Ioannou George N, Green Pamela K, Berry Kristin, Graf Solomon A
Division of Gastroenterology, Department of Medicine Veterans Affairs Puget Sound Health Care System and University of Washington Seattle WA.
Research and Development Veterans Affairs Puget Sound Health Care System Seattle WA.
Hepatol Commun. 2019 Jun 11;3(8):1124-1136. doi: 10.1002/hep4.1389. eCollection 2019 Aug.
It is unclear whether eradication of hepatitis C virus (HCV) leads to a reduction in the risk of hematologic malignancies. We aimed to determine the impact of sustained virologic response (SVR) induced by either direct-acting antivirals (DAAs) or interferon (IFN) on the risk of hematologic malignancies. We identified 69,581 patients who initiated antiviral treatment in the Veterans Affairs national health care system from January 1, 1999, to December 31, 2015, including 40,410 (58%) IFN-only regimens, 4,546 (6.5%) DAA + IFN regimens, and 24,625 (35%) DAA-only regimens. We retrospectively followed patients to identify incident cases of hematologic malignancies or monoclonal gammopathy of unknown significance (MGUS), a premalignant precursor of multiple myeloma. Among patients treated with IFN, SVR was significantly associated with a reduction in the risk of lymphoma (adjusted hazard ratio [AHR], 0.70; 95% confidence interval [CI], 0.51-0.97), multiple myeloma (AHR, 0.40; 95% CI, 0.20-0.77), MGUS (AHR, 0.65; 95% CI, 0.42-0.99), or all hematologic malignancies and MGUS combined (AHR, 0.67; 95% CI, 0.53-0.84) over a mean follow-up of 10.6 years. In contrast, among patients treated with DAA, SVR was not associated with the risk of lymphoma, multiple myeloma, MGUS, or all hematologic malignancies and MGUS combined (AHR, 1.08; 95% CI, 0.66-1.78) during a mean follow-up of 2.9 years. Neither IFN-induced SVR nor DAA-induced SVR was associated with risk of colon cancer or prostate cancer, which were chosen as comparison/control malignancies. We describe novel strong associations between IFN-induced SVR and lymphoma, multiple myeloma, MGUS, and all hematologic malignancies combined. Surprisingly, these associations were not observed with DAA-induced SVR.
丙型肝炎病毒（HCV）根除是否会降低血液系统恶性肿瘤的风险尚不清楚。我们旨在确定直接抗病毒药物（DAA）或干扰素（IFN）诱导的持续病毒学应答（SVR）对血液系统恶性肿瘤风险的影响。我们识别出1999年1月1日至2015年12月31日期间在退伍军人事务部国家医疗保健系统中开始抗病毒治疗的69581名患者，其中包括40410名（58%）仅使用IFN的治疗方案、4546名（6.5%）DAA + IFN治疗方案以及24625名（35%）仅使用DAA的治疗方案。我们对患者进行回顾性随访，以识别血液系统恶性肿瘤或意义未明的单克隆丙种球蛋白病（MGUS，多发性骨髓瘤的癌前病变）的发病病例。在接受IFN治疗的患者中，在平均10.6年的随访期内，SVR与淋巴瘤风险降低显著相关（调整后风险比[AHR]，0.70；95%置信区间[CI]，0.51 - 0.97）、多发性骨髓瘤（AHR，0.40；95% CI，0.20 - 0.77）、MGUS（AHR，0.65；95% CI，0.42 - 0.99）或所有血液系统恶性肿瘤和MGUS合并症（AHR，0.67；95% CI，0.53 - 0.84）相关。相比之下，在接受DAA治疗的患者中，在平均2.9年的随访期内，SVR与淋巴瘤、多发性骨髓瘤、MGUS或所有血液系统恶性肿瘤和MGUS合并症的风险无关（AHR，1.08；95% CI，0.66 - 1.78）。IFN诱导的SVR和DAA诱导的SVR均与结肠癌或前列腺癌的风险无关，这两种癌症被选为对照恶性肿瘤。我们描述了IFN诱导的SVR与淋巴瘤、多发性骨髓瘤、MGUS以及所有血液系统恶性肿瘤合并症之间新的强关联。令人惊讶的是，DAA诱导的SVR未观察到这些关联。
