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Semin Liver Dis 2024; 44(01): 001-022
DOI: 10.1055/s-0044-1779520
Review Article

UDCA for Drug-Induced Liver Disease: Clinical and Pathophysiological Basis

Fernando Bessone
1   Hospital Provincial del Centenario, Facultad de Ciencias Médicas, Servicio de Gastroenterología y Hepatología, Universidad Nacional de Rosario, Rosario, Argentina
,
Geraldine L. Hillotte
2   Instituto de Fisiología Experimental (IFISE-CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina
,
Natalia Ahumada
1   Hospital Provincial del Centenario, Facultad de Ciencias Médicas, Servicio de Gastroenterología y Hepatología, Universidad Nacional de Rosario, Rosario, Argentina
,
Fernanda Jaureguizahar
1   Hospital Provincial del Centenario, Facultad de Ciencias Médicas, Servicio de Gastroenterología y Hepatología, Universidad Nacional de Rosario, Rosario, Argentina
,
Anabela C. Medeot
,
Marcelo G. Roma
2   Instituto de Fisiología Experimental (IFISE-CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina
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Abstract

Drug-induced liver injury (DILI) is an adverse reaction to medications and other xenobiotics that leads to liver dysfunction. Based on differential clinical patterns of injury, DILI is classified into hepatocellular, cholestatic, and mixed types; although hepatocellular DILI is associated with inflammation, necrosis, and apoptosis, cholestatic DILI is associated with bile plugs and bile duct paucity. Ursodeoxycholic acid (UDCA) has been empirically used as a supportive drug mainly in cholestatic DILI, but both curative and prophylactic beneficial effects have been observed for hepatocellular DILI as well, according to preliminary clinical studies. This could reflect the fact that UDCA has a plethora of beneficial effects potentially useful to treat the wide range of injuries with different etiologies and pathomechanisms occurring in both types of DILI, including anticholestatic, antioxidant, anti-inflammatory, antiapoptotic, antinecrotic, mitoprotective, endoplasmic reticulum stress alleviating, and immunomodulatory properties. In this review, a revision of the literature has been performed to evaluate the efficacy of UDCA across the whole DILI spectrum, and these findings were associated with the multiple mechanisms of UDCA hepatoprotection. This should help better rationalize and systematize the use of this versatile and safe hepatoprotector in each type of DILI scenarios.

Keywords

ursodeoxycholic acid - hepatotoxicity - cholestatic DILI - hepatocellular DILI


Publication History

Article published online:
20 February 2024

© 2024. Thieme. All rights reserved.

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  • References

  • 1 Vuppalanchi R, Liangpunsakul S, Chalasani N. Etiology of new-onset jaundice: how often is it caused by idiosyncratic drug-induced liver injury in the United States?. Am J Gastroenterol 2007; 102 (03) 558-562 , quiz 693
    CrossrefPubMedGoogle Scholar
  • 2 Friis H, Andreasen PB. Drug-induced hepatic injury: an analysis of 1100 cases reported to the Danish Committee on Adverse Drug Reactions between 1978 and 1987. J Intern Med 1992; 232 (02) 133-138
    CrossrefPubMedGoogle Scholar
  • 3 Weiler N, Schlotmann A, Schnitzbauer AA, Zeuzem S, Welker MW. The epidemiology of acute liver failure. Dtsch Arztebl Int 2020; 117 (04) 43-50
    CrossrefPubMedGoogle Scholar
  • 4 Norman BH. Drug induced liver injury (DILI). Mechanisms and medicinal chemistry avoidance/mitigation strategies. J Med Chem 2020; 63 (20) 11397-11419
    CrossrefPubMedGoogle Scholar
  • 5 Chalasani NP, Hayashi PH, Bonkovsky HL, Navarro VJ, Lee WM, Fontana RJ. Practice Parameters Committee of the American College of Gastroenterology. ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol 2014; 109 (07) 950-966 , quiz 967
    CrossrefPubMedGoogle Scholar
  • 6 Kleiner DE, Chalasani NP, Lee WM. et al; Drug-Induced Liver Injury Network (DILIN). Hepatic histological findings in suspected drug-induced liver injury: systematic evaluation and clinical associations. Hepatology 2014; 59 (02) 661-670
    CrossrefPubMedGoogle Scholar
  • 7 Giordano C, Rivas J, Zervos X. An update on treatment of drug-induced liver injury. J Clin Transl Hepatol 2014; 2 (02) 74-79
    PubMedGoogle Scholar
  • 8 Hu PF, Xie WF. Corticosteroid therapy in drug-induced liver injury: pros and cons. J Dig Dis 2019; 20 (03) 122-126
    CrossrefPubMedGoogle Scholar
  • 9 Simental-Mendía M, Sánchez-García A, Simental-Mendía LE. Effect of ursodeoxycholic acid on liver markers: a systematic review and meta-analysis of randomized placebo-controlled clinical trials. Br J Clin Pharmacol 2020; 86 (08) 1476-1488
    CrossrefPubMedGoogle Scholar
  • 10 Reardon J, Hussaini T, Alsahafi M. et al. Ursodeoxycholic acid in treatment of non-cholestatic liver diseases: a systematic review. J Clin Transl Hepatol 2016; 4 (03) 192-205
    PubMedGoogle Scholar
  • 11 Huang F. Ursodeoxycholic acid as a potential alternative therapeutic approach for neurodegenerative disorders: effects on cell apoptosis, oxidative stress and inflammation in the brain. Brain Behav Immun Health 2021; 18: 100348
