title: 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.
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Motomura
authors.forename: Ken
authors.initials: K
authors.lastname: Shirabe
authors.forename: Norihiro
authors.initials: N
authors.lastname: Furusyo
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Yoshizumi
authors.forename: Toru
authors.initials: T
authors.lastname: Ikegami
authors.forename: Yuji
authors.initials: Y
authors.lastname: Soejima
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Akahoshi
authors.forename: Morimasa
authors.initials: M
authors.lastname: Tomikawa
authors.forename: Takasuke
authors.initials: T
authors.lastname: Fukuhara
authors.forename: Jun
authors.initials: J
authors.lastname: Hayashi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D016207:Cytokines / Q000096:biosynthesis; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D010535:Laparoscopy / Q000379:methods*; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery / Q000821:virology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D012254:Ribavirin / Q000627:therapeutic use; D012720:Severity of Illness Index; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013156:Splenectomy / Q000379:methods*; D016896:Treatment Outcome; D014452:Ubiquitins / Q000096:biosynthesis; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012254:Ribavirin; D014452:Ubiquitins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C571406:PEG-IFN-SA; C074034:ISG15 protein, human