Hepatitis B in children: Complexities in management
Hepatitis B in children: Complexities in management
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DOI：
10.1111/j.1399-3046.2005.00393.x
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发表时间：
2005-10-01
影响因子：
1.3
通讯作者：
Kerkar, N
中科院分区：
文献类型：
--
作者：
Kerkar, N
慢性乙肝病毒感染的定义是乙肝表面抗原(HBs)在血清中持续存在6个月。发生慢性乙肝病毒感染的风险从新生儿的90%到免疫能力正常的成年人的5%不等。通过围产期感染获得的乙肝病毒具有较长的免疫耐受期，其特征是存在乙肝e抗原(HBeAg)、高HBVDNA和正常的丙氨酸氨基转移酶(ALT)水平。高效、多特异性的辅助性和细胞毒性T细胞应答是控制乙肝病毒感染的关键。慢性乙肝病毒感染的特征是病毒特异性T细胞的低反应状态。慢性乙肝病毒感染的治疗目标是消除或显著抑制乙肝病毒的复制，防止肝病进展为肝硬变，并有可能发展为肝功能衰竭或肝细胞癌(HCC)。在成人中，目前获得许可用于治疗乙肝病毒感染的药物有：干扰素-α(干扰素-α)、拉米夫定(LMV)和阿德福韦酯(ADV)，前两种药物也获准用于儿童。干扰素-α具有更持久的反应、固定的治疗时间和缺乏抗药性突变的优势。与核苷类似物相比，干扰素-α的缺点包括需要每周三次注射，成本更高，副作用更多。核苷类似物可以口服，并用于失代偿期肝硬变和移植受者。ADV和新药如替尼福韦可以成功地治疗延长LMV治疗后产生的突变。目前的方案将免疫耐受的乙肝病毒儿童排除在外。建议对所有慢性乙肝病毒感染的儿童定期进行肝脏超声扫描和甲胎蛋白(AFP)筛查。身体供体器官的严重短缺导致边缘(包括抗-HBc阳性)身体供体肝脏被用于具有高度医疗紧迫感的选定移植候选者；所有肝脏移植中有5%-10%是因为乙肝病毒。使用乙肝免疫球蛋白和核苷类似物使乙肝肝移植后的结果与其他诊断的患者相当，如果不是略好的话。未来的治疗应该基于将乙肝病毒特异性T细胞反应恢复到与控制乙肝病毒的受试者相似的水平。
Chronic hepatitis B virus (HBV) infection by definition is persistence of hepatitis B surface antigen (HBsAg) in the serum for >= 6 months. The risk of developing chronic HBV infection ranges from 90% in neonates to < 5% in immunocompetent adults. HBV acquired by perinatal infection has a prolonged immune-tolerant phase, characterized by the presence of hepatitis Be antigen (HBeAg), high HBV-DNA and normal alanine aminotransferase (ALT) levels. Efficient and multi-specific helper and cytotoxic T-cell response is essential for controlling HBV infection. Chronic HBV infection is characterized by a state of HBV-specific T-cell hyporesponsiveness. The goal of therapy in chronic HBV infection is to eliminate or significantly suppress HBV replication and prevent the progression of liver disease to cirrhosis with the potential development of liver failure or hepatocellular carcinoma (HCC). In adults, drugs currently licensed for treatment of HBV infection: are interferon-alpha (IFN-alpha), lamivudine (LMV) and adefovir dipivoxil (ADV), the first two are also licensed to use in children. IFN-alpha has the advantage of having a more durable response, fixed duration of treatment and lack of resistant mutants. The disadvantages of IFN-alpha include need for thrice-weekly injections, higher cost and more side-effects compared with the nucleoside analogues. Nucleoside analogues can be given orally and used in decompensated cirrhosis and transplant recipients. ADV and newer drugs like tenefovir can successfully treat mutants produced after prolonged LMV therapy. Current protocols exclude children with immunotolerant HBV. Periodic screening with liver ultrasound scan and alpha-fetoprotein (AFP) in all children with chronic HBV infection is recommended. The severe shortage of cadaveric donor organs has led to the use of marginal (including anti-HBc-positive) cadaveric donor livers in selected transplant candidates with high medical urgency; 5-10% of all liver transplants are because of HBV. Using hepatitis B immunoglobulin and nucleoside analogues has made the outcome following liver transplantation for hepatitis B, comparable with, if not slightly better, than that in patients with other diagnoses. Future treatments should be based on the restoration of HBV-specific T-cell responses to levels similar to that seen in subjects controlling HBV.