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No Incidence of Liver Cancer Was Observed in A Retrospective Study of Patients with Aristolochic Acid Nephropathy

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Abstract

Objective

To assess the risk of aristolochic acid (AA)-associated cancer in patients with AA nephropathy (AAN).

Methods

A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014. Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer. The primary endpoint was the incidence of liver cancer, and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014.

Results

A total of 337 patients diagnosed with AAN were included in this study. From the initiation of taking AA to the termination of follow-up, 39 patients were diagnosed with cancer. No cases of liver cancer were observed throughout the entire follow-up period, with urinary cancer being the predominant type (34/39, 87.17%). Logistic regression analysis showed that age, follow-up period, and diabetes were potential risk factors, however, the dosage of the drug was not significantly associated with urinary cancer.

Conclusions

No cases of liver cancer were observed at the end of follow-up. However, a high prevalence of urinary cancer was observed in AAN patients. Establishing a direct causality between AA and HCC is challenging.

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References

  1. Vanherweghem JL, Depierreux M, Tielemans C, Abramowicz D, Dratwa M, Jadoul M, et al. Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs. Lancet 1993;341:387–391.

    Article  CAS  PubMed  Google Scholar 

  2. Boot A, Jiang N, Rozen SG. Toward clinical understanding of aristolochic acid upper-tract urothelial carcinoma. Theranostics 2020;10:5578–5580.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Lu H, Liang Y, Guan B, Shi Y, Gong Y, Li J, et al. Aristolochic acid mutational signature defines the low-risk subtype in upper tract urothelial carcinoma. Theranostics 2020;10:4323–4333.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Nault JC, Letouzé E. Mutational processes in hepatocellular carcinoma: the story of aristolochic acid. Semin Liver Dis 2019;39:334–340.

    Article  CAS  PubMed  Google Scholar 

  5. Bastek H, Zubel T, Stemmer K, Mangerich A, Beneke S, Dietrich DR. Comparison of aristolochic acid I derived DNA adduct levels in human renal toxicity models. Toxicology 2019;420:29–38.

    Article  CAS  PubMed  Google Scholar 

  6. Jadot I, Declèves AE, Nortier J, Caron N. An integrated view of aristolochic acid nephropathy: update of the literature. Int J Mol Sci 2017;18:297.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Schmeiser HH, Nortier JL, Singh R, Gamboa da Costa G, Sennesael J, Cassuto-Viguier E, et al. Exceptionally long-term persistence of DNA adducts formed by carcinogenic aristolochic acid I in renal tissue from patients with aristolochic acid nephropathy. Int J Cancer 2014;135:502–507.

    Article  CAS  PubMed  Google Scholar 

  8. Anger EE, Yu F, Li J. Aristolochic acid-induced nephrotoxicity: molecular mechanisms and potential protective approaches. Int J Mol Sci 2020;21:1157.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Zhao H, Jiang N, Han Y, Yang M, Gao P, Xiong X, et al. Aristolochic acid induces renal fibrosis by arresting proximal tubular cells in G2/M phase mediated by HIF-1 α. FASEB J 2020; 34:12599–12614.

    Article  CAS  PubMed  Google Scholar 

  10. Pu XY, Shen JY, Deng ZP, Zhang ZA. Oral exposure to aristolochic acid I induces gastric histological lesions with non-specific renal injury in rat. Exp Toxicol Pathol 2016;68:315–320.

    Article  CAS  PubMed  Google Scholar 

  11. Wang L, Li C, Tian J, Liu J, Zhao Y, Yi Y, et al. Genome-wide transcriptional analysis of aristolochia manshuriensis induced gastric carcinoma. Pharm Biol 2020;58:98–106.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Ng AWT, Poon SL, Huang MN, Lim JQ, Boot A, Yu W, et al. Aristolochic acids and their derivatives are widely implicated in liver cancers in Taiwan and throughout Asia. Sci Transl Med 2017;9:eaan6446.

    Article  PubMed  Google Scholar 

  13. Chen CJ, Yang YH, Lin MH, Lee CP, Tsan YT, Lai MN, et al. Herbal medicine containing aristolochic acid and the risk of hepatocellular carcinoma in patients with hepatitis B virus infection. Int J Cancer 2018;143:1578–1587.

    Article  CAS  PubMed  Google Scholar 

  14. Chen CJ, Yang YH, Lin MH, Lee CP, Tsan YT, Lai MN, et al. Herbal medicine containing aristolochic acid and the risk of primary liver cancer in patients with hepatitis C virus infection. Cancer Epidemiol Biomarkers Prev 2019;28:1876–1883.

    Article  CAS  PubMed  Google Scholar 

  15. Lu ZN, Luo Q, Zhao LN, Shi Y, Wang N, Wang L, et al. The mutational features of aristolochic acid-induced mouse and human liver cancers. Hepatology 2020;71:929–942.

    Article  CAS  PubMed  Google Scholar 

  16. Yang L, Su T, Li XM, Wang X, Cai SQ, Meng LQ, et al. Aristolochic acid nephropathy: variation in presentation and prognosis. Nephrol Dial Transplant 2012;27:292–298.

