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Different Toxicity of Aristolochic Acids in Kidney and Liver

  Introduction Aristolochic acid (AAs) is a group of nitrophenanthrene compounds comprised of AAI, AAII, AAIII and AAIV, which are widely found in Aristolochia plants and used in herbal therapy and traditional Chinese medicine [1]. Consistent use of aristolochic acids- containing drugs could lead to aristolochic acid nephropathy and subsequent urinary tract tumors [2-4]. Active metabolites of AAs form adducts with DNA, inducing characteristic A-T transversion (A:T to T:A mutation) known as AA mutational signature [5]. In 2017, a study has analyzed AA mutational signature of several datasets and concluded that AAs and their derivatives were widely implicated in liver cancers in Taiwan and throughout Asia [6]. Ever since the paper published, there has been an intensive debate on whether the prevalence of AA signature mutation is high in HCC patients and if this mutation spectra is really correlate with traditional Chinese medicine consumption in Asia. Since no case report has