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BMC Gastroenterology

, 12:158

Hepatobiliary and pancreatic disorders

Abstract

BackgroundIL28B 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.

MethodsThirty-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.

ResultsSustained 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 × 10-μl vs 168.7 × 10-μl, P < 0.01, which was maintained during the course of PEG-IFN-RBV therapy.

ConclusionsIL28B 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.

KeywordsIL28B ITPA Splenectomy Liver cirrhosis AbbreviationsGWASGenome-wide association study

HbHemoglobin

HCVHepatitis C virus

ISGInterferon-stimulated gene

LSLaparoscopic splenectomy

PD-1Programmed death-1

PEG-IFNPegylated-interferon

RBVRibavirin

RT-PCRReverse transcriptase polymerase chain reaction

SNPSingle nucleotide polymorphism

SpxSplenectomy

SVRSustained virological response

ETREnd of treatment response

VRVirological response.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-230X-12-158 contains supplementary material, which is available to authorized users.

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Autor: Takashi Motomura - Ken Shirabe - Norihiro Furusyo - Tomoharu Yoshizumi - Toru Ikegami - Yuji Soejima - Tomohiko Akahoshi -

Fuente: https://link.springer.com/







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