初级保健提供者需要认识肝癌什么？

StephenW

What primary care providers need to know about hepatocellular carcinoma†
初级保健提供者需要认识肝癌什么？
Parul Dureja Agarwal M.D.*

Article first published online: 23 JAN 2013在网上公布：2013年1月23日
Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and is a major global health problem. Most cases of HCC (85%) arise in eastern Asia and sub-Saharan Africa, and they are associated with chronic hepatitis B virus (HBV) infection. In contrast, the dominant risk factor in the United States, Europe, and Japan is chronic hepatitis C virus (HCV) infection. In the United States, the age-adjusted incidence rates for HCC have tripled since the early 1980s, with the greatest proportional increases occurring among whites and younger patients (45-60 years old).1
原发性肝癌的肝细胞肝癌（HCC）是最常见的形式是一个重要的全球性健康问题。多数情况下，肝癌（85％）发生在东亚和撒哈拉以南的非洲地区，他们都与慢性乙型肝炎病毒（HBV）感染。与此相反，在美国，欧洲和日本的主要的危险因素是慢性丙型肝炎病毒（HCV）感染。在美国，为HCC的年龄调整发病率自20世纪80年代初的3倍，最大的发生在白人中的比例增加，年轻患者（45-60岁）

What Are the Risk Factors for Developing HCC?
发展为HCC的危险因素是什么？

Most cases of HCC (approximately 90%) are associated with a known risk factor. More than half of HCC cases worldwide can be attributed to chronic HBV infection, and the risk is increased in patients with a high viral load and a longer period of infection. Cirrhosis of any cause is an important risk factor for the development of HCC. The incidence of HCC in individuals with cirrhosis varies from 1% to 8% per year, with the greatest risk (estimated to be 3%-8% per year) among those with viral hepatitis (particularly HCV).2 Obesity and diabetes, often contributing to fatty liver disease, are also independent risk factors for the development of HCC and may act synergistically with other risk factors such as viral hepatitis.3, 4 Coinfection with HIV is also an additive risk factor for HCC in patients with chronic viral hepatitis.5 Smokers have a higher risk than nonsmokers.6 In all populations, HCC has a strong male preponderance, with the male-to-female ratio estimated to be 2.4.
大多数情况下，HCC（约90％）关联一个已知的危险因素。超过一半的全球肝癌病例可以归因于慢性HBV感染者，患者具有高病毒载量和较长的感染的风险增加。任何原因引起的肝硬化是肝癌的发展，一个重要的危险因素。在个人与肝硬化，肝癌的发病率从1％到8％的速度增长，在病毒性肝炎（尤其是HCV.2 肥胖和糖尿病的风险最大（估计每年为3％-8％），常脂肪肝疾病，也发展为肝细胞癌的独立危险因素，并与其他危险因素如病毒肝细胞，可能有协同作用，合并感染HIV也是添加剂慢性肝炎患者肝癌的危险因素。 5吸烟者有较高的风险比nonsmokers. 6 在所有人群，肝癌具有较强的男性优势，与男性与女性的比例估计为2.4。

StephenW

Is Surveillance Effective?
监控有效吗？
Surveillance is the repeated application of a screening test to an at-risk population with the aim of detecting disease at an earlier stage when potential curative options are available and thus reducing disease-related mortality. HCC is a condition that readily lends itself to surveillance because the at-risk population can be identified on the basis of the presence of chronic viral hepatitis and/or cirrhosis. Uncontrolled studies and one randomized control trial in China [which involved 18,816 patients with chronic HBV infections who were randomized to biannual surveillance with ultrasonography and serum α-fetoprotein (AFP) or no surveillance] strongly suggest that surveillance reduces patient mortality because of the increased applicability of curative measures (e.g., resection) to HCC-detected patients.8–10
监视是重复一个筛选试验中的应用时，在较早的阶段检测疾病的目的的一个高危人群潜在的治疗选项可用，从而减少与疾病相关的死亡率。 HCC是一个条件，容易监视的高危人群，因为可识别的基础上，慢性病毒性肝炎和/或肝硬化的存在。不受控制的研究和1项随机对照试验在中国涉及18,816例慢性HBV感染者谁是随机一年两次的监测，B超和血清α-胎儿蛋白（AFP）或无监视强烈建议，监视降低了患者的死亡率，因为增加的适用性HCC-已检测到patients.8-10的治疗措施（例如，切除）

