病毒为什么有会导致肝癌的风险

jbjcmj

病毒导致纤维化，进而导致肝硬化，这好理解。导致肝癌怎么理解？



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我随心动

CA有些遗传因素。

StephenW

回复 jbjcmj 的帖子

我个人的看法：
癌症是细胞无控制的增长。

在肝硬化，肝细胞不断死亡, 其他肝细胞分裂，以取代死去的细胞。太多和不断的细胞分裂，增加突变(mutation)的风险。如果突变导致细胞无控制分裂, 由于遗传因素(如我随心动版主说)和其他未知因素, 这将会导致肝癌。

Table 2. Target Subjects for HCC Surveillance                        

Cirrhosis, threshold incidence (>1.5%	Incidence	Noncirrhotic HBV carrier, threshold incidence (>0.2%)	Incidence
HBV cirrhosis	3%–8%/y	Asian men >40 y	0.4%–0.6%/y
HCV cirrhosis	3%–5%/y	Asian women > 50 y	0.3%–0.6%/y
Primary biliary cirrhosis	3%–5%/y	Family history of HCC	Unknown
Nonalcoholic steatohepatitis	2.6%/y	African race	Unknown
Other cause of cirrhosis	Unknown

Cirrhosis is the single most important risk factor for HCC, and most patients with HCC have underlying liver cirrhosis. According to a guideline from AASLD, surveillance is recommended when the HCC incidence is higher than 1.5% in a patient with cirrhosis. This category of patients includes those with cirrhosis from viral hepatitis, nonalcoholic steatohepatitis, and primary biliary cirrhosis, and thus these patients should be under a surveillance program. In addition, experts recommend patients with other types of cirrhosis to receive surveillance, although firm data about the incidence of HCC in this group of patients are lacking.

StephenW

http://www.medscape.com/viewarticle/756445_4
Is Serum Alpha-Fetoprotein Beneficial for HCC surveillance?
There is broad agreement that serum AFP alone is inadequate as an independent tool for HCC surveillance and must not be used. For example, investigators of the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis trial serially measured the serum AFP every 3 months before the diagnosis of HCC and reported that serum AFP has inadequate efficacy as a surveillance test. Many other studies investigating the performance of AFP were in the setting of diagnosis rather than surveillance, where pretest probabilities are higher and the performance of the test is overestimated. The biggest limitation of serum AFP, when used alone, is its low sensitivity. Whereas the test might be made sufficiently specific if a high cutoff value is used, modest elevations might be seen in patients with viral hepatitis especially hepatitis C, pregnant women, and in those with tumors other than HCC, most notably gonadal tumors. Thus, depending on the cutoff value, serum AFP has suboptimal sensitivity and/or specificity. More recent serum markers such as des-carboxy prothrombin and the ratio of lecithinbound AFP to total AFP are even less sensitive than AFP for the detection of early-stage HCCs and have not been shown to be useful for surveillance.
Compared with US alone, the combination of US and serum AFP might slightly enhance the sensitivity to detect an HCC lesion. A study from China showed that the combination of US and serum AFP increases the liver cancer detection rate by 9%. However, the combination was associated with a 2.4-fold increase in false positivity and a 2.2-fold decrease in the positive predictive value. A cost-effectiveness analysis performed in the United States showed abdominal US is most cost-effective, and addition of AFP to US in HCC surveillance provides a small gain at a significant increase in cost. This increase in cost stems not only from adding the cost of AFP testing but also from the expenses needed to investigate false-positive results. For this reason, the AASLD guideline recommends the use of US alone for the surveillance of HCC.
Despite these limitations of serum AFP, a recent study that used the Surveillance Epidemiology and End Results-Medicare database reported that the combination of serum AFP and US, followed by serum AFP alone, is most commonly used for HCC surveillance in the United States. The reality in practice is that AFP is widely available and inexpensive. Proponents point out that given the poor adherence to US-based surveillance, even a suboptimal test might still be better than complete lack of any surveillance. This might be more relevant in settings with limited health care access and resources, such as in Alaskan natives with chronic HBV infection in whom serum AFP was found to be beneficial.

How Often Should Tests be Repeated?
Most guidelines recommend surveillance to be conducted every 6 months. The principle for determining the interval for surveillance is that it should not be based on the anticipated incidence of HCC, but on the rate of tumor growth. Even if the incidence is high, if all of the tumors grow slowly, infrequent surveillance would be sufficient. On the other hand, if many tumors grow fast, frequent surveillance is needed for any hope of early diagnosis to exist. Thus, the absolute risk (incidence) of HCC determines whether surveillance should be performed, whereas the rate of tumor growth dictates the interval for surveillance.
It is currently uncertain whether surveillance every 6 months is superior to every 12 months in decreasing HCC mortality and improving patient survival ([url=]Table 3[/url]). Several retrospective studies showed that there is no difference in survival between 6-month and 12-month surveillance intervals. However, the most recent study showed that surveillance every 6 months improved patient survival compared with that every 12 months. In short, to date, there is no robust evidence from a randomized controlled trial to determine the optimal surveillance interval. Most hepatologists tend to err on being more conservative with frequent (ie, semiannual) surveillance.
                                                

