Steatohepatitic Variant of Hepatocellular Carcinoma Is Associated With Both Alcoholic Steatohepatitis and Nonalcoholic Steatohepatitis: A Study of 2 Cohorts With Molecular Insights

Qin, Jia; Higashi, Takaaki; Nakagawa, Shigeki; Yamashita, Yo-ichi; Beppu, Toru; Baba, Hideo; Kobayashi, Masahiro; Kumada, Hiromitsu; Gunasekaran, Ganesh; Schiano, Thomas D.; Thung, Swan N.; Fiel, Maria Isabel; Hoshida, Yujin; Ward, Stephen C.

Am J Surg Pathol. 2020 Jun 30.

doi: 10.1097/PAS.0000000000001533.

ABSTRACT

Steatohepatitic hepatocellular carcinoma (SH-HCC) is a variant of hepatocellular carcinoma (HCC) with established association with nonalcoholic steatohepatitis (NASH), while its association with alcoholic steatohepatitis (ASH) is unclear. We studied 2 cohorts of patients who underwent resection for HCC in the setting of steatohepatitis. In our Mount Sinai (New York) cohort, we found SH-HCC in 17/24 (71%) patients with NASH and in 14/19 (74%) patients with ASH, while SH-HCC was the predominant tumor morphology in 12/24 (50%) in the NASH group and 9/19 (47%) in the ASH group. Upon review, 12/19 patients diagnosed with ASH also had diabetes and/or a body mass index >30. When these patients were removed, we still found similar rates of SH-HCC (6/7 [86%] showed SH-HCC, while SH-HCC was predominant in 3/7 [43%]. Interestingly, glycogenated hepatocyte nuclei were seen in the nontumor liver in 4/7 (57%) of these cases. In our Japan cohort, we also found similar rates of SH-HCC in NASH and ASH patients with HCC, 15/58 (26%), and 16/45 (36%), respectively. We determined molecular subclassification of tumors from the Japan cohort and found no difference in the distribution of S1, S2 and S3 subclasses among the ASH and NASH groups, though, among cases of SH-HCC, there was a trend toward an association of ASH with S1 (P=0.054) and NASH with S3 (P=0.052). Our study shows that SH-HCC is common in both ASH and NASH and that both underlying liver diseases produce tumors with similar molecular profiles, though different pathways may underlie the development of SH-HCC in ASH versus NASH.

原文献地址:

https://pubmed.ncbi.nlm.nih.gov/32618599/

脂肪性肝炎型肝细胞癌与酒精性和非酒精性脂肪性肝炎均相关: 两个具有分子洞察力的队列研究

摘要

脂肪性肝炎型细胞肝癌（SH-HCC）是肝细胞癌（HCC）的一个亚型, 与非酒精性脂肪性肝炎（NASH）有密切关联, 但与酒精性脂肪性肝炎（ASH）的关联尚不清楚。我们研究了有脂肪性肝炎并进行HCC切除术的患者2个对列。在纽约西奈山队列中, 我们发现SH-HCC发生在17/24（71％）的NASH患者和14/19（74％）的ASH患者中, 并且SH-HCC是NASH组中19/24（50％）, ASH组中9/19（47％）的主要肿瘤形态。诊断为ASH的12/19患者同时也患有糖尿病和/或体重指数> 30。当这些患者被剔除后, 我们仍然发现相似的SH-HCC发生率（6/7 [86％]）, SH-HCC作为主要肿瘤形态仍占3/7 [43％]。有趣的是, 在非肿瘤肝中有4/7（57％）可以看到观察到糖化的肝细胞核。在日本队列中, 我们也发现SH-HCC在NASH和ASH患者中发生率相似, 分别为15/58（26％）和16/45 （36％）。我们进一步分析了来自日本队列的肿瘤分子亚型, 尽管在SH-HCC病例中存在ASH与S1（P = 0.054）和NASH与S3（P = 0.052）相关的趋势,  但在ASH和NASH组中S1, S2和S3亚型的分布没有明显统计学差异。我们的研究表明, 尽管ASH和NASH形成SH-HCC的途径可能不同, 但SH-HCC在ASH和NASH两者中都很常见, 而且这两种脂肪性肝炎相关的SH-HCC具有相似的分子特征。

I 译者点评(Comments)

1. 肝细胞癌（HCC）是世界范围内导致癌症死亡的第四大病因, 大多数病例发生在慢性肝病的基础中, 例如HBV, HCV, ASH以及NASH。近年来随着肥胖病的流行以及抗HCV病毒的有效药物治疗, 脂肪性肝炎正日益成为HCC的主要病因。

2. SH-HCC是近年来认识到的一种HCC亚型。HCC还有很多其他分子学分类, 比如这篇文章中提到的S1， S2 和S3分类。S1 常为SH-HCC和有大量免疫细胞浸润的HCC。S2 常为粗梁型/紧凑型 (macrotrabecular/compact) HCC并伴血清α-甲胎蛋白高（> 400 ng / ml）增高。S3 常为微骨小梁型 (microtrabecular), 透明细胞型 (clear cell ) 或低级别组织学的HCC。S1, S2 和S3 HCC有不同的分子学改变 (1)。

3. SH-HCC可发生在有或无脂肪性肝炎, 有或无肝硬化, 以及任何原因导致的肝脏疾病的基础上 (2, 3)。

4. 病理诊断SH-HCC应注意与脂肪性肝炎和脂肪性肝炎型局灶性结节增生区别 (4) 。

II 相关文献(Related references)

1. Tan PS, et al. Clinicopathological indices to predict hepatocellular carcinoma molecular classification. Liver Int. 2016 Jan;36(1):108-18. doi: 10.1111/liv.12889

2. Yeh MM, et al. Steatohepatitic variant of hepatocellular carcinoma in the absence of metabolic syndrome or background steatosis: a clinical, pathological, and genetic study. Hum Pathol . 2015 Nov;46(11):1769-75. doi: 10.1016/j.humpath.2015.07.018

3. Salomao M, et al. The steatohepatitic variant of hepatocellular carcinoma and its association with underlying steatohepatitis. Hum Pathol. 2012 May;43(5):737-46. doi: 10.1016/j.humpath.2011.07.005

4. Deniz K, et al. Steatohepatitis-like Changes in Focal Nodular Hyperplasia, A Finding to Distinguish From Steatohepatitic Variant of Hepatocellular Carcinoma. Am J Surg Pathol. 2017 Feb;41(2):277-281. doi: 10.1097/PAS.0000000000000781

III 文献译者