Prevention of perinatal hepatitis B transmission in Haimen City,China: Results of a community public health initiative

In regions where hepatitis B virus (HBV) is endemic, perinatal transmission is common. Infected newborns have a 90% chance of developing chronic HBV infection, and 1 in 4 will die prematurely from HBV-related liver disease. In 2010, the Hepatitis B Foundation and the Haimen City CDC launched the Gateway to Care campaign in Haimen City, China to improve awareness, prevention, and control of HBV infection citywide. The campaign included efforts to prevent perinatal HBV transmission by screening all pregnant women for hepatitis B surface antigen (HBsAg), following those who tested positive, and administering immunoprophylaxis to their newborns at birth. Of 5407 pregnant women screened, 185 were confirmed HBsAg-positive and followed until delivery. At age one, 175 babies were available for follow up testing. Of those, 137 tested negative for HBsAg and positive for antibodies to HBsAg, indicating protection. An additional 34 HBsAg-negative babies also tested negative for antibodies to HBsAg or had indeterminate test results, were considered to have had inadequate immune responses to the vaccine, and were given a booster dose. A higher prevalence of nonresponse to HBV vaccine was observed among babies born to hepatitis B e antigen (HBeAg)-positive mothers and mothers with high HBV DNA titers. The remaining 4 babies tested positive for HBsAg and negative for antibodies, indicative of active HBV infection. The mothers of all 4 had viral loads ≥8 × 10⁶ copies/ml in the third trimester. Although inadequate response or nonresponse to HBV vaccine was more common among babies born to HBeAg-positive and/or high viral load mothers, these risk factors did not completely predict nonresponsiveness. All babies born to HBV-infected mothers should be tested upon completion of the vaccine series to ascertain adequate protection. Some babies of HBeAg-positive mothers with high viral load may still become HBV infected despite timely immunoprophylaxis with HBV vaccine and HBIG.     

乙型肝炎病毒 B、C 基因型与临床表现

目的：研究广东地区乙型肝炎病毒基因型分布情况,B、C 基因型与乙型肝炎患者临床表现之间的关系。方法：回顾性分析172例慢性乙型肝炎病毒患者[慢性乙型病毒性肝炎（CHB）、乙型肝炎后肝硬化（LC）、原发性肝癌（HCC）]的乙型肝炎病毒基因分型结果,并根据基因分型结果进行分组,比较 B、C基因型患者的临床表现、HBeAg 定性、HBV-DNA 定量、ALT 及 AST 结果。结果：172例患者的乙肝病毒型分别为 B 型94例（54.7％）、C 型69例（40.1％）、D 型3例（1.7％）、未分型6例（3.5％）;C 型在 LC 组、HCC组中的比例与 CHB 组比较,差异有统计学意义（P﹤0.05）;C 型的 HBeAg 阳性率高于 B 型（P﹤0.05）;B、C型两组的 ALT、AST 差异有显著统计学意义（P﹤0.01）;两组基因型间 HBV-DNA 水平的差异无统计学意义（P﹥0.05）。结论：广东地区 HBV 感染以 B、C 基因型为主,以 B 型居高;C 基因型肝功能损害更严重,发展为肝硬化、肝癌的可能性更大,感染不同 HBV 基因型与 HBV-DNA 水平无明显相关。     

Pegylated IFN-α2b added to ongoing lamivudine therapy in patients with lamivudine-resistant chronic hepatitis B

AIM: To investigate the role of pegylated-interferon (IFN)α-2b in the management of patients with lamivudine-resistant chronic hepatitis B. METHODS: Twenty consecutive anti-HBe positive patients were treated with pegylated IFNα-2b (100μg sc once weekly) for 12 mo. There was no interruption in lamivudine therapy. Hematology, liver biochemistry, serum HBV DNA levels were detected by PCR, and vital signs were also assessed. Liver histology was assessed in some patients at entry and at wk 52 for comparison. RESULTS: Nine patients (45%) had a partial viro-logical end-treatment response; seven patients (35%) showed complete virological end-treatment response. Eight patients (40%) showed biochemical end-treatment response. There was a trend for higher virological response rates in patients who had previously responded to IFN and relapsed compared to IFN non-responders (four out of seven patients vs none out of six patients, respectively; P=0.1). Patients without virological end-treatment response showed significant worsening of fibrosis [median score 2 (range, 1 to 3) vs median score 3 (range, 1 to 4)], in the first and second biopsy respectively (P=0.014), whereas necroinflammatory activity was not significantly affected. Patients with complete or partial virological end-treatment response did not show any significant changes in histological findings, possibly due to the small number of patients with paired biopsies (n = 5). Nevertheless, after 12 mo of follow-up, only one patient (5%) showed sustained virological response and only 2 patients (10%) showed sustained biochemical response. Two patients (10%) discontinued pegylated IFN both after 6 mo of treatment due to flu-like symptoms. CONCLUSION: Pegylated IFNα-2b, when added to ongoing lamivudine therapy in patients with lamivudine-resistant chronic hepatitis B, induces sustained responses only in a small minority of cases.     

