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- Title
Association between alanine aminotransferase elevation and UGT1A1*6 polymorphisms in daclatasvir and asunaprevir combination therapy for chronic hepatitis C.
- Authors
Maekawa, Shinya; Sato, Mitsuaki; Kuratomi, Natsuhiko; Inoue, Taisuke; Suzuki, Yuichiro; Tatsumi, Akihisa; Miura, Mika; Matsuda, Shuya; Muraoka, Masaru; Nakakuki, Natsuko; Amemiya, Fumitake; Takano, Shinichi; Fukasawa, Mitsuharu; Nakayama, Yasuhiro; Yamaguchi, Tatsuya; Sato, Tadashi; Sakamoto, Minoru; Murakawa, Miyako; Nakagawa, Mina; Asahina, Yasuhiro
- Abstract
Background: Liver damage presented as alanine aminotransferase (ALT) elevation and high ALT-caused treatment discontinuation occurs with high frequency in Japanese patients receiving daclatasvir plus asunaprevir (DCV/ASV) therapy for hepatitis C virus (HCV) infection, and its mechanism is unknown.Methods: A total of 247 Japanese patients consisting of two independent cohorts with genotype-1b HCV infection receiving DCV/ASV therapy were included. The association of ALT levels during therapy and single nucleotide polymorphisms (SNP) of five drug-metabolizing enzyme loci selected for their possible influence on NS3/4A and NS5A inhibitors was investigated.Results: Among five SNPs, we found a significant correlation between the presence of the UGT1A1 rs4148323 A allele and ALT elevation (Grade 3 elevation in AA 57%, AG 18%, and GG 4%, P = 8.4E − 06) and drug discontinuation (AA 22%, AG 11%, and GG 2.5%, P = 8.7E − 04), while no association was observed with ALT values at baseline (Grade 3 elevation AA 0%, AG 4%, and GG 2%, P = 0.5). In contrast, patients with risk A allele for drug-induced ALT elevation had a tendency to respond more favorably to treatment (AA 100%, AG 93%, and GG 90%, P = 0.29).Conclusions: Through the analysis we suggest that the A allele in UGT1A1 rs4148323 (UGT1A1*6), which is highly prevalent in the Japanese population, should be considered a risk for the development of DCV/ASV therapy-induced ALT elevation. Pretreatment SNP testing of UGT1A1*6 might be beneficial for the prediction of liver damage induced by DCV/ASV or even by DCV/ASV plus beclabuvir.
- Subjects
ALANINE aminotransferase; HEPATITIS C treatment; LIVER diseases; SINGLE nucleotide polymorphisms; HEPATITIS C virus
- Publication
Journal of Gastroenterology, 2018, Vol 53, Issue 6, p780
- ISSN
0944-1174
- Publication type
Article
- DOI
10.1007/s00535-017-1405-3