Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No. 32, West Second Section, First Ring Road, Qingyang District, Chengdu, 610072, China.
BMC Cancer. 2024 Mar 4;24(1):291. doi: 10.1186/s12885-024-12031-0.
For chronic hepatitis B virus (HBV) infection patients, increasing evidence has demonstrated the effectiveness of expanding the indications and applicable population for antiviral therapy. However, the expanded indication of antiviral therapy for hepatocellular carcinoma (HCC) remains to be further explored.
196 HBV-related HCC patients who received radical hepatectomy and nucleos(t)ide analogues (NAs) therapy at Sichuan Provincial People's Hospital were enrolled in this study. HCC recurrence, overall survival (OS), early virological (VR) and biochemical responses (BR) of patients were compared between different NAs therapy and the use of anti-programmed cell death protein 1 (PD-1) therapy.
NAs therapy at different timing of surgery was a strong independent risk factor for postoperative recurrence and overall mortality of HBV-related HCC patients. Furthermore, in HCC patients who received postoperative anti-PD-1 therapy, patients with HBV DNA < 1000 copy/mL had significantly better recurrence-free survival (RFS) and OS than those with HBV DNA ≥ 1000 copy/mL (HR: 7.783; P = 0.002; HR: 6.699; P < 0.001). However, the differences of RFS and OS rates between entecavir group and tenofovir disoproxil fumarate group were not statistically significant. Similar results were also observed in the rates of early VR, BR and combined VR and BR.
Timely and reasonable preoperative NAs therapy showed clinical benefit in improving the prognosis of patients with HBV-related HCC, even in the case of normal alanine aminotransferase (ALT) level and negative hepatitis e antigen (HBeAg). Furthermore, a possible synergistic effect between antiviral therapy and anti-PD-1 therapy was founded and need further verification.
对于慢性乙型肝炎病毒（HBV）感染患者，越来越多的证据表明扩大抗病毒治疗的适应证和适用人群是有效的。然而，肝癌（HCC）抗病毒治疗的扩展适应证仍有待进一步探索。
本研究纳入了在四川省人民医院接受根治性肝切除术和核苷（酸）类似物（NAs）治疗的 196 例 HBV 相关 HCC 患者。比较了不同 NAs 治疗和使用抗程序性细胞死亡蛋白 1（PD-1）治疗的患者的 HCC 复发、总生存率（OS）、早期病毒学（VR）和生化反应（BR）。
手术时不同 NAs 治疗是 HBV 相关 HCC 患者术后复发和总死亡率的独立强危险因素。此外，在接受术后抗 PD-1 治疗的 HCC 患者中，HBV DNA<1000 拷贝/mL 的患者无复发生存率（RFS）和 OS 明显优于 HBV DNA≥1000 拷贝/mL 的患者（HR：7.783；P=0.002；HR：6.699；P<0.001）。然而，恩替卡韦组和替诺福韦酯组的 RFS 和 OS 率差异无统计学意义。早期 VR、BR 和联合 VR 和 BR 的比率也观察到了类似的结果。
术前及时、合理的 NAs 治疗显示出改善 HBV 相关 HCC 患者预后的临床获益，即使在丙氨酸氨基转移酶（ALT）水平正常和乙型肝炎 e 抗原（HBeAg）阴性的情况下也是如此。此外，还发现抗病毒治疗与抗 PD-1 治疗之间可能存在协同作用，需要进一步验证。
