ITPA polymorphism effects on decrease of hemoglobin during sofosbuvir and ribavirin combination treatment for chronic hepatitis C.
BACKGROUND
Polymorphisms in the inosine triphosphatase (ITPA) gene is associated with anemia induced by peg-interferon (PEG-IFN) plus ribavirin (RBV) treatment for patients with chronic hepatitis C virus (HCV) infection. However, the effect of ITPA polymorphism on sofosbuvir plus RBV treatment is unknown.


METHODS
Two hundred and forty-four patients with chronic HCV genotype 2 infection without decompensated liver cirrhosis were treated with sofosbuvir plus RBV for 12 weeks. The effects of ITPA polymorphism on hemoglobin levels and RBV dose reduction and treatment response were analyzed. ITPA (rs1127354) was genotyped using the Invader assay. Multivariate regression analysis was performed to identify factors associated with sustained virological response (SVR).


RESULTS
Overall, SVR12 was achieved in 231 (94.7%) patients, based on intention to treat analysis. During the therapy, reduction of hemoglobin levels was significantly greater in ITPA genotype CC patients than CA/AA patients. Therefore, the cumulative proportion of patients with RBV dose reduction was significantly higher and total dose of RBV was significantly lower in patients with CC genotype compared to CA/AA genotypes. SVR12 rates were similar between ITPA genotypes CC and CA/AA (94.7 and 94.4%, respectively, P = 0.933). Multivariate logistic regression analysis identified FIB4 index <3.25 (odds ratio [OR], 9.388 for ≥3.25; P = 0.005) and low body weight (OR, 1.059, for high body weight; P = 0.017) as independent predictors for SVR12.


CONCLUSIONS
ITPA polymorphism influences hemoglobin levels and incidence of RBV dose reduction during sofosbuvir plus RBV therapy. However, ITPA genotype CC patients can expect a curative effect equivalent to CA/AA patients for chronic HCV genotype 2 infection.
Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Kei
K
Morio
Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Michio
M
Imamura
Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Yoshiiku
Y
Kawakami
Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Takashi
T
Nakahara
Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Yuko
Y
Nagaoki
Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Tomokazu
T
Kawaoka
Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Masataka
M
Tsuge
Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Akira
A
Hiramatsu
Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Hiroshi
H
Aikata
Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Clair Nelson
CN
Hayes
Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Grace Naswa
GN
Makokha
Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.|Laboratory for Digestive Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Hiroshima, Japan.
Hidenori
H
Ochi
Onomichi General Hospital, Hiroshima, Japan.
Hajime
H
Amano
Tsuchiya General Hospital, Hiroshima, Japan.
Keiko
K
Arataki
Chugoku Rousai Hospital, Hiroshima, Japan.
Takashi
T
Moriya
Saiseikai Kure Hospital, Hiroshima, Japan.
Hiroyuki
H
Ito
Hiroshima Red Cross Hospital, Hiroshima, Japan.
Keiji
K
Tsuji
Kure Medical Center, Hiroshima, Japan.
Hiroshi
H
Kohno
Hiroshima City Asa Hospital, Hiroshima, Japan.
Koji
K
Waki
Mazda Hospital, Hiroshima, Japan.
Toru
T
Tamura
Nakamura Clinic, Hiroshima, Japan.
Toshio
T
Nakamura
Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. chayama@hiroshima-u.ac.jp.|Laboratory for Digestive Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Hiroshima, Japan. chayama@hiroshima-u.ac.jp.
Kazuaki
K
Chayama
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006454:Hemoglobins / Q000378:metabolism; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics*; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D000069474:Sofosbuvir / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D000097630:Inosine Triphosphatase
D000998:Antiviral Agents; D006454:Hemoglobins; D011755:Pyrophosphatases; D012254:Ribavirin; D000069474:Sofosbuvir; D000097630:Inosine Triphosphatase
Chronic hepatitis C; Hemoglobin; ITPA; Ribavirin; Sofosbuvir