[肝胆速递] 乙肝表面抗原监测和慢性肝炎治疗

deng245

HBCAB也不容忽视、看过许多病友干扰素抗病毒过程中HBCAB的变化也是很明显的。

StephenW

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"可以伴随一波转氨酶升高。"
That is, no damage during immune tolerance phase, but during the immune clearance phase, there are cycles of elevated ALT. Many believe it is these "flares" over a prolonged period of indecisive clearance, that the liver is damaged.

也就是说，在免疫耐受阶段无肝损害. 但在免疫清除期，有ALT升高周期。许多人认为正是这些“flares“在长时间的间隙期，即肝脏受损。

temp

deng245 发表于 2011-6-3 09:08
HBCAB也不容忽视、看过许多病友干扰素抗病毒过程中HBCAB的变化也是很明显的。 ...

我也试图用核心抗体和/或PRE-S抗原来第一时间发现肝内病毒感染的新增（此时血清HBVDNA根本测不出来），但这方面数据少得可怜，比S抗原的数据还要少。你若有这方面的心得，还请不吝指教。

lifevendor

StephenW 发表于 2011-5-30 10:12
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"可能可以导致体内的HBV特异性T细胞重新响应，导致感染细胞死亡？转氨酶升高？"

“A decrease in HBV load seems to precede the detectionofHBV-specific T-cell responses, both in patients resolving naturalinfectionsand in those displaying flare-ups of hepatitis associated withHBeAgseroconversion during chronic infection. Reducing HBV load byantiviralchemotherapy may therefore increase the responsiveness of HBV-specificT cells,which are hyporesponsive in cases of persistent HBV or viralantigenstimulation. Indeed, HBV-specific T cells are detectable during thefirst fewmonths of lamivudine treatment [33]. However, this restoration ofT-cellactivity is partial and transient and does not leadto anincrease in HBeAg seroconversion [34]. ”

时间顺序是，1. 首先，治疗前，病人由于长期的受到高载量的病毒，还有HbsAg的存在，这些东西的存在导致了体内的免疫系统受到破坏，比如说针对HBV的特异性的T细胞的含量非常低，或者对这些可以生产HBV特异性的T细胞的途径有破坏（一些错误的信息导致），这也就是我们说的免疫耐受的一个状态
（这里定义HBV特异性T细胞为免疫机制A，可能还有其他的免疫机制）2. 然后，再给予抗病毒药物的治疗的时候，有两种情况：a. alt正常的情况 b.alt非常高的情况
（免疫机制已经开始）。通常情况a是不给于核苷治疗的，因为效果差，但是核苷也能导致病毒的下降，下降很慢，理论上表抗原这时候的变化需要了解（如temp所说）核苷类药物这个时候可以导致DNA变化很慢，HbsAg呢？如果一切都以HBV-DNA来判断，这里估计又有问题？b. alt非常高的情况，理论上这个情况下面有类似免疫机制A的机制介入，杀死感染肝细胞导致alt升高了，核苷类药物在这个时候介入，可以快速下降病毒（这里我们依然是以HBV-DNA为唯一指标，没有考虑HbsAg，部分的考虑alt）。按照上面英文中的说法，当病毒下降到一定程度的时候，“可能”会出现HBV特异性的T细胞响应，因为拉米夫定治疗的前几个月内可以检测到HBV特异T细胞，但是拉米夫定治疗的患者都是alt已经很高的患者，治疗前可能体内就已经有T细胞了，抗病毒治疗后期反而压制了这种特异性的免疫反应？。我们所有考虑的都是DNA，而DNA到底给我们多少指示？我们是否真的需要从新考虑HbsAg在各个阶段的指标意义，而且HbsAg比DNA更靠近终点，这点我非常同意Temp

lifevendor

temp 发表于 2011-6-3 15:43
我也试图用核心抗体和/或PRE-S抗原来第一时间发现肝内病毒感染的新增（此时血清HBVDNA根本测不出来），但 ...

很多情况下血清HBV-DNA迷惑了我们，让我们反而越走越远。以后指标应该更偏向于蛋白，唯一的坏处是蛋白的定量比DNA要差很多。

StephenW

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声明：以下只是我自己的思想，没有科学证据, 因此，可以是错误的
时间顺序是，1. 首先，治疗前，病人由于长期的受到高载量的病毒，还有HbsAg的存在，这些东西的存在导致了体内的免疫系统受到破坏，比如说针对HBV的特异性的T细胞的含量非常低，或者对这些可以生产HBV特异性的T细胞的途径有破坏（一些错误的信息导致），这也就是我们说的免疫耐受的一个状态
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我不喜欢"免疫系统受到破坏"这个词. 以前，我与MP4争辩过. 我学习了"免疫系统受到病毒控制,压抑".
Remember, during acute Hepatitis, ALT can be > 1000, indicating death of large number of infected liver cells. If the immune system continues to fight, this can lead to death of the infected person. If the infected person dies, all the virus will also die. So from an evolution view point,it is better for the virus to "control" its infection rate, at the same time, it is also better for our immune system to "limit" its own response.
记住，在急性肝炎，谷丙转氨酶可>1000，表明受感染肝细胞的大量死亡。如果免疫系统继续战斗，这会导致受感染者死亡。如果受感染者死亡，所有的病毒也会死亡。因此，从进化角度来看，病毒应该“控制“其感染率, 在同一时间，我们的免疫系统，应该“限制“反应。