    CrossrefPubMedGoogle Scholar
  • 12 Kusaczuk M. Tauroursodeoxycholate-bile acid with chaperoning activity: molecular and cellular effects and therapeutic perspectives. Cells 2019; 8 (12) 1471
    CrossrefPubMedGoogle Scholar
  • 13 Robles-Díaz M, Nezic L, Vujic-Aleksic V, Björnsson ES. Role of ursodeoxycholic acid in treating and preventing idiosyncratic drug-induced liver injury. A systematic review. Front Pharmacol 2021; 12: 744488
    CrossrefPubMedGoogle Scholar
  • 14 Fontana RJ, Liou I, Reuben A. et al. AASLD practice guidance on drug, herbal, and dietary supplement-induced liver injury. Hepatology 2023; 77 (03) 1036-1065
    CrossrefPubMedGoogle Scholar
  • 15 Bessone F, Hernandez N, Tagle M. et al. Drug-induced liver injury: a management position paper from the Latin American Association for Study of the liver. Ann Hepatol 2021; 24: 100321
    CrossrefPubMedGoogle Scholar
  • 16 Salmon L, Montet JC, Oddoze C, Montet AM, Portugal H, Michel BF. [Ursodeoxycholic acid and prevention of tacrine-induced hepatotoxicity: a pilot study]. Therapie 2001; 56 (01) 29-34
    PubMedGoogle Scholar
  • 17 Saito Z, Kaneko Y, Kinoshita A. et al. Effectiveness of hepatoprotective drugs for anti-tuberculosis drug-induced hepatotoxicity: a retrospective analysis. BMC Infect Dis 2016; 16 (01) 668
    CrossrefPubMedGoogle Scholar
  • 18 Lee J, Ji SC, Kim B. et al. Exploration of biomarkers for amoxicillin/clavulanate-induced liver injury: multi-omics approaches. Clin Transl Sci 2017; 10 (03) 163-171
    CrossrefPubMedGoogle Scholar
  • 19 Kim DJ, Chung H, Ji SC. et al. Ursodeoxycholic acid exerts hepatoprotective effects by regulating amino acid, flavonoid, and fatty acid metabolic pathways. Metabolomics 2019; 15 (03) 30
    CrossrefPubMedGoogle Scholar
  • 20 Singh C, Bishop P, Willson R. Extreme hyperbilirubinemia associated with the use of anabolic steroids, health/nutritional supplements, and ethanol: response to ursodeoxycholic acid treatment. Am J Gastroenterol 1996; 91 (04) 783-785
    PubMedGoogle Scholar
  • 21 Kojima M, Kamoi K, Ukimura O. et al. Clinical utility of ursodeoxycholic acid in preventing flutamide-induced hepatopathy in patients with prostate cancer: a preliminary study. Int J Urol 2002; 9 (01) 42-46
    CrossrefPubMedGoogle Scholar
  • 22 Mohammed Saif M, Farid SF, Khaleel SA, Sabry NA, El-Sayed MH. Hepatoprotective efficacy of ursodeoxycholic acid in pediatrics acute lymphoblastic leukemia. Pediatr Hematol Oncol 2012; 29 (07) 627-632
    CrossrefPubMedGoogle Scholar
  • 23 Ito T, Ozaki Y, Son Y. et al. Combined use of ursodeoxycholic acid and bosentan prevents liver toxicity caused by endothelin receptor antagonist bosentan monotherapy: two case reports. J Med Case Rep 2014; 8: 250
    CrossrefPubMedGoogle Scholar
  • 24 European Association for the Study of the Liver. Clinical practice guideline panel: chair; panel members; EASL Governing Board representative. EASL clinical practice guidelines: drug-induced liver injury. J Hepatol 2019; 70 (06) 1222-1261
    CrossrefPubMedGoogle Scholar
  • 25 Devarbhavi H, Aithal G, Treeprasertsuk S. et al; Asia Pacific Association of Study of Liver. Drug-induced liver injury: Asia Pacific Association of Study of Liver consensus guidelines. Hepatol Int 2021; 15 (02) 258-282
    CrossrefPubMedGoogle Scholar
  • 26 Aithal GP, Watkins PB, Andrade RJ. et al. Case definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther 2011; 89 (06) 806-815
    CrossrefPubMedGoogle Scholar
  • 27 Danan G, Benichou C. Causality assessment of adverse reactions to drugs–I. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries. J Clin Epidemiol 1993; 46 (11) 1323-1330
    CrossrefPubMedGoogle Scholar
  • 28 Schölmerich J, Becher MS, Schmidt K. et al. Influence of hydroxylation and conjugation of bile salts on their membrane-damaging properties–studies on isolated hepatocytes and lipid membrane vesicles. Hepatology 1984; 4 (04) 661-666
    CrossrefPubMedGoogle Scholar
  • 29 Perez MJ, Briz O. Bile-acid-induced cell injury and protection. World J Gastroenterol 2009; 15 (14) 1677-1689
    CrossrefPubMedGoogle Scholar
  • 30 Roma MG, Toledo FD, Boaglio AC, Basiglio CL, Crocenzi FA, Sánchez Pozzi EJ. Ursodeoxycholic acid in cholestasis: linking action mechanisms to therapeutic applications. Clin Sci (Lond) 2011; 121 (12) 523-544
    CrossrefPubMedGoogle Scholar
  • 31 Veith A, Moorthy B. Role of cytochrome P450s in the generation and metabolism of reactive oxygen species. Curr Opin Toxicol 2018; 7: 44-51
    CrossrefPubMedGoogle Scholar
  • 32 Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol 2003; 552 (Pt 2): 335-344
    CrossrefPubMedGoogle Scholar
  • 33 Druckova A, Mernaugh RL, Ham AJ, Marnett LJ. Identification of the protein targets of the reactive metabolite of Teucrin A in vivo in the rat. Chem Res Toxicol 2007; 20 (10) 1393-1408
    CrossrefPubMedGoogle Scholar
  • 34 Tyo KE, Liu Z, Petranovic D, Nielsen J. Imbalance of heterologous protein folding and disulfide bond formation rates yields runaway oxidative stress. BMC Biol 2012; 10: 16
