Montalto Giuseppe, Cervello Melchiorre, Giannitrapani Lydia, Dantona Fabio, Terranova Angela, Castagnetta Luigi A M
Institute of Internal Medicine, Institute of Development Biology, CNR, University of Palermo, Palermo, Italy.
Ann N Y Acad Sci. 2002 Jun;963:13-20. doi: 10.1111/j.1749-6632.2002.tb04090.x.
The incidence of hepatocellular carcinoma is increasing in many countries. The estimated number of new cases annually is over 500,000, and the yearly incidence comprises between 2.5 and 7% of patients with liver cirrhosis. The incidence varies between different geographic areas, being higher in developing areas; males are predominantly affected, with a 2:3 male/female ratio. The heterogeneous geographic distribution reflects the epidemiologic impact of the main etiologic factors and environmental risk, which are the hepatitis B (HBV) and hepatitis C (HCV) viruses. The percentage of cases of hepatocellular carcinoma attributable to HBV worldwide is 52.3% and is higher in Asia where the seroprevalence of HBsAg in the population is high. However, the vaccination campaign against this virus in some eastern countries has tended to lower the incidence of new cases of hepatocellular carcinoma. The percentage of cases of hepatocellular carcinoma attributable to HCV is 25%, and it is more prevalent in Japan, Spain, and Italy where the association between hepatocellular carcinoma and antibodies to HCV ranges between 50 and 70%. In most cases hepatocellular carcinoma develops in cirrhotic livers, where the persistent proliferation of liver cells represents the key factor of progression to hepatocellular carcinoma independent of the etiology. Another minor risk factor is aflatoxin B1 consumption, which is responsible for most cases of hepatocellular carcinoma in Africa, where the consumption of contaminated foods is common. Other known risk factors are some hereditary diseases, such as hemochromatosis, porphyria cutanea tarda, hereditary tyrosinemia, and alpha1 anti-trypsin deficiency. The natural history of hepatocellular carcinoma is heterogeneous and is influenced by nodule dimension, the mono- or plurifocality of lesions at diagnosis, the growth rate of the tumor, and the stage of the underlying cirrhosis. Available data to date suggest that tumor growth in a cirrhotic liver is variable and that the time in which a lesion in undetectable until it becomes 2 cm is between 4 and 12 months. Therefore, the suggested interval for surveillance screening with ultrasound in patients with liver cirrhosis has been set at 6 months. Patients who should benefit from screening programs are those who would be treated with curative therapy if diagnosed with hepatocellular carcinoma. Thus, the ideal target population should be limited to Child-Pugh's class A cirrhotic patients without significant comorbidity.
许多国家肝细胞癌的发病率正在上升。每年估计的新发病例数超过50万，年发病率占肝硬化患者的2.5%至7%。发病率在不同地理区域有所不同，发展中地区更高；男性受影响为主，男女比例为2:3。这种异质性的地理分布反映了主要病因和环境风险因素（即乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV））的流行病学影响。全球范围内，由HBV导致的肝细胞癌病例所占比例为52.3%，在亚洲更高，因为亚洲人群中HBsAg的血清阳性率较高。然而，一些东方国家针对这种病毒开展的疫苗接种运动已使肝细胞癌新发病例的发病率有所降低。由HCV导致的肝细胞癌病例所占比例为25%，在日本、西班牙和意大利更为普遍，在这些国家，肝细胞癌与抗HCV抗体之间的关联在50%至70%之间。在大多数情况下，肝细胞癌发生于肝硬化肝脏，其中肝细胞的持续增殖是进展为肝细胞癌的关键因素，与病因无关。另一个次要风险因素是黄曲霉毒素B1的摄入，在非洲，食用受污染食物很常见，黄曲霉毒素B1是导致大多数肝细胞癌病例的原因。其他已知的风险因素包括一些遗传性疾病，如血色素沉着症、迟发性皮肤卟啉症、遗传性酪氨酸血症和α1抗胰蛋白酶缺乏症。肝细胞癌的自然病程是异质性的，受结节大小、诊断时病变的单灶性或多灶性、肿瘤生长速度以及潜在肝硬化阶段的影响。迄今为止的现有数据表明，肝硬化肝脏中的肿瘤生长情况各不相同，一个病变在不可检测直至长到2厘米的时间为4至12个月。因此，建议对肝硬化患者进行超声监测筛查的间隔时间为6个月。应从筛查项目中受益的患者是那些如果被诊断为肝细胞癌将接受根治性治疗的患者。因此，理想的目标人群应限于无严重合并症的Child-Pugh A级肝硬化患者。
