HCV可以与非肝癌的治疗重新激活

StephenW

HCV Can Reactivate with Treatment of Non-hepatic Cancer
FEBRUARY 02, 2018
Kenneth Bender, PharmD, MA
Harrys Torres, MDHarrys Torres, MD
Hepatitis C virus (HCV) reactivation to occur in approximately 1 out of 5 patients treated for non-hepatic cancer, posing renewed risk for hepatic injury and possibly complicating the cancer treatment.

Harrys Torres, MD, Department of Infectious Diseases, University of Texas MD Anderson Cancer Center, Houston, TX and colleagues reported that reactivation occurred in 23 of 100 patients (23%) in a 36-week prospective study. Ten of these patients (43%) experienced a hepatitis flare, 6 of whom then required discontinuation or dose reduction of cancer treatment.

"Although hepatitis flares were observed, no patient had liver failure or died of a liver-related cause," researchers wrote, "however, hepatitis flare caused modification of cancer treatment, and such modification may have a negative effect on oncologic outcomes."

In an editorial accompanying the study, Michael Kriss, MD and Matthew Burchill, PhD, of University of Colorado School of Medicine’s Division of Gastroenterology and Hepatology, suggest that the duration of the study may not have been sufficient to be reassured by hepatic injuries being relatively benign.

"While it has been reported that an increase in HCV viral load correlates with rapid progression to end-stage liver disease, clinical and scientific consensus of this correlation has yet to be established," Kriss and Burchill wrote. "Therefore, it is imperative to determine if treatment of HCV with DAAs (direct-acting antivirals) prior to or concurrent with chemotherapy are attractive options to prevent HCVr (reactivation) and long-term liver-related outcomes."

The prospective study involved 50 HCV-infected patients receiving treatment for hematologic malignancies and 50 treated for solid tumors between November 2012 and July 2016. HCV reactivation was defined as an increase in HCV-RNA of at least 1 log10 IU/mL, and hepatitis flare as an increase in alanine aminotransferase to at least 3 times upper limit of normal.

The 23 patients with HCV reactivation included 18 (36%) with hematologic malignancies and 5 (10%) with solid tumors.  These patients were more likely than those without reactivation to have had a prolonged lymphopenia (median 95 versus 22 days) and to have received rituximab (44% versus 9%) or high-does steroids (57% versus 21%).

Kriss and Burchill suggest that the findings support an interrelationship between the clinical phenomena of HCV reactivation and the immunologic mechanisms underlying both hepatologic and oncologic outcomes in HCV-infected cancer patients.

They point to a confliction, however, in the finding that rituximab was significantly associated with HCV reactivation.  While rituximab induces the selective depletion of B lymphocytes through antibody-dependent cellular cytotoxicity and that this contributes to its association with hepatitis B virus reactivation, immune system mechanisms responding to HCV infection are largely independent of B lymphocytes.

Torres and colleagues indicated that the potential risk of developing HCV reactivation should not be considered a contraindication for chemotherapy.

"Our findings should help HCV-infected cancer patients have a wide access to many types of chemotherapy, with close monitoring while receiving regimens associated with HCV reactivation," they concluded.

Kriss and Burchill elaborate on that precaution.

"The data from Torres et al demonstrate that care needs to be taken in monitoring HCVr  in patients, particularly those receiving targeted immunotherapies that manipulate the components of the immune system that control HCV,” they wrote.

The study, "Hepatitis C virus reactivation in patients receiving cancer treatment: A prospective observational study" was published online in Hepatology last month.

StephenW

HCV可以与非肝癌的治疗重新激活
2018年2月2日
Kenneth Bender，麻省PharmD
哈里斯托雷斯，马里兰州托雷斯医学博士
5例接受非肝癌治疗的患者中约有1例发生丙型肝炎病毒（HCV）再激活，造成肝脏损伤再次发生，并可能使癌症治疗复杂化。

德克萨斯州大学安德森癌症中心，德克萨斯州休斯敦传染病部门的Harrys Torres博士及其同事报告说，在36周的前瞻性研究中，100例患者中有23例（23％）发生再激活。其中10例（43％）发生肝炎，其中6例需要停药或剂量减少。

研究人员写道：“尽管观察到肝炎发作，但没有肝功能衰竭或因肝脏相关原因死亡的患者，然而肝炎引起了癌症治疗的改变，这种改变可能对肿瘤的治疗产生负面影响。

在一项伴随这项研究的评论中，科罗拉多大学医学院胃肠病学和肝病学系的Michael Kriss博士和Matthew Burchill博士表示，研究的持续时间可能不足以让肝损伤相对放心良性。

据报道，虽然HCV病毒载量的增加与终末期肝病的快速进展相关，但这种相关性的临床和科学共识尚未建立，“Kriss和Burchill写道。 “因此，确定在化疗之前或同时使用DAA（直接作用抗病毒药物）治疗HCV是否是预防HCVr（再激活）和长期肝脏相关结果的有吸引力的选择是必要的。

前瞻性研究涉及2012年11月至2016年7月期间接受治疗血液系统恶性肿瘤的50位HCV感染患者和50位实体瘤患者.HCV再激活定义为HCV RNA至少增加1 log10 IU / mL，肝炎作为丙氨酸转氨酶增加到正常上限的至少3倍。

23例HCV再激活的患者中，18例（36％）患有血液系统恶性肿瘤，5例（10％）患有实体瘤。这些患者比那些没有再激活的患者更有可能长时间淋巴细胞减少（中位数为95和22天），接受利妥昔单抗（44％比9％）或高剂量类固醇（57％比21％）。

Kriss和Burchill认为，这些发现支持HCV复发的临床现象与HCV感染癌症患者的肝病和肿瘤结局的免疫机制之间的相互关系。

然而，他们指出了一个冲突，即利妥昔单抗与HCV再激活显着相关。虽然利妥昔单抗通过抗体依赖性细胞毒性诱导B淋巴细胞的选择性消耗，并且这有助于其与乙型肝炎病毒再激活的关联，但是响应于HCV感染的免疫系统机制在很大程度上不依赖于B淋巴细胞。

Torres及其同事指出，开发HCV再激活的潜在风险不应被视为化疗的禁忌症。

他们总结说：“我们的发现将有助于丙型肝炎病毒感染的癌症患者获得多种类型的化疗，密切监测，同时接受与HCV再激活相关的治疗方案。

Kriss和Burchill详细说明了这个预防措施。

他们写道：“Torres等人的数据表明，在监测患者中的HCVr时尤其需要注意，特别是接受靶向免疫治疗的患者，这些免疫治疗可以控制免疫系统中控制HCV的成分。

这项研究，“接受癌症治疗的患者的丙型肝炎病毒再激活：一项前瞻性观察研究”上个月在线发表在肝病学上。