Hepatology research : the official journal of the Japan Society of Hepatology · 2026
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.
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Yoshimaru Yoko, Nagaoka Katsuya, Setoyama Hiroko, Mizuta Takahiro, Toyota Toshinori, Maeda Daiki, Kurano Sotaro, Tanaka Kentaro, Inada Hiroki, Narahara Satoshi, Iio Etsuko, Nagaoka Maiko, Nakai Yukiko, Watanabe Takehisa, Uoshima Haruki, Tateyama Masakuni, Tanaka Motohiko, Tanaka Yasuhito
Аннотация
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.
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.