《亚太肝病学年会汇编》关于重肝问题与主流的分歧

清除cccDNA

主流和亚太肝病学年会汇编 下面的重肝问题的分歧，是在适应免疫的 CTL上，主流认为是肝损伤的祸首，而后者认为不引起肝损伤。谁是谁非先不讨论。问题是，后者并没有否定免疫致病论。他们结论是，肝损伤是综合天然免疫的综合结果。


HBV-specific CD8 T cells quantity is not proportional to the
extend of liver damage. （实事， 不与主流观点有冲突。这点也不能支持谁是凶手的结论）
Hepatic flares are likely a result of complex and still undetermined
interactions between innate and adaptive immune mechanisms
within the liver.

The prevailing idea is that the hepatic flares are the result of a
quantitative recovery of HBV-specific T cell response.
（他们理解错了主流吧，我看了论文也不少，主流是这样认识的吗？骆老的理论也属主流，CD4＋T CELL 不会导致肝损伤，而主流是肝损伤是CD8＋T CELL 应答、巨噬细胞、NK的结果。）

These acute exacerbations of liver damage (called hepatic
flares, HF) can occur spontaneously, be induced by IFN-a therapy or by
the withdrawal of treatment with nucleoside analogues [2]. They are often
preceded by high levels of HBV replication and by progressive accumulation
of HBV antigens [3] and are characterized by an increase liver
pathological activity (manifested as an increase in the level of ALT).
However, there are scarce experimental evidences to support such a
scenario, which are limited to data showing [5] an increment on
CD4+ T cell proliferation against the whole HBcAg around the time
of hepatic flares
（CD4+ T cell 非肝损伤机制清除HBV，分泌伽马干扰素，共识了）

Moreover, two other important points need to be taken in account: the
first is that the frequency of circulating and intrahepatic HBV-specific
CD8+ cells in patients with chronic HBV infection correlate with
HBV control and not with liver damage.
（这点不奇怪，很正常。不与主流冲突。只是主流未认清CD8+ cells的性质，并不能证明CD8+ cells永远不会导致肝损伤）
Secondly, work in animal
models has clearly shown that the bulk of liver damage is not direCD8+ cellsy
cause by HBV-specific CD8+ cells, but is mainly caused by their
ability to trigger a series of secondary events including hepatic
granulocyte infiltration, chemokine production and subsequent
recruitment of an inflammatory infiltrate composed of macrophages,
NK cells and T cells
（不奇怪，不能推翻免疫治病论。只是讨论在此情况、此环境下，谁是凶手的问题。环境不同，另当别论）
CTL有很积极的一面，我当时只是认为是 有是有非，如果能证实在人体内的HBV引起的严重肝损失与CTL无关，只是天然免疫的结果，那是好事，是有是无非了。但是，a干扰素的作用原理是什么？被认为是扩增DC，适应免疫的应答，也就是扩增一个T细胞应答。a干扰素会引起肝损伤加剧，那么就是干扰素后的CTL攻击导致肝损伤。此推论有何疑问呢？

As a consequence, there is no direct
correlation between HBV-specific CD8+ cells frequency and the extent of
liver damage, and hepatic flares cannot be simply associated with an
increment of the HBV-specific T cell response
（其关系恐怕是他们未发现而已，除非他们证实，大量病例，任何情况，在人体的严重肝损伤与CD8+ cells无关）。
与主流区别不大，只是在复杂的免疫应答中，争论谁是主要凶手罢了。

hundun

难怪去中大复试的时候，导师只问英文
他X的我讨厌英文