Prieto M, Berenguer M, Rayón J M, Córdoba J, Argüello L, Carrasco D, García-Herola A, Olaso V, De Juan M, Gobernado M, Mir J, Berenguer J
Hepatogastroenterology Service, Hospital Universitario La Fe, Valencia,
Hepatology. 1999 Jan;29(1):250-6. doi: 10.1002/hep.510290122.
The natural history of hepatitis C virus (HCV) infection following liver transplantation and predictors of disease severity remain controversial. The aims of the study were to assess in a homogeneous population of 81 cyclosporine-based HCV-infected liver transplant recipients mostly infected with genotype 1b and undergoing strict protocol annual biopsies: 1) the histological progression of posttransplantation HCV disease and, in particular, the incidence of HCV-related graft cirrhosis within the first 5 years after surgery; and 2) the relationship between progression to cirrhosis and i) rejection episodes and ii) first-year liver biopsy findings. We studied 81 consecutive HCV-RNA-positive patients (96% genotype 1b) undergoing liver transplantation between 1991 and 1996 with a minimum histological follow-up of 1 year. All patients received cyclosporine-based immunosuppression and underwent protocol yearly liver biopsies for the first 5 years. The mean histological follow-up was 32 months (range, 12-60 months). Biopsies were scored according to the histological activity index (HAI), with separate evaluation of grade (activity) and stage (fibrosis). Histological hepatitis, present in 97% of patients in the most recent biopsy, was moderate or severe in 64%. Twelve patients developed HCV-related cirrhosis at a median time of 24 months (range, 12-48 months), with an actuarial rate of HCV-cirrhosis of 3.7%, 8.5%, 16%, 28%, and 28% at 1, 2, 3, 4, and 5 years, respectively. Rejection was significantly more common among patients with cirrhosis versus those without (83% vs. 48%; P =.02), with an association between the incidence of cirrhosis and the number of rejection episodes: 5%, 15%, and 50% in patients without rejection, one and two episodes, respectively (P =.001). The degree of activity and fibrosis score in the first-year biopsy were higher in patients who developed cirrhosis than in those who did not (P =.008 and.18, respectively). In conclusion, HCV genotype 1b-infected liver recipients are at a high risk of developing graft cirrhosis in the first 4 to 5 years following transplantation, especially those with previous rejection episodes. First-year liver biopsies may help to sooner identify patients at the highest risk, improving further patient management.
肝移植后丙型肝炎病毒（HCV）感染的自然史以及疾病严重程度的预测因素仍存在争议。本研究的目的是在81例以环孢素为基础、主要感染1b基因型HCV且接受严格年度活检方案的肝移植受者这一同质人群中评估：1）移植后HCV疾病的组织学进展，尤其是术后前5年内HCV相关移植肝硬化的发生率；2）肝硬化进展与i）排斥反应发作和ii）第一年肝活检结果之间的关系。我们研究了1991年至1996年间连续81例HCV-RNA阳性患者（96%为1b基因型）接受肝移植，组织学随访至少1年。所有患者均接受以环孢素为基础的免疫抑制治疗，并在最初5年内每年接受方案规定的肝活检。组织学平均随访时间为32个月（范围12 - 60个月）。活检根据组织学活动指数（HAI）评分，分别评估分级（活动度）和分期（纤维化）。在最近一次活检中，97%的患者存在组织学肝炎，其中64%为中度或重度。12例患者在中位时间24个月（范围12 - 48个月）出现HCV相关肝硬化，1、2、3、4和5年时HCV肝硬化的精算发生率分别为3.7%、8.5%、16%、28%和28%。肝硬化患者的排斥反应明显比无肝硬化患者更常见（83%对48%；P = 0.02），肝硬化发生率与排斥反应发作次数之间存在关联：无排斥反应、有一次和两次排斥反应发作的患者分别为5%、15%和50%（P = 0.001）。发生肝硬化的患者第一年活检中的活动度和纤维化评分高于未发生肝硬化的患者（分别为P = 0.008和0.18）。总之，1b基因型HCV感染的肝移植受者在移植后的前4至5年内发生移植肝硬化的风险很高，尤其是那些有过排斥反应发作的患者。第一年的肝活检可能有助于更早地识别风险最高的患者，改善进一步的患者管理。
