1.Cleavland clinic: "How do you get chronic hepatitis B?
Chronic hepatitis B develops when your immune system fails to fight off the virus. Most people successfully fight it off during the acute phase of the infection. The acute phase is when your immune system recognizes the virus and launches its attack."
All 75 patients were cared for as inpatients for a few days on supportive treatment: Hydration, glucose, and electrolytic balance. Three patients with particularly high levels of liver damage were treated with entecavir until anti-HBsAg seroconversion. After clinical improvement, all patients were discharged, and most were further followed at the same center as outpatients. Clinical data recorded during the hospital stay or collected during follow-up visits were analyzed for the study. None of the patients reported or were documented as having been vaccinated. Twenty-six patients were lost during follow-up after a short hospital stay, 49 were followed as outpatients for a variable amount of time. Of these, 44 were followed to HBsAg clearance or for longer than five years. For the purposes of this study, HBsAg clearance was defined as the intermediate time between the last positive and the first negative result. By this definition, 36/44 patients cleared HBsAg within six months (Rapid Resolvers, RR), as shown in Figure 2A. Of the other eight (Slow Resolvers, SR), three (3/44, 6.8%) developed a true chronic HBeAg+ infection (>4 years now, two of them requiring chronic antiviral treatment). SR were infected with: Four genotype A, two genotype F, and one of genotype D and B respectively. Of these, two genotype A and one genotype B infections became chronic. Genotype D infection in adults showed the lowest probability of lasting longer than six months (6.7% vs. 22% non–D genotypes, not significant).
All 75 patients were cared for as inpatients for a few days on supportive treatment: Hydration, glucose, and electrolytic balance. Three patients with particularly high levels of liver damage were treated with entecavir until anti-HBsAg seroconversion. After clinical improvement, all patients were discharged, and most were further followed at the same center as outpatients. Clinical data recorded during the hospital stay or collected during follow-up visits were analyzed for the study. None of the patients reported or were documented as having been vaccinated. Twenty-six patients were lost during follow-up after a short hospital stay, 49 were followed as outpatients for a variable amount of time. Of these, 44 were followed to HBsAg clearance or for longer than five years. For the purposes of this study, HBsAg clearance was defined as the intermediate time between the last positive and the first negative result. By this definition, 36/44 patients cleared HBsAg within six months (Rapid Resolvers, RR), as shown in Figure 2A. Of the other eight (Slow Resolvers, SR), three (3/44, 6.8%) developed a true chronic HBeAg+ infection (>4 years now, two of them requiring chronic antiviral treatment). SR were infected with: Four genotype A, two genotype F, and one of genotype D and B respectively. Of these, two genotype A and one genotype B infections became chronic. Genotype D infection in adults showed the lowest probability of lasting longer than six months (6.7% vs. 22% non–D genotypes, not significant).
Chronic hepatitis B develops when your immune system fails to fight off the virus. Most people successfully fight it off during the acute phase of the infection. The acute phase is when your immune system recognizes the virus and launches its attack."
https://my.clevelandclinic.org/health/diseases/4246-hepatitis-b
2. 维基百科
"婴儿经由母亲垂直感染B型肝炎后，有90%的机率成为慢性B型肝炎带原者；而5岁后才感染B型肝炎者，长大后只有不到10%会成为慢性带原者[4]。虽然大部分慢性肝炎患者没有症状，但却有机会发展为肝硬化甚至肝癌[2]，亦为慢性肝炎患者死因的15%至25%[1]。"
3. 这是一份44个乙肝住院病人的5年追踪报告，41个病人清除了表面抗原 ，3/44(6.8%)转为慢性感染
Genes (Basel). 2018 Jun; 9(6): 293. Published online 2018 Jun 12. doi: 10.3390/genes9060293 PMCID: PMC6027296 PMID: 29895748 Long-Term Follow-Up of Acute Hepatitis B: New Insights in Its Natural History and Implications for Antiviral Treatment Stefano Menzo,1,* Claudia Minosse,2 Donatella Vincenti,2 Laura Vincenzi,3 Fabio Iacomi,3 Paola Zaccaro,2 Gianpiero D’Offizi,3 and Maria R. Capobianchi2 3.2. Clinical Outcome, Natural History and HBsAg ClearanceAll 75 patients were cared for as inpatients for a few days on supportive treatment: Hydration, glucose, and electrolytic balance. Three patients with particularly high levels of liver damage were treated with entecavir until anti-HBsAg seroconversion. After clinical improvement, all patients were discharged, and most were further followed at the same center as outpatients. Clinical data recorded during the hospital stay or collected during follow-up visits were analyzed for the study. None of the patients reported or were documented as having been vaccinated. Twenty-six patients were lost during follow-up after a short hospital stay, 49 were followed as outpatients for a variable amount of time. Of these, 44 were followed to HBsAg clearance or for longer than five years. For the purposes of this study, HBsAg clearance was defined as the intermediate time between the last positive and the first negative result. By this definition, 36/44 patients cleared HBsAg within six months (Rapid Resolvers, RR), as shown in Figure 2A. Of the other eight (Slow Resolvers, SR), three (3/44, 6.8%) developed a true chronic HBeAg+ infection (>4 years now, two of them requiring chronic antiviral treatment). SR were infected with: Four genotype A, two genotype F, and one of genotype D and B respectively. Of these, two genotype A and one genotype B infections became chronic. Genotype D infection in adults showed the lowest probability of lasting longer than six months (6.7% vs. 22% non–D genotypes, not significant).