Who Should Receive Surveillance?
谁应该接受监督？
The guidelines of the American Association for the Study of Liver Diseases (AASLD) recommend HCC surveillance for all patients with cirrhosis who could be treated if they were diagnosed with HCC as well as some patients with chronic HBV infections even in the absence of cirrhosis. Patients with advanced cirrhosis should be evaluated for liver transplantation. Patients who are not transplant candidates should not undergo continued surveillance, whereas patients with cirrhosis awaiting liver transplantation should receive surveillance.11

美国肝病研究学会（AASLD）的指导方针，建议所有肝硬化患者可以治疗，如果他们被诊断为肝癌，以及一些患者即使在无肝硬化的慢性乙肝病毒感染的肝癌监测。晚期肝硬化的患者，应评估肝移植。谁是病人移植候选人不应进行持续监控，而肝硬化患者等待肝移植的患者应该接受surveillance.11

StephenW

How Should Surveillance Be Performed?
应该如何进行监控？

The AASLD guidelines recommend abdominal ultrasound (US) as the imaging test of choice for HCC surveillance. It has a sensitivity of 60% to 80% and a specificity > 90% for the detection of HCC.11 US is well tolerated and without risk, has a relatively moderate cost, and improves in sensitivity with serial testing. Abdominal computed tomography (CT) scanning has fallen out of favor on account of its cost and the radiation risk with repeated use. Magnetic resonance (MR) scanning is more expensive than US, is demanding of the patient, and potentially has a high false-positive rate. Suspicious lesions found on US should be further evaluated with one-time multiphase CT or MR. Serum AFP is the most common serological test used for surveillance of HCC, although it has mainly been studied as a diagnostic tool. The diagnostic sensitivity of AFP is only approximately 60%, and its performance as a surveillance tool is worse still. AFP levels often fluctuate, especially in patients with chronic viral HCV (false positives), whereas only 10% to 20% of tumors at an early stage present with abnormal AFP levels (false negatives). Combining AFP with US increases costs but improves detection by only 6% to 8% and is, therefore, not recommended by the AASLD. The surveillance interval is based on the tumor doubling time as well as the tumor incidence in the at-risk population. On the basis of these factors, a 6-month interval is considered optimal.12
AASLD指南建议腹部超声波（美国）的首选肝癌监测的成像试验。它具有的灵敏度为60％〜80％，特异性>的检测的HCC.11美国90％是良好的耐受性，并没有危险的情况下，有一个相对适中的成本，并提高与串行测试的灵敏度。腹部电脑断层扫描（CT）扫描失宠考虑其成本和重复使用的辐射风险。磁共振（MR）扫描是比美国更昂贵的，在病人的要求，并有可能具有较高的假阳性率。在美国发现的可疑病变应进一步评估一次性多相CT或MR。血清AFP是最常见的血清学试验用于HCC监视，虽然它主要研究了作为一个诊断工具。 AFP是诊断的敏感性仅约60％，其性能的监测工具是更糟糕的是。 AFP水平经常波动，尤其是在患者与慢性病毒性肝炎丙型肝炎病毒（误报），而只有10％〜20％的肿瘤在早期阶段，目前AFP水平异常（假阴性）。结合AFP与美国只有6％至8％，增加了成本，而且提高了检测的，因此，不建议由AASLD。肿瘤倍增时间，以及肿瘤的高危人群中的发病率的基础上的监视间隔。这些因素的基础上，有6个月的时间间隔被认为最佳.12

