title: Peginterferon-Α_2B plus ribavirin is more effective than peginterferon-Α_2A plus ribavirin in menopausal women with chronic hepatitis C.
abstract: Under-enrolment of women to randomized clinical trials, including chronic hepatitis C, has long been recognized. The aim of this study was to identify factors predictive of sustained virological response (SVR) to PEG IFN/Ribavirin antiviral therapy in relation to gender and reproductive status of female patients involved. Seven hundred and forty-six treatment-naïve patients (431 men, 315 women) treated with Peg-IFNα-2a (180 μg/week) or Peg-IFNα-2b (1.5 μg/kg/week) plus ribavirin (800-1400 mg/day) for 24 or 48 weeks were studied between 2006 and 2010. Differences in SVR rate, overall and by gender were assessed after adjustment and propensity score matching. SVR was obtained in 44.2% of Peg-IFNα-2a-treated patients and in 51.2% of Peg-IFNα-2b-treated patients (intention-to-treat; P = 0.139). Age, fibrosis stage and genotype 2 and 3 were independently associated with SVR by multivariate analysis. Analysing by gender, the difference in SVR between PEG-IFNα types was not significant in men but highly significant in women (Peg-IFNα-2a:39.1%vs Peg-IFNα-2b:54.4%, P = 0.007). This was attributable to a higher SVR rate with Peg-IFNα-2b in the difficult postmenopausal population (26.9% Peg-IFNα-2a vs 46.0% Peg-IFNα-2b, P = 0.040). In women, absence of menopause, genotype 2 hepatitis C virus infection and use of Peg-IFNα-2b were independently associated with SVR. In conclusion, predictive factors for SVR are different in men and women. Factors differing between genders are menopause, severe steatosis and peg-interferon used. The higher SVR rate with Peg-IFNα-2b in menopausal women is likely attributable to more favourable pharmacokinetics that allows Peg-IFNα-2b to reach visceral fat and oppose the increased cytokine production and enhanced inflammatory status in menopause.
authors.affiliation: Department of Gastroenterology, Azienda Ospedaliero-Universitaria & University of Modena and Reggio Emilia, Modena, Italy. erica.villa@unimore.it
authors.forename: E
authors.initials: E
authors.lastname: Villa
authors.forename: C
authors.initials: C
authors.lastname: Cammà
authors.forename: A
authors.initials: A
authors.lastname: Di Leo
authors.forename: A
authors.initials: A
authors.lastname: Karampatou
authors.forename: M
authors.initials: M
authors.lastname: Enea
authors.forename: S
authors.initials: S
authors.lastname: Gitto
authors.forename: V
authors.initials: V
authors.lastname: Bernabucci
authors.forename: L
authors.initials: L
authors.lastname: Losi
authors.forename: N
authors.initials: N
authors.lastname: De Maria
authors.forename: B
authors.initials: B
authors.lastname: Lei
authors.forename: A
authors.initials: A
authors.lastname: Ferrari
authors.forename: R
authors.initials: R
authors.lastname: Vukotic
authors.forename: P
authors.initials: P
authors.lastname: Vignoli
authors.forename: M
authors.initials: M
authors.lastname: Rendina
authors.forename: A
authors.initials: A
authors.lastname: Francavilla
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008593:Menopause; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D012737:Sex Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a