Skip to main content

Advertisement

SpringerLink
Log in

Hepatic dysfunction secondary to Kawasaki disease: characteristics, etiology and predictive role in coronary artery abnormalities

  • Original Article
  • Published:
Clinical and Experimental Medicine Aims and scope Submit manuscript

Abstract

Coronary artery abnormalities (CAAs) are prominent during the acute Kawasaki disease (KD) episode and represent the major contributors to the long-term prognosis. Several meta-analysis and published scoring systems have identified hepatic dysfunction as an independent predictor of CAA risks. The medical records of 210 KD children were reviewed. Blood samples were collected from all subjects at 24 h pre-therapy and 48 h post-therapy, respectively. Liver function test (LFT) and inflammatory mediators were detected. Multivariate logistic regression analysis was conducted to identify the reliable biomarkers predicting whether CAAs existed or not in KD patients. 90.95% of KD patients had at least 1 abnormal LFT. Hypoalbuminemia was the most prevalent type of hepatic dysfunction, followed by elevated aspartate aminotransferase, low TP, low A/G and hyperbilirubinemia, respectively. The elevated inflammatory mediators (procalcitonin and C-reactive protein) and moderate dose of aspirin played a synthetic role in hepatic dysfunction secondary to KD. However, LFT presented no significant differences between infectious and noninfectious conditions. By a multivariate analysis, a lower albumin/globulin ratio (A/G, OR 13.50, 95% CI 3.944–46.23) served as an independent predictor of CAAs and had a sensitivity of 56.25%, and a specificity of 61.11% at a cutoff value of < 1.48. In conclusion, hepatic dysfunction is a common complication during the acute KD episode, characterized by elevated serum liver enzymes, hypoalbuminemia and hyperbilirubinemia. Systemic inflammation and aspirin, rather than infectious agents, are both the major contributors of hepatic dysfunction secondary to KD. A lower A/G serves as an independent predictor of CAAs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Wu MH, Lin MT, Chen HC, Kao FY, Huang SK. Postnatal risk of acquiring Kawasaki disease: a nationwide birth cohort database study. J Pediatr. 2017;180:80–6.

    Article  PubMed  Google Scholar 

  2. Makino N, Nakamura Y, Yashiro M, et al. Descriptive epidemiology of Kawasaki disease in Japan, 2011–2012: from the results of the 22nd nationwide survey. J Epidemiol. 2015;25:239–45.

    Article  PubMed  Google Scholar 

  3. McCrindle BW, Rowley AH, Newburger JW, et al. American heart association rheumatic fever, endocarditis, and kawasaki disease committee of the council on cardiovascular disease in the young; council on cardiovascular and stroke nursing; council on cardiovascular surgery and anesthesia; and council on epidemiology and prevention. Diagnosis, treatment, and long-term management of kawasaki disease: a scientific statement for health professionals from the american heart association. Circulation. 2017;135:e927–99.

    Article  PubMed  Google Scholar 

  4. Hu P, Jiang GM, Wu Y, et al. TNF-α is superior to conventional inflammatory mediators in forecasting IVIG nonresponse and coronary arteritis in Chinese children with Kawasaki disease. Clin Chim Acta. 2017;471:76–80.

    Article  CAS  PubMed  Google Scholar 

  5. Kato H, Sugimura T, Akagi T, et al. Long-term consequences of Kawasaki disease. A 10-to 21-year follow-up study of 594 patients. Circulation. 1996;94:1379–85.

    Article  CAS  PubMed  Google Scholar 

  6. Kobayashi T, Inoue Y, Takeuchi K, et al. Prediction of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease. Circulation. 2006;113:2606–12.

    Article  PubMed  Google Scholar 

  7. Egami K, Muta H, Ishii M, et al. Prediction of resistance to intravenous immunoglobulin treatment in patients with Kawasaki disease. J Pediatr. 2006;149:237–40.

    Article  CAS  PubMed  Google Scholar 

  8. Bai L, Feng T, Yang L, et al. Retrospective analysis of risk factors associated with Kawasaki disease in China. Oncotarget. 2017;8:54357–63.

