Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
Liver Unit, Hospital Clinic, IDIBAPS, University of Barcelona, CIBERehd, Barcelona, Spain.
J Hepatol. 2016 Oct;65(4):719-726. doi: 10.1016/j.jhep.2016.04.008. Epub 2016 Apr 13.
BACKGROUND & AIMS: The success of direct-acting antivirals (DAA) against hepatitis C is a major breakthrough in hepatology. Until now, however, there are very few data on the effect of hepatitis C virus (HCV) eradication in patients who have already developed hepatocellular carcinoma.
The study included patients with HCV infection and prior history of treated hepatocellular carcinoma who achieved complete response and lacked 'non-characterized nodules' at the time they underwent anti-HCV treatment with all-oral DAAs in 4 hospitals. Patients receiving interferon as part of the antiviral regimen were excluded. The baseline characteristics, laboratory and radiologic tumor response were registered in all patients before starting antiviral therapy and during the follow-up according to the clinical practice policy.
Between 2014 and 2015, 103 patients with prior hepatocellular carcinoma received DAA, 58 of them met the inclusion criteria. After a median follow-up of 5.7months, 3 patients died and 16 developed radiologic tumor recurrence (27.6%). The pattern of recurrence was: intrahepatic growth (3 patients), new intrahepatic lesion (1 nodule in 5 patients, up to 3 nodules less or equal to 3cm in 4 cases and multifocal in one patient) and infiltrative ill-defined hepatocellular carcinoma and/or extra-hepatic lesions in 3 patients.
Our data show an unexpected high rate and pattern of tumor recurrence coinciding with HCV clearance and, although based in a very small cohort of patients, should be taken as a note of caution and prime a large scale assessment that exceeds the individual investigators capacity.
High rate of cancer recurrence after DAA treatment in patients with prior hepatocellular carcinoma. Disruption of immune surveillance may facilitate the emergence of metastatic clones.
直接作用抗病毒药物（DAA）在丙型肝炎治疗方面的成功是肝病学的一大突破。然而，到目前为止，关于已经患有肝细胞癌的患者中丙型肝炎病毒（HCV）清除的效果的数据非常有限。
本研究纳入了在 4 家医院接受全口服 DAA 治疗以清除 HCV 的患者，这些患者既往患有 HCV 感染且经治疗的肝细胞癌病史，在接受抗 HCV 治疗时达到完全缓解且缺乏“非特征性结节”。排除接受干扰素作为抗病毒方案一部分的患者。所有患者在开始抗病毒治疗前和随访期间根据临床实践政策登记基线特征、实验室和影像学肿瘤反应。
2014 年至 2015 年期间，有 103 例既往患有肝细胞癌的患者接受了 DAA 治疗，其中 58 例符合纳入标准。中位随访 5.7 个月后，3 例患者死亡，16 例患者发生影像学肿瘤复发（27.6%）。复发模式为：肝内生长（3 例）、新的肝内病变（5 例中有 1 个结节，4 例中最多 3 个结节且直径均小于或等于 3cm，1 例为多灶性）、浸润性不明确的肝细胞癌和/或肝外病变（3 例）。
我们的数据显示，在清除 HCV 的同时，肿瘤复发的发生率和模式出乎意料地高，尽管这是基于一个非常小的患者队列，但应引起警惕，并需要进行超出个别研究者能力的大规模评估。
既往患有肝细胞癌的患者在接受 DAA 治疗后癌症复发率高。免疫监视的破坏可能促进转移性克隆的出现。
