Robust Antibody and Cytokine Response to Hepatitis B Vaccine Among Not-in-treatment Patients With Chronic Hepatitis C：An Open-label Control Study in China
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 300
- 主要终点
- Antibody to the hepatitis B surface antigen response and cytokine response to hepatitis B vaccination in patients with chronic HCV.
研究概览
简要总结
Background Hepatitis B virus (HBV) co-infection in individuals with hepatitis C virus (HCV) can enhance the severity of hepatitis and the risks of liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis B vaccine is an effective measure to prevent HBV infection. Whether patients with HCV infection have non-protective antibody responses to hepatitis B vaccination more frequently than healthy subjects is still controversial and studies about cytokine response have been seldom reported.
Methods Not-in-treatment patients with chronic HCV infection and 1:2 community/gender matched healthy control were obtained from a community-based screening. All participants received three doses of hepatitis B vaccine (20 μg HBsAg/ml/dose) on 0, 1 and 6 months schedule. Anti-HBs was tested 1 month after the third dose of vaccination and was compared between two groups. Spot-forming cells (SFCs) of interferon-γ (IFN-γ), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-5 (IL-5) and interleukin-6 (IL-6) produced by lymphocyte were tested by enzyme-linked immunospot (ELISPOT) and were compared between two groups.
详细描述
Study design and participants The study was conducted in three counties (Yucheng, Xintai and Dongchangfu) of Shandong province, China, which had the highest reported HCV case numbers in the province. Potential patients with chronic HCV infection were recruited by checking the medical records of the hospitals or by inquiring of village doctors. Healthy individuals were randomly selected by 3 to 5 times of potential patients with HCV infection in the same county. Questionnaire investigation was made and blood samples were collected for each potential patient and healthy individual in the same way.
Questionnaire survey We performed a questionnaire-based survey to collect the base line information of the participants, including demographic information (age, sex, height and weight), medical history (allergy, diagnosis and treatment of chronic hepatitis C, vaccination, fever, and other acute diseases), and behavioral status (smoking, drinking, pregnancy and lactation).
Hepatitis B vaccination and follow-up Three doses of hepatitis B vaccine made by Recombinant DNA Techniques in Saccharomyces Cerevisiae (20 μg HBsAg/1.0ml per dose, Shenzhen Kangtai Biological Products Co., Ltd., Shenzhen, Guangdong Province, China) were given intramuscularly in the deltoid region to all participants at 0, 1 and 6 months respectively. Blood samples from the participants were collected one month after the first and the third dose of vaccination.
Laboratory assays and physical examination Screening test and physical examination HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, anti-HCV and HCV RNA were assayed for all subjects at inclusion visits; serum bilirubin, serum albumin, prothrombin time, plasma ALT and aspartate aminotransferase (AST) were detected for HCV group. HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc were assayed by Abbott Chemiluminesent Microparticle ImmunoAssay (CMIA) (Abbott Ireland Diagnostics Division, Sligo, Ireland). Anti-HCV was measured by ELISA with a commercial kit (Intec products, INC, Xiamen, China). HCV RNA was measured by Quantitative Real-time PCR with commercially available kits (QIAGEN, Shenzhen, China). Serum bilirubin, albumin, prothrombin time, plasma ALT and AST were measured using standard reagent and methods. In order to assess disease activity, each patient with HCV infection received clinical examination, including interrogation, physical examination and ultrasonography.
Anti-HBs assay after vaccination Anti-HBs was detected using CMIA (Abbott Ireland Diagnostics Division, Sligo, Ireland) one month after the first and the third dose of vaccination. Although without serological HBV markers, subjects were defined as having a history of HBV infection or hepatitis B vaccination if anti-HBs ≥100 mIU/ml one month after the first dose of vaccination.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 22 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Inclusion criteria for HCV group were as follows: (1) aged ≥ 22 years and Han nationality; (2) no history of hepatitis B vaccination; (3) not-in-treatment patients with anti-HCV and HCV RNA positive; (4) diagnosis of chronic hepatitis C on the basis of self-reported history of HCV infection (more than 6 months) and screening tests for inclusion; (5) negative for HBsAg, anti-HBs, hepatitis B e antigen (HBeAg), antibody to hepatitis B e antigen (anti-HBe) and antibody to hepatitis B core antigen (anti-HBc).
- •Inclusion criteria for healthy control group were as follows: (1) aged ≥ 22 years and Han nationality; (2) no history of hepatitis B vaccination; (3) negative for anti-HCV and HCV RNA; (4) negative for HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc; (5) no self-reported acute and chronic diseases.
排除标准
- •(1) allergy to any vaccine component; (2) pregnancy or lactation; (3) axillary temperature ≥38℃ in the past three days, acute disease in the past seven days or vaccination history of any vaccine in the past four weeks; (4) suffering from diseases that may influence immune function, such as severe cirrhosis with Child-Pugh score >5, renal failure, bleeding diathesis, malignant tumor and HIV infection; (5) have received or being taking antiviral treatment; (6) chronic liver diseases except causing by HCV.
结局指标
主要结局
Antibody to the hepatitis B surface antigen response and cytokine response to hepatitis B vaccination in patients with chronic HCV.
时间窗: one month after the third dose of vaccination
Three doses of hepatitis B vaccine made by Recombinant DNA Techniques in Saccharomyces Cerevisiae (20 μg HBsAg/1.0ml per dose, Shenzhen Kangtai Biological Products Co., Ltd., Shenzhen, Guangdong Province, China) were given intramuscularly in the deltoid region to all participants at 0, 1 and 6 months respectively. Blood samples from the participants were collected one month after the third dose of vaccination. Anti-HBs was assayed by Abbott Chemiluminesent Microparticle ImmunoAssay (CMIA) (Abbott Ireland Diagnostics Division, Sligo, Ireland) one month after the first and the third dose of vaccination. Spot-forming Cells (SFCs) were enumerated with ImmunoSpotTM system (Cellular Technology Ltd.). Differences between HCV group and healthy control group in anti-HBs and immunodotting spots were examined.
次要结局
- The occurrence and severity of solicited local reactions at the injection site, solicited systemic reactions, and any unsolicited adverse after hepatitis B vaccination in patients with chronic HCV(from the first dose of vaccination to one month after the third dose of vaccination)