Homocysteine levels and sustained virological response to pegylated-interferon alpha2b plus ribavirin therapy for chronic hepatitis C: a prospective study.
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.
Borgia
Guglielmo
G
Dipartimento di Medicina Pubblica e Sicurezza Sociale - Sezione di Malattie Infettive, Università di Napoli Federico II, Napoli, Italy. borgia@unina.it
Gentile
Ivan
I
Fortunato
Giuliana
G
Borrelli
Francesco
F
Borelli
Salvatore
S
de Caterina
Maurizio
M
Di Taranto
Maria Donata
MD
Simone
Maria
M
Borgia
Federico
F
Viola
Chiara
C
Reynaud
Laura
L
Cerini
Raimondo
R
Sacchetti
Lucia
L
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
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