title: Homocysteine levels and sustained virological response to pegylated-interferon alpha2b plus ribavirin therapy for chronic hepatitis C: a prospective study.
abstract: BACKGROUND
  Chronic hepatitis C affects about 3% of the world's population. Pegylated interferon (IFN) alpha plus ribavirin is the gold standard treatment. Methylenetetrahydrofolate reductase(MTHFR) is a key enzyme in the metabolism of homocysteine. MTHFR gene polymorphisms and high levels of homocysteine are associated with a high degree of steatosis and fibrosis, conditions associated with a low sustained virological response (SVR) rate.
  
  
  OBJECTIVE
  To evaluate whether MTHFR polymorphisms and homocysteine levels are predictors of the outcome of treatment in 102 prospectively enrolled patients with chronic hepatitis C naive to treatment.
  
  
  METHODS
  Patients were treated with pegylated interferon alpha-2b plus ribavirin. All patients underwent blood tests, assessment of homocysteine, vitamin B(12), folate, hepatitis C virus (HCV)-RNA levels, screening for MTHFR gene polymorphisms and liver ultrasound examination.
  
  
  RESULTS
  Homocysteine levels were deranged (>16 micromol/L) in 10.5% of MTHFR wild-type patients vs 40.3% of non-wild-type patients (P=0.015). Homocysteine levels were 14.4 micromol/L in SVR patients and 15.5 micromol/L in non-SVR patients (P=0.049). The SVR rate was 40.0% in MTHFR wild-type patients, 52.0% in heterozygote mutants and 39.3% in homozygote mutants (P=0.467). At logistic regression analysis, genotypes 2 and 3 (odds ratio: 12.328, 95% confidence interval: 3.390-44.837, P=0.0001), homocysteine <16 micromol/L (odds ratio: 3.397, 95% confidence interval: 1.033-11.177, P=0.044) and aspartate aminotransferase (AST) levels <48 U/L (odds ratio: 3.262, 95% confidence interval: 1.125-9.458, P=0.029) were independent predictors of SVR.
  
  
  CONCLUSIONS
  In patients with chronic hepatitis C, homocysteine levels are associated with the outcome of pegylated-IFNalpha plus ribavirin treatment, while polymorphisms of MTHFR are not.
authors.affiliation: Dipartimento di Medicina Pubblica e Sicurezza Sociale - Sezione di Malattie Infettive, Università di Napoli Federico II, Napoli, Italy. borgia@unina.it
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Borgia
authors.forename: Ivan
authors.initials: I
authors.lastname: Gentile
authors.forename: Giuliana
authors.initials: G
authors.lastname: Fortunato
authors.forename: Francesco
authors.initials: F
authors.lastname: Borrelli
authors.forename: Salvatore
authors.initials: S
authors.lastname: Borelli
authors.forename: Maurizio
authors.initials: M
authors.lastname: de Caterina
authors.forename: Maria Donata
authors.initials: MD
authors.lastname: Di Taranto
authors.forename: Maria
authors.initials: M
authors.lastname: Simone
authors.forename: Federico
authors.initials: F
authors.lastname: Borgia
authors.forename: Chiara
authors.initials: C
authors.lastname: Viola
authors.forename: Laura
authors.initials: L
authors.lastname: Reynaud
authors.forename: Raimondo
authors.initials: R
authors.lastname: Cerini
authors.forename: Lucia
authors.initials: L
authors.lastname: Sacchetti
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005492:Folic Acid / Q000097:blood; D016174:Hepacivirus / Q000187:drug effects*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use*; D007558:Italy; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics; D011092:Polyethylene Glycols; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D012372:ROC Curve; D011994:Recombinant Proteins; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use*; D014805:Vitamin B 12 / Q000097:blood
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D006710:Homocysteine; D011092:Polyethylene Glycols; D012254:Ribavirin; D005492:Folic Acid; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); C417083:peginterferon alfa-2b; D014805:Vitamin B 12