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Relationships between serum asunaprevir concentration and alanine aminotransferase elevation during daclatasvir plus asunaprevir for chronic HCV genotype 1b infection
Author(s) -
Akuta Norio,
Sezaki Hitomi,
Suzuki Fumitaka,
Kawamura Yusuke,
Hosaka Tetsuya,
Kobayashi Masahiro,
Kobayashi Mariko,
Saitoh Satoshi,
Suzuki Yoshiyuki,
Arase Yasuji,
Ikeda Kenji,
Kumada Hiromitsu
Publication year - 2016
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.24360
Subject(s) - daclatasvir , virology , alanine aminotransferase , genotype , alanine , medicine , biology , hepatitis c virus , virus , amino acid , biochemistry , gene , ribavirin
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. J. Med. Virol. 88:506–511, 2016 . © 2015 Wiley Periodicals, Inc.