    Article  CAS  PubMed  Google Scholar 

  17. Ministry of Health of the People’s Republic of China. Updated standards for the diagnosis and treatment of primary liver cancer. Chin J Hepatol (Chin) 2020;33:112–128.

    Google Scholar 

  18. Na YQ, Sun G, eds. Chinese diagnosis and treatment of urological diseases guide. Beijing: People’s Medical Publishing House; 2009:3–115.

    Google Scholar 

  19. Ban TH, Min JW, Seo C, Kim DR, Lee YH, Chung BH, et al. Update of aristolochic acid nephropathy in Korea. Kor J Intern Med 2018;33:961–969.

    Article  CAS  Google Scholar 

  20. Shan H, Tian W, Hong Y, Xu B, Wang C, Yu B, et al. Clinicopathologic characteristics and prognosis of upper tract urothelial carcinoma complicated with aristolochic acid nephropathy after radical nephroureterectomy. BMC Complement Med Ther 2020;20:166.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Zhang HM, Zhao XH, Sun ZH, Li GC, Liu GC, Sun LR, et al. Recognition of the toxicity of aristolochic acid. J Clin Pharm Ther 2019;44:157–162.

    Article  PubMed  Google Scholar 

  22. Hoang ML, Chen CH, Chen PC, Roberts NJ, Dickman KG, Yun BH, et al. Aristolochic acid in the etiology of renal cell carcinoma. Cancer Epidemiol Biomarkers Prev 2016;25:1600–1608.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Hu X, Shen J, Pu X, Zheng N, Deng Z, Zhang Z, et al. Urinary time- or dose-dependent metabolic biomarkers of aristolochic acid-induced nephrotoxicity in rats. Toxicol Sci 2017;156:123–132.

    CAS  PubMed  Google Scholar 

  24. Fang ZE, Guo Y, Wang Z, He T, Wang J, Bai Z, et al. Asari Radix et Rhizoma consumption lacks relevance for hepatocellular carcinoma in patients: a retrospective cohort study. Chin Herb Med 2022;14:470–475.

    PubMed  PubMed Central  Google Scholar 

  25. Xiong G, Yao L, Hong P, Yang L, Ci W, Liu L, et al. Aristolochic acid containing herbs induce gender-related oncological differences in upper tract urothelial carcinoma patients. Cancer Manag Res 2018;10:6627–6639.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Sun M, Zhang J, Zheng C, Liu Y, Lin F, Xu F, et al. Analysis of potential risk factors for cancer incidence in patients with aristolochic acid nephropathy from Wenzhou, China. Renal Failure 2015;37:209–213.

    Article  PubMed  Google Scholar 

  27. Bara TJr, Gurzu S, Sugimura H, Bara T, Beleaua MA, Jung I. A systematic review of the possible carcinogenic role of the aristolochic acid. Rom J Morphol Embryol 2017;58:41–44.

    PubMed  Google Scholar 

Download references

Acknowledgments

We would like to gratefully thank all patients for their trust and providing their respective data.

Author information

Authors and Affiliations

  1. Renal Division, Department of Medicine, Peking University First Hospital, Beijing, 100034, China

    Tao Su & Li Yang

  2. Department of Pharmacy, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, 400021, China

    Zhi-e Fang

  3. Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China

    Zhi-e Fang, Chun-yu Wang, Jia-bo Wang, Dong Ji, Zhao-fang Bai & Xiao-he Xiao

  4. China Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China

    Zhi-e Fang, Chun-yu Wang, Jia-bo Wang, Zhao-fang Bai & Xiao-he Xiao

  5. Phase I Clinical Trials Unit, Department of Medicine for Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China

    Yu-ming Guo

  6. Department of Pharmacy, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250000, China

    Chun-yu Wang

  7. National Key Laboratory of Kidney Diseases, Beijing, 100039, China

    Zhao-fang Bai & Xiao-he Xiao

Authors
  1. Tao Su
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  2. Zhi-e Fang
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  3. Yu-ming Guo
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  7. Zhao-fang Bai
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  8. Li Yang
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Contributions

Tao S and Fang ZE contributed equally to this work. Bai ZF, Yang L and Xiao XH contributed to the research conception and design. Su T, Fang ZE, and Guo YM participated in data interpretation and manuscript review and writing. Wang CY, Wang JB, and Ji D were responsible for data collection and analysis. All authors contributed to the scientific discussion of the data and of the manuscript.

Corresponding author

Correspondence to Xiao-he Xiao.

Ethics declarations

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Additional information

Supported by National Key Technology R&D Program (No. 2018ZX09101002-001-002), Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (No. ZYYCXTD-C-202005), the Science and Technology Project Affiliated to the Education Department of Chongqing Municipality (No. KJQN202215119)

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Su, T., Fang, Ze., Guo, Ym. et al. No Incidence of Liver Cancer Was Observed in A Retrospective Study of Patients with Aristolochic Acid Nephropathy. Chin. J. Integr. Med. 30, 99–106 (2024). https://doi.org/10.1007/s11655-023-3560-0

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  • DOI: https://doi.org/10.1007/s11655-023-3560-0

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