Erschienen in:
01.11.2017 | Original Article—Liver, Pancreas, and Biliary Tract
Association between alanine aminotransferase elevation and UGT1A1*6 polymorphisms in daclatasvir and asunaprevir combination therapy for chronic hepatitis C
verfasst von:
Shinya Maekawa, Mitsuaki Sato, Natsuhiko Kuratomi, Taisuke Inoue, Yuichiro Suzuki, Akihisa Tatsumi, Mika Miura, Shuya Matsuda, Masaru Muraoka, Natsuko Nakakuki, Fumitake Amemiya, Shinichi Takano, Mitsuharu Fukasawa, Yasuhiro Nakayama, Tatsuya Yamaguchi, Tadashi Sato, Minoru Sakamoto, Miyako Murakawa, Mina Nakagawa, Yasuhiro Asahina, Nobuyuki Enomoto
Erschienen in:
Journal of Gastroenterology
|
Ausgabe 6/2018
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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.