Nzeako U C, Goodman Z D, Ishak K G
Division of Hepatic Pathology, Armed Forces Institute of Pathology, Washington D.C., USA.
Am J Gastroenterol. 1996 May;91(5):879-84.
In a recent review of hepatocellular carcinoma (HCC) in North American residents, we were surprised to learn that 42.6% of these tumors in the 1980-1993 consultation files of the Armed Forces Institute of Pathology had arisen in noncirrhotic livers. We subsequently noted that the nonneoplastic livers of a number of these had nodular regenerative hyperplasia (NRH), a condition that has been associated with liver cell dysplasia, a putative premalignant lesion. To investigate the possibility that NRH might be a precursor of HCC, we studied those cases in which there was an association of HCC and NRH and examined the possible role of portal vein obstruction in NRH occurring in livers with HCC.
Subjects were selected based on study criteria and histological slides, clinical/autopsy records were reviewed, and features of neoplastic and nonneoplastic liver were noted. Simple statistical comparisons were made between the groups with and without NRH with respect to defined variables.
Of 804 patients suitable for study, 342 were noncirrhotic, and 23 of these had NRH. Mean age of patients with NRH was 65 +/- 13.6 (SD) yr. Seventeen of these (73.9%) had liver cell dysplasia, and 16 (69.6%) had portal venous invasion. Liver cell dysplasia occurred in a significantly greater proportion of those with NRH than those without (p < 0.01), but there was no significant difference between both groups with regard to portal venous invasion. Three patients (13%) had received chemotherapy and/or radiotherapy before diagnosis of NRH.
These findings may be due to the development of HCC within the dysplastic foci that occur in livers with NRH, but the findings do not exclude the converse possibility that NRH may also develop in a noncirrhotic liver with HCC, secondary to portal venous invasion with portal vein occlusion. The temporal relationship between HCC and NRH is probably determined in each case by the particular interaction of multiple pathogenetic factors. Among patients with HCC, factors other than the portal vein obstruction by tumor invasion may play a role in the pathogenesis of NRH.
在最近一项针对北美居民肝细胞癌（HCC）的综述中，我们惊讶地发现，在武装部队病理研究所1980 - 1993年会诊档案中的这些肿瘤中，有42.6%发生于非肝硬化肝脏。我们随后注意到其中一些人的非肿瘤性肝脏存在结节性再生性增生（NRH），这种情况与肝细胞发育异常有关，而肝细胞发育异常是一种假定的癌前病变。为了研究NRH可能是HCC的前驱病变的可能性，我们研究了那些HCC与NRH相关的病例，并探讨了门静脉阻塞在伴有HCC的肝脏中发生NRH时可能起的作用。
根据研究标准选择研究对象，查阅组织学切片、临床/尸检记录，并记录肿瘤性和非肿瘤性肝脏的特征。对有和没有NRH的两组患者在特定变量方面进行简单的统计学比较。
在804例适合研究的患者中，342例为非肝硬化患者，其中23例有NRH。有NRH的患者平均年龄为65±13.6（标准差）岁。其中17例（73.9%）有肝细胞发育异常，16例（69.6%）有门静脉侵犯。有NRH的患者中肝细胞发育异常的比例显著高于无NRH的患者（p<0.01），但两组在门静脉侵犯方面无显著差异。3例患者（13%）在诊断NRH之前接受过化疗和/或放疗。
这些发现可能是由于在有NRH的肝脏中发育异常灶内发生了HCC，但这些发现并不排除相反的可能性，即NRH也可能在伴有HCC的非肝硬化肝脏中继发于门静脉侵犯和门静脉阻塞而发生。HCC与NRH之间的时间关系可能在每种情况下由多种致病因素的特定相互作用决定。在HCC患者中，除肿瘤侵犯导致的门静脉阻塞外，其他因素可能在NRH的发病机制中起作用。