IL-12A、IL-1B、IL-17A单核苷酸多态性与慢性乙型肝炎恩替卡韦治疗HBeAg血清学转换的遗传关联研究

目的 通过遗传关联研究观察慢性HBV感染免疫相关重要细胞因子IL-12、IL-1B、IL-17的基因多态性与恩替卡韦抗病毒治疗HBeAg血清学转换之间的关联.方法 对109例恩替卡韦抗病毒治疗的HBeAg阳性慢性乙型肝炎患者每3个月进行肝功能、乙肝标志物、HBV DNA检测,进行HBeAg血清学转换评估,治疗24个月时的应答情况作为判定应答与否的标准.发生HBeAg血清学转换者为应答组;未发生HBeAg血清学转换者为无应答组;分析IL-12A rs568408、IL-1 B rs1143623、IL-17Ars8193036基因型与HBeAg血清学转换之间的关联.结果 29例获得HBeAg血清学转换(应答组),80例未获得HBeAg血清学转换(无应答组),总体应答率26.6％.IL-12A rs568408与HBeAg血清学转换显著相关,GA基因型发生HBeAg血清转换的易感性显著高于GG基因型[OR =3.72(1.34～10.32),P=0.012].未发现IL-1B rs1143623[OR=1.99 (0.72 ～5.44),P=0.17]和IL-17Ars8193036 [OR=1.54 (0.32 ～7.33),P=0.60]与HBeAg血清学转换存在关联.结论 IL-12Ars568408与慢性乙型肝炎恩替卡韦治疗HBeAg血清学转换存在关联.     

定量检测710例肝病患者HBsAg和H BeAg临床意义

目的：了解乙型肝炎与肝硬化患者表面抗原（HBsAg）与e抗原（HBeAg）定量变化规律,探讨分层次联合抗病毒治疗并争取满意效果的可行性。方法采用荧光磁微粒酶免法检测710例 HBV 相关肝病患者 HBsAg 和HBeAg,用SPSS19．0软件包进行统计学处理。结果 HBsAg＜0．2 IU/mL 61例,占8．5％;HBsAg＞0．2 IU/mL～＜100 IU/mL 为低水平 HBsAg组,55例,占7．7％;HBsAg ＞100 IU/mL～＜1000 IU/mL 为中等水平 HBsAg 组,142例,占20％;HBsAg 1000～5000 IU/mL为高水平 HBsAg 组,211例,占29．7％;HBsAg＞5000 IU/mL 为超高水平HBsAg组,241例,占33．9％;各型肝炎随年龄增大,HBsAg 定量值逐步下降,转阴高峰集中在46岁左右;HBeAg 阴性组（＜1．0 CI）453例,占63．8％;低水平 HBeAg阳性组（＞1．0 CI～＜10 CI）96例,占13．5％;中等量水平 HBeAg 阳性组（＞10 CI～＜100 CI）55例,占7．7％;高水平 HBeAg 阳性组（＞100 CI～＜500 CI）23例,占3．2％;超高水平HBeAg阳性组（＞500 CI）83例,占11．6％;从慢性 HBV携带者,慢性乙型肝炎,代偿期肝硬化到失代偿期肝硬化,年龄逐步增大,HBsAg和 HBeAg定量秩均值逐步下降,卡方检验有显著性差异。结论 HBsAg 和 HBeAg 定量随年龄增加与病情发展逐步下降,根据 HBsAg,HBeAg 和 HBV DNA定量进行分层次联合抗病毒治疗可争取较满意效果。     

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。