In patients with cirrhosis, nodules less than 1 cm in size that are detected on US should be followed with repeat US every 3 months to assess for interval changes (Fig. 1). For lesions that are enlarging or nodules greater than 1 cm in size, diagnostic imaging with 4-phase multidetector computed tomography (MDCT) or dynamic MR should be obtained. The diagnosis of HCC for nodules greater than 1 cm in size can be made with noninvasive criteria based on imaging and laboratory findings, and this often obviates the need for biopsy. The radiological hallmark of HCC is intense contrast uptake in the arterial phase followed by contrast washout in the venous/late phase; these features have a specificity and a positive predictive value of almost 100%. Biopsy is recommended for all nodules occurring in noncirrhotic livers or for cases in which a nodule has an inconclusive or atypical appearance against the background of cirrhosis. Negative biopsy findings do not exclude HCC because the false-negative rate for biopsying can reach 30%. For a pathological diagnosis, an immunohistochemistry staining panel consisting of glypican 3, heat shock protein 70, and glutamine synthetase can provide 100% specificity for HCC, albeit with lesser sensitivity (72%).13
在肝硬化患者中，结节小于1厘米大小上检测到美国后，应该重复美国每3个月评估的时间间隔的变化（图1）。对于病变，扩大或结节大于1厘米大小的4相多排计算机断层扫描（MDCT）或动态MR，影像诊断与应该得​​到的。可以用大于1厘米大小的结节肝癌的诊断成像和实验室研究结果的基础上的非侵入性的标准，而这往往省却了需要进行活检。 HCC的放射性标志的是在动脉在静脉/后期阶段，然后通过对比冲刷的强烈对比吸收，这些功能几乎达到100％，特异性和阳性预测值。活检是建议所有发生在肝硬化的肝脏结节或结节的案件中，一个不确定的或非典型的外观对肝硬化的背景。活检结果阴性不能排除的HCC，因为假阴性率biopsying的可以达到30％。对于病理诊断，免疫组织化学染色面板肌醇蛋白聚糖3，热休克蛋白70，和谷氨酰胺合成酶的组成，可以提供100％的肝癌特异性，尽管较低的灵敏度（72％）.13

StephenW

How Is HCC Best Managed?
是如何HCC最佳管理？
Given the complexity of HCC and cirrhosis and the plethora of treatment options, I believe that patients with possible or likely HCC are best served by referral to centers of expertise with multidisciplinary teams (or tumor boards) that include hepatologists, oncologists, radiologists, surgeons, and pathologists. Potential curative options for early-stage disease include ablation, surgical resection, and liver transplantation. For intermediate- or advanced-stage disease, the only therapies that have been shown to prolong life include liver-directed therapy with transarterial chemoembolization and systemic chemotherapy with sorafenib.
肝癌和肝硬化的复杂性和大量的治疗方案，我认为有可能或可能的肝癌患者最好的服务转介中心的多学科团队（或肿瘤板），包括肝病，肿瘤科，放射科，外科医生的专业知识，和病理学家。潜在的治疗方案的早期阶段的疾病，包括消融，手术切除，肝移植。中级或高级阶段的疾病，唯一的治疗方法已被证明，以延长寿命，包括肝与索拉非尼治疗肝动脉栓塞化疗和全身化疗。

Summary
总结
HCC is a global health problem with a rising incidence in the United States. Until recently, HCC was universally fatal. The 21st century has seen a significant change in the management of HCC, and it is now a potentially curable cancer if it is detected early. To minimize disease-related mortality, it is imperative for providers caring for at-risk patients to employ consistent surveillance, rigorously investigate screen-detected lesions, and make provisions for appropriate therapy based on the stage of disease.

HCC是一个全球性的健康问题，一个在美国的发病率不断上升。直到最近，HCC是普遍致命的。 21世纪已经出现了显着变化在肝癌的管理，它现在是一个可能治愈的癌症，如果早期发现。为了尽量减少与疾病相关的死亡率，必须为供应商，照顾高危患者采用一致的监视，严格调查屏检测到的病变，并规定适当的治疗根据疾病的阶段。

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