    CrossrefPubMedGoogle Scholar
  • 35 Lapenna D, Ciofani G, Festi D. et al. Antioxidant properties of ursodeoxycholic acid. Biochem Pharmacol 2002; 64 (11) 1661-1667
    CrossrefPubMedGoogle Scholar
  • 36 Okada K, Shoda J, Taguchi K. et al. Ursodeoxycholic acid stimulates Nrf2-mediated hepatocellular transport, detoxification, and antioxidative stress systems in mice. Am J Physiol Gastrointest Liver Physiol 2008; 295 (04) G735-G747
    CrossrefPubMedGoogle Scholar
  • 37 Mitsuyoshi H, Nakashima T, Sumida Y. et al. Ursodeoxycholic acid protects hepatocytes against oxidative injury via induction of antioxidants. Biochem Biophys Res Commun 1999; 263 (02) 537-542
    CrossrefPubMedGoogle Scholar
  • 38 Serviddio G, Pereda J, Pallardó FV. et al. Ursodeoxycholic acid protects against secondary biliary cirrhosis in rats by preventing mitochondrial oxidative stress. Hepatology 2004; 39 (03) 711-720
    CrossrefPubMedGoogle Scholar
  • 39 Kawata K, Kobayashi Y, Souda K. et al. Enhanced hepatic Nrf2 activation after ursodeoxycholic acid treatment in patients with primary biliary cirrhosis. Antioxid Redox Signal 2010; 13 (03) 259-268
    CrossrefPubMedGoogle Scholar
  • 40 Rodríguez-Ortigosa CM, Cincu RN, Sanz S, Ruiz F, Quiroga J, Prieto J. Effect of ursodeoxycholic acid on methionine adenosyltransferase activity and hepatic glutathione metabolism in rats. Gut 2002; 50 (05) 701-706
    CrossrefPubMedGoogle Scholar
  • 41 Kim DJ, Yoon S, Ji SC. et al. Ursodeoxycholic acid improves liver function via phenylalanine/tyrosine pathway and microbiome remodelling in patients with liver dysfunction. Sci Rep 2018; 8 (01) 11874
    CrossrefPubMedGoogle Scholar
  • 42 Castiella A, Zapata E, Lucena MI, Andrade RJ. Drug-induced autoimmune liver disease: a diagnostic dilemma of an increasingly reported disease. World J Hepatol 2014; 6 (04) 160-168
    CrossrefPubMedGoogle Scholar
  • 43 Park BK, Boobis A, Clarke S. et al. Managing the challenge of chemically reactive metabolites in drug development. Nat Rev Drug Discov 2011; 10 (04) 292-306
    CrossrefPubMedGoogle Scholar
  • 44 Guicciardi ME, Gores GJ. Life and death by death receptors. FASEB J 2009; 23 (06) 1625-1637
    CrossrefPubMedGoogle Scholar
  • 45 Chakraborty M, Fullerton AM, Semple K. et al. Drug-induced allergic hepatitis develops in mice when myeloid-derived suppressor cells are depleted prior to halothane treatment. Hepatology 2015; 62 (02) 546-557
    CrossrefPubMedGoogle Scholar
  • 46 Krenkel O, Mossanen JC, Tacke F. Immune mechanisms in acetaminophen-induced acute liver failure. Hepatobiliary Surg Nutr 2014; 3 (06) 331-343
    CrossrefPubMedGoogle Scholar
  • 47 Tanaka H, Makino Y, Miura T. et al. Ligand-independent activation of the glucocorticoid receptor by ursodeoxycholic acid. Repression of IFN-gamma-induced MHC class II gene expression via a glucocorticoid receptor-dependent pathway. J Immunol 1996; 156 (04) 1601-1608
    CrossrefPubMedGoogle Scholar
  • 48 Solá S, Amaral JD, Castro RE. et al. Nuclear translocation of UDCA by the glucocorticoid receptor is required to reduce TGF-β1-induced apoptosis in rat hepatocytes. Hepatology 2005; 42 (04) 925-934
    CrossrefPubMedGoogle Scholar
  • 49 Miura T, Ouchida R, Yoshikawa N. et al. Functional modulation of the glucocorticoid receptor and suppression of NF-kappaB-dependent transcription by ursodeoxycholic acid. J Biol Chem 2001; 276 (50) 47371-47378
    CrossrefPubMedGoogle Scholar
  • 50 Wree A, Dechêne A, Herzer K. et al. Steroid and ursodeoxycholic acid combination therapy in severe drug-induced liver injury. Digestion 2011; 84 (01) 54-59
    CrossrefPubMedGoogle Scholar
  • 51 Pusl T, Vennegeerts T, Wimmer R, Denk GU, Beuers U, Rust C. Tauroursodeoxycholic acid reduces bile acid-induced apoptosis by modulation of AP-1. Biochem Biophys Res Commun 2008; 367 (01) 208-212
    CrossrefPubMedGoogle Scholar
  • 52 Ko WK, Lee SH, Kim SJ. et al. Anti-inflammatory effects of ursodeoxycholic acid by lipopolysaccharide-stimulated inflammatory responses in RAW 264.7 macrophages. PLoS One 2017; 12 (06) e0180673
    CrossrefPubMedGoogle Scholar
  • 53 Yoshikawa M, Tsujii T, Matsumura K. et al. Immunomodulatory effects of ursodeoxycholic acid on immune responses. Hepatology 1992; 16 (02) 358-364
    CrossrefPubMedGoogle Scholar
  • 54 Lacaille F, Paradis K. The immunosuppressive effect of ursodeoxycholic acid: a comparative in vitro study on human peripheral blood mononuclear cells. Hepatology 1993; 18 (01) 165-172
    PubMedGoogle Scholar
  • 55 O'Dwyer AM, Lajczak NK, Keyes JA, Ward JB, Greene CM, Keely SJ. Ursodeoxycholic acid inhibits TNFα-induced IL-8 release from monocytes. Am J Physiol Gastrointest Liver Physiol 2016; 311 (02) G334-G341
    CrossrefPubMedGoogle Scholar
  • 56 Calmus Y, Gane P, Rouger P, Poupon R. Hepatic expression of class I and class II major histocompatibility complex molecules in primary biliary cirrhosis: effect of ursodeoxycholic acid. Hepatology 1990; 11 (01) 12-15
    CrossrefPubMedGoogle Scholar
  • 57 Iorga A, Dara L, Kaplowitz N. Drug-induced liver injury: cascade of events leading to cell death, apoptosis or necrosis. Int J Mol Sci 2017; 18 (05) 1018
