Impact of Etiological Shifts and the Rising Burden of Non–B Non–C Hepatocellular Carcinoma on Surveillance and Prognosis: Insights From a 20-Year Retrospective Observational Study

IF 3.7 3区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Hepatology Research Pub Date : 2026-07-07 Epub Date: 2026-03-18 DOI:10.1111/hepr.70161

Yoko Yoshimaru, Katsuya Nagaoka, Hiroko Setoyama, Takahiro Mizuta, Toshinori Toyota, Daiki Maeda, Sotaro Kurano, Kentaro Tanaka, Hiroki Inada, Satoshi Narahara, Etsuko Iio, Maiko Nagaoka, Yukiko Nakai, Takehisa Watanabe, Haruki Uoshima, Masakuni Tateyama, Motohiko Tanaka, Yasuhito Tanaka

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Abstract

Aim

This study evaluated surveillance impact on outcomes in 1143 patients with first-onset hepatocellular carcinoma (HCC) treated between 2003 and 2023, focusing on the etiological shift toward non-B non-C (NBNC) liver disease.

Methods

Patients were stratified by etiology: hepatitis B virus (HBV, n = 182), hepatitis C virus (HCV, n = 555), and NBNC (n = 375). Surveillance was defined as ≥ 1 annual imaging examination. We assessed surveillance impact on overall survival (OS) using multivariable Cox regression analysis and analyzed diagnostic modalities and tumor markers stratified by etiology.

Results

Over the 20-year period, HCV-related HCC decreased whereas NBNC––HCC significantly increased, mainly driven by SLD. A total of 654 patients (58.8%) underwent regular surveillance. Compared with nonsurveilled patients, surveillance patients had significantly higher early-stage diagnosis (79.8% vs. 36.9% and p < 0.001) and curative treatment rates (52.8% vs. 21.6% and p < 0.001). Multivariable analysis confirmed surveillance as an independent prognostic factor for OS (n = 1,085, hazard ratio: 0.61, and p < 0.001). Notably, in the NBNC group, nearly 60% of early-stage cases were detected via CT/MRI, significantly higher than in viral etiologies. Furthermore, des-gamma-carboxy prothrombin (DCP)-only positivity was highest in patients with NBNC (22.4%), whereas AFP-only positivity was rare (4.5%).

Conclusions

Although regular surveillance provides a robust survival benefit independent of liver function, a critical “surveillance gap” persists in the rapidly expanding NBNC population. The high reliance on CT/MRI and DCP in NBNC patients suggests that standard ultrasound and AFP-based strategies may have limitations in this group. Etiology-specific protocols integrating cross-sectional imaging and combined biomarkers warrant further consideration to bridge this gap.

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病因转移和非乙型非丙型肝细胞癌负担增加对监测和预后的影响：来自20年回顾性观察研究的见解

目的：本研究评估了监测对2003年至2023年间1143例首发肝细胞癌（HCC）患者预后的影响，重点关注非b非c （NBNC）肝病的病因转变。方法：根据病因对患者进行分层：乙型肝炎病毒（HBV, 182）、丙型肝炎病毒（HCV, 555）和乙型肝炎病毒（NBNC, 375）。监测定义为≥1次年度影像学检查。我们使用多变量Cox回归分析评估了监测对总生存期（OS）的影响，并分析了诊断方式和按病因分层的肿瘤标志物。结果：在20年期间，hcv相关HCC减少，而NBNC- HCC显著增加，主要由SLD驱动。654例（58.8%）患者接受了定期监测。与未接受监测的患者相比，接受监测的患者的早期诊断率明显更高（79.8% vs. 36.9%和p）。结论：尽管定期监测提供了独立于肝功能的强大生存益处，但在迅速扩大的NBNC人群中仍然存在关键的“监测缺口”。NBNC患者对CT/MRI和DCP的高度依赖表明，标准超声和基于afp的策略在该组中可能存在局限性。结合横断面成像和联合生物标志物的病因特异性方案值得进一步考虑，以弥合这一差距。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hepatology Research 医学-胃肠肝病学

CiteScore

8.30

自引率

14.30%

发文量

124

审稿时长

1 months

期刊介绍： Hepatology Research (formerly International Hepatology Communications) is the official journal of the Japan Society of Hepatology, and publishes original articles, reviews and short comunications dealing with hepatology. Reviews or mini-reviews are especially welcomed from those areas within hepatology undergoing rapid changes. Short communications should contain concise definitive information.