Grob P J
Schweiz Med Wochenschr. 1986 Aug 23;116(34):1133-45.
Epidemiologically, two main geographical areas for hepatocellular carcinoma (HCC) can be distinguished: China, other parts of Asia and parts of Africa are high incidence zones for HCC. The HBsAg-associated form accounts for more than 90% of all cases. HBV-infections are frequent and most often occur early in life. Also, the prevalence of HBsAg carriers is high. HCC most often appears in midlife and in patients with formerly quiescent chronic hepatitis and cirrhosis. The USA, Western and Northern Europe represent low incidence zones for HCC, with the HBsAg-associated form accounting for less than 40% of all cases. HBV infections occur less frequently and most often after adolescence. The HBsAg carrier rate is low. HCC most often develops in elderly men with formerly active chronic hepatitis and cirrhosis. For the development of HBsAg-associated HCC the integration of viral DNA (HBV-DNA) into the host genome seems crucial; it may occur after a longterm productive HBV infection which is then associated with a semi- or non-productive infection. Initially the HBV-DNA is integrated at random and later becomes monoclonal. HBsAg negative HCC may be due to oncogenic stimuli resulting from recurrent bouts of liver destruction and regeneration induced by alcohol, other hepatotoxic substances or by the virus(es) responsible for chronic non-A/non-B hepatitis. Defective immune elimination of HBV-infected cells also appears crucial for the development of HCC, in three stages: initially not all HBV-infected cells are destroyed and chronic infection results. Then cells with latent HBV infection are insufficiently eliminated and finally HCC-cells escape from immune elimination altogether. Hepatitis B vaccination is the most promising measure for prevention of HBsAg-associated HCC. Other strategies such as immune modulation and/or virostatic principles are considered.
从流行病学角度来看，肝细胞癌（HCC）主要可分为两个地理区域：中国、亚洲其他地区以及非洲部分地区是HCC的高发区。与乙肝表面抗原（HBsAg）相关的HCC形式占所有病例的90%以上。乙肝病毒（HBV）感染很常见，且大多发生在生命早期。此外，HBsAg携带者的患病率很高。HCC最常出现在中年以及既往患有静止性慢性肝炎和肝硬化的患者中。美国、西欧和北欧是HCC的低发区，与HBsAg相关的HCC形式占所有病例的比例不到40%。HBV感染发生频率较低，且大多发生在青春期之后。HBsAg携带率较低。HCC最常发生在既往患有活动性慢性肝炎和肝硬化的老年男性中。对于与HBsAg相关的HCC的发生，病毒DNA（HBV-DNA）整合到宿主基因组中似乎至关重要；它可能发生在长期的HBV增殖性感染之后，随后与半增殖性或非增殖性感染相关。最初，HBV-DNA随机整合，随后变为单克隆。HBsAg阴性的HCC可能是由于酒精、其他肝毒性物质或导致慢性非甲非乙型肝炎的病毒引起的反复肝脏破坏和再生所产生的致癌刺激。对HBV感染细胞的免疫清除缺陷对于HCC的发生似乎也很关键，可分为三个阶段：最初并非所有HBV感染细胞都被破坏，从而导致慢性感染。然后，潜伏性HBV感染的细胞未被充分清除，最终HCC细胞完全逃脱免疫清除。乙肝疫苗接种是预防与HBsAg相关的HCC最有前景的措施。还考虑了其他策略，如免疫调节和/或抗病毒原理。
