数、HBsAg水平均较治疗前显著降低,同组治疗前后差异有统计学意义（P＜0.05）;且干扰素组、阿德福韦酯组患者 ALT 在治疗48、72周时均高于联合治疗组,差异有统计学意义（P＜0.05）;两组HBV DNA拷贝数从治疗24周起就高于联合治疗组,差异有统计学意义（P＜0.05）;干扰素组HBsAg水平在治疗24周、48、72周时均高于联合治疗组,而阿德福韦酯组HBsAg水平仅在治疗48周时高于联合治疗组,差异有统计学意义（P＜0.05）。结论聚乙二醇干扰素α-2a联合阿德福韦酯治疗HBeAg阴性慢性乙型肝炎具有较好的临床疗效,两药有一定的协同作用,优于两药单独应用。     

Randomised controlled trial: effect of metformin add-on therapy on functional cure in entecavir-treated patients with chronic hepatitis B

Introduction and ObjectivesHepatitis B surface antigen (HBsAg) clearance, indicating functional cure or resolved chronic hepatitis B (CHB), remains difficult to achieve via nucleos(t)ide analogue monotherapy. We investigated whether metformin add-on therapy could help achieve this goal in entecavir-treated patients with hepatitis B e antigen (HBeAg)-negative CHB.Patients and MethodsPatients with HBeAg-negative CHB who met eligibility criteria (entecavir treatment for > 12 months, HBsAg < 1000 IU/mL) were randomly assigned (1:1) to receive 24 weeks of either metformin (1000 mg, oral, once a day) or placebo (oral, once a day) add-on therapy. The group allocation was blinded for both patients and investigators. Efficacy and safety analyses were based on the intention-to-treat set. The primary outcome, serum HBsAg level (IU/mL) at weeks 24 and 36, was analysed using mixed models.ResultsSixty eligible patients were randomly assigned to the metformin (n = 29) and placebo (n = 31) groups. There was no substantial between-group difference in the HBsAg level at week 24 (adjusted mean difference 0.05, 95% confidence interval -0.04 to 0.13, p = 0.278) or week 36 (0.06, -0.03 to 0.15, p = 0.187), and no significant effect of group-by-time interaction on the HBsAg level throughout the trial (p = 0.814). The occurrence of total adverse events between the two groups was comparable (9 [31.0%] of 29 vs. 5 [16.1%] of 31, p = 0.227) and no patient experienced serious adverse events during the study.ConclusionAlthough it was safe, metformin add-on therapy did not accelerate HBsAg clearance in entecavir-treated patients with HBeAg-negative CHB.