Effect of laparoscopic splenectomy in patients with Hepatitis C and cirrhosis carrying IL28B minor genotype

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Figure 1

IL28B genetic polymorphism and response to PEG-IFN/RBV (black bar: SVR, grey bar: ETR-relapse, white bar: NR). Each number represents the rate in percentile). (A) IL28B genetic polymorphism and response rate among patients with HCV-induced cirrhosis. (B) Response rate between Spx and non-Spx groups. (C) IL28B genetic polymorphism and each response rate in the Spx and non-Spx groups.

Figure 2

ITPA genetic polymorphism and PEG-IFN/RBV-induced anemia. (A) ITPA genetic polymorphism and Hb decline at 4 weeks after initiation of therapy among patients with HCV-induced cirrhosis. (B) ITPA genetic polymorphism and treatment-induced anemia in Spx and non-Spx groups. (C) The changes of Hb levels among ITPA major carriers in the comparison of Spx and non-Spx groups.

Figure 3

ITPA genetic polymorphism and thrombocytopenia. (A) The progression of thrombocytopenia between CC and CA/AA allele carriers in non-Spx group. (B) The progression of thrombocytopenia between CC and CA/AA allele carriers in Spx group. (C) The changes of platelet count was compared between Spx and non-Spx groups.

Figure 4

IL28B genetic polymorphism and splenic ISG expression. Both splenic ISG15 and PKR mRNA expression was higher in patients carrying the TT allele of IL28B.