Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
BMC Gastroenterol. 2012 Nov 12;12:158. doi: 10.1186/1471-230X-12-158.
IL28B and ITPA genetic variants are associated with the outcome of pegylated-interferon and ribavirin (PEG-IFN/RBV) therapy. However, the significance of these genetic variants in cirrhotic patients following splenectomy has not been determined.
Thirty-seven patients with HCV-induced cirrhosis who underwent laparoscopic splenectomy (Spx group) and 90 who did not (non-Spx group) were genotyped for IL28B and ITPA. The outcome or adverse effects were compared in each group. Interferon-stimulated gene 15 (ISG15) and protein kinase R expression in the spleen was measured using total RNA extracted from exenterate spleen.
Sustained virological response (SVR) rate was higher in patients carrying IL28B major genotype following splenectomy (50% vs 27.3%) and in patients carrying minor genotype in the Spx group compared to non-Spx group (27.3% vs 3.6%, P < 0.05). Pretreatment splenic ISG expression was higher in patients carrying IL28B major. There was no difference in progression of anemia or thrombocytopenia between patients carrying each ITPA genotype in the Spx group. Although splenectomy did not increase hemoglobin (Hb) level, Hb decline tended to be greater in the non-Spx group. In contrast, splenectomy significantly increased platelet count (61.1 × 103/μl vs 168.7 × 103/μl, P < 0.01), which was maintained during the course of PEG-IFN/RBV therapy.
IL28B genetic variants correlated with response to PEG-IFN/RBV following splenectomy. Splenectomy improved SVR rate among patients carrying IL28B minor genotype and protected against anemia and thrombocytopenia during the course of PEG-IFN/RBV therapy regardless of ITPA genotype.
IL28B 和 ITPA 基因变异与聚乙二醇干扰素和利巴韦林（PEG-IFN/RBV）治疗的结果相关。然而，这些基因变异在脾切除术后肝硬化患者中的意义尚未确定。
对 37 例接受腹腔镜脾切除术（Spx 组）和 90 例未接受脾切除术（非 Spx 组）的 HCV 诱导肝硬化患者进行 IL28B 和 ITPA 基因分型。比较两组的结局或不良反应。采用脾切除术切除的脾脏总 RNA 测量干扰素刺激基因 15（ISG15）和蛋白激酶 R 的表达。
脾切除术后携带 IL28B 主要基因型的患者持续病毒学应答（SVR）率较高（50% vs 27.3%），携带 Spx 组小基因型的患者 SVR 率高于非 Spx 组（27.3% vs 3.6%，P < 0.05）。携带 IL28B 主要基因型的患者术前脾脏 ISG 表达较高。在 Spx 组中，携带每种 ITPA 基因型的患者之间，贫血或血小板减少症的进展没有差异。尽管脾切除术没有增加血红蛋白（Hb）水平，但非 Spx 组的 Hb 下降趋势更大。相比之下，脾切除术显著增加血小板计数（61.1×103/μl vs 168.7×103/μl，P < 0.01），并在 PEG-IFN/RBV 治疗过程中维持。
IL28B 基因变异与脾切除术后 PEG-IFN/RBV 的反应相关。脾切除术提高了携带 IL28B 小基因型患者的 SVR 率，并在 PEG-IFN/RBV 治疗过程中保护了患者免受贫血和血小板减少症的影响，无论 ITPA 基因型如何。