    PubMed  PubMed Central  Google Scholar 

  9. Eladawy M, Dominguez SR, Anderson MS, Glodé MP. Abnormal liver panel in acute kawasaki disease. Pediatr Infect Dis J. 2011;30:141–4.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Kobayashi T, Fuse S, Sakamoto N, et al. Z Score Project Investigators. A new Z score curve of the coronary arterial internal diameter using the lambda-mu-sigma method in a pediatric population. J Am Soc Echocardiogr. 2016;29:794–801.

    Article  PubMed  Google Scholar 

  11. Wu Y, Liu FF, Xu Y, et al. Interleukin-6 is prone to be a candidate biomarker for predicting incomplete and IVIG nonresponsive Kawasaki disease rather than coronary artery aneurysm. Clin Exp Med. 2019;19:173–81.

    Article  PubMed  CAS  Google Scholar 

  12. Burns JC, Glodé MP. Kawasaki syndrome. Lancet. 2004;364:533–44.

    Article  PubMed  Google Scholar 

  13. Tizard E. Complications of Kawasaki disease. Curr. Paediatr. 2005;15:62–8.

    Google Scholar 

  14. Ohshio G, Furukawa F, Fujiwara H, Hamashima Y. Hepatomegaly and splenomegaly in Kawasaki disease. Pediatr Pathol. 1985;4:257–64.

    Article  CAS  PubMed  Google Scholar 

  15. Bader-Meunier B, Hadchouel M, Fabre M, Arnoud MD, Dommergues JP. Intrahepatic bile duct damage in children with Kawasaki disease. J Pediatr. 1992;120:750–2.

    Article  CAS  PubMed  Google Scholar 

  16. Tremoulet AH, Jain S, Chandrasekar D, Sun X, Sato Y, Burns JC. Evolution of laboratory values in patients with Kawasaki disease. Pediatr Infect Dis J. 2011;30:1022–6.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Okada Y, Minakami H, Tomomasa T, et al. Serum procalcitonin concentration in patients with Kawasaki disease. J Infect. 2004;48:199–205.

    Article  PubMed  Google Scholar 

  18. Samadli S, Liu FF, Mammadov G, et al. The time option of IVIG treatment is associated with therapeutic responsiveness and coronary artery abnormalities but not with clinical classification in the acute episode of Kawasaki disease. Pediatr Rheumatol Online J. 2019;17:53.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Si F, Wu Y, Gao F, Feng S, Liu R, Yi Q. Relationship between IL-27 and coronary arterial lesions in children with Kawasaki disease. Clin Exp Med. 2017;17:451–7.

    Article  CAS  PubMed  Google Scholar 

  20. Su Y, Feng S, Luo L, Liu R, Yi Q. Association between IL-35 and coronary arterial lesions in children with Kawasaki disease. Clin Exp Med. 2019;19:87–92.

    Article  CAS  PubMed  Google Scholar 

  21. Amano S, Hazama F, Hamashima Y. Pathology of Kawasaki disease: II. Distribution and incidence of the vascular lesions. Jpn Circ J. 1979;43:741-8.

    Article  CAS  PubMed  Google Scholar 

  22. Seki S, Habu Y, Kawamura T, et al. The liver as a crucial organ in the first line of host defense: the roles of Kupffer cells, natural killer (NK) cells and NK1.1 Ag + T cells in T helper 1 immune responses. Immunol Rev. 2000;174:35–46.

    Article  CAS  PubMed  Google Scholar 

  23. Ishihara K, Miyazaki A, Nabe T, et al. Group IVA phospholipase A2 participates in the progression of hepatic fibrosis. FASEB J. 2012;26:4111–21.

    Article  CAS  PubMed  Google Scholar 

  24. Zalewski A, Macphee C. Role of lipoprotein-associated phospholipase A2 in atherosclerosis: biology, epidemiology, and possible therapeutic target. Arterioscler Thromb Vasc Biol. 2005;25:923–31.

    Article  CAS  PubMed  Google Scholar 

  25. Tanaseanu C, Tudor S, Tamsulea I, Marta D, Manea G, Moldoveanu E. Vascular endothelial growth factor, lipoporotein-associated phospholipase A2, sP-selectin and antiphospholipid antibodies, biological markers with prognostic value in pulmonary hypertension associated with chronic obstructive pulmonary disease and systemic lupus erithematosus. Eur J Med Res. 2007;12:145–51.

