Mohamad Bashar, Shah Vaishal, Onyshchenko Mykola, Elshamy Mohammed, Aucejo Federico, Lopez Rocio, Hanouneh Ibrahim A, Alhaddad Razan, Alkhouri Naim
Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA.
Hepatol Int. 2016 Jul;10(4):632-9. doi: 10.1007/s12072-015-9679-0. Epub 2015 Nov 11.
The incidence of hepatocellular carcinoma (HCC) has increased significantly in United States over the last few decades in parallel with the epidemic of nonalcoholic fatty liver disease (NAFLD). Limited data suggests that HCC could arise in steatotic liver without the presence of cirrhosis. The present study was conducted to characterize patients with NAFLD presenting with HCC in non-cirrhotic liver (NCL) compared to the NAFLD- HCC patients in association with cirrhotic liver (CL).
A retrospective analysis of all patients diagnosed with HCC and NAFLD diagnosis seen at our institution between 2003 and 2012 was done. The patients were characterized based on demographic and clinical variables as well as histological and tumor features. Comparisons between the NCL and CL groups were done using analysis of variance (ANOVA) or the non-parametric Kruskal-Wallis tests and Pearson's chi-square tests or Fisher's Exact tests as appropriate. P value of <0.05 was considered statistically significant.
Thirty-six patients with NAFLD and HCC in NCL (HCC-NCL group) were identified and compared to 47 patients with NAFLD-HCC and Liver Cirrhosis (HCC-LC group). Liver fibrosis was not present in 55.9 % of patients in the HCC-NCL group (F0), stage 1 was present in 17.6 %, stage 2 in 8.8 % and stage 3 in 17.6 %. Lobular inflammation was present in 63.6 % of non-cirrhotic patients. Patients in the HCC-NCL were older (67.5 ± 12.3 vs. 62.7 ± 8.1 years), and less likely to be obese (52 % vs. 83 %) or have type 2 diabetes (38 % vs. 83 %), with p value <0.05 for all. More importantly, compared with the HCC-CL group, those in the HCC-NCL group were more likely to present with a single nodule (80.6 % vs. 52.2 %), larger nodule size (>5 cm) (77.8 % vs. 10.6 %), and receive hepatic resection as the modality of HCC treatment (66.7 % vs. 17 %); and were less likely to receive loco-regional therapy (22.3 % vs. 61.7 %) or orthotopic liver transplantation (OLT) (0 % vs. 72.3 %), with p value <0.001 for all. Furthermore, 86 % of patients without cirrhosis had HCC recurrence compared to only 14 % in patients with cirrhosis (p < 0.001). Unadjusted analysis indicates that non-cirrhotics had worse survival with mortality rate of 47 % vs. 28 % in CL group (p = 0.03); however this difference in survival between two groups was not significant after adjusting for age or OLT (p > 0.05).
Patients with HCC in the absence of liver cirrhosis are more likely to present at an older age with larger tumor and have higher rates of tumor recurrence. Studies to assess the cost-effectiveness of HCC surveillance in this group should be conducted.
在过去几十年中，美国肝细胞癌（HCC）的发病率随着非酒精性脂肪性肝病（NAFLD）的流行而显著增加。有限的数据表明，HCC可能在无肝硬化的脂肪性肝脏中发生。本研究旨在对非肝硬化肝脏（NCL）中出现HCC的NAFLD患者与合并肝硬化肝脏（CL）的NAFLD-HCC患者进行特征描述。
对2003年至2012年期间在我们机构诊断为HCC和NAFLD的所有患者进行回顾性分析。根据人口统计学和临床变量以及组织学和肿瘤特征对患者进行特征描述。NCL组和CL组之间的比较采用方差分析（ANOVA）或非参数Kruskal-Wallis检验以及Pearson卡方检验或Fisher精确检验（视情况而定）。P值<0.05被认为具有统计学意义。
确定了36例NCL中患有NAFLD和HCC的患者（HCC-NCL组），并与47例患有NAFLD-HCC和肝硬化的患者（HCC-LC组）进行比较。HCC-NCL组中55.9%的患者无肝纤维化（F0），17.6%为1期，8.8%为2期，17.6%为3期。63.6%的非肝硬化患者存在小叶炎症。HCC-NCL组患者年龄较大（67.5±12.3岁对62.7±8.1岁），肥胖可能性较小（52%对83%）或患2型糖尿病的可能性较小（38%对83%），所有这些的P值均<0.05。更重要的是，与HCC-CL组相比，HCC-NCL组患者更有可能表现为单个结节（80.6%对52.2%）、结节尺寸更大（>5 cm）（77.8%对10.6%），并接受肝切除术作为HCC的治疗方式（66.7%对17%）；接受局部区域治疗的可能性较小（22.3%对61.7%）或原位肝移植（OLT）的可能性较小（0%对72.3%），所有这些的P值均<0.001。此外，无肝硬化患者中有86%发生HCC复发，而肝硬化患者中仅为14%（P<0.001）。未调整分析表明，非肝硬化患者的生存率较差，死亡率为47%，而CL组为28%（P = 0.03）；然而，在调整年龄或OLT后，两组之间这种生存差异并不显著（P>0.05）。
无肝硬化的HCC患者更可能在年龄较大时出现较大肿瘤，且肿瘤复发率较高。应开展研究评估该组中HCC监测的成本效益。