一旦发现血液中乙肝病毒量过高（激活复制活跃）医生就会建议病人做B超，检查肝脏损害程度。。
Genes (Basel). 2018 Jun; 9(6): 293. Published online 2018 Jun 12. doi: 10.3390/genes9060293 PMCID: PMC6027296 PMID: 29895748 Long-Term Follow-Up of Acute Hepatitis B: New Insights in Its Natural History and Implications for Antiviral Treatment Stefano Menzo,1,* Claudia Minosse,2 Donatella Vincenti,2 Laura Vincenzi,3 Fabio Iacomi,3 Paola Zaccaro,2 Gianpiero D’Offizi,3 and Maria R. Capobianchi2 3.2. Clinical Outcome, Natural History and HBsAg Clearance
All 75 patients were cared for as inpatients for a few days on supportive treatment: Hydration, glucose, and electrolytic balance. Three patients with particularly high levels of liver damage were treated with entecavir until anti-HBsAg seroconversion. After clinical improvement, all patients were discharged, and most were further followed at the same center as outpatients. Clinical data recorded during the hospital stay or collected during follow-up visits were analyzed for the study. None of the patients reported or were documented as having been vaccinated. Twenty-six patients were lost during follow-up after a short hospital stay, 49 were followed as outpatients for a variable amount of time. Of these, 44 were followed to HBsAg clearance or for longer than five years. For the purposes of this study, HBsAg clearance was defined as the intermediate time between the last positive and the first negative result. By this definition, 36/44 patients cleared HBsAg within six months (Rapid Resolvers, RR), as shown in Figure 2A. Of the other eight (Slow Resolvers, SR), three (3/44, 6.8%) developed a true chronic HBeAg+ infection (>4 years now, two of them requiring chronic antiviral treatment). SR were infected with: Four genotype A, two genotype F, and one of genotype D and B respectively. Of these, two genotype A and one genotype B infections became chronic. Genotype D infection in adults showed the lowest probability of lasting longer than six months (6.7% vs. 22% non–D genotypes, not significant).