（这里定义HBV特异性T细胞为免疫机制A，可能还有其他的免疫机制）2. 然后，再给予抗病毒药物的治疗的时候，有两种情况：a. alt正常的情况 b.alt非常高的情况
（免疫机制已经开始）。通常情况a是不给于核苷治疗的，因为效果差，但是核苷也能导致病毒的下降，
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This is a very good point. "That the hbvdna should decrease" should be tested. In the past, before measuring hbvdna is possible, the only way to gauge whether a medical drug is working or not, is to check the ALT. Since ALT is low at the beginning, therefore it seems pointless to take medication.
这是一个非常好的指向。“这应该减少HBVDNA的“应进行测试。在过去，可测量hbvdna前，只有检查ALT才能衡量医疗是否有功效。由于ALT在开始时低，因此看起来似乎毫无意义服药。

下降很慢，理论上表抗原这时候的变化需要了解（如temp所说）核苷类药物这个时候可以导致DNA变化很慢，HbsAg呢？如果一切都以HBV-DNA来判断，这里估计又有问题？b. alt非常高的情况，理论上这个情况下面有类似免疫机制A的机制介入，杀死感染肝细胞导致alt升高了，核苷类药物在这个时候介入，可以快速下降病毒（这里我们依然是以HBV-DNA为唯一指标，没有考虑HbsAg，部分的考虑alt）。
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Under this double attack, ALT should then decrease. That is why, antiviral treatment is recommended when ALT is high.
在此双重攻击，谷丙转氨酶应该随后减少。这就是为什么，当ALT是高的时,建议抗病毒治疗.

按照上面英文中的说法，当病毒下降到一定程度的时候，“可能”会出现HBV特异性的T细胞响应，因为拉米夫定治疗的前几个月内可以检测到HBV特异T细胞，但是拉米夫定治疗的患者都是alt已经很高的患者，治疗前可能体内就已经有T细胞了，抗病毒治疗后期反而压制了这种特异性的免疫反应？。
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"因为拉米夫定治疗的前几个月" 我的理解是不同.
"Indeed, HBV-specific T cells are detectable during the first few months of lamivudine treatment. However, this restoration of T-cell activity is partial and transient and does not lead to an increase in HBeAg seroconversion"您的翻译:
事实上，在拉米夫定的初期治疗的几个月内，HBV特异性的T细胞是可以被检测到的【33】。
然而，恢复T细胞的过程是不完全的而且持续很短暂，并不能导致增加HbeAg血清转换【34】
为什么只有短暂的(transient)？

"我们所有考虑的都是DNA，而DNA到底给我们多少指示？我们是否真的需要从新考虑HbsAg在各个阶段的指标意义，而且HbsAg比DNA更靠近终点，这点我非常同意Temp
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我也非常同意.

StephenW

我想补充。
上述讨论仅涉及对HBV特异性免疫系统。我们的免疫系统对其它病原体应该是正常的.

I want to add.
The above discussion refers only to the immune system specific for hbv. Our immune system against other pathogens should be normal.

lifevendor

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谢谢.
"被感染的肝细胞的表面如果出现HbeAg" - 这是一个关键, 所以被感染的肝细胞的表面是不是出现HbeAg?

"Thus, HBe protein differs in almost all aspects from HBc protein, although the primary sequence of these
two molecules is almost identical. Part of the HBe protein is transported to the plasma membrane.[123] Another
part is further cleaved within the arginine-rich domain by a Golgi protease and then secreted as a dimeric protein
with disulfi de bonds between Cys-7 and Cys-61.[124–126] Another part of the HBe protein does not reach the ER
lumen and is not cleaved at all. The P25e protein exposes a nuclear transport signal.127 Thus, HBe proteins of variable
length are found in practically all compartments of the cell and are secreted. Furthermore, uncleaved HBe
precursor protein accumulates as phosphoprotein.128"

lifevendor

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'HBe protein is not essential for the viral life-cycle. Variants
without functional pre-C sequence and HBe protein
arise often during acute or chronic HBV infection (see
Chapter 11). Nevertheless, all known hepadnaviruses
from duck to humans have an HBe protein, and revertants
may occur after cessation of interferon treatment.
Using a different expression strategy, murine leukaemia
viruses have also developed the ability to produce a secretory
form of their nucleoprotein, the glycosylated gag
protein.
High levels of secreted HBe protein are found in low symptomatic,
highly viraemic virus carriers. Elimination
of HBeAg is usually accompanied by a fl are-up of
immune pathogenesis and a decrease of viraemia (see
Chapters 15 and 16).  高水平分泌Hbe蛋白往往发生在那些没有症状，但是血液病毒含量非常高的患者身上。An HBe-negative variant of wood-chuck hepatitis B virus was infectious for newborn
woodchucks, but it could not induce persistent infection,
whereas the HBe-expressing virus results in persistent
infection.129 Hbe的表达导致感染的顽固性.These observations suggest that HBe protein
may somehow suppress the immune elimination of
HBV-producing hepatocytes. Indeed, HBeAg was found
to induce immunotolerance against HBV-infected cells.
Depleting infl ammatory HBeAg- and HBcAg-specifi c
Th1 cells that are necessary for viral clearance,130 HBeAg
is thought to support viral persistence." Hbe蛋白可能以某种方式来抑制体内的免疫清除体内的生产HBV的肝细胞，事实上，HbeAg被发现可以导致对HBV感染细胞的免疫耐受。消耗炎症性Hbeag和HBcAg 特异性的Th1细胞是清除病毒所必需的。HbeAg被认为是支持病毒的长期顽固坚持。

StephenW

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Many thanks. I read further on:

This is really exciting. This seems to suggest if we can eliminate secreted HBeAg in the blood, through HBeAb, then our immune system can keep HBV under control. This is exactly what happens when we enter the Inactive Phase!. But once, the virus mutates, we are back into the HBeAg-ve but Active phase!. Am I reading this correctly?