Honma Yuichi, Shibata Michihiko, Morino Kahori, Koya Yudai, Hayashi Tsuguru, Ogino Noriyoshi, Kusanaga Masashi, Oe Shinji, Miyagawa Koichiro, Abe Shintaro, Tabaru Akinari, Harada Masaru
Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
Department of Gastroenterology, Moji Medical Center, 3-1 Higashiminato-machi, Moji-ku, Kitakyushu, 801-8502, Japan.
Dig Dis Sci. 2023 Feb;68(2):685-698. doi: 10.1007/s10620-022-07686-3. Epub 2022 Sep 14.
The incidence of extrahepatic malignancies (EHMs) after hepatitis C virus (HCV) eradication by interferon (IFN)-based and IFN-free direct-acting antivirals (DAAs) treatment remains unclear.
The aim was to evaluate the cumulative incidence of EHMs diagnosed for the first time after the antiviral treatments.
We analyzed a total 527 patients with chronic HCV infection and without prior history of any malignancies who achieved sustained virological response by antiviral treatments, including IFN-based (n = 242) or IFN-free DAAs (n = 285). The baseline predictors for EHM occurrence were analyzed using Cox regression analysis.
Thirty-two patients were diagnosed with EHMs, 14 in IFN-based and 18 in IFN-free DAAs, respectively. The total duration of follow-up was 1,796 person-years in IFN-based and 823 person-years in IFN-free DAAs. The incidence of EHMs in IFN-based and IFN-free DAAs was 7.8 and 21.9 per 1,000 person-years, respectively. The cumulative incidence of EHMs was significantly higher in IFN-free DAAs than IFN-based (p = 0.002). IFN-free DAAs was a single independent predictor for incidence of EHMs (p = 0.012). As for gender, the incidence of EHMs was significantly higher in IFN-free DAAs only in the female cohort (p = 0.002). After propensity score matching, IFN-free DAAs was a single independent predictor for incidence of EHMs in the female patients (p = 0.045).
The incidence of EHMs after HCV eradication is higher in IFN-free DAAs than IFN-based regimens, especially in female patients. We should carefully follow-up not only HCC but also EHMs after IFN-free DAAs regimens.
经基于干扰素（IFN）和不含IFN的直接抗病毒药物（DAA）治疗清除丙型肝炎病毒（HCV）后，肝外恶性肿瘤（EHM）的发生率仍不明确。
旨在评估抗病毒治疗后首次诊断的EHM的累积发生率。
我们分析了总共527例慢性HCV感染且无任何恶性肿瘤病史的患者，这些患者通过抗病毒治疗实现了持续病毒学应答，包括基于IFN的治疗（n = 242）或不含IFN的DAA治疗（n = 285）。使用Cox回归分析来分析EHM发生的基线预测因素。
32例患者被诊断为EHM，其中基于IFN的治疗组有14例，不含IFN的DAA治疗组有18例。基于IFN的治疗组的总随访时长为1796人年，不含IFN的DAA治疗组为823人年。基于IFN的治疗组和不含IFN的DAA治疗组中EHM的发生率分别为每1000人年7.8例和21.9例。不含IFN的DAA治疗组中EHM的累积发生率显著高于基于IFN的治疗组（p = 0.002）。不含IFN的DAA治疗是EHM发生率的单一独立预测因素（p = 0.012）。在性别方面，仅在女性队列中，不含IFN的DAA治疗组中EHM的发生率显著更高（p = 0.002）。在倾向得分匹配后，不含IFN的DAA治疗是女性患者中EHM发生率的单一独立预测因素（p = 0.045）。
HCV清除后，不含IFN的DAA治疗组中EHM的发生率高于基于IFN的治疗方案，尤其是在女性患者中。我们不仅应仔细随访肝细胞癌，还应在不含IFN的DAA治疗方案后仔细随访EHM。