    CrossrefPubMedGoogle Scholar
  • 58 Guicciardi ME, Malhi H, Mott JL, Gores GJ. Apoptosis and necrosis in the liver. Compr Physiol 2013; 3 (02) 977-1010
    CrossrefPubMedGoogle Scholar
  • 59 Karch J, Molkentin JD. Regulated necrotic cell death: the passive aggressive side of Bax and Bak. Circ Res 2015; 116 (11) 1800-1809
    CrossrefPubMedGoogle Scholar
  • 60 Kim JS, He L, Lemasters JJ. Mitochondrial permeability transition: a common pathway to necrosis and apoptosis. Biochem Biophys Res Commun 2003; 304 (03) 463-470
    CrossrefPubMedGoogle Scholar
  • 61 Brunelle JK, Letai A. Control of mitochondrial apoptosis by the Bcl-2 family. J Cell Sci 2009; 122 (Pt 4): 437-441
    CrossrefPubMedGoogle Scholar
  • 62 Toledo FD, Basiglio CL, Barosso IR. et al. Mitogen-activated protein kinases are involved in hepatocanalicular dysfunction and cholestasis induced by oxidative stress. Arch Toxicol 2017; 91 (06) 2391-2403
    CrossrefPubMedGoogle Scholar
  • 63 Lemasters JJ, Nieminen AL, Qian T. et al. The mitochondrial permeability transition in cell death: a common mechanism in necrosis, apoptosis and autophagy. Biochim Biophys Acta 1998; 1366 (1–2): 177-196
    CrossrefPubMedGoogle Scholar
  • 64 Villanueva-Paz M, Morán L, López-Alcántara N. et al. Oxidative stress in drug-induced liver injury (DILI): from mechanisms to biomarkers for use in clinical practice. Antioxidants 2021; 10 (03) 390
    CrossrefPubMedGoogle Scholar
  • 65 Sharma M, Gadang V, Jaeschke A. Critical role for mixed-lineage kinase 3 in acetaminophen-induced hepatotoxicity. Mol Pharmacol 2012; 82 (05) 1001-1007
    CrossrefPubMedGoogle Scholar
  • 66 Win S, Than TA, Min RW, Aghajan M, Kaplowitz N. c-Jun N-terminal kinase mediates mouse liver injury through a novel Sab (SH3BP5)-dependent pathway leading to inactivation of intramitochondrial Src. Hepatology 2016; 63 (06) 1987-2003
    CrossrefPubMedGoogle Scholar
  • 67 Dhanasekaran DN, Reddy EP. JNK signaling in apoptosis. Oncogene 2008; 27 (48) 6245-6251
    CrossrefPubMedGoogle Scholar
  • 68 Fuchs SY, Adler V, Pincus MR, Ronai Z. MEKK1/JNK signaling stabilizes and activates p53. Proc Natl Acad Sci U S A 1998; 95 (18) 10541-10546
    CrossrefPubMedGoogle Scholar
  • 69 Davis RJ. Signal transduction by the JNK group of MAP kinases. Cell 2000; 103 (02) 239-252
    CrossrefPubMedGoogle Scholar
  • 70 Coronella-Wood J, Terrand J, Sun H, Chen QM. c-Fos phosphorylation induced by H2O2 prevents proteasomal degradation of c-Fos in cardiomyocytes. J Biol Chem 2004; 279 (32) 33567-33574
    CrossrefPubMedGoogle Scholar
  • 71 Dunnill CJ, Ibraheem K, Mohamed A, Southgate J, Georgopoulos NT. A redox state-dictated signalling pathway deciphers the malignant cell specificity of CD40-mediated apoptosis. Oncogene 2017; 36 (18) 2515-2528
    CrossrefPubMedGoogle Scholar
  • 72 Whitfield J, Neame SJ, Paquet L, Bernard O, Ham J. Dominant-negative c-Jun promotes neuronal survival by reducing BIM expression and inhibiting mitochondrial cytochrome c release. Neuron 2001; 29 (03) 629-643
    CrossrefPubMedGoogle Scholar
  • 73 Hemann MT, Lowe SW. The p53-Bcl-2 connection. Cell Death Differ 2006; 13 (08) 1256-1259
    CrossrefPubMedGoogle Scholar
  • 74 Yamakuchi M, Ferlito M, Lowenstein CJ. miR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci U S A 2008; 105 (36) 13421-13426
    CrossrefPubMedGoogle Scholar
  • 75 Botla R, Spivey JR, Aguilar H, Bronk SF, Gores GJ. Ursodeoxycholate (UDCA) inhibits the mitochondrial membrane permeability transition induced by glycochenodeoxycholate: a mechanism of UDCA cytoprotection. J Pharmacol Exp Ther 1995; 272 (02) 930-938
    PubMedGoogle Scholar
  • 76 Rodrigues CM, Fan G, Ma X, Kren BT, Steer CJ. A novel role for ursodeoxycholic acid in inhibiting apoptosis by modulating mitochondrial membrane perturbation. J Clin Invest 1998; 101 (12) 2790-2799
    CrossrefPubMedGoogle Scholar
  • 77 Rodrigues CM, Ma X, Linehan-Stieers C, Fan G, Kren BT, Steer CJ. Ursodeoxycholic acid prevents cytochrome c release in apoptosis by inhibiting mitochondrial membrane depolarization and channel formation. Cell Death Differ 1999; 6 (09) 842-854
    CrossrefPubMedGoogle Scholar
  • 78 Rodrigues CM, Fan G, Wong PY, Kren BT, Steer CJ. Ursodeoxycholic acid may inhibit deoxycholic acid-induced apoptosis by modulating mitochondrial transmembrane potential and reactive oxygen species production. Mol Med 1998; 4 (03) 165-178
    CrossrefPubMedGoogle Scholar
  • 79 Geetha A, Parameswari S. Effect of ursodeoxycholic acid on hydrogen peroxide induced lipid peroxidation in sheep liver mitochondria. Indian J Physiol Pharmacol 2002; 46 (03) 343-348
    PubMedGoogle Scholar
  • 80 Azzaroli F, Mehal W, Soroka CJ. et al. Ursodeoxycholic acid diminishes Fas-ligand-induced apoptosis in mouse hepatocytes. Hepatology 2002; 36 (01) 49-54
    CrossrefPubMedGoogle Scholar
  • 81 Phillips AC, Vousden KH. E2F-1 induced apoptosis. Apoptosis 2001; 6 (03) 173-182
    CrossrefPubMedGoogle Scholar