StephenW

血清α-甲胎蛋白是有利于肝癌监测？

有广泛的协议，仅血清AFP是作为一个独立的肝癌监视工具的不足，不得用于。例如，C型肝炎抗病毒药物长期反对治疗肝硬化试验的调查连续测量每3个月前诊断肝癌的血清AFP报道，血清AFP作为监督检验不足的疗效。许多其他研究调查法新社性能监控，验前概率更高，性能测试被高估，而不是设置在诊断。血清AFP的最大的限制，单独使用时，其敏感性较低。鉴于测试可能不够具体，如果使用高截止值，可能会被视为温和海拔在病毒性肝炎尤其是丙型肝炎，孕妇，并在那些与其他的肿瘤，比肝癌，最显着的性腺肿瘤患者。因此，根据截止值，血清AFP最理想的的灵敏度和/或特异性。如DES -羧基凝血酶原和lecithinbound法新社的比例，以总法新社最近的血清标志物检测早期肝癌，甚至小于法新社敏感，并没有被证明是用于监视非常有用。

与美国，仅美国和血清AFP的结合可能会略有提高灵敏度检测肝癌病灶。来自中国的研究表明，美国和血清AFP的结合，增加9％的肝癌检出率。然而，结合相关联，在假阳性增加2.4倍和阳性预测值的2.2倍下降。一个在美国进行的成本效益分析表明，腹部美国是最具成本效益，此外AFP的肝癌监视美国提供了一个小的收获在成本显著增加。源于成本的增加，不仅增加法新社测试的成本，但也从调查的假阳性结果所需的费用。出于这个原因，肝病学会的指引建议单独用于监测HCC的美国。

尽管这些限制，血清AFP，最近的一项研究，使用的监测流行病学和最终结果，医疗保险数据库报告，结合血清AFP和美国，其次是血清AFP单独，是最常用的肝癌在美国的监视。在实践中的现实是，AFP是广泛使用的和廉价的。支持者指出，总部设在美国的监视依从性差，即使是最理想的测试仍可能比完全没有任何监控。这可能是有限的卫生保健的访问和资源，如在阿拉斯加血清AFP在其中发现有利于当地人的慢性乙肝病毒感染的设置更有意义。
测试应该多久屡禁不止？

大部分的指引建议进行每6个月的监视。监视的时间间隔确定的原则是，它不应该是基于上肝癌的预期发病率，但对肿瘤的生长速度。即使发病率较高，如果所有的肿瘤生长缓慢，罕见的监控就足够了。另一方面，如果许多肿瘤生长快，需要经常监视任何希望的早期诊断存在。因此，绝对肝癌的风险（发病率）决定是否应进行监控，而肿瘤的生长速度决定进行监视的时间间隔。

这是目前不确定是否监视每6个月优于降低肝癌死亡率和改善病人的生存期（见表3）每12个月。几个回顾性研究表明，有6个月和12个月的监测间隔之间的差异是没有生存的。然而，最近的研究表明，监测，每6个月，每12个月相比，提高了病人的生存期。总之，迄今为止，没有一项随机对照试验的强有力的证据，以确定最佳的监控间隔。大多数肝病往往更频繁（即，每半年一次）监测保守ERR。

大鹏鸟

比较复杂的一个问题，这也是目前科研的热点之一啊。作为一个相关的科学工作者，有以下看法：
第一。确实如上面战友所说，在肝硬化，肝细胞不断死亡, 其他肝细胞分裂，以取代死去的细胞。太多和不断的细胞分裂，增加突变(mutation)的风险。如果突变导致细胞无控制分裂, 这将会导致肝癌。 这其实是很多癌症发生的原因(当然只是可以这么理解，没有涉及到分子水平），比如胃溃疡导致的胃癌，经常吃热烫食物导致的食管癌，也可以用类似的原因解释。
第二、肝癌里面很多是乙肝感染者，而乙肝病毒一个很大的特点就是可以整合到基因组，一整合就坏事，万一整合到原癌基因旁边，把他激活了，那就癌了，另外乙肝病毒基因组编码的hbx蛋白也是一个很重要的因素，现在很多科学家都在研究它在肝癌中的作用。X蛋白是一种多功能的病毒调节因子，通过调节细胞和病毒的转录活性、信号转导途径、基因毒性应激反应、蛋白质降解等多个方面，直接或间接地影响乙肝病毒的复制和肝细胞的增殖与死亡，并具有促肝细胞转化的作用。因此，揭示X基因和X蛋白致癌的分子机制具有十分重要的意义。南开大学的研究人员从慢性肝病患者的血清和组织中分离得到乙型肝炎病毒X基因突变株，发现X蛋白羧基端27个氨基酸缺失对人正常肝细胞的生长具有明显的促进作用，并进一步证明该X蛋白突变体通过激活癌细胞NF-κB、Survivin和人端粒酶逆转录酶启动子的转录活性，上调c-Myc蛋白和增殖细胞核抗原的表达促进肝细胞的增殖。



呵呵，自己的理解加百度，大家凑合看吧，看完了别忘了，感染病毒的那么多，得肝癌的才有多少啊，关键是自己，要心情舒畅啊，扼住命运的咽喉！

scilab

得肝癌的也不少了.