Home⇛The PCMC Journal⇛vol. 20 no. 1 (2024)

A systematic review on the effectiveness of N-acetylcysteine in children with dengue-associated liver injury

DJ G Leaño | Meadina G Cruz

Discipline: medicine by specialism

 

Abstract:

OBJECTIVES: This study aimed to determine the effectiveness of N-acetylcysteine (NAC) in reversal of liver enzyme abnormalities among pediatric patients with dengue induced liver injury. MATERIALS AND METHODS: The preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P 2020) declaration was used to create this systematic review. The study population included children (<18 years old) diagnosed with dengue-associated Liver Injury and given NAC. The outcome of interest was full recovery. A search was performed in PubMed/MEDLINE, EMBASE, Google Scholar, HERDIN PLUS, WPRIM, clinicaltrials.gov, and Cochrane databases on March 2023. The New Castle-Ottawa Quality Assessment Scale was adapted for risk of bias assessment for cohort studies. RESULTS: Three case series and one pre-post cohort study published from 2013 to 2022 were included. The studies were of acceptable quality. In two studies with overall 10 pediatric patients given NAC for dengue-related ALF, all recovered without adverse events. In one study with 4 patients given NAC, half survived with their liver function tests returning to normal values. Finally, in one comparative study, the durations of time before the liver function tests returned to normal levels, and the mortality rates between those treated with and without N-acetyl cysteine were not significantly different. All studies reported no occurrence of adverse drug reaction related to NAC. CONCLUSION: : This systematic review shows limited evidence on the effectiveness of NAC in the reversal of liver enzymes among pediatric patients because of the low incidence of dengue induced liver injury seen in observational studies. Given that NAC is reported by all four studies to be accessible, effective, and with no attributable adverse events, its use can be considered. However, clinicians must still be cautioned given the limited available evidence.



References:

  1. Undurraga EA, Edillo FE, Erasmo JN, Alera MT, Yoon IK, Largo FM, Shepard DS. Disease burden of dengue in the Philippines: adjusting for underreporting by comparing active and passive dengue surveillance in Punta Princesa, Cebu City. Am. J. Trop. Med. Hyg. 2017 Apr 4;96(4):887.
  2. Dengue and severe dengue [Internet]. World Health Organization. Available from: https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue
  3. Schaefer TJ, Panda PK, Wolford RW. Dengue fever [Internet]. 2022.
  4. Samanta J, Sharma V. Dengue and its effects on liver. World J Clin Cases. 2015 Feb 16;3(2):125-31. doi: 10.12998/wjcc.v3.i2.125. PMID: 25685758; PMCID: PMC4317605.
  5. Senanayake MP, Jayamanne MD, Kankananarachchi I. N-acetylcysteine in children with acute liver failure complicating dengue viral infection. Ceylon Med J. 2013 Jun;58(2):80-2. doi: 10.4038/cmj.v58i2.5684. PMID: 23817939.
  6. Dissanayake DMDIB, Gunaratne WMSN, Kumarihamy KWMPP, Kularatne SAM, Kumarasiri PVR. Use of intravenous N-acetylcysteine in acute severe hepatitis due to severe dengue infection: a case series. BMC Infect Dis. 2021 Sep 20;21(1):978. doi: 10.1186/s12879-021-06681-9. PMID: 34544380; PMCID: PMC8454086.
  7. Lim G, Lee JH. N-acetylcysteine in children with dengue-associated liver failure: a case report. J Trop Pediatr. 2012 Oct;58(5):409-13. doi: 10.1093/tropej/fmr108. Epub 2011 Dec 23. PMID: 22199018.
  8. Laoprasopwattana K, Jundee P, Pruekprasert P, Geater A. Outcome of Severe Dengue Viral Infection-caused Acute Liver Failure in Thai Children. J Trop Pediatr. 2016 Jun;62(3):200-5. doi: 10.1093/tropej/fmv099. Epub 2016 Feb 6. PMID: 26851434.
  9. Tafere GG, Wondafrash DZ, Demoz FB. Repurposing of N-Acetylcysteine for the Treatment of Dengue Virus-Induced Acute Liver Failure. Hepat Med. 2020 Nov 3;12:173-178. doi: 10.2147/HMER.S263840. PMID: 33177895; PMCID: PMC7650016.
  10. Tan JM, Tan NW, Ong C, Thoon KC, Chong CY. Dengue Fever Associated Liver Failure. Pediatric Infect Dis. 2016;1(31):2573-0282.
  11. Medimarketing Inc. Search Drug Information, Interactions, Images, Dosage & Side Effects. MIMS Philippine [Internet]. 2023/ Available from: https://www.mims.com/philippines/
  12. Ong EP, Obeles AJT, Ong BAG, Tantengco OAG. Perspectives and lessons from the Philippines’ decades-long battle with dengue. Lancet Reg Health West Pac. 2022 Jun 24;24:100505. doi: 10.1016/j.lanwpc.2022.100505. PMID: 35789734; PMCID: PMC9249805.
  13. Sharma PK, Kumar M, Sahani A, Goyal R, Aggarwal GK, Kumar V. Severe hepatic-neurological complications of dengue fever in children from a tertiary care center in North India. Age (years). 2016 May 1;5:0-75.
  14. Laoprasopwattana K, Khantee P, Saelim K, Geater A. Mortality Rates of Severe Dengue Viral Infection Before and After Implementation of a Revised Guideline for Severe Dengue. Pediatr Infect Dis J. 2022 Mar 1;41(3):211-216. doi: 10.1097/INF.0000000000003411. PMID: 34840312.
  15. Chongsrisawat V, Hutagalung Y, Poovorawan Y. Liver function test results and outcomes in children with acute liver failure due to dengue infection. Southeast Asian J Trop Med Public Health. 2009 Jan;40(1):47-53. PMID: 19323033.
  16. Seneviratne SL, Malavige GN, de Silva HJ. Pathogenesis of liver involvement during dengue viral infections. Trans R Soc Trop Med Hyg. 2006 Jul;100(7):608-14. doi: 10.1016/j.trstmh.2005.10.007. Epub 2006 Feb 17. PMID: 16483623.
  17. Marianneau P, Cardona A, Edelman L, Deubel V, Desprès P. Dengue virus replication in human hepatoma cells activates NF-kappaB which in turn induces apoptotic cell death. J Virol. 1997 Apr;71(4):3244-9. doi: 10.1128/JVI.71.4.3244-3249.1997. PMID: 9060688; PMCID: PMC191457.
  18. Pagliari C, Quaresma JA, Fernandes ER, Stegun FW, Brasil RA, de Andrade HF Jr, Barros V, Vasconcelos PF, Duarte MI. Immunopathogenesis of dengue hemorrhagic fever: contribution to the study of human liver lesions. J Med Virol. 2014 Jul;86(7):1193-7. doi: 10.1002/jmv.23758. Epub 2013 Sep 23. PMID: 24114877.
  19. Chandrasena L, De Silva A, De Mel C, Peiris H, Abesuriya V, De Mel S, Seneviratne S, Bandara S. Glutathione enzymes and liver injury in acute dengue viral infection. J.Biosci. 2019 Oct 18;7(10):61.
  20. Guabiraba R, Besnard AG, Marques RE, Maillet I, Fagundes CT, Conceição TM, Rust NM, Charreau S, Paris I, Lecron JC, Renauld JC, Quesniaux V, Da Poian AT, Arruda LB, Souza DG, Ryffel B, Teixeira MM. IL-22 modulates IL-17A production and controls inflammation and tissue damage in experimental dengue infection. Eur J Immunol. 2013 Jun;43(6):1529-44. doi: 10.1002/eji.201243229. Epub 2013 Apr 17. PMID: 23505056.
  21. Chia PY, Thein TL, Ong SWX, Lye DC, Leo YS. Severe dengue and liver involvement: an overview and review of the literature. Expert Rev Anti Infect Ther. 2020 Mar;18(3):181-189. doi: 10.1080/14787210.2020.1720652. Epub 2020 Feb 3. PMID: 31971031.
  22. World Health Organization. Global strategy for dengue prevention and control 2012-2020.
  23. Kumarasena RS, Mananjala Senanayake S, Sivaraman K, de Silva AP, Dassanayake AS, Premaratna R, Wijesiriwardena B, de Silva HJ. Intravenous N-acetylcysteine in dengue-associated acute liver failure. Hepatol Int. 2010 May 28;4(2):533-4. doi: 10.1007/s12072-010-9176-4. PMID: 20827413; PMCID: PMC2900558.
  24. Abeysekera RA, Illangasekera U, Jayalath T, Sandeepana AG, Kularatne SA. Successful use of intravenous N-acetylcysteine in dengue haemorrhagic fever with acute liver failure. Ceylon Med J. 2012 Dec;57(4):166-7. doi: 10.4038/cmj.v57i4.5085. PMID: 23292059.

Tools


Copyright © 2024  KITE Digital Educational Solutions |  Exclusively distributed by CE-Logic