  • 82 Rodrigues CM, Solá S, Brito MA, Brondino CD, Brites D, Moura JJ. Amyloid beta-peptide disrupts mitochondrial membrane lipid and protein structure: protective role of tauroursodeoxycholate. Biochem Biophys Res Commun 2001; 281 (02) 468-474
    CrossrefPubMedGoogle Scholar
  • 83 Qiao L, Yacoub A, Studer E. et al. Inhibition of the MAPK and PI3K pathways enhances UDCA-induced apoptosis in primary rodent hepatocytes. Hepatology 2002; 35 (04) 779-789
    CrossrefPubMedGoogle Scholar
  • 84 Schoemaker MH, Conde de la Rosa L, Buist-Homan M. et al. Tauroursodeoxycholic acid protects rat hepatocytes from bile acid-induced apoptosis via activation of survival pathways. Hepatology 2004; 39 (06) 1563-1573
    CrossrefPubMedGoogle Scholar
  • 85 Miller SD, Greene CM, McLean C. et al. Tauroursodeoxycholic acid inhibits apoptosis induced by Z alpha-1 antitrypsin via inhibition of Bad. Hepatology 2007; 46 (02) 496-503
    CrossrefPubMedGoogle Scholar
  • 86 Scheid MP, Schubert KM, Duronio V. Regulation of bad phosphorylation and association with Bcl-x(L) by the MAPK/Erk kinase. J Biol Chem 1999; 274 (43) 31108-31113
    CrossrefPubMedGoogle Scholar
  • 87 Schratt G, Philippar U, Hockemeyer D, Schwarz H, Alberti S, Nordheim A. SRF regulates Bcl-2 expression and promotes cell survival during murine embryonic development. EMBO J 2004; 23 (08) 1834-1844
    CrossrefPubMedGoogle Scholar
  • 88 Townsend KJ, Zhou P, Qian L. et al. Regulation of MCL1 through a serum response factor/Elk-1-mediated mechanism links expression of a viability-promoting member of the BCL2 family to the induction of hematopoietic cell differentiation. J Biol Chem 1999; 274 (03) 1801-1813
    CrossrefPubMedGoogle Scholar
  • 89 Sommerfeld A, Reinehr R, Häussinger D. Tauroursodeoxycholate protects rat hepatocytes from bile acid-induced apoptosis via β1-integrin- and protein kinase A-dependent mechanisms. Cell Physiol Biochem 2015; 36 (03) 866-883
    CrossrefPubMedGoogle Scholar
  • 90 Shah SA, Volkov Y, Arfin Q, Abdel-Latif MM, Kelleher D. Ursodeoxycholic acid inhibits interleukin 1 β [corrected] and deoxycholic acid-induced activation of NF-kappaB and AP-1 in human colon cancer cells. Int J Cancer 2006; 118 (03) 532-539
    CrossrefPubMedGoogle Scholar
  • 91 Yamakuchi M, Lowenstein CJ. MiR-34, SIRT1 and p53: the feedback loop. Cell Cycle 2009; 8 (05) 712-715
    CrossrefPubMedGoogle Scholar
  • 92 Amaral JD, Castro RE, Solá S, Steer CJ, Rodrigues CM. p53 is a key molecular target of ursodeoxycholic acid in regulating apoptosis. J Biol Chem 2007; 282 (47) 34250-34259
    CrossrefPubMedGoogle Scholar
  • 93 Amaral JD, Castro RE, Solá S, Steer CJ, Rodrigues CM. Ursodeoxycholic acid modulates the ubiquitin-proteasome degradation pathway of p53. Biochem Biophys Res Commun 2010; 400 (04) 649-654
    CrossrefPubMedGoogle Scholar
  • 94 Youle RJ, Strasser A. The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol 2008; 9 (01) 47-59
    CrossrefPubMedGoogle Scholar
  • 95 Liu H, Lo CR, Czaja MJ. NF-kappaB inhibition sensitizes hepatocytes to TNF-induced apoptosis through a sustained activation of JNK and c-Jun. Hepatology 2002; 35 (04) 772-778
    CrossrefPubMedGoogle Scholar
  • 96 Zhang W, Steer CJ, Douglas KT, Rodrigues CM. Binding studies of bile acids using the native fluorescence of the tryptophan residue of Bax protein. Biosci Rep 2006; 26 (03) 245-250
    CrossrefPubMedGoogle Scholar
  • 97 Chen S, Melchior Jr WB, Guo L. Endoplasmic reticulum stress in drug- and environmental toxicant-induced liver toxicity. J Environ Sci Health Part C Environ Carcinog Ecotoxicol Rev 2014; 32 (01) 83-104
    CrossrefPubMedGoogle Scholar
  • 98 Hetz C, Zhang K, Kaufman RJ. Mechanisms, regulation and functions of the unfolded protein response. Nat Rev Mol Cell Biol 2020; 21 (08) 421-438
    CrossrefPubMedGoogle Scholar
  • 99 Rasheva VI, Domingos PM. Cellular responses to endoplasmic reticulum stress and apoptosis. Apoptosis 2009; 14 (08) 996-1007
    CrossrefPubMedGoogle Scholar
  • 100 Puthalakath H, O'Reilly LA, Gunn P. et al. ER stress triggers apoptosis by activating BH3-only protein Bim. Cell 2007; 129 (07) 1337-1349
    CrossrefPubMedGoogle Scholar
  • 101 Yamaguchi H, Wang HG. CHOP is involved in endoplasmic reticulum stress-induced apoptosis by enhancing DR5 expression in human carcinoma cells. J Biol Chem 2004; 279 (44) 45495-45502
    CrossrefPubMedGoogle Scholar
  • 102 Urano F, Wang X, Bertolotti A. et al. Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 2000; 287 (5453) 664-666
    CrossrefPubMedGoogle Scholar
  • 103 Nakagawa T, Yuan J. Cross-talk between two cysteine protease families. Activation of caspase-12 by calpain in apoptosis. J Cell Biol 2000; 150 (04) 887-894
    CrossrefPubMedGoogle Scholar
  • 104 Ozcan U, Yilmaz E, Ozcan L. et al. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science 2006; 313 (5790) 1137-1140
    CrossrefPubMedGoogle Scholar
  • 105 Uppala JK, Gani AR, Ramaiah KVA. Chemical chaperone, TUDCA unlike PBA, mitigates protein aggregation efficiently and resists ER and non-ER stress induced HepG2 cell death. Sci Rep 2017; 7 (01) 3831
    CrossrefPubMedGoogle Scholar
