Pulmonology Division, Lady Davis Carmel Medical Center, Haifa, Israel.
Bruce Rappaport Faculty of Medicine, The Technion-Israel Institute of Technology, Haifa, Israel.
J Gastrointest Cancer. 2020 Jun;51(2):584-590. doi: 10.1007/s12029-019-00293-y.
Direct antiviral agents (DAAs) have become the treatment of choice for chronic hepatitis C virus (HCV). A safety concern was raised about a possible relationship between DDAs and malignancies. We report unexpected development of extrahepatic malignancies after DAA treatment.
Four hundred thirty-one patients were treated with DAAs in our unit between January 2015 and February 2018. The most common regimen used the combination of paritaprevir/ritonavir/ombitasvir with/without dasabuvir (PrOD) (141 patients, 32.7%). The most common genotype was G1b (317 patients, 73.5%).
Nine patients (2.08%) were diagnosed with malignancies after treatment: three patients developed lymphoma, one laryngeal carcinoma, one pancreatic adenocarcinoma, one cervix carcinoma, one lung carcinoma, one developed recurrent transitional cell carcinoma of the urinary bladder, and one developed recurrent metastatic breast cancer. The incidence of these malignancies in the cohort was 696 to 100,000 for lymphoma and 232 to 100,000 for each one of the other malignancies described, while the incidence in the general population is 20, 8.8, 1.7, 44.7, 142, and 89.7 to 100,000, respectively. Five of these patients were treated with PrOD, two with sofosbuvir and daclatasvir, one with simeprevir and sofosbuvir, and one with ledipasvir and sofosbuvir. The occurrence of the malignancies was 3 months to 4 years after the end of the treatment. Besides, 10 patients (2.3%) developed HCC and one developed recurrent aggressive HCC.
This report raises a question about a possible relationship between treatment with DAAs and development of extrahepatic malignancies. Thus, data collection from larger cohorts is critical to determine the relationship possibility.
直接抗病毒药物（DAA）已成为慢性丙型肝炎病毒（HCV）治疗的首选药物。人们对 DAA 与恶性肿瘤之间可能存在的关系提出了安全方面的担忧。我们报告了在 DAA 治疗后意外发生的肝外恶性肿瘤。
我们单位在 2015 年 1 月至 2018 年 2 月期间用 DAA 治疗了 431 例患者。最常用的方案是使用 paritaprevir/ritonavir/ombitasvir 联合/不联合 dasabuvir（PrOD）（141 例患者，32.7%）。最常见的基因型是 G1b（317 例患者，73.5%）。
9 例患者（2.08%）在治疗后被诊断患有恶性肿瘤：3 例患者发生淋巴瘤，1 例喉癌，1 例胰腺腺癌，1 例宫颈癌，1 例肺癌，1 例复发性膀胱癌，1 例复发性转移性乳腺癌。在该队列中，这些恶性肿瘤的发病率分别为每 100,000 人中有 696 例发生淋巴瘤和 232 例发生其他描述的每种恶性肿瘤，而在普通人群中，其发病率分别为每 100,000 人中有 20 例、8.8 例、1.7 例、44.7 例、142 例和 89.7 例。其中 5 例患者接受了 PrOD 治疗，2 例患者接受了 sofosbuvir 和 daclatasvir 治疗，1 例患者接受了 simeprevir 和 sofosbuvir 治疗，1 例患者接受了 ledipasvir 和 sofosbuvir 治疗。这些恶性肿瘤发生在治疗结束后 3 个月至 4 年之间。此外，有 10 例患者（2.3%）发生 HCC，1 例患者发生复发性侵袭性 HCC。
本报告提出了一个问题，即 DAA 治疗与肝外恶性肿瘤的发生之间可能存在关系。因此，从更大的队列中收集数据对于确定这种关系的可能性至关重要。
