Sorbonne Université, Départment d'Hématologie clinique, Assistance Publique Hôpitaux de Paris, Hospital Pitié-Salpétrière, Paris, France.
Sorbonne Université, Centre Régional de Pharmacovigilance, Assistance Publique Hôpitaux de Paris, Hospital Pitié-Salpétrière, Paris, France.
Clin Res Hepatol Gastroenterol. 2022 Oct;46(8):102000. doi: 10.1016/j.clinre.2022.102000. Epub 2022 Aug 3.
After several cases of peculiar hematological malignancies following introduction of new oral anti-hepatitis C virus (HCV) treatments in our recent practice, we aimed to systematically identify all cases of hematological malignancies (HM) in patients with chronic HCV infection and to compare them according to the prescription of oral anti-HCV Direct Acting Antivirals (DAA) treatment or not.
MATERIAL/METHODS: In this single-center retrospective observational study, we included all patients with confirmed HM and chronic HCV infection managed between 2010 and 2019 in the Pitié-Salpêtrière hospital, Paris. Non-inclusion criteria were a benign hematological disorder, an HM preceding chronic HCV infection and HCV acute infection. We compared characteristics of patients who received DAA before HM diagnosis to those with no DAA before HM.
Over the 10 years, 61 cases of HM among HCV infected patients were identified (female 29%, median age of 58.0 years [IQR 17]). Twenty-one received DAA before the onset of HM (Group DAA+) and 40 did not (Group DAA-) including 22 having received DAA after HM. In the DAA+ group, oral NS5B, NS5A and NS3A inhibitors were used in 90, 76 and 29% respectively. HM developed in the two years following DAA initiation in 76%. Eight (38%) had Non-Hodgkin Lymphoma, 5 (24%) had an Acute Myeloid Leukaemia (AML) including two with a mixed phenotype, 2 each had Hodgkin Lymphoma, Multiple Myeloma or a myeloproliferative disorder and one each had a chronic Lymphocytic Leukaemia or AL Amyloidosis. In the Group DAA-, HM were NHL in 20(50%) patients, Myeloproliferative neoplasms in 7 (17%), Multiple Myeloma in 5, Hodgkin Lymphoma in 3, Myelodysplastic syndrome and AML in 2 (5%) each and Acute Lymphoblastic Leukaemia in one. No significant difference between the groups DAA + and - was found according to age, sex, HCV genotype, viral load, co-infection or type and exposition of previous HCV treatments. AML, liver transplantation and cirrhosis were significantly more frequent in the DAA+ group (p = 0.020, 0.045 and 0.032, respectively).
AML seemed more frequent after using DAA treatments, notably in severe HCV patients including cirrhotic and/or liver transplanted patients. A multicentric observational study is ongoing to confirm and explore the results.
在我们最近的实践中，新型口服抗丙型肝炎病毒（HCV）药物引入后出现了几例特殊血液恶性肿瘤病例，因此我们旨在系统地确定所有慢性 HCV 感染患者中的血液恶性肿瘤（HM）病例，并根据口服抗 HCV 直接作用抗病毒药物（DAA）治疗的处方与否进行比较。
材料/方法：在这项单中心回顾性观察性研究中，我们纳入了 2010 年至 2019 年期间在巴黎皮提-萨尔佩特里埃医院接受治疗的所有确诊 HM 合并慢性 HCV 感染的患者。排除标准为良性血液系统疾病、HM 先于慢性 HCV 感染以及 HCV 急性感染。我们比较了在 HM 诊断前接受 DAA 治疗的患者和在 HM 诊断前未接受 DAA 治疗的患者的特征。
在 10 年期间，我们共发现 61 例 HCV 感染患者发生 HM（女性占 29%，中位年龄为 58.0 岁[IQR 17]）。21 例在 HM 发病前接受了 DAA（DAA+组），40 例未接受（DAA-组），其中 22 例在 HM 后接受了 DAA。在 DAA+组中，90%、76%和 29%分别使用了 NS5B、NS5A 和 NS3A 抑制剂。76%的 HM 在 DAA 起始后的两年内发生。8 例（38%）患有非霍奇金淋巴瘤，5 例（24%）患有急性髓系白血病（AML），其中包括 2 例混合表型，2 例各有 1 例霍奇金淋巴瘤、多发性骨髓瘤或骨髓增生性疾病，1 例各有 1 例慢性淋巴细胞白血病或 AL 淀粉样变性。在 DAA-组中，20 例（50%）患者为 NHL，7 例（17%）为骨髓增生性肿瘤，5 例为多发性骨髓瘤，3 例为霍奇金淋巴瘤，2 例为骨髓增生异常综合征和 AML，1 例为急性淋巴细胞白血病。在 DAA+组和 DAA-组之间，年龄、性别、HCV 基因型、病毒载量、合并感染或先前 HCV 治疗的类型和暴露情况无显著差异。DAA+组中 AML、肝移植和肝硬化的发生率明显更高（p=0.020、0.045 和 0.032）。
在使用 DAA 治疗后，AML 似乎更为常见，尤其是在包括肝硬化和/或肝移植患者在内的严重 HCV 患者中。目前正在进行一项多中心观察性研究，以确认和探讨这些结果。
