title: Impact of comorbid hepatic steatosis on treatment of chronic hepatitis C in Japanese patients and the relationship with genetic polymorphism of IL28B, PNPLA3 and LDL receptor.
abstract: The impact of hepatic steatosis on interferon therapy for patients with chronic hepatitis C (CHC) has been associated with single-nucleotide polymorphisms (SNP) of IL28B, patatin-like phospholipase domain-containing protein 3 (PNPLA3), and low-density lipoprotein (LDL) receptor. Whether this holds true for Japanese patients, however, remains unresolved. The present study prospectively enrolled 226 Japanese patients with CHC, and investigated the impact of hepatic steatosis and its related SNPs, including rs8099917 of IL28B, rs738409 of PNPLA3, and rs14158 of LDL receptor, on outcomes of peg-interferon and ribavirin therapy. In multivariate logistic regression analysis, significant factors affecting the severity of hepatic steatosis were high body mass index and the minor alleles of IL28B SNP (p＝0.020 and 0.039, respectively). The risk alleles of PNPLA3 SNP also showed weak association (p＝0.059). Severe steatosis and the minor alleles of IL28B SNP were significantly associated with null or partial virological response in patients with HCV genotype 1, as were female gender, and low LDL cholesterol (p＝0.049, and ＜0.001, respectively). The SNP genotype of PNPLA3 and LDL receptor did not have a significant impact on therapeutic outcomes. With respect to the SNP sites examined, the SNP of PNPLA3 has a weak association with severe hepatic steatosis, but not with the outcome of interferon therapy.
authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Moritou
authors.forename: Fusao
authors.initials: F
authors.lastname: Ikeda
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Iwasaki
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Baba
authors.forename: Kouichi
authors.initials: K
authors.lastname: Takaguchi
authors.forename: Tomonori
authors.initials: T
authors.lastname: Senoh
authors.forename: Takuya
authors.initials: T
authors.lastname: Nagano
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yasunaka
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohnishi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miyake
authors.forename: Akinobu
authors.initials: A
authors.lastname: Takaki
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nouso
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000368:Aged; D005234:Fatty Liver / Q000235:genetics*; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D007378:Interleukins / Q000235:genetics*; D008049:Lipase / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011973:Receptors, LDL / Q000235:genetics*; D000095022:Interferon Lambda; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D007372:Interferons; D007378:Interleukins; D008049:Lipase; D008565:Membrane Proteins; D011973:Receptors, LDL; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent