Filipec Kanizaj Tajana, Colić Cvrlje Vesna, Mrzljak Anna, Ostojić Rajko
Department of Gastroenterology, University Department of Medicine, Merkur University Hospital, Zagreb, Croatia.
Acta Med Croatica. 2009 Dec;63(5):451-7.
Recurrent infection with HCV after liver transplantation is almost universal and is associated with substantial morbidity, mortality and graft loss. In contrast to immunocompetent individuals, HCV infection in immunosuppressed transplant recipients usually has an accelerated course. Acute hepatitis develops in approximately 75% of HCV recipients in the first six months following orthotopic liver transplantation (OLT). By the fifth postoperative year, over 80% of HCV-infected liver transplant recipients will develop histologic evidence of chronic allograft injury secondary to hepatitis C, with up to 30% developing cirrhosis. While the choice of calcineurin inhibitor has not been clearly shown to affect histologic recurrence of hepatitis C or the frequency of rejection in HCV-infected recipients, cumulative exposure to corticosteroids is associated with increased mortality, higher levels of HCV viremia and more severe histologic recurrence. Unfortunately, treatment of chronic HCV in liver transplant recipients is suboptimal. Combination therapy with interferon (pegylated and nonpegylated forms) plus ribavirin appears to provide maximum benefits. Drug therapy is usually administered for recurrent disease. No prophylactic therapy is available. Preemptive regimens offer no distinctive advantages over treatments initiated for recurrent disease. Overall, treatment is poorly tolerated, with frequent need for dose reductions, especially for cytopenias, and drug discontinuation in up to 50% of patients. Optimizing drug doses is important in maximizing sustained virologic response rates. The achieved SVR is between 33% and 42% in randomized studies treating patients with histologic recurrence and 0% to 33% when used in a preemptive protocol. The potential factors that influence this low SVR rate are: 1) high percentage of patients with genotype 1 virus; 2) high viral load at the start of treatment; 3) high percentage of prior non-responders to therapy; 4) side effects that often make the use of standard doses and duration of treatment difficult; 5) the use or not of growth factors; and 6) the effect of immunosuppression. In post-transplant patients with recurrent HCV disease, combination Peg alfa-2b or alfa-2a in standard dose and ribavirin (800-1200 mg either ab initio or as an increasing dose) regimen for 48 weeks was significantly better than no therapy, but not than any other therapy.
肝移植后丙型肝炎病毒（HCV）的反复感染几乎是普遍现象，且与高发病率、死亡率及移植物丢失相关。与免疫功能正常的个体不同，免疫抑制的移植受者中的HCV感染通常病程进展加速。在原位肝移植（OLT）后的头六个月内，约75%的HCV感染受者会发生急性肝炎。术后第五年时，超过80%的HCV感染肝移植受者会出现丙型肝炎继发的慢性移植物损伤的组织学证据，高达30%的患者会发展为肝硬化。虽然尚未明确显示钙调神经磷酸酶抑制剂的选择会影响HCV感染受者丙型肝炎的组织学复发或排斥反应的发生率，但累积使用皮质类固醇与死亡率增加、HCV病毒血症水平升高及更严重的组织学复发相关。不幸的是，肝移植受者慢性HCV的治疗并不理想。干扰素（聚乙二醇化和非聚乙二醇化形式）联合利巴韦林的联合疗法似乎能带来最大益处。药物治疗通常用于复发性疾病。尚无预防性治疗方法。抢先治疗方案与针对复发性疾病开始的治疗相比并无明显优势。总体而言，治疗耐受性差，经常需要减少剂量，尤其是针对血细胞减少症，高达50%的患者需要停药。优化药物剂量对于最大化持续病毒学应答率很重要。在治疗有组织学复发的患者的随机研究中，实现的持续病毒学应答率为33%至42%，而在抢先治疗方案中使用时为0%至33%。影响这种低持续病毒学应答率的潜在因素有：1）基因型1病毒感染患者比例高；2）治疗开始时病毒载量高；3）既往治疗无应答者比例高；4）副作用常常使标准剂量和治疗持续时间的使用变得困难；5）是否使用生长因子；6）免疫抑制的影响。在移植后患有复发性HCV疾病的患者中，标准剂量的聚乙二醇化α-2b或α-2a联合利巴韦林（初始剂量或递增剂量为800 - 1200 mg）治疗48周的方案明显优于不治疗，但并不优于任何其他治疗。
