Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Taipei, Taiwan, ROC.
University of Taipei, Taipei, Taiwan, ROC.
J Chin Med Assoc. 2021 Jun 1;84(6):606-613. doi: 10.1097/JCMA.0000000000000530.
The main etiologies of hepatocellular carcinoma (HCC) were often hepatitis B virus (HBV) or C and alcohol, rarely autoimmune and biliary diseases. Nonalcoholic fatty liver disease (NAFLD) has been an emerging role that could lead to chronic liver disease, nonalcoholic steatohepatitis, cirrhosis, and eventually HCC in recent years. The aim of our study is to investigate and compare the clinical features of HCC in patients with NAFLD and HBV, including age, gender, cirrhosis, liver function tests, largest tumor size, and cancer stage at the time of diagnosis. The survival outcome was compared between the two groups and the significant predictors of mortality were also analyzed in all patients with HCC.
Most patients with HCC were recruited from the database of Cancer Registries in Taipei City Hospital, Ren-Ai Branch, from 2011 to 2017; and the other patients consecutively from the HCC multidisciplinary conference between January 2018 and December 2019. NAFLD was defined as nonviral hepatitis B (negative HBsAg and either positive anti-HBs or negative anti-HBc), nonviral hepatitis C (negative antihepatitis C virus [HCV]), nonalcoholic (alcohol consumption of <30 g/d for men and <20 g/d for women) liver disease, or present or past histological or ultrasonographic evidence of fatty liver. Totally, 23 NAFLD-related and 156 HBV-related HCC patients were enrolled in our study for further analysis.
NAFLD-related HCC patients were significantly older (median age: 70.0 [61.0-79.0] years vs. 63.0 [56.0-72.0] years, p = 0.012) and heavier (median body mass index [BMI]: 26.6 [24.2-30] kg/m2 vs. 24.8 [22.0-27.1] kg/m2, p = 0.044) than those with HBV-related HCC. They were also more susceptible to diabetes mellitus (DM), and 60.9% (14 of 23) of them had this comorbidity compared with 29.5% (46 of 156) of those with HBV-related HCC (p = 0.003). Only 34.8% (8 of 23) and 71.2% (111 of 156) of patients with NAFLD- and HBV-related HCC were cirrhotic, respectively (p = 0.001). However, gender, tobacco use, international normalized ratio, albumin, creatinine, and cholesterol levels were not significantly different between the two groups. Tumor characteristics such as the Barcelona clinic liver cancer stage, largest tumor size, tumor number, extrahepatic metastasis, and treatment modalities had no significant difference between such groups.According to the Kaplan-Meier method analysis, the overall survival was not significantly different between these two patient groups (log-rank test, p = 0.101). To evaluate which patient group would lead to poor prognosis, we analyzed the survival of all patients through multivariate Cox proportional hazard regression after controlling other factors that may influence the hazard ratio. The analysis revealed that NAFLD and HBV infection as the cause of HCC are not risk factors of poor prognosis.
In conclusion, our study showed NAFLD-related HCC patients were older, heavier, and more had DM than HBV-related. In addition, more NAFLD-related HCC patients were noncirrhotic than HBV-related. The survival rate was similar between NAFLD and HBV-related HCC patients.
肝细胞癌(HCC)的主要病因通常是乙型肝炎病毒(HBV)或丙型肝炎病毒和酒精,很少由自身免疫性和胆道疾病引起。近年来,非酒精性脂肪性肝病(NAFLD)已成为一种新兴的病因,可导致慢性肝病、非酒精性脂肪性肝炎、肝硬化,并最终导致 HCC。我们的研究目的是调查和比较 NAFLD 与 HBV 相关 HCC 患者的临床特征,包括年龄、性别、肝硬化、肝功能试验、最大肿瘤大小和诊断时的癌症分期。比较两组患者的生存结果,并分析所有 HCC 患者的死亡预测因素。
大多数 HCC 患者均从台北市立仁爱医院癌症登记资料库中招募,时间为 2011 年至 2017 年;其他患者则连续从 2018 年 1 月至 2019 年 12 月 HCC 多学科会议中招募。NAFLD 的定义为非病毒性乙型肝炎(HBsAg 阴性且抗-HBs 阳性或抗-HBc 阴性)、非病毒性丙型肝炎(抗丙型肝炎病毒[HCV]阴性)、非酒精性(男性酒精摄入量<30g/d,女性<20g/d)肝病,或存在或既往有组织学或超声检查证据的脂肪肝。共有 23 例与 NAFLD 相关的 HCC 患者和 156 例 HBV 相关的 HCC 患者纳入本研究进行进一步分析。
与 HBV 相关的 HCC 患者相比,NAFLD 相关的 HCC 患者年龄明显更大(中位数年龄:70.0[61.0-79.0]岁 vs. 63.0[56.0-72.0]岁,p=0.012)和体重更重(中位数 BMI:26.6[24.2-30]kg/m2 vs. 24.8[22.0-27.1]kg/m2,p=0.044)。他们也更容易患有糖尿病,60.9%(23 例中有 14 例)的患者有这种合并症,而 HBV 相关 HCC 患者中只有 29.5%(156 例中有 46 例)(p=0.003)。只有 34.8%(23 例中有 8 例)和 71.2%(156 例中有 111 例)的患者患有肝硬化(p=0.001)。然而,两组患者的性别、吸烟、国际标准化比值、白蛋白、肌酐和胆固醇水平无显著差异。两组患者的肿瘤特征如巴塞罗那临床肝癌分期、最大肿瘤大小、肿瘤数量、肝外转移和治疗方式均无显著差异。根据 Kaplan-Meier 方法分析,两组患者的总体生存率无显著差异(对数秩检验,p=0.101)。为了评估哪个患者组会导致预后不良,我们在控制其他可能影响危险比的因素后,通过多变量 Cox 比例风险回归分析对所有患者的生存情况进行了分析。分析显示,NAFLD 和 HBV 感染作为 HCC 的病因不是预后不良的危险因素。
总之,我们的研究表明,与 HBV 相关的 HCC 患者相比,NAFLD 相关的 HCC 患者年龄更大、体重更重、糖尿病更多。此外,与 HBV 相关的 HCC 患者相比,更多的 NAFLD 相关 HCC 患者是非肝硬化的。NAFLD 相关 HCC 患者和 HBV 相关 HCC 患者的生存率相似。