世界肝炎日｜我们距离彻底治愈乙肝还有多久？
澎湃新闻记者 姚易琪
2023-07-28 07:10
来源：澎湃新闻
? 生命科学 >
·肝炎中最难医治的就是乙肝，目前医学界还无法彻底治愈乙肝，临床主要的乙肝治疗措施为抗病毒治疗。根据治疗目标不同，分为长期抑制病毒和追求临床治愈（病毒的基因还在病人细胞里，只是通过免疫治疗，消除血液中的病毒）两种。从目前整体情况来看，通过口服药，长期抑制病毒的患者更多。
2023年7月28日是第13个“世界肝炎日”，今年中国的宣传主题为“坚持早预防，加强检测发现，规范抗病毒治疗”。肝炎到底有几种？肝炎会传染吗？能治愈吗？
对于这些疑惑，澎湃科技采访了四川大学华西医院感染性疾病中心副主任医师杜凌遥，他表示，肝炎有很多种，可分为传染性肝炎、非传染性肝炎，以及药物性肝炎、自身免疫性肝炎。其中，最常见也最难治愈的，就是类属传染性肝炎的慢性乙型病毒性肝炎，简称“乙肝”，可通过输血、性接触、母婴三种途径传播。杜凌遥表示：“很多人担心跟肝炎患者共同进餐会得肝炎，的确，甲型肝炎和戊型肝炎会通过粪-口途径传播，不过这两种肝炎的治愈率也比乙肝要高。另外建议有肝病家族史的人定期检查肝功能，因为密切的生活接触也可能传染乙型、丙型和丁型肝炎。”
杜凌遥说，由于乙肝疫苗的预防率较高，“在没有感染的状态下，成功接种乙肝疫苗能够获得约95%的保护效果”，所以新发乙肝病例较少，但目前，我国依然是乙肝大国，因为既往诊断还有筛查率较低，且 1992年以前，中国还未推广接种乙肝疫苗，所以既往肝炎患者较多，存量较大，有很大一批通过母婴传播感染乙肝的患者。
在治疗方面，因乙肝病毒特殊的存在形式，目前还未能彻底治愈乙肝，只能达到控制病毒，或临床治愈（病毒的基因还在病人细胞里，只是通过免疫治疗，消除血液中的病毒）的效果。杜凌遥说：“不管是控制病毒，还是临床治愈，都有其局限性，若只想控制病毒，可采取口服核苷类似物的方式，但缺点在于需长期、甚至终身服药，还会产生耐药性；若想临床治愈，首先治愈率较低，其次注射药物价格较贵。因此，彻底治愈乙肝，一直是医学界努力的方向。”
至于肝炎和肝癌的关系，杜凌遥称，肝炎并不一定会发展成肝癌，但肝炎是造成肝癌的风险因素之一，不同肝炎诱发肝癌的机制也不一样，此外，还有肝炎病毒影响原癌基因（存在于生物正常细胞基因组中的癌基因）等更复杂的原因，也会造成肝癌。
【对话】
肝炎传染途径有哪些？
澎湃科技：肝炎分几类，最常见的肝炎是哪种，临床表现有什么？
杜凌遥（四川大学华西医院感染性疾病中心副主任医师）：肝炎有很多种，有传染性的肝炎——病毒性肝炎，还有一些没有传染性的肝炎，比如脂肪性肝炎，分为酒精性脂肪肝和非酒精性脂肪肝，还有药物性肝炎，自身免疫性肝炎。没有传染性的肝炎要么是基因的问题，要么就和自身生活习惯有关，比如经常喝酒、吃伤肝的药物等。
病毒性肝炎也分为两大类，一类是嗜肝病毒（肝炎病毒）引起的肝炎，我们经常说的甲乙丙丁戊型肝炎就是嗜肝病毒引起的肝炎；一类是非嗜肝病毒引起的肝炎，临床上较常见的是巨细胞病毒（CMV）或者是EB病毒（人类疱疹病毒4型）引起的肝炎。但不管哪种肝炎，它的临床表现都是统一的，比如转氨酶升高（谷丙转氨酶，在肝脏有损伤的时候最先出现异常）、肝脏穿刺活检后发现肝脏有炎症等。总体来看，无论什么原因引起的肝炎，表现症状大都是乏力、厌油、纳差（吃不下东西），有些人还会有恶心呕吐等消化道症状。
在中国，最常见的就是乙肝，目前乙肝的新发病率已经较低，既往肝炎患者较多，存量较大。主要原因在于既往诊断还有筛查率比较低。并且 1992年以前，我国没有推广接种乙肝疫苗，对乙肝的阻断成功率也非常低，因此有很大一批通过母婴传播感染上乙肝的患者。
当然现在的乙肝疫苗预防成功率已经非常高了，在没有感染的状态下，成功接种乙肝疫苗能够获得约95%的保护效果。
澎湃科技：不同肝炎的传播途径有哪些？
杜凌遥：乙肝、丙肝和丁肝通过输血、性接触、母婴这三个主要途径传播；甲肝、戊肝主要通过消化道，也就是粪-口途径传播。如果有肝炎家族病史，建议去医院检查一下。
澎湃科技：肝炎和肝癌的关系是什么？
