Kawai Hirokazu, Nomoto Minoru, Suda Takeshi, Kamimura Kenya, Tsuchiya Atsunori, Tamura Yasushi, Yano Masahiko, Takamura Masaaki, Igarashi Masato, Wakai Toshifumi, Yamagiwa Satoshi, Matsuda Yasunobu, Ohkoshi Shogo, Kurosaki Isao, Shirai Yoshio, Okada Masahiko, Aoyagi Yutaka
Hirokazu Kawai, Department of Clinical Laboratory, Niigata University Medical and Dental Hospital, Niigata 951-8510, Japan.
World J Hepatol. 2011 Jan 27;3(1):15-23. doi: 10.4254/wjh.v3.i1.15.
To reveal the manner of hepatocellular carcinoma (HCC) development in patients with nonalcoholic steatohepatitis (NASH) focusing on multicentric occurrence (MO) of HCC.
We compared clinicopathological characteristics between patients with and without MO of HCC arising from NASH background. The clinical features were implicated with reference to the literature available.
MO of HCC was identified with histological proof in 4 out of 12 patients with NASH-related HCC (2 males and 2 females). One patient had synchronous MO; an advanced HCC, two well-differentiated HCCs and a dysplastic nodule, followed by the development of metachronous MO of HCC. The other three patients had multiple advanced HCCs accompanied by a well-differentiated HCC or a dysplastic nodule. Of these three patients, one had synchronous MO, one had metachronous MO and the other had both synchronous and metachronous MO. There were no obvious differences between the patients with or without MO in terms of liver function tests, tumor markers and anatomical extent of HCC. On the other hand, all four patients with MO of HCC were older than 70 years old and had the comorbidities of obesity, type 2 diabetes mellitus (T2DM), hypertension and cirrhosis. Although these conditions were not limited to MO of HCC, all the conditions were met in only one of eight patients without MO of HCC. Thus, concurrence of these conditions may be a predisposing situation to synchronous MO of HCC. In particular, old age, T2DM and cirrhosis were suggested to be prerequisite for MO because these factors were depicted in common among two other cases with MO of HCC under NASH in the literature.
The putative predisposing factors and necessary preconditions for synchronous MO of HCC in NASH were suggested in this study. Further investigations are required to clarify the accurate prevalence and predictors of MO to establish better strategies for treatment and prevention leading to the prognostic improvement in NASH.
以肝细胞癌（HCC）的多中心发生（MO）为重点，揭示非酒精性脂肪性肝炎（NASH）患者中HCC的发展方式。
我们比较了NASH背景下发生HCC的患者与未发生HCC的患者之间的临床病理特征。参考现有文献探讨了临床特征。
12例NASH相关HCC患者中，4例经组织学证实存在HCC的MO（2例男性和2例女性）。1例患者为同步MO；1例进展期HCC、2例高分化HCC和1个发育异常结节，随后发生异时性HCC的MO。另外3例患者有多个进展期HCC，伴有1例高分化HCC或1个发育异常结节。这3例患者中，1例为同步MO，1例为异时性MO，另1例既有同步MO又有异时性MO。在肝功能检查、肿瘤标志物和HCC的解剖范围方面，有MO和无MO的患者之间没有明显差异。另一方面，所有4例有HCC的MO的患者年龄均超过70岁，并有肥胖、2型糖尿病（T2DM）、高血压和肝硬化的合并症。虽然这些情况并不局限于HCC的MO，但8例无HCC的MO的患者中只有1例同时具备所有这些情况。因此，这些情况的同时出现可能是HCC同步MO的易感情况。特别是，高龄、T2DM和肝硬化被认为是MO的先决条件，因为在文献中另外2例NASH下有HCC的MO的病例中也共同出现了这些因素。
本研究提出了NASH中HCC同步MO的假定易感因素和必要前提条件。需要进一步研究以明确MO的准确患病率和预测因素，从而制定更好的治疗和预防策略，改善NASH的预后。