  • 106 Gani AR, Uppala JK, Ramaiah KV. Tauroursodeoxycholic acid prevents stress induced aggregation of proteins in vitro and promotes PERK activation in HepG2 cells. Arch Biochem Biophys 2015; 568: 8-15
    CrossrefPubMedGoogle Scholar
  • 107 Omura T, Asari M, Yamamoto J. et al. Sodium tauroursodeoxycholate prevents paraquat-induced cell death by suppressing endoplasmic reticulum stress responses in human lung epithelial A549 cells. Biochem Biophys Res Commun 2013; 432 (04) 689-694
    CrossrefPubMedGoogle Scholar
  • 108 Xie Q, Khaoustov VI, Chung CC. et al. Effect of tauroursodeoxycholic acid on endoplasmic reticulum stress-induced caspase-12 activation. Hepatology 2002; 36 (03) 592-601
    CrossrefPubMedGoogle Scholar
  • 109 Lim SC, Choi JE, Kang HS, Han SI. Ursodeoxycholic acid switches oxaliplatin-induced necrosis to apoptosis by inhibiting reactive oxygen species production and activating p53-caspase 8 pathway in HepG2 hepatocellular carcinoma. Int J Cancer 2010; 126 (07) 1582-1595
    CrossrefPubMedGoogle Scholar
  • 110 Moriwaki K, Chan FK. RIP3: a molecular switch for necrosis and inflammation. Genes Dev 2013; 27 (15) 1640-1649
    CrossrefPubMedGoogle Scholar
  • 111 Columbano A. Cell death: current difficulties in discriminating apoptosis from necrosis in the context of pathological processes in vivo. J Cell Biochem 1995; 58 (02) 181-190
    CrossrefPubMedGoogle Scholar
  • 112 Hisadome T, Nakama T, Itoh H, Furusawa T. Physical-chemical properties of chenodeoxycholic acid and ursodeoxycholic acid. Gastroenterol Jpn 1980; 15 (03) 257-263
    CrossrefPubMedGoogle Scholar
  • 113 Paumgartner G, Pauletzki J, Sackmann M. Ursodeoxycholic acid treatment of cholesterol gallstone disease. Scand J Gastroenterol Suppl 1994; 204: 27-31
    CrossrefPubMedGoogle Scholar
  • 114 Crosignani A, Setchell KD, Invernizzi P, Larghi A, Rodrigues CM, Podda M. Clinical pharmacokinetics of therapeutic bile acids. Clin Pharmacokinet 1996; 30 (05) 333-358
    CrossrefPubMedGoogle Scholar
  • 115 Lazaridis KN, Gores GJ, Lindor KD. Ursodeoxycholic acid ‘mechanisms of action and clinical use in hepatobiliary disorders’. J Hepatol 2001; 35 (01) 134-146
    CrossrefPubMedGoogle Scholar
  • 116 Morgan RE, Trauner M, van Staden CJ. et al. Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci 2010; 118 (02) 485-500
    CrossrefPubMedGoogle Scholar
  • 117 Fickert P, Zollner G, Fuchsbichler A. et al. Effects of ursodeoxycholic and cholic acid feeding on hepatocellular transporter expression in mouse liver. Gastroenterology 2001; 121 (01) 170-183
    CrossrefPubMedGoogle Scholar
  • 118 Zollner G, Fickert P, Fuchsbichler A. et al. Role of nuclear bile acid receptor, FXR, in adaptive ABC transporter regulation by cholic and ursodeoxycholic acid in mouse liver, kidney and intestine. J Hepatol 2003; 39 (04) 480-488
    CrossrefPubMedGoogle Scholar
  • 119 Zollner G, Wagner M, Moustafa T. et al. Coordinated induction of bile acid detoxification and alternative elimination in mice: role of FXR-regulated organic solute transporter-alpha/beta in the adaptive response to bile acids. Am J Physiol Gastrointest Liver Physiol 2006; 290 (05) G923-G932
    CrossrefPubMedGoogle Scholar
  • 120 Schuetz EG, Strom S, Yasuda K. et al. Disrupted bile acid homeostasis reveals an unexpected interaction among nuclear hormone receptors, transporters, and cytochrome P450. J Biol Chem 2001; 276 (42) 39411-39418
    CrossrefPubMedGoogle Scholar
  • 121 Marschall HU, Wagner M, Zollner G. et al. Complementary stimulation of hepatobiliary transport and detoxification systems by rifampicin and ursodeoxycholic acid in humans. Gastroenterology 2005; 129 (02) 476-485
    CrossrefPubMedGoogle Scholar
  • 122 Hofmann AF. Bile acids: the good, the bad, and the ugly. News Physiol Sci 1999; 14: 24-29
    PubMedGoogle Scholar
  • 123 Benz C, Angermüller S, Töx U. et al. Effect of tauroursodeoxycholic acid on bile-acid-induced apoptosis and cytolysis in rat hepatocytes. J Hepatol 1998; 28 (01) 99-106
    CrossrefPubMedGoogle Scholar
  • 124 Heuman DM, Pandak WM, Hylemon PB, Vlahcevic ZR. Conjugates of ursodeoxycholate protect against cytotoxicity of more hydrophobic bile salts: in vitro studies in rat hepatocytes and human erythrocytes. Hepatology 1991; 14 (05) 920-926
    CrossrefPubMedGoogle Scholar
  • 125 Basiglio CL, Mottino AD, Roma MG. Tauroursodeoxycholate counteracts hepatocellular lysis induced by tensioactive bile salts by preventing plasma membrane-micelle transition. Chem Biol Interact 2010; 188 (03) 386-392
    CrossrefPubMedGoogle Scholar
  • 126 Heuman DM, Mills AS, McCall J, Hylemon PB, Pandak WM, Vlahcevic ZR. Conjugates of ursodeoxycholate protect against cholestasis and hepatocellular necrosis caused by more hydrophobic bile salts. In vivo studies in the rat. Gastroenterology 1991; 100 (01) 203-211
    CrossrefPubMedGoogle Scholar
  • 127 Sokol RJ, Devereaux M, Khandwala R, O'Brien K. Evidence for involvement of oxygen free radicals in bile acid toxicity to isolated rat hepatocytes. Hepatology 1993; 17 (05) 869-881
    CrossrefPubMedGoogle Scholar
  • 128 Borgognone M, Pérez LM, Basiglio CL, Ochoa JE, Roma MG. Signaling modulation of bile salt-induced necrosis in isolated rat hepatocytes. Toxicol Sci 2005; 83 (01) 114-125
