You Ga Ram, Park Shin Young, Cho Su Hyeon, Cho Sung Bum, Koh Yang Seok, Lee Chang Hun, Jo Hoon Gil, Choi Sung Kyu, Yoon Jae Hyun
Department of Gastroenterology and Hepatology, Chonnam National University Hwasun Hospital and Medical School, Hwasun 58128, Republic of Korea.
Department of Gastroenterology and Hepatology, Chonnam National University Hospital and Medical School, Gwangju 61469, Republic of Korea.
Cancers (Basel). 2025 Apr 23;17(9):1417. doi: 10.3390/cancers17091417.
BACKGROUND/OBJECTIVES: Extrahepatic recurrence (EHR) is a significant negative prognostic factor in hepatocellular carcinoma (HCC). Although EHR is commonly observed in high-risk patients following HCC hepatectomy, its occurrence without concurrent intrahepatic HCC remains poorly understood. Therefore, this study aims to examine the clinical characteristics and risk factors associated with EHR in patients without intrahepatic HCC at diagnosis.
This study included 1066 treatment-naïve patients who underwent curative hepatectomy for HCC at four tertiary academic centers between January 2004 and December 2019. After excluding those with intrahepatic recurrence (IHR), concurrent EHR, or incomplete clinical records, 569 patients were included in the final analysis. Risk factors for EHR were assessed using multivariate Cox regression over a median follow-up period of 3.91 years.
Among the cohort, 38 patients developed EHR post-surgery without residual intrahepatic HCC, with a median follow-up of 1.04 years. These patients experienced earlier initial HCC recurrence than those without EHR (1.73 vs. 4.43 years). Multivariate analysis revealed significant associations between EHR and microvascular invasion (hazard ratio [HR]: 2.418, = 0.020), tumor necrosis (HR: 2.592, = 0.009), and initial tumor staging beyond the Milan criteria (HR: 3.008, = 0.001). Moreover, Cox regression analysis revealed that EHR strongly correlated with decreased post-hepatectomy survival (HR: 14.044, < 0.001). Cumulative EHR and survival rates were closely linked to the number of risk factors present.
EHR without detectable IHR is significant and warrants close monitoring in high-risk patients.
背景/目的：肝外复发（EHR）是肝细胞癌（HCC）的一个重要不良预后因素。虽然EHR在HCC肝切除术后的高危患者中很常见，但在无肝内HCC同时存在的情况下其发生情况仍知之甚少。因此，本研究旨在探讨诊断时无肝内HCC患者中与EHR相关的临床特征和危险因素。
本研究纳入了2004年1月至2019年12月期间在四个三级学术中心接受HCC根治性肝切除术的1066例未经治疗的患者。排除肝内复发（IHR）、同时存在EHR或临床记录不完整的患者后，569例患者纳入最终分析。在中位随访期3.91年期间，使用多变量Cox回归评估EHR的危险因素。
在该队列中，38例患者术后发生EHR且无残留肝内HCC，中位随访时间为1.04年。这些患者比无EHR的患者更早出现初始HCC复发（1.73年对4.43年）。多变量分析显示EHR与微血管侵犯（风险比[HR]：2.418，P = 0.020）、肿瘤坏死（HR：2.592，P = 0.009）以及初始肿瘤分期超出米兰标准（HR：3.008，P = 0.001）之间存在显著关联。此外，Cox回归分析显示EHR与肝切除术后生存率降低密切相关（HR：14.044，P < 0.001）。累积EHR和生存率与存在的危险因素数量密切相关。
无可检测到的IHR的EHR很重要，高危患者需密切监测。
