Globke Brigitta, Raschzok Nathanael, Teegen Eva-Maria, Pratschke Johann, Schott Eckart, Eurich Dennis
General, Visceral and Transplant Surgery, Charité Campus Virchow, Berlin, Germany.
General, Visceral, Thoracic and Vascular Surgery, Charité Campus Mitte, Berlin, Germany.
Transpl Infect Dis. 2017 Feb;19(1). doi: 10.1111/tid.12647. Epub 2017 Jan 11.
Hepatitis C virus (HCV) recurrence after liver transplantation (LT) used to be a serious problem in the era of interferon-based treatment. Since the introduction of modern directly acting antivirals, treatment has become easier and shorter. According to published data, in the natural course of hepatitis C infection the duration of antiviral treatment with sofosbuvir (SOF) and ledipasvir (LDV) may be shortened to 12 instead of 24 weeks, using ribavirin (RBV) in addition. Furthermore, the question of whether or not RBV is really necessary, in a 12-week SOF/LDV treatment in the post-transplant setting, is still unanswered.
At our institution, 100 liver transplant patients with HCV recurrence underwent interferon-free SOF-based treatment. A total of 51 patients received SOF/LDV with or without RBV. Twenty-nine HCV genotype 1 or 4 patients with histologically proven stage 0-2 fibrosis were treated with SOF/LDV for 12 weeks; another 22 patients with advanced fibrosis (stage 3-4) either received SOF/LDV plus weight-adjusted RBV or prolonged treatment for 24 weeks.
End of treatment response and sustained virological response (SVR) were achieved in 100% of the 51 patients, irrespective of the treatment group. Patients with prolonged treatment duration or with RBV developed significantly more adverse events (AEs) compared to the SOF/LDV group: 19 (86.4%) vs 8 (27.6%), P<.001. One of the predominant and most relevant AEs was the development of anemia in 43.1% of 10 patients receiving RBV, which was a significant result (P<.001). RBV co-medication had to be reduced in 11 (55%) patients and then stopped in 8 (40%) patients because of AEs. No significant difference was observed among the groups regarding kidney function.
The SOF/LDV combination is a reliable therapy of recurrent HCV infection after LT. It is easy to administer and to achieve SVR in immunocompromised patients without interactions with immunosuppressive medications. Considering the high rate of AEs, frequent discontinuation of RBV treatment, and the 100% SVR, the use of RBV as co-medication in a 12-week SOF/LDV regimen does not seem to be justified after LT.
在基于干扰素治疗的时代，肝移植（LT）后丙型肝炎病毒（HCV）复发曾是一个严重问题。自从现代直接作用抗病毒药物问世以来，治疗变得更加容易且疗程更短。根据已发表的数据，在丙型肝炎感染的自然病程中，使用索磷布韦（SOF）和来迪派韦（LDV）进行抗病毒治疗的疗程可能从24周缩短至12周，同时加用利巴韦林（RBV）。此外，在移植后环境中，对于12周的SOF/LDV治疗是否真的需要RBV这一问题仍未得到解答。
在我们机构，100例HCV复发的肝移植患者接受了基于SOF的无干扰素治疗。共有51例患者接受了含或不含RBV的SOF/LDV治疗。29例经组织学证实为0-2期纤维化的HCV 1型或4型患者接受了12周的SOF/LDV治疗；另外22例晚期纤维化（3-4期）患者要么接受了SOF/LDV加根据体重调整剂量的RBV治疗，要么接受了24周的延长治疗。
51例患者中100%实现了治疗结束时应答和持续病毒学应答（SVR），无论治疗组如何。与SOF/LDV组相比，治疗疗程延长或使用RBV的患者发生的不良事件（AE）明显更多：19例（86.4%）对8例（27.6%），P<0.001。主要且最相关的不良事件之一是接受RBV的10例患者中有43.1%发生贫血，这是一个显著结果（P<0.001）。由于不良事件，11例（55%）患者不得不减少RBV联合用药，8例（40%）患者随后停止用药。各治疗组在肾功能方面未观察到显著差异。
SOF/LDV联合用药是肝移植后复发性HCV感染的可靠治疗方法。它易于给药，并且在免疫功能低下的患者中易于实现SVR，且与免疫抑制药物无相互作用。考虑到不良事件发生率高、RBV治疗频繁停药以及100%的SVR率，在肝移植后12周的SOF/LDV方案中使用RBV作为联合用药似乎不合理。