    CrossrefPubMedGoogle Scholar
  • 129 Zhou Y, Doyen R, Lichtenberger LM. The role of membrane cholesterol in determining bile acid cytotoxicity and cytoprotection of ursodeoxycholic acid. Biochim Biophys Acta 2009; 1788 (02) 507-513
    CrossrefPubMedGoogle Scholar
  • 130 Heuman DM, Bajaj RS, Lin Q. Adsorption of mixtures of bile salt taurine conjugates to lecithin-cholesterol membranes: implications for bile salt toxicity and cytoprotection. J Lipid Res 1996; 37 (03) 562-573
    CrossrefPubMedGoogle Scholar
  • 131 Sodeman T, Bronk SF, Roberts PJ, Miyoshi H, Gores GJ. Bile salts mediate hepatocyte apoptosis by increasing cell surface trafficking of Fas. Am J Physiol Gastrointest Liver Physiol 2000; 278 (06) G992-G999
    CrossrefPubMedGoogle Scholar
  • 132 Higuchi H, Bronk SF, Takikawa Y. et al. The bile acid glycochenodeoxycholate induces trail-receptor 2/DR5 expression and apoptosis. J Biol Chem 2001; 276 (42) 38610-38618
    CrossrefPubMedGoogle Scholar
  • 133 Reinehr R, Becker S, Keitel V, Eberle A, Grether-Beck S, Häussinger D. Bile salt-induced apoptosis involves NADPH oxidase isoform activation. Gastroenterology 2005; 129 (06) 2009-2031
    CrossrefPubMedGoogle Scholar
  • 134 Qiao L, Studer E, Leach K. et al. Deoxycholic acid (DCA) causes ligand-independent activation of epidermal growth factor receptor (EGFR) and FAS receptor in primary hepatocytes: inhibition of EGFR/mitogen-activated protein kinase-signaling module enhances DCA-induced apoptosis. Mol Biol Cell 2001; 12 (09) 2629-2645
    CrossrefPubMedGoogle Scholar
  • 135 Adachi T, Kaminaga T, Yasuda H, Kamiya T, Hara H. The involvement of endoplasmic reticulum stress in bile acid-induced hepatocellular injury. J Clin Biochem Nutr 2014; 54 (02) 129-135
    CrossrefPubMedGoogle Scholar
  • 136 Bessone F, Hernández N, Tanno M, Roma MG. Drug-induced vanishing bile duct syndrome: from pathogenesis to diagnosis and therapeutics. Semin Liver Dis 2021; 41 (03) 331-348
    Article in Thieme ConnectPubMedGoogle Scholar
  • 137 Parola M, Cheeseman KH, Biocca ME, Dianzani MU, Slater TF. Biochemical studies on bile duct epithelial cells isolated from rat liver. J Hepatol 1990; 10 (03) 341-345
    CrossrefPubMedGoogle Scholar
  • 138 Celli A, Que FG, Gores GJ, LaRusso NF. Glutathione depletion is associated with decreased Bcl-2 expression and increased apoptosis in cholangiocytes. Am J Physiol 1998; 275 (04) G749-G757
    PubMedGoogle Scholar
  • 139 Que FG, Phan VA, Phan VH, LaRusso NF, Gores GJ. GUDC inhibits cytochrome c release from human cholangiocyte mitochondria. J Surg Res 1999; 83 (02) 100-105
    CrossrefPubMedGoogle Scholar
  • 140 Miyaguchi S, Mori M. Ursodeoxycholic acid (UDCA) suppresses liver interleukin 2 mRNA in the cholangitis model. Hepatogastroenterology 2005; 52 (62) 596-602
    PubMedGoogle Scholar
  • 141 Xia X, Francis H, Glaser S, Alpini G, LeSage G. Bile acid interactions with cholangiocytes. World J Gastroenterol 2006; 12 (22) 3553-3563
    CrossrefPubMedGoogle Scholar
  • 142 Trauner M, Fickert P, Halilbasic E, Moustafa T. Lessons from the toxic bile concept for the pathogenesis and treatment of cholestatic liver diseases. Wien Med Wochenschr 2008; 158 (19–20): 542-548
    CrossrefPubMedGoogle Scholar
  • 143 Hohenester S, Wenniger LM, Paulusma CC. et al. A biliary HCO3- umbrella constitutes a protective mechanism against bile acid-induced injury in human cholangiocytes. Hepatology 2012; 55 (01) 173-183
    CrossrefPubMedGoogle Scholar
  • 144 Gotthardt D, Runz H, Keitel V. et al. A mutation in the canalicular phospholipid transporter gene, ABCB4, is associated with cholestasis, ductopenia, and cirrhosis in adults. Hepatology 2008; 48 (04) 1157-1166
    CrossrefPubMedGoogle Scholar
  • 145 He K, Cai L, Shi Q, Liu H, Woolf TF. Inhibition of MDR3 activity in human hepatocytes by drugs associated with liver injury. Chem Res Toxicol 2015; 28 (10) 1987-1990
    CrossrefPubMedGoogle Scholar
  • 146 Pauli-Magnus C, Meier PJ. Hepatobiliary transporters and drug-induced cholestasis. Hepatology 2006; 44 (04) 778-787
    CrossrefPubMedGoogle Scholar
  • 147 Renner EL, Lake JR, Cragoe Jr EJ, Van Dyke RW, Scharschmidt BF. Ursodeoxycholic acid choleresis: relationship to biliary HCO-3 and effects of Na+-H+ exchange inhibitors. Am J Physiol 1988; 254 (2, Pt 1): G232-G241
    PubMedGoogle Scholar
  • 148 Knyrim K, Vakil N, Pfab R, Classen M. The effects of intraduodenal bile acid administration on biliary secretion of ionized calcium and carbonate in man. Hepatology 1989; 10 (02) 134-142
    CrossrefPubMedGoogle Scholar
  • 149 Van Nieuwkerk CM, Elferink RP, Groen AK. et al. Effects of ursodeoxycholate and cholate feeding on liver disease in FVB mice with a disrupted mdr2 P-glycoprotein gene. Gastroenterology 1996; 111 (01) 165-171
    CrossrefPubMedGoogle Scholar
  • 150 Arenas F, Hervias I, Uriz M, Joplin R, Prieto J, Medina JF. Combination of ursodeoxycholic acid and glucocorticoids upregulates the AE2 alternate promoter in human liver cells. J Clin Invest 2008; 118 (02) 695-709