    CAS  PubMed  Google Scholar 

  26. Prete M, Fatone MC, Vacca A, Racanelli V, Perosa F. Severe pulmonary hypertension as the initial manifestation of systemic lupus erythematosus: a case report and review of the literature. Clin Exp Rheumatol. 2014;32:267–74.

    CAS  PubMed  Google Scholar 

  27. Sauer M, Doß S, Ehler J, Mencke T, Wagner NM. Procalcitonin impairs liver cell viability and function in vitro: a potential new mechanism of liver dysfunction and failure during sepsis? Biomed Res Int. 2017;2017:6130725.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Principi N, Rigante D, Esposito S. The role of infection in Kawasaki syndrome. J Infect. 2013;67:1–10.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Hall M, Hoyt L, Ferrieri P, Schlievert PM, Jenson HB. Kawasaki syndrome-like illness associated with infection caused by enterotoxin B-secreting Staphylococcus aureus. Clin Infect Dis. 1999;29:586–9.

    Article  CAS  PubMed  Google Scholar 

  30. Matsubara K, Fukaya T, Miwa K, et al. Development of serum IgM antibodies against superantigens of Staphylococcus aureus and Streptococcus pyogenes in Kawasaki disease. Clin Exp Immunol. 2006;143:427–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kanegane H, Tsuji T, Seki H, et al. Kawasaki disease with a concomitant primary Epstein-Barr virus infection. Acta Paediatr Jpn. 1994;36:713–6.

    Article  CAS  PubMed  Google Scholar 

  32. Embil JA, McFarlane ES, Murphy DM, Krause VW, Stewart HB. Adenovirus type 2 isolated from a patient with fatal Kawasaki disease. Can Med Assoc J. 1985;132:1400.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Hagiwara K, Komura H, Kishi F, Kaji T, Yoshida T. Isolation of human herpesvirus-6 from an infant with Kawasaki disease. Eur J Pediatr. 1992;151:867–8.

    Article  CAS  PubMed  Google Scholar 

  34. Johnson D, Azimi P. Kawasaki disease associated with Klebsiella pneumoniae bacteremia and parainfluenza type 3 virus infection. Pediatr Infect Dis. 1985;4:100.

    Article  CAS  PubMed  Google Scholar 

  35. Matsuno S, Utagawa E, Sugiura A. Association of rotavirus infection with Kawasaki syndrome. J Infect Dis. 1983;148:177.

    Article  CAS  PubMed  Google Scholar 

  36. Hu P, Wang J, Fan XC, Hu B, Lu L. Hypertension triggers the rupture of coronary artery aneurysm in an 8-year-old boy with Kawasaki disease. J Clin Hypertens (Greenwich). 2014;16:766–7.

    Article  PubMed Central  Google Scholar 

  37. Hu P, Guan Y, Fan XC, Lu FY, Song LM. Incomplete Kawasaki disease induced by measles in a 6-month-old male infant. Int J Dermatol. 2016;55:e34–6.

    Article  PubMed  Google Scholar 

  38. Peng Y, Liu X, Duan Z, et al. Prevalence and characteristics of arthritis in Kawasaki disease: a Chinese cohort study. Clin Exp Med. 2019;19:167–72.

    Article  PubMed  Google Scholar 

  39. Jordan-Villegas A, Chang ML, Ramilo O, Mejías A. Concomitant respiratory viral infections in children with Kawasaki disease. Pediatr Infect Dis J. 2010;29:770–2.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Ramphul K, Mejias SG. Kawasaki disease: a comprehensive review. Arch Med Sci Atheroscler Dis. 2018;3:e41–5.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Onouchi Z, Kawasaki T. Overview of pharmacological treatment of Kawasaki disease. Drugs. 1999;58:813–22.

    Article  CAS  PubMed  Google Scholar 

  42. Baumer JH, Love SJ, Gupta A, Haines LC, Maconochie I, Dua JS. Salicylate for the treatment of Kawasaki disease in children. Cochrane Database Syst Rev. 2006;4:CD004175.

