title: Relationships between serum asunaprevir concentration and alanine aminotransferase elevation during daclatasvir plus asunaprevir for chronic HCV genotype 1b infection.
abstract: Alanine aminotransferase (ALT) elevations were the most frequent adverse events during all-oral combinations with daclatasvir and asunaprevir for patients with hepatitis C virus (HCV) infection, but the underline mechanisms are unclear. Seventy patients with chronic HCV genotype 1b infection, who were introduced daclatasvir 60 mg once daily plus asunaprevir 100 mg twice daily for 24 weeks, were measured serum asunaprevir concentrations at the one point or more of 2, 4, and 8 weeks after the start of treatment. In 4 and 8 weeks after the start of treatment, asunaprevir concentrations in patients with albumin levels <3.6 g/dl at baseline were significantly higher than those in patients with albumin levels ≥3.6 g/dl. The baseline factors did not affect to ALT severe elevations (≥300 IU/l). At 2 weeks after the start of treatment, ALT severe elevations with asunaprevir concentrations of ≥800 ng/ml (54.5%) tended to indicate the higher rates than those of <800 ng/ml (17.6%). Furthermore, the discontinuation or reduction of asunaprevir improved ALT levels, regardless the significant decrease of serum asunaprevir concentrations. In conclusion, serum albumin levels affected to serum asunaprevir concentrations, and serum asunaprevir concentrations might partly affect to ALT severe elevations. Further large-scale prospective studies are needed to investigate the impact of the discontinuation or reduction of asunaprevir to help in the design of more effective therapeutic regimens.
authors: Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
authors: Norio
authors: N
authors: Akuta
authors: Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
authors: Hitomi
authors: H
authors: Sezaki
authors: Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
authors: Fumitaka
authors: F
authors: Suzuki
authors: Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
authors: Yusuke
authors: Y
authors: Kawamura
authors: Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
authors: Tetsuya
authors: T
authors: Hosaka
authors: Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
authors: Masahiro
authors: M
authors: Kobayashi
authors: Liver Research Laboratory, Toranomon Hospital, Tokyo, Japan.
authors: Mariko
authors: M
authors: Kobayashi
authors: Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
authors: Satoshi
authors: S
authors: Saitoh
authors: Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
authors: Yoshiyuki
authors: Y
authors: Suzuki
authors: Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
authors: Yasuji
authors: Y
authors: Arase
authors: Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
authors: Kenji
authors: K
authors: Ikeda
authors: Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
authors: Hiromitsu
authors: H
authors: Kumada
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood*; D002219:Carbamates; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D007546:Isoquinolines / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D012709:Serum Albumin / Q000032:analysis; D013449:Sulfonamides / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives; D019562:Viral Load
chemical_list: D002219:Carbamates; D007093:Imidazoles; D007546:Isoquinolines; D011759:Pyrrolidines; D012709:Serum Albumin; D013449:Sulfonamides; D000410:Alanine Transaminase; D014633:Valine; C549273:daclatasvir; C571889:asunaprevir
keywords: HCV; alanine aminotransferase; albumin; asunaprevir concentration; daclatasvir