    PubMedGoogle Scholar
  • 151 Hempfling W, Dilger K, Beuers U. Systematic review: ursodeoxycholic acid – adverse effects and drug interactions. Aliment Pharmacol Ther 2003; 18 (10) 963-972
    CrossrefPubMedGoogle Scholar
  • 152 Ebhohon E, Chung RT. Systematic review: efficacy of therapies for cholestatic pruritus. Therap Adv Gastroenterol 2023; 16: 17 562848231172829
    CrossrefPubMedGoogle Scholar
  • 153 Lang SM, Ortmann J, Rostig S, Schiffl H. Ursodeoxycholic acid attenuates hepatotoxicity of multidrug treatment of mycobacterial infections: a prospective pilot study. Int J Mycobacteriol 2019; 8 (01) 89-92
    CrossrefPubMedGoogle Scholar
  • 154 Wong SP, Chu CM, Kan CH, Tsui HS, Ng WL. Successful treatment of leflunomide-induced acute pneumonitis with cholestyramine wash-out therapy. J Clin Rheumatol 2009; 15 (08) 389-392
    CrossrefPubMedGoogle Scholar
  • 155 Bohan TP, Helton E, McDonald I. et al. Effect of L-carnitine treatment for valproate-induced hepatotoxicity. Neurology 2001; 56 (10) 1405-1409
    CrossrefPubMedGoogle Scholar
  • 156 Lee WM, Hynan LS, Rossaro L. et al; Acute Liver Failure Study Group. Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. Gastroenterology 2009; 137 (03) 856-864 , 864.e1
    CrossrefPubMedGoogle Scholar
  • 157 Piotrowicz A, Polkey M, Wilkinson M. Ursodeoxycholic acid for the treatment of flucloxacillin-associated cholestasis. J Hepatol 1995; 22 (01) 119-120
    CrossrefPubMedGoogle Scholar
  • 158 Cicognani C, Malavolti M, Morselli-Labate AM, Sama C, Barbara L. Flutamide-induced toxic hepatitis. Potential utility of ursodeoxycholic acid administration in toxic hepatitis. Dig Dis Sci 1996; 41 (11) 2219-2221
    PubMedGoogle Scholar
  • 159 Katsinelos P, Vasiliadis T, Xiarchos P. et al. Ursodeoxycholic acid (UDCA) for the treatment of amoxycillin-clavulanate potassium (Augmentin)-induced intra-hepatic cholestasis: report of two cases. Eur J Gastroenterol Hepatol 2000; 12 (03) 365-368
    CrossrefPubMedGoogle Scholar
  • 160 Agca E, Akcay A, Simsek H. Ursodeoxycholic acid for terbinafine-induced toxic hepatitis. Ann Pharmacother 2004; 38 (06) 1088-1089
    CrossrefPubMedGoogle Scholar
  • 161 Smith LA, Ignacio JR, Winesett MP. et al. Vanishing bile duct syndrome: amoxicillin-clavulanic acid associated intra-hepatic cholestasis responsive to ursodeoxycholic acid. J Pediatr Gastroenterol Nutr 2005; 41 (04) 469-473
    CrossrefPubMedGoogle Scholar
  • 162 Jorge OA, Jorge AD. Hepatotoxicity associated with the ingestion of Centella asiatica. Rev Esp Enferm Dig 2005; 97 (02) 115-124
    CrossrefPubMedGoogle Scholar
  • 163 Sánchez-Osorio M, Duarte-Rojo A, Martínez-Benítez B, Torre A, Uribe M. Anabolic-androgenic steroids and liver injury. Liver Int 2008; 28 (02) 278-282
    CrossrefPubMedGoogle Scholar
  • 164 Gallelli L, Staltari O, Palleria C, De Sarro G, Ferraro M. Hepatotoxicity induced by methimazole in a previously healthy patient. Curr Drug Saf 2009; 4 (03) 204-206
    CrossrefPubMedGoogle Scholar
  • 165 Studniarz M, Czubkowski P, Cielecka-Kuszyk J. et al. Amoxicillin/clavulanic acid-induced cholestatic liver injury after pediatric liver transplantation. Ann Transplant 2012; 17 (01) 128-131
    CrossrefPubMedGoogle Scholar
  • 166 Goossens N, Spahr L, Rubbia-Brandt L. Severe immune-mediated drug-induced liver injury linked to ibandronate: a case report. J Hepatol 2013; 59 (05) 1139-1142
    CrossrefPubMedGoogle Scholar
  • 167 Asgarshirazi M, Shariat M, Dalili H, Keihanidoost Z. Ursodeoxycholic acid can improve liver transaminase quantities in children with anticonvulsant drugs hepatotoxicity: a pilot study. Acta Med Iran 2015; 53 (06) 351-355
    PubMedGoogle Scholar
  • 168 Li L, Zheng S, Chen Y. Stevens-Johnson syndrome and acute vanishing bile duct syndrome after the use of amoxicillin and naproxen in a child. J Int Med Res 2019; 47 (09) 4537-4543
    CrossrefPubMedGoogle Scholar
  • 169 Kurokawa K, Hara M, Iwakami SI. et al. Cholestatic liver injury induced by pembrolizumab in a patient with lung adenocarcinoma. Intern Med 2019; 58 (22) 3283-3287
    CrossrefPubMedGoogle Scholar
  • 170 Fernandes CT, Iqbal U, Tighe SP, Ahmed A. Kratom-induced cholestatic liver injury and its conservative management. J Investig Med High Impact Case Rep 2019; 7: 23 24709619836138
    PubMedGoogle Scholar
  • 171 Onishi S, Tajika M, Bando H. et al. Ursodeoxycholic acid and bezafibrate were useful for steroid-refractory, immune-related hepatitis: a case report. J Med Case Rep 2020; 14 (01) 230
    CrossrefPubMedGoogle Scholar
  • 172 Ahmed S, Onteddu NK, Jabur A, Vulasala SSR, Kolli S. Delayed presentation of drug-induced hepatic injury. Cureus 2020; 12 (08) e9713
    PubMedGoogle Scholar
  • 173 Teixeira M, Macedo S, Batista T, Martins S, Correia A, Matos LC. Flucloxacillin-induced hepatotoxicity - association with HLA-B*5701. Rev Assoc Med Bras 2020; 66 (01) 12-17
    CrossrefPubMedGoogle Scholar
  • 174 Ireland PJ, Hardy T, Burt AD, Donnelly MC. Drug-induced hepatocellular injury due to herbal supplement ashwagandha. J R Coll Physicians Edinb 2021; 51 (04) 363-365
    CrossrefPubMedGoogle Scholar