Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Histopathology. 2018 May;72(6):990-996. doi: 10.1111/his.13453. Epub 2018 Feb 15.
The use of direct-acting anti-viral agents (DAAs) has resulted in extremely high sustained virological response (SVR) rates in patients being treated while on liver transplantation (LT) waiting lists. The aim of this study was to evaluate the histological findings of hepatitis C virus (HCV) patients who achieved SVR after receiving DAA treatment [SVR(+)] prior to LT, and compare them with HCV patients who had not achieved SVR [SVR(-)].
Fifty-eight adult HCV patients who underwent LT at our institution from 2014 to 2016 were included in the study. Two pathologists, blinded to SVR status, simultaneously evaluated the histological sections. Assessment included the Histology Activity Index (HAI/modified Knodell score), fibrosis stage (Ishak score), and Laennec cirrhosis stage. The study group comprised 25 SVR(+) patients (56% male; mean age, 63.8 years), and the control group comprised 33 SVR(-) patients (69% male; mean age, 61.7 years). There was no significant difference in HAI between the groups (P = 0.414). Patients who achieved SVR also did not show less portal inflammation (P = 0.787), interface hepatitis (P = 0.999), confluent necrosis (P = 0.627) or spotty necrosis (P = 0.093) than the control group. There was a trend towards a higher degree of inflammation in patients who achieved SVR in <24 weeks (P = 0.07). The degree of focal lytic necrosis/apoptosis and portal inflammation was more prominent in SVR(+) patients with shorter SVR-LT intervals.
Our study is the first to report persistent inflammation in HCV patients who received DAAs prior to LT. This supports the notion that inflammation is immunologically driven and that inflammation persists despite the absence of virus.
直接作用抗病毒药物(DAAs)的使用使正在接受肝移植(LT)等待名单治疗的患者的持续病毒学应答(SVR)率极高。本研究的目的是评估在 LT 之前接受 DAA 治疗(SVR(+))后获得 SVR 的丙型肝炎病毒(HCV)患者的组织学发现,并将其与未获得 SVR 的 HCV 患者(SVR(-))进行比较。
本研究纳入了 2014 年至 2016 年期间在我院接受 LT 的 58 例成年 HCV 患者。两位病理学家对 SVR 状态不知情,同时评估了组织学切片。评估包括组织学活动指数(HAI/改良 Knodell 评分)、纤维化分期(Ishak 评分)和 Laennec 肝硬化分期。研究组包括 25 例 SVR(+)患者(56%为男性;平均年龄 63.8 岁),对照组包括 33 例 SVR(-)患者(69%为男性;平均年龄 61.7 岁)。两组间 HAI 无显著差异(P=0.414)。获得 SVR 的患者也没有表现出更少的门脉炎症(P=0.787)、界面肝炎(P=0.999)、融合性坏死(P=0.627)或斑状坏死(P=0.093)。获得 SVR 的患者中,SVR-LT 间隔<24 周者炎症程度较高(P=0.07)。SVR(+)患者的局灶性溶酶体坏死/凋亡和门脉炎症程度更明显,SVR-LT 间隔较短。
本研究首次报道了在 LT 前接受 DAA 治疗的 HCV 患者持续存在炎症。这支持炎症是免疫驱动的观点,即尽管没有病毒,但炎症仍然存在。