title: Interleukin-28 and hepatitis C virus genotype-4: treatment-induced clearance and liver fibrosis.
abstract: OBJECTIVE
  To investigate the association between interleukin-28B (IL28B) genotype and response to treatment and hepatic fibrosis in patients with hepatitis C virus (HCV) genotype 4.
  
  
  METHODS
  Two hundred and one HCV-genotype 4 patients were included. All patients were treated with Peginterferon alph2a/Ribavirin for 48 wk. End of treatment response (ETR) was defined as loss of detectable serum HCV RNA at the end of treatment. Sustained viral response (SVR) was defined as loss of detectable serum HCV RNA at the end of 24 wk follow up. Genotyping of IL28B rs12979860 was performed using the TaqMan assay. We used logistic regression to estimate the adjusted odds ratio (aOR) and 95%CI.
  
  
  RESULTS
  The study included 201 HCV-genotype 4 patients. The majority of patients were men (89.6%), with a median age of 47 years, inter-quartile range (40-51). Approximately 62.5% of patients had ETR, and 49.6% had SVR. Individuals who achieved SVR were more likely to be younger (χ(2) = 4.91, P = 0.027), and less likely to have fibrosis (χ(2) = 15.54, P < 0.0001), or inflammation (χ(2) = 7.58, P = 0.006). The genotype distribution of rs12979860 was 36.2%, 49.0% and 14.8% for genotypes CC, CT, and TT, respectively. In these participants, rs12979860 genotype distribution did not differ by gender (P = 0.466), pretreatment viral load (P = 0.600), inflammation (P = 0.435), or fibrosis (P = 0.291). The frequencies of IL28B rs12979860 genotypes were TT (14.8%), CT (49.0%), and CC (36.2%). Compared to rs12979860 genotype TT, aORs (95%CI) for ETR and SVR were: CC genotype, [17.55 (5.34-57.69) and 5.92 (2.09-16.76), respectively]; CT genotype, [5.15 (1.80-14.78) and 2.48 (0.94-6.52), respectively]. In the current study, the patients who did not achieve ETR or SVR had a lower prevalence of rs12979860 CC (17.4% and 23.3%, respectively) than individuals who had ETR or SVR (47.9% and 47.2%, respectively). Individuals with rs12979860 CC genotype had approximately 6 times the odds of SVR compared to individuals with TT genotype (aOR = 5.92; 95%CI: 2.09-16.76). Similarly, patients with CT genotype had SVR more often than patients with TT genotype (aOR = 2.48; 95%CI: 0.94-6.52). Carrying at least one copy of the C allele (genotypes CT and CC) had almost 8 times the probability of ETR compared to those with genotype rs12979860 TT (aOR = 7.87; 95%CI: 2.84-21.82), and approximately 3 times the odds of SVR compared to those with genotype rs12979860 TT (aOR = 3.46; 95%CI: 1.37-8.74). In addition, data were consistent with a significant gene-dose relationship (aOR = 4.05/allele; 95%CI: 2.27-7.22). The association between rs12979860 genotype and SVR was similar among those who achieved and those who did not achieve SVR.
  
  
  CONCLUSIONS
  In HCV-genotype 4 patients, rs12979860 is a sensitive predictor of viral clearance, independent of viral load, age, gender or fibrosis, with no similar relation to severity of fibrosis.
authors: Department of Gastroenterology and Hepatology, Hamad Hospital, Doha 3050, Qatar. mod2002@qatar-med.cornell.edu
authors: Moutaz
authors: M
authors: Derbala
authors: Nasser
authors: N
authors: Rizk
authors: Fatima
authors: F
authors: Shebl
authors: Saad
authors: S
authors: Alkaabi
authors: Nazeeh
authors: N
authors: Eldweik
authors: Anil
authors: A
authors: John
authors: Manik
authors: M
authors: Sharma
authors: Rafie
authors: R
authors: Yaqoob
authors: Muneera
authors: M
authors: Almohanadi
authors: Mohammed
authors: M
authors: Butt
authors: Khaled
authors: K
authors: Alejji
mesh_terms: D000328:Adult; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification*; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008103:Liver Cirrhosis / Q000150:complications / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000627:therapeutic use; D015203:Reproducibility of Results; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D000095022:Interferon Lambda
chemical_list: D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a
keywords: Genotype 4; Hepatic fibrosis; Hepatitis C virus; Interleukin-28B; rs12979860