    Google Scholar 

  43. Matsubara T, Mason W, Kashani IA, Kligerman M, Burns JC. Gastrointestinal hemorrhage complicating aspirin therapy in acute Kawasaki disease. J Pediatr. 1996;128:701–3.

    Article  CAS  PubMed  Google Scholar 

  44. Lee JH, Hung HY, Huang FY. Kawasaki disease with Reye syndrome: report of one case. Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi. 1992;33:67–71.

    CAS  PubMed  Google Scholar 

  45. Aithal GP, Day CP. Nonsteroidal anti-inflammatory drug-induced hepatotoxicity. Clin Liver Dis. 2007;11:563–75.

    Article  PubMed  Google Scholar 

  46. Chen J, Liu Y, Liu W, Wu Z. A meta-analysis of the biomarkers associated with coronary artery lesions secondary to Kawasaki disease in Chinese children. J Huazhong Univ Sci Technolog Med Sci. 2011;31:705.

    Article  CAS  PubMed  Google Scholar 

  47. Lin MT, Chang CH, Sun LC, et al. Risk factors and derived formosa score for intravenous immunoglobulin unresponsiveness in Taiwanese children with Kawasaki disease. J Formos Med Assoc. 2016;115:350–5.

    Article  CAS  PubMed  Google Scholar 

  48. Tang Y, Yan W, Sun L, et al. Prediction of intravenous immunoglobulin resistance in Kawasaki disease in an East China population. Clin Rheumatol. 2016;35:2771–6.

    Article  PubMed  Google Scholar 

  49. Hua W, Ma F, Wang Y, et al. A new scoring system to predict Kawasaki disease with coronary artery lesions. Clin Rheumatol. 2019;38:1099–107.

    Article  PubMed  Google Scholar 

  50. Kuwabara M, Yashiro M, Kotani K, et al. Cardiac lesions and initial laboratory data in Kawasaki disease: a nationwide survey in Japan. J Epidemiol. 2015;25:189–93.

    Article  PubMed  Google Scholar 

  51. Nicholson JP, Wolmarans MR, Park GR. The role of albumin in critical illness. Br J Anaesth. 2000;85:599–610.

    Article  CAS  PubMed  Google Scholar 

  52. Ballmer PE. Causes and mechanisms of hypoalbuminaemia. Clin Nutr. 2001;20:271–3.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This study was supported by the New Technology Project of the First Affiliated Hospital, Anhui Medical University (2014-01).

Author information

Author notes

  1. Goshgar Mammadov, Hui Hui Liu and Wei Xia Chen: contributed equally to this work and should be considered co-first authors.

Authors and Affiliations

  1. Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, No. 218 Ji-Xi Road, Hefei, 230022, People’s Republic of China

    Goshgar Mammadov, Hui Hui Liu, Wei Xia Chen, Guo Zhen Fan, Rui Xue Li, Fei Fei Liu, Sama Samadli, Jing Jing Wang, Yang Fang Wu, Huang Huang Luo, Dong Dong Zhang, Wei Wei & Peng Hu

Authors
  1. Goshgar Mammadov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hui Hui Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wei Xia Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Guo Zhen Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rui Xue Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fei Fei Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sama Samadli
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jing Jing Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yang Fang Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Huang Huang Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Dong Dong Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Wei Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Peng Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by GM, HHL and WXC. The first draft of the manuscript was written by GM, HHL and WXC and all authors commented on previous versions of the manuscript. All authors contributed to the data interpretation and manuscript revision. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Peng Hu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The research was in compliance with the Declaration of Helsinki. Approval for this research was acquired from the Medical Ethic Committee of the First Affiliated Hospital of Anhui Medical University (Code number; LLSC/20150009).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mammadov, G., Liu, H.H., Chen, W.X. et al. Hepatic dysfunction secondary to Kawasaki disease: characteristics, etiology and predictive role in coronary artery abnormalities. Clin Exp Med 20, 21–30 (2020). https://doi.org/10.1007/s10238-019-00596-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10238-019-00596-1

Keywords

Search

Navigation