Yilmaz Nevin, Shiffman Mitchell L, Stravitz R Todd, Sterling Richard K, Luketic Velimir A, Sanyal Arun J, Mills A Scott, Contos Melissa J, Coterell Adrian, Maluf Daniel, Posner Marc P, Fisher Robert A
Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA.
Liver Transpl. 2007 Jul;13(7):975-83. doi: 10.1002/lt.21117.
Recurrence of hepatitis C virus (HCV) following liver transplantation (LT) is universal. A subset of these patients develop advanced fibrosis and cirrhosis and it is believed that this leads to increased posttransplantation mortality. The specific aims of this study were to determine the incidence of advanced fibrosis and those factors associated with this process, and to evaluate causes for mortality in patients with recurrent HCV. A total of 227 patients who underwent LT with chronic HCV were monitored prospectively. The mean age of this group at LT was 49.5 yr; 76% were male and 85% were Caucasian. Fibrosis progression was monitored by protocol liver biopsy, initially performed 6 months after LT and then at 6- to 24-month intervals. Advanced fibrosis, defined as the bridging fibrosis or cirrhosis, developed in 1%, 11%, 25%, and 41% of patients after 1, 3, 5, and 6-10 yr, respectively. Acute cellular rejection hepatic steatosis, a persistent elevation in serum alanine aminotransferase and donor-race were associated with the development of advanced fibrosis. In contrast, the development of advanced fibrosis was not affected by the use of interferon prior to undergoing LT, cytomegalovirus disease, or donor age. A total of 60 patients (26%) died over 15 yr of follow-up. Although graft failure accounted for 45% of deaths in patients with advanced fibrosis, this represented only 8% of all deaths in patients with recurrent HCV. Sepsis was the most common cause of death and this was observed with similar frequency in patients who developed advanced fibrosis (45%) and in those with less advanced fibrosis (47%). In conclusion, approximately 41% of patients with recurrent HCV developed advanced fibrosis 6-10 yr after LT. However, complications associated with sepsis, not recurrent cirrhosis, was the most common cause of death in patients with recurrent HCV and this was similar in patients with or without advanced fibrosis.
肝移植(LT)后丙型肝炎病毒(HCV)复发是普遍现象。这些患者中有一部分会发展为重度肝纤维化和肝硬化,据信这会导致移植后死亡率增加。本研究的具体目的是确定重度肝纤维化的发生率及其相关因素,并评估复发性HCV患者的死亡原因。对总共227例接受慢性HCV肝移植的患者进行了前瞻性监测。该组患者肝移植时的平均年龄为49.5岁;76%为男性,85%为白种人。通过方案肝活检监测纤维化进展,最初在肝移植后6个月进行,然后每隔6至24个月进行一次。重度肝纤维化定义为桥接纤维化或肝硬化,分别在1年、3年、5年和6至10年后发生在1%、11%、25%和41%的患者中。急性细胞排斥、肝脂肪变性、血清丙氨酸转氨酶持续升高和供体种族与重度肝纤维化的发生有关。相比之下,肝移植前使用干扰素、巨细胞病毒病或供体年龄对重度肝纤维化的发生没有影响。在15年的随访中共有60例患者(26%)死亡。虽然移植物功能衰竭占重度肝纤维化患者死亡的45%,但这仅占复发性HCV患者所有死亡的8%。脓毒症是最常见的死亡原因,在发生重度肝纤维化的患者(45%)和肝纤维化程度较轻的患者(47%)中观察到的频率相似。总之,约41%的复发性HCV患者在肝移植后6至10年发展为重度肝纤维化。然而,与脓毒症相关的并发症而非复发性肝硬化是复发性HCV患者最常见的死亡原因,在有或没有重度肝纤维化的患者中情况相似。