杜凌遥：肝炎是促发肝癌的一个风险因素，不同肝炎诱发肝癌的机制也不一样。有些是因为肝脏在反复炎症损伤的过程中会触发肝癌的发生通路，然后产生肝癌。还有些肝脏在损伤修复的过程中会形成肝结节，也会增大肝癌的发生风险。还有一些更复杂的原因，比如肝炎病毒影响了一些原癌基因（存在于生物正常细胞基因组中的癌基因）、抑癌基因（一类存在于正常细胞内可抑制细胞生长，并具有潜在抑癌作用的基因）等。因此，和健康群体相比，当然肝炎患者发生肝癌的风险会增高。
澎湃科技：日常发生哪些现象需要我们警惕？如果怀疑有肝炎，应该做什么检查？
杜凌遥：首先要关注自己的生活环境还有家族史。密切接触、共同生活的人是否有肝炎，你的父母辈，以及其他有血缘关系的亲属是否患有肝炎、肝硬化甚至肝癌病史；其次是看是否有上述提到的肝炎相关临床表现；另外还要关注风险因素，比如，是否去了肝炎高发地区，是否在这些地方有不洁饮食或者高危行为。
如果要检测，首先应该做肝功能检查，因为不管哪类肝炎，都会出现肝功能损害现象。如果肝功能有问题，就要根据风险因素进一步鉴别肝炎类别，这时我们建议大家做肝炎病毒标志物筛查。具体来说，主要检查乙肝两对半（表面抗原、表面抗体、E抗原、E抗体、核心抗体）、甲肝抗体，丙肝抗体等等。
如果没有任何的风险因素，检查频率约为每年一次，如果既往已经诊断为慢性肝炎的患者，我们建议三个月检查一次。
肝炎能治好吗？
澎湃科技：肝炎的治愈率大概是多少？现在最难治的肝炎是哪一种肝炎？
杜凌遥：像丙型肝炎这样的慢性肝炎，通过抗病毒治疗，临床治愈率在95%以上。但如果是乙肝，治愈非常困难，很难达到彻底治愈，目前只能在部分人群中做到临床治愈，即病毒的基因还在病人细胞里，只是通过免疫治疗，消除血液中的病毒，实现“两对半”的转换，降低病毒对肝功能的损害，进而降低未来发生肝硬化、肝癌的风险。
肝炎中最难医治的就是乙肝，因为乙肝病毒会整合到人的基因里。乙肝病毒在复制产生子代病毒的过程中，会产生共价闭合环状的脱氧核糖核酸（cccDNA），这是一部分处于游离状态，就像卫星一样存在我们的肝细胞里的病毒基因，另外一部分则直接整合进入肝细胞基因里，这种独特的存在形式，导致它非常难清除。
澎湃科技：临床主要的乙肝治疗措施是什么，有何优缺点？
杜凌遥：主要的乙肝治疗措施为抗病毒来治疗。根据治疗目标不同，分为长期抑制病毒和追求临床治愈两种。临床治愈最主要的还是使用干扰素，这是一种免疫治疗方法。长期抑制病毒通常是通过口服核苷类似物（天然核苷的模拟物，已被广泛用作化学生物学工具，且作为抗肿瘤药物和小分子抗病毒药物用于多种疾病治疗），比如替诺福韦（Tenofovir）、恩替卡韦（Entecavir）等来实现。
不同疗法也有其优缺点。干扰素治疗的优点很明显，至少在现在已经上市的药物中，这是目前能够达到临床治愈的唯一手段。然而，干扰素治疗也存在一些不足。首先它的治愈率有限，有些研究数据显示，干扰素治疗的临床治愈率约有30%左右。其次，抗病毒药的药费较贵，副作用较大。虽然目前很多地方干扰素已经纳入了医保报销，可以大大降低患者经济负担，但是仍需谨慎对待干扰素治疗，需要在使用前做好筛查评估，在使用时定期监测不良反应。
从目前整体情况来看，还是选择口服药的患者更多，虽然大多数情况下，它只能长期抑制病毒，但是口服药便宜，抑制效率高，副作用少，安全性好。不过口服药的缺点也显而易见，长期甚至终身服药是现阶段很多患者不得不面临的挑战，此外还存在长期用药的不良反应、耐药性等问题。
所以提高临床治愈率、追求完全治愈，就是目前乙肝治疗还未满足的临床需求。当然，如果有新药能实现这一目标，我们还要考虑可及性、性价比等问题，但首先要实现这一医学突破。
澎湃科技：2023年1月，《新英格兰医学杂志》（NEJM）发表研究称，发现了新的乙肝疗效判断标志物HBV RNA和HBcrAg，这意味着什么？
杜凌遥：其实这两个标志物已经被发现很多年了，此次研究是发现了这两个新型标志物，和细胞里的病毒基因组，也就是共价闭合环状的脱氧核糖核酸（cccDNA，病毒复制的中介，慢性乙肝持续感染的元凶）存在一定的线性关系。
这只是意味着我们发现了一个比较便捷的，衡量细胞里乙肝病毒量的方法。按照以往的技术，我们就必须做肝脏穿刺，取一些肝脏细胞进行检测。但现在发现血液里的指标和细胞里的指标有相关性，我们就可以通过血液里的指标检测去估算细胞里的乙肝病毒量。但是它只是一个检测指标而已，可以衡量疗效，和乙肝治疗本身没有直接关系。