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.

原文獻地址:

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

脂肪性肝炎型肝細胞癌與酒精性和非酒精性脂肪性肝炎均相關: 兩個具有分子洞察力的隊列研究

摘要

脂肪性肝炎型細胞肝癌（SH-HCC）是肝細胞癌（HCC）的一個亞型, 與非酒精性脂肪性肝炎（NASH）有密切關聯, 但與酒精性脂肪性肝炎（ASH）的關聯尚不清楚。我們研究了有脂肪性肝炎并進行HCC切除術的患者2個對列。在紐約西奈山隊列中, 我們發現SH-HCC發生在17/24（71％）的NASH患者和14/19（74％）的ASH患者中, 并且SH-HCC是NASH組中19/24（50％）, ASH組中9/19（47％）的主要腫瘤形態。診斷為ASH的12/19患者同時也患有糖尿病和/或體重指數> 30。當這些患者被剔除后, 我們仍然發現相似的SH-HCC發生率（6/7 [86％]）, SH-HCC作為主要腫瘤形態仍占3/7 [43％]。有趣的是, 在非腫瘤肝中有4/7（57％）可以看到觀察到糖化的肝細胞核。在日本隊列中, 我們也發現SH-HCC在NASH和ASH患者中發生率相似, 分別為15/58（26％）和16/45 （36％）。我們進一步分析了來自日本隊列的腫瘤分子亞型, 盡管在SH-HCC病例中存在ASH與S1（P = 0.054）和NASH與S3（P = 0.052）相關的趨勢,  但在ASH和NASH組中S1, S2和S3亞型的分布沒有明顯統計學差異。我們的研究表明, 盡管ASH和NASH形成SH-HCC的途徑可能不同, 但SH-HCC在ASH和NASH兩者中都很常見, 而且這兩種脂肪性肝炎相關的SH-HCC具有相似的分子特征。

I 譯者點評(Comments)

1. 肝細胞癌（HCC）是世界范圍內導致癌癥死亡的第四大病因, 大多數病例發生在慢性肝病的基礎中, 例如HBV, HCV, ASH以及NASH。近年來隨著肥胖病的流行以及抗HCV病毒的有效藥物治療, 脂肪性肝炎正日益成為HCC的主要病因。

2. SH-HCC是近年來認識到的一種HCC亞型。HCC還有很多其他分子學分類, 比如這篇文章中提到的S1， S2 和S3分類。S1 常為SH-HCC和有大量免疫細胞浸潤的HCC。S2 常為粗梁型/緊湊型 (macrotrabecular/compact) HCC并伴血清α-甲胎蛋白高（> 400 ng / ml）增高。S3 常為微骨小梁型 (microtrabecular), 透明細胞型 (clear cell ) 或低級別組織學的HCC。S1, S2 和S3 HCC有不同的分子學改變 (1)。

3. SH-HCC可發生在有或無脂肪性肝炎, 有或無肝硬化, 以及任何原因導致的肝臟疾病的基礎上 (2, 3)。

4. 病理診斷SH-HCC應注意與脂肪性肝炎和脂肪性肝炎型局灶性結節增生區別 (4) 。

II 相關文獻(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 文獻譯者