ITPA and SLC29A1 Genotyping for the Prediction of Ribavirin Dose Reduction in Anti-HCV Triple Therapy with Protease Inhibitors.
Chronic hepatitis C is one of the most important causes of liver disease, leading to cirrhosis, hepatic decompensation and hepatocellular carcinoma. Recently some important advances in therapy have been achieved with the introduction of first wave, first generation direct acting antiviral agents (DAAs) such as boceprevir (BOC), in combination with pegylated interferon (Peg-IFN) and ribavirin (RBV). The superior rate of sustained virological response with this treatment is accompanied by an elevated frequency of anaemia. Several studies have evidenced the importance of single nucleotide polymorphisms (SNPs) in inosine triphosphatase (ITPA) and solute carrier family 29, member 1 (SLC29A1) genes in the development of this adverse event. Here, we investigated haemoglobin levels and the best-known functional SNPs in ITPA and SLC29A1 genes in 22 patients treated with triple therapy with BOC/Peg-IFN/RBV. The identification of ITPA protective and SLC29A1 risk genotypes still appears to be a current methodology in RBV dosing during hepatitis C virus therapy with DAAs.
Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
Andrea
A
Lombardi
Simona
S
Landonio
Carlo
C
Magni
Stefania
S
Cheli
Cristina
C
Mazzali
Mario U
MU
Mondelli
Giuliano
G
Rizzardini
Emilio
E
Clementi
Felicia Stefania
FS
Falvella
D000328:Adult; D000368:Aged; D000740:Anemia / Q000097:blood / Q000139:chemically induced; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D033721:Equilibrative Nucleoside Transporter 1 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006454:Hemoglobins / Q000378:metabolism; D016174:Hepacivirus / Q000187:drug effects; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011392:Proline / Q000031:analogs & derivatives / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000627:therapeutic use*; D011755:Pyrophosphatases / Q000235:genetics*; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D000097630:Inosine Triphosphatase
D000998:Antiviral Agents; D033721:Equilibrative Nucleoside Transporter 1; D006454:Hemoglobins; D011392:Proline; D011480:Protease Inhibitors; D011755:Pyrophosphatases; D012254:Ribavirin; C438649:SLC29A1 protein, human; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase