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World J Hepatol. 2021 Jul 27;13(7):747-762. doi: 10.4254/wjh.v13.i7.747.

Liver injury associated with drug intake during pregnancy.

World journal of hepatology

Priyanka Kamath, Ashwin Kamath, Sheetal D Ullal

Affiliations

  1. Department of Pharmacology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India - 575001.
  2. Department of Pharmacology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India - 575001. [email protected].

PMID: 34367496 PMCID: PMC8326163 DOI: 10.4254/wjh.v13.i7.747

Abstract

Drug use during pregnancy is not common. Drug-induced liver injury (DILI) is a potential complication that is rare but can adversely affect both the mother and the fetus. Although many drugs can directly cause hepatotoxicity, idiosyncratic liver injury is common in pregnancy. Underreporting of adverse drug reactions, lack of adequate literature regarding drug safety in pregnancy, and the inherent difficulty in diagnosing DILI during pregnancy make the management of this condition challenging. This review attempts to describe the existing literature regarding DILI in pregnancy, which is mainly in the form of case reports; several studies have looked at the safety of antithyroid drugs, antiretroviral drugs, and paracetamol, which have an indication for use in pregnancy; the relevant data from these studies with regard to DILI has been presented. In addition, the review describes the diagnosis of DILI, grading the disease severity, assessment of causality linking the drug to the adverse event, regulatory guidelines for evaluating the potential of drugs to cause liver injury, efforts to ensure better participation of women in clinical trials and studies in pregnant women population in particular, and the challenges involved in generating adequate research evidence. The establishment of DILI registries in various countries is an encouraging development; however, there is a need for promoting active, spontaneous reporting of adverse events during pregnancy to ensure rapid generation of evidence regarding the safety of a drug in pregnant women.

©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.

Keywords: Adverse effects; Drug induced liver injury; Liver failure; Pregnancy outcome; Pregnant women; Registries

Conflict of interest statement

Conflict-of-interest statement: Authors declare no conflict of interests for this article.

References

  1. BMJ Open. 2015 Jul 23;5(7):e007970 - PubMed
  2. Clin Toxicol (Phila). 2019 Aug;57(8):712-717 - PubMed
  3. HIV Med. 2007 Jan;8(1):64-9 - PubMed
  4. AIDS. 2010 Jan 2;24(1):109-14 - PubMed
  5. Cesk Patol. 2001 Jul;37(3):118-22 - PubMed
  6. Am J Gastroenterol. 2016 Jul;111(7):958-65 - PubMed
  7. Case Rep Gastroenterol. 2013 May 25;7(2):240-4 - PubMed
  8. J Hepatol. 2011 Sep;55(3):683-691 - PubMed
  9. Endocrine. 2010 Aug;38(1):24-8 - PubMed
  10. HIV Clin Trials. 2012 Jan-Feb;13(1):46-59 - PubMed
  11. Clin Liver Dis (Hoboken). 2019 Mar 04;13(2):51-57 - PubMed
  12. Clin Pharmacokinet. 2017 Nov;56(11):1303-1330 - PubMed
  13. Obstet Gynecol. 2010 Aug;116 Suppl 2:515-517 - PubMed
  14. J Gynecol Obstet Biol Reprod (Paris). 1990;19(2):192-6 - PubMed
  15. Med Mal Infect. 2012 Sep;42(9):421-8 - PubMed
  16. South Med J. 1990 Aug;83(8):953-5 - PubMed
  17. Clin Mol Hepatol. 2020 Apr;26(2):142-154 - PubMed
  18. Ann Saudi Med. 2014 Nov-Dec;34(6):541-3 - PubMed
  19. J Med Toxicol. 2012 Jun;8(2):176-8 - PubMed
  20. J Pediatr. 2014 Oct;165(4):672-7.e2 - PubMed
  21. Clin Pharmacokinet. 2018 Nov;57(11):1421-1433 - PubMed
  22. Obstet Gynecol. 2001 Nov;98(5 Pt 2):909-11 - PubMed
  23. Am J Obstet Gynecol. 1966 Jun 15;95(4):523-9 - PubMed
  24. Rev Bras Ginecol Obstet. 2008 Jan;30(1):19-24 - PubMed
  25. Przegl Lek. 1999;56(6):459-62 - PubMed
  26. Pharmacoepidemiol Drug Saf. 2011 Sep;20(9):895-902 - PubMed
  27. Clin Infect Dis. 2016 Mar 15;62(6):761-769 - PubMed
  28. BMC Psychiatry. 2020 Mar 12;20(1):118 - PubMed
  29. Clin Gastroenterol Hepatol. 2018 Sep;16(9):1495-1502 - PubMed
  30. Gut. 2014 Mar;63(3):451-7 - PubMed
  31. Ann Acad Med Singap. 2004 Mar;33(2):204-8 - PubMed
  32. Gastroenterology. 2013 Jun;144(7):1419-25, 1425.e1-3; quiz e19-20 - PubMed
  33. J Infect. 2012 Apr;64(4):409-16 - PubMed
  34. Arch Pediatr. 2011 Oct;18(10):1100-2 - PubMed
  35. PLoS One. 2020 Jun 2;15(6):e0234153 - PubMed
  36. J Antimicrob Chemother. 1994 Mar;33(3):387-401 - PubMed
  37. AIDS. 2009 Nov 27;23(18):2425-30 - PubMed
  38. Drug Saf. 2009;32(2):147-58 - PubMed
  39. Hepatology. 2017 Oct;66(4):1275-1285 - PubMed
  40. Gastroenterology. 2015 Jun;148(7):1340-52.e7 - PubMed
  41. Obstet Gynecol. 1993 Oct;82(4 Pt 2 Suppl):687-9 - PubMed
  42. Eur J Obstet Gynecol Reprod Biol. 2011 Jul;157(1):18-21 - PubMed
  43. Int J Clin Oncol. 2020 Jan;25(1):203-209 - PubMed
  44. Antimicrob Agents Chemother. 1977 Nov;12(5):630-5 - PubMed
  45. Ned Tijdschr Geneeskd. 2004 Oct 9;148(41):2021-5 - PubMed
  46. Obstet Gynecol. 2005 Nov;106(5 Pt 1):1032-8 - PubMed
  47. J Hepatol. 2019 Jun;70(6):1222-1261 - PubMed
  48. Anaesth Intensive Care. 2015 Nov;43(6):793-4 - PubMed
  49. Drug Metab Dispos. 2013 Feb;41(2):263-9 - PubMed
  50. Am J Gastroenterol. 2012 Sep;107(9):1380-7 - PubMed
  51. Surg Pathol Clin. 2018 Jun;11(2):297-311 - PubMed
  52. Front Pharmacol. 2019 Jul 29;10:853 - PubMed
  53. Hepatol Commun. 2017 Jun 28;1(6):494-500 - PubMed
  54. Clin Infect Dis. 2014 Dec 15;59 Suppl 7:S437-44 - PubMed
  55. HIV Med. 2007 Sep;8(6):357-66 - PubMed
  56. Br J Clin Pharmacol. 2004 Jul;58(1):71-80 - PubMed
  57. Hepatology. 2010 Dec;52(6):2065-76 - PubMed
  58. SAGE Open Med. 2020 Jun 20;8:2050312120935471 - PubMed
  59. Clin Liver Dis. 2017 Feb;21(1):103-113 - PubMed
  60. Arh Hig Rada Toksikol. 2009 Sep;60(3):357-61 - PubMed
  61. Drug Saf. 2017 Sep;40(9):783-787 - PubMed
  62. EBioMedicine. 2017 Dec;26:152-156 - PubMed
  63. Hum Reprod. 1999 Sep;14(9):2249-51 - PubMed
  64. J Endocrinol Invest. 1990 Dec;13(11):937-41 - PubMed
  65. Obstet Gynecol. 1997 Oct;90(4 Pt 2):658-9 - PubMed
  66. Int J Med Sci. 2018 May 22;15(8):796-801 - PubMed
  67. JGH Open. 2019 Oct 24;4(3):332-339 - PubMed
  68. Clin Investig. 1994 Oct;72(10):794-8 - PubMed
  69. Aust N Z J Obstet Gynaecol. 1994 May;34(2):211-3 - PubMed
  70. Braz J Infect Dis. 2007 Jun;11(3):314-7 - PubMed
  71. Ecotoxicol Environ Saf. 2012 Jun;80:280-7 - PubMed
  72. Gut. 2002 Dec;51(6):876-80 - PubMed
  73. Am J Obstet Gynecol. 2015 Apr;212(4):524.e1-7 - PubMed
  74. Ann Pharmacother. 2003 Feb;37(2):224-8 - PubMed
  75. Clin Pharmacol Ther. 2011 Jun;89(6):806-15 - PubMed
  76. Aust N Z J Obstet Gynaecol. 2006 Jun;46(3):256-7 - PubMed
  77. South Med J. 2005 Nov;98(11):1118-22 - PubMed
  78. Clin Exp Obstet Gynecol. 2002;29(4):304-5 - PubMed
  79. Am J Gastroenterol. 2014 Jul;109(7):950-66; quiz 967 - PubMed
  80. Orv Hetil. 2010 Mar 14;151(11):457-61 - PubMed
  81. Hepatology. 1994 Dec;20(6):1437-41 - PubMed
  82. Rheumatology (Oxford). 2018 Jul 1;57(suppl_5):v2-v8 - PubMed
  83. Gastroenterology. 2014 Apr;146(4):914-28 - PubMed
  84. Transplant Proc. 2013 Jun;45(5):2063-5 - PubMed
  85. Hum Reprod Update. 2016 Mar-Apr;22(2):240-59 - PubMed
  86. J Int Assoc Physicians AIDS Care (Chic). 2012 Mar-Apr;11(2):142-9 - PubMed
  87. J Clin Endocrinol Metab. 2016 Apr;101(4):1606-14 - PubMed
  88. J Clin Pharm Ther. 2007 Oct;32(5):483-7 - PubMed
  89. N Engl J Med. 2019 Oct 3;381(14):1333-1346 - PubMed
  90. Int J Infect Dis. 2020 Sep;98:138-143 - PubMed
  91. Expert Opin Drug Metab Toxicol. 2010 Jun;6(6):689-99 - PubMed
  92. N Engl J Med. 2019 Jul 18;381(3):264-273 - PubMed
  93. J Clin Pharm Ther. 2010 Jun;35(3):361-3 - PubMed
  94. BMC Complement Altern Med. 2013 Dec 12;13:355 - PubMed
  95. Drug Saf. 1996 Jul;15(1):79-85 - PubMed
  96. Curr Opin Gastroenterol. 2019 May;35(3):183-190 - PubMed
  97. Gastroenterol Jpn. 1989 Feb;24(1):65-9 - PubMed
  98. J Acquir Immune Defic Syndr. 2007 Apr 1;44(4):371-6 - PubMed
  99. Eur Thyroid J. 2012 Apr;1(1):41-4 - PubMed
  100. AIDS. 2005 May 20;19(8):795-9 - PubMed
  101. A A Pract. 2019 May 1;12(9):302-304 - PubMed
  102. BMC Pregnancy Childbirth. 2019 Jun 11;19(1):199 - PubMed
  103. Arch Gynecol Obstet. 2002 Jan;266(1):25-9 - PubMed
  104. Hepatol Commun. 2020 Mar 13;4(5):631-645 - PubMed
  105. Am J Obstet Gynecol. 1995 Jan;172(1 Pt 1):222-4 - PubMed
  106. Cochrane Database Syst Rev. 2019 Jul 05;7:CD012546 - PubMed
  107. Braz J Infect Dis. 2007 Dec;11(6):544-8 - PubMed
  108. S Afr Med J. 2012 Oct 08;102(11 Pt 1):855-9 - PubMed
  109. PLoS Med. 2016 Nov 1;13(11):e1002160 - PubMed
  110. BMJ Case Rep. 2014 Feb 27;2014: - PubMed
  111. Gastroenterology. 2019 Jun;156(8):2230-2241.e11 - PubMed
  112. HIV Med. 2006 May;7(4):255-60 - PubMed
  113. Public Health Rep. 1989 Mar-Apr;104(2):151-5 - PubMed
  114. N Engl J Med. 2011 Jul 7;365(1):11-20 - PubMed
  115. Obstet Med. 2016 Mar;9(1):21-7 - PubMed
  116. J Med Case Rep. 2011 Sep 19;5:461 - PubMed
  117. Interdiscip Sci. 2019 Jun;11(2):273-281 - PubMed
  118. Transplant Proc. 2018 Dec;50(10):3995-3999 - PubMed
  119. Medicine (Baltimore). 2017 Dec;96(52):e9346 - PubMed
  120. J Reprod Med. 2002 Jul;47(7):584-6 - PubMed

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