Clinical importance of pharmacogenetics in the treatment of hepatitis C virus infection.
Globally, over 4% of the world population is affected by hepatitis C virus (HCV) infection. The current standard of care for hepatitis C infection is combination therapy with pegylated interferon and ribavirin for 48 weeks, which yield a sustained virological response in only a little over half of the patients with genotype 1 HCV. We investigated the clinical importance of pharmacogenetics in treatment efficacy and prediction of hematotoxicity. A total of 148 patients infected with HCV were enrolled. All patients were treated for a period of 48 weeks or less with pegylated interferon and ribavirin. Four genotypes were investigated: inosine triphosphatase (ITPA) rs1127354, C20orf194 rs6051702, interferon lambda (IFNL)3 rs8099917, IFNL3÷4 rs12979860 in the population from southwestern Romania. Genetic variants for rs129798660 and rs6051702 proved once more to represent an indisputable clinical tool for predicting sustained virological response (SVR) (69.23%, chi-square p=0.007846, p<0.05 and 63.29%, chi-square p=0.007846, p<0.05, respectively). ITPA genetic variants protect against ribavirin-induced hemolytic anemia and C20orf194 also proved to be protective against thrombocytopenia. These clinical findings strengthen the belief that pharmacogenetics should play a constant role in treatment decisions for patients infected with hepatitis C virus.
Department of Family Medicine, University of Medicine and Pharmacy of Craiova, Romania; kamalconstantin@gmail.com.
Adina Maria
AM
Kamal
Paul
P
MitruŢ
Kamal Constantin
KC
Kamal
Oana Sorina
OS
Tica
Mihaela
M
Niculescu
Dragoş Ovidiu
DO
Alexandru
Andrei Adrian
AA
Tica
D000998:Antiviral Agents / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D006454:Hemoglobins / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D011092:Polyethylene Glycols / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011755:Pyrophosphatases / Q000235:genetics; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D000097630:Inosine Triphosphatase; D000095022:Interferon Lambda
D000998:Antiviral Agents; D006454:Hemoglobins; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011755:Pyrophosphatases; D011994:Recombinant Proteins; D012254:Ribavirin; D000097630:Inosine Triphosphatase; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a