Evolution of hepatitis C viral quasispecies after liver transplantation
Evolution of hepatitis C viral quasispecies after liver transplantation
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DOI：
10.1053/gast.2002.36546
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发表时间：
2002-11-01
期刊：
影响因子：
29.4
通讯作者：
Di Bisceglie, AM
中科院分区：
文献类型：
--
作者：
Lyra, AC;Fan, XF;Di Bisceglie, AM
背景和目的：确定 HCV 准种多样性是否与原位肝移植 (OLT) 后肝脏疾病进展呈正相关。方法：我们根据随访时肝纤维化的阶段，对 11 例因 HCV 相关性肝硬化并复发丙型肝炎而接受 OLT 的患者进行了研究。轻度组有1期或2期纤维化；严重组，3期或4期纤维化。通过移植前和移植后血清样本的克隆和测序来评估 HCV 准种多样性。结果：在轻度纤维化组中，OLT后样本内高变区1（HVR1）遗传距离和非同义替换增加，而在重度纤维化组中，这些参数在随访中下降。相比之下，在 HVR1 两侧的相邻序列中，两组的样本内多样性进展相似。 OLT后肝纤维化阶段与氨基酸复杂度呈负相关。在所有患者中，氨基酸变化的估计率最初较大，并在 36 个月后变得更加稳定。结论：OLT 后，更复杂的 HCV HVR1 准种群体与轻度疾病复发相关：在那些患有严重复发性丙型肝炎的患者中，HCV 似乎面临更大的免疫压力。病毒氨基酸序列的最大变化发生在 OLT 后的前 36 个月。
Background & Aims: To determine whether HCV quasispecies diversity correlated positively with liver disease progression after orthotopic liver transplantation (OLT). Methods: We studied 11 patients undergoing OLT for HCV-related cirrhosis with recurrent hepatitis C in 2 groups according to the stage of hepatic fibrosis on follow-up. The mild group had stage 1 or 2 fibrosis; the severe group, stage 3 or 4 fibrosis. HCV quasispecies diversity was assessed by cloning and sequencing in pretransplantation and posttransplantation serum samples. Results: In the mild fibrosis group, intrasample hypervariable region 1(HVR1) genetic distance and non-synonymous substitutions increased after OLT, whereas in the severe fibrosis group,, these parameters decreased in follow-up. In contrast, intrasample diversity progressed similarly in both groups in the adjacent sequences flanking HVR1. There was an inverse correlation between the stage of hepatic fibrosis and amino acid complexity after OLT. Among all patients, the estimated rate of amino acid change was greater initially and became more constant after 36 months. Conclusions: After OLT, a more complex HCV HVR1 quasispecies population was associated with mild disease recurrence: Among those patients with severe recurrent hepatitis C, HCV appeared to be under greater immune pressure. The greatest change in viral amino acid sequences occurred in the first 36 months after OLT.