Cornella Scott L, Stine Jonathan G, Kelly Virginia, Caldwell Stephen H, Shah Neeral L
Department of Medicine, University of Virginia , Charlottesville, VA , USA.
Postgrad Med. 2015 May;127(4):413-7. doi: 10.1080/00325481.2015.1021660. Epub 2015 Mar 7.
Obtaining a sustained virologic response (SVR) in patients with chronic hepatitis C virus (HCV) can decrease hepatic complications and be curative, however, extrahepatic manifestations including mixed cryoglobulinemia (MCN) may persist with interferon-based therapy. Our objective was to review our experience in treating patients with new oral antiviral agents and to assess common factors associated with MCN persistence despite SVR.
We analyzed a case series of five patients with genotype one chronic HCV complicated by MCN who had persistence of cryoglobulins despite completion of triple therapy with oral antiviral agents (boceprivir, telaprivir or sofosbuvir).
Patients with cirrhosis appear to have a decreased ability to clear immune complexes. We observed that early viral response by week 8 of therapy and longer periods of undetectable virus on treatment correlated with eventual clearance of serum cryoglobulins in patients without cirrhosis. Two patients were treated with anti-B-cell agent rituximab prior to starting therapy for HCV; this did not lead to a more effective clearance of cryoglobulins.
We suggest that a longer treatment course than the standard 24 weeks with triple therapy could aid in the clearance of these immune complexes and cryoglobulins in cirrhotics. More studies to determine the ideal duration of treatment for chronic HCV and coincident MCN are needed, especially in light of the new all oral direct-acting antiviral regimens that are now recommended for HCV treatment.
在慢性丙型肝炎病毒(HCV)患者中获得持续病毒学应答(SVR)可减少肝脏并发症并实现治愈,然而,包括混合性冷球蛋白血症(MCN)在内的肝外表现可能会在基于干扰素的治疗后持续存在。我们的目的是回顾我们使用新型口服抗病毒药物治疗患者的经验,并评估尽管获得了SVR但MCN仍持续存在的常见相关因素。
我们分析了一组5例基因型1慢性HCV合并MCN的患者病例系列,这些患者在完成口服抗病毒药物(博赛匹韦、特拉匹韦或索磷布韦)三联疗法后冷球蛋白仍持续存在。
肝硬化患者清除免疫复合物的能力似乎有所下降。我们观察到,在治疗第8周时的早期病毒应答以及治疗期间更长时间检测不到病毒与无肝硬化患者血清冷球蛋白的最终清除相关。2例患者在开始HCV治疗前接受了抗B细胞药物利妥昔单抗治疗;这并未导致冷球蛋白更有效的清除。
我们建议,对于肝硬化患者,采用比标准的24周三联疗法更长的治疗疗程可能有助于清除这些免疫复合物和冷球蛋白。需要更多研究来确定慢性HCV合并MCN的理想治疗时长,尤其是鉴于目前推荐用于HCV治疗的新型全口服直接作用抗病毒方案。