Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima, Japan.
Center for Digestive and Liver Diseases, Miyazaki Medical Center Hospital, Miyazaki, Miyazaki, Japan.
PLoS One. 2020 Aug 13;15(8):e0237475. doi: 10.1371/journal.pone.0237475. eCollection 2020.
Direct-acting antivirals (DAAs) against hepatitis C virus (HCV) exert high anti-HCV activity and are expected to show anti-inflammatory effects associated with HCV elimination. Furthermore, hepatocellular carcinoma (HCC) is known to dedifferentiate from hypovascular tumors, such as dysplastic nodules or well-differentiated HCC, to hypervascular tumors. We therefore explored whether or not DAAs can suppress the growth and hypervascularization of hypovascular tumors.
We enrolled 481 patients with HCV genotype 1 infection who were treated with Daclatasvir and Asunaprevir therapy. Of these, 29 patients had 33 hypovascular tumors, which were confirmed by contrast-enhanced MRI or CT before therapy. We prospectively analyzed the cumulative incidence of HCC, i.e. the growth or hypervascularization of hypovascular tumors, and compared the HCC development rates between patients with hypovascular tumors and those without any tumors.
The mean size of the hypovascular tumors was 11.3 mm. Twenty seven of 29 patients who achieved an SVR had 31 nodules, 19 of 31 nodules (61.3%) showed tumor growth or hypervascularization, and 12 (38.7%) nodules showed no change or improvement. The cumulative incidence rates of tumor growth or hypervascularization were 19.4% at 1 year, 36.0% at 2 years, 56.6% at 3 years, and 65.3% at 4 years. Among the patients who achieved a sustained virologic response, the cumulative HCC development rates of patients with hypovascular tumors was significantly higher than in those without any tumors. A Cox proportional hazard analysis showed that a history of HCC therapy, the presence of a hypovascular tumor, and AFP >4.6 ng/mL at the end of treatment were independent risk factors for HCC development.
Hypovascular tumors developed into HCC at a high rate despite the elimination of HCV by DAAs. As patients with hypovascular tumors were shown to have a high risk of HCC development, they should undergo strict HCC surveillance.
直接作用抗病毒药物（DAAs）对丙型肝炎病毒（HCV）具有高效的抗病毒活性，并且有望显示与 HCV 消除相关的抗炎作用。此外，肝细胞癌（HCC）已知从低血管性肿瘤（如发育不良结节或高分化 HCC）分化为高血管性肿瘤。因此，我们探讨了 DAA 是否可以抑制低血管性肿瘤的生长和高血管化。
我们纳入了 481 例丙型肝炎基因型 1 感染患者，他们接受了达拉他韦和阿昔洛韦治疗。其中，29 例患者有 33 个低血管性肿瘤，这些肿瘤在治疗前通过对比增强 MRI 或 CT 得到确认。我们前瞻性分析了 HCC 的累积发生率，即低血管性肿瘤的生长或高血管化，并比较了低血管性肿瘤患者和无任何肿瘤患者的 HCC 发展率。
低血管性肿瘤的平均大小为 11.3mm。29 例达到 SVR 的患者中有 27 例有 31 个结节，其中 19 个结节（61.3%）显示肿瘤生长或高血管化，12 个结节（38.7%）没有变化或改善。肿瘤生长或高血管化的累积发生率在 1 年时为 19.4%，在 2 年时为 36.0%，在 3 年时为 56.6%，在 4 年时为 65.3%。在达到持续病毒学应答的患者中，低血管性肿瘤患者的 HCC 累积发展率明显高于无任何肿瘤的患者。Cox 比例风险分析显示，HCC 治疗史、低血管性肿瘤存在以及治疗结束时 AFP>4.6ng/mL 是 HCC 发展的独立危险因素。
尽管 DAA 消除了 HCV，但低血管性肿瘤仍以高比例发展为 HCC。由于低血管性肿瘤患者 HCC 发展的风险较高，因此应进行严格的 HCC 监测。
