We previously reported on the trends in the etiologies of hepatocellular carcinoma (HCC) diagnosed in patients between 1995 and 2009. The aims of our updated study were to evaluate the incidence, nonhepatitis B and nonhepatitis C viral (NBNC) etiologies, and clinical characteristics of HCCs occurring in patients between 1992 and 2018. The study enrolled 2171 consecutive patients with HCC between 1992 and 2018. Their medical records were reviewed. The patients were divided into two groups, patients with early diagnoses from 1992 to 2009 and those with late diagnoses from 2010 to 2018. NBNC-HCC occurred in 514 patients (23.6%). The percentage of patients with HCC who had NBNC-HCC increased from 26.5% in 2009 to 46.3% in 2018. Patients with NBNC-HCC were older (median ages from 67 to 73 years). Type 2 diabetes mellitus (48.5–60.3%: P = 0.008), hypertension (48.5–57.4%: P = 0.047), and hyperlipidemia (39.2–53.8%: P = 0.001) increased significantly in recent years. The median FIB-4 index decreased (4.37–3.61: P = 0.026) and the median platelet count increased (15.1–17.9 × 104/μL: P = 0.013). Among the 514 patients with NBNC-HCC, 194 underwent hepatic resection for nonalcoholic steatohepatitis (NASH) (15%), alcoholic liver disease (ALD) (29%), and cryptogenic hepatitis (56%). Cirrhosis was detected in 72%, 39%, and 16% of patients with NASH, ALD, and cryptogenic hepatitis, respectively. The prevalence of cirrhosis in patients with NASH was significantly higher than the prevalence of cirrhosis in the other groups (P < 0.001). Overall, 70% of the non-malignant liver tissue of patients with NBNC-HCC was not involved with cirrhosis. On the other hand, the median FIB-4 index in patients with cryptogenic HCC was 2.56, which was a significantly lower value than those values in the other groups of patients. The FIB-4 index considered as one of useful screening of HCC. The prevalence of NBNC-HCC has increased rapidly even in a regional university hospital. Metabolic syndrome may be an important risk factor for HCC. HCC was also found in patients with non-cirrhotic livers. The FIB-4 index may be a useful screening method for HCC in patients with NBNC.

中文翻译：

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非 HBV 和非 HCV 相关肝细胞癌的发病率增加：单机构 20 年研究

我们之前报道了 1995 年至 2009 年间在患者中诊断出的肝细胞癌 (HCC) 病因趋势。我们更新研究的目的是评估发病率、非乙型肝炎和非丙型肝炎病毒 (NBNC) 病因以及临床特征。 1992 年至 2018 年间患者发生 HCC。该研究招募了 1992 年至 2018 年间连续 2171 名 HCC 患者。审查了他们的医疗记录。将患者分为两组，1992年至2009年早期诊断的患者和2010年至2018年晚期诊断的患者。514例患者（23.6%）发生NBNC-HCC。患有 NBNC-HCC 的 HCC 患者百分比从 2009 年的 26.5% 增加到 2018 年的 46.3%。 NBNC-HCC 患者年龄较大（中位年龄为 67 至 73 岁）。2 型糖尿病 (48.5–60.3%: P = 0.008), 高血压（48.5-57.4%：P = 0.047）和高脂血症（39.2-53.8%：P = 0.001）近年来显着增加。FIB-4 指数中位数下降（4.37-3.61：P = 0.026），血小板计数中位数增加（15.1-17.9 × 104/μL：P = 0.013）。在 514 名 NBNC-HCC 患者中，194 名因非酒精性脂肪性肝炎 (NASH) (15%)、酒精性肝病 (ALD) (29%) 和隐源性肝炎 (56%) 接受了肝切除术。分别在 72%、39% 和 16% 的 NASH、ALD 和隐源性肝炎患者中检测到肝硬化。NASH 患者的肝硬化患病率显着高于其他组的肝硬化患病率（P < 0.001）。总体而言，NBNC-HCC 患者的非恶性肝组织中有 70% 与肝硬化无关。另一方面，隐源性 HCC 患者的 FIB-4 指数中位数为 2.56，明显低于其他组患者。FIB-4 指数被认为是一种有用的 HCC 筛查指标。即使在地区大学医院，NBNC-HCC 的患病率也迅速增加。代谢综合征可能是 HCC 的重要危险因素。在非肝硬化患者中也发现了 HCC。FIB-4 指数可能是 NBNC 患者 HCC 的有用筛查方法。在非肝硬化患者中也发现了 HCC。FIB-4 指数可能是 NBNC 患者 HCC 的有用筛查方法。在非肝硬化患者中也发现了 HCC。FIB-4 指数可能是 NBNC 患者 HCC 的有用筛查方法。