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Journal of Medical Toxicology logoLink to Journal of Medical Toxicology
. 2010 Mar 17;6(4):420–423. doi: 10.1007/s13181-010-0019-4

Corticosteroid Therapy in a Case of Severe Cholestasic Hepatitis Associated with Amoxicillin–Clavulanate

José-Ignacio Herrero-Herrero 1, Judit García-Aparicio 1,
PMCID: PMC3550477  PMID: 20237968

Abstract

Amoxicillin–clavulanate is the most common drug involved in drug-induced liver injury and the single most frequently prescribed product leading to hospitalization for drug-induced liver disease in Spain. The liver damage most frequently associated with amoxicillin–clavulanate is cholestasic type. The latency period between first intake and onset of symptoms is 3–4 weeks on average. A 76-year-old man developed fever, pruritus, and jaundice 3 weeks after having completed treatment with amoxicillin–clavulanate. Liver function tests showed cholestasic hepatitis (up to 50.75 mg/dL of total serum bilirubin level). The ultrasound-guided liver biopsy revealed severe canalicular cholestasis and portal and lobular eosinophilic infiltrates. Prednisone and ursodeoxycholic acid therapy were then prescribed. The patient became symptom-free with normal liver function tests. Amoxicillin–clavulanate can cause hepatocellular, cholestasic, or mixed liver injury. The presence of eosinophilic infiltrates in the liver biopsy and the clinical signs of hypersensitivity in some of the cholestasic cases suggest a pathophysiological immunoallergic mechanism. For this reason, corticosteroid treatment should be considered for patients with severe cholestasic liver injury.

Keywords: Drug-induced liver injury, Hepatotoxicity, Amoxicillin–clavulanate

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References

  • 1.Lucena MI, Andrade RJ, Fernández MC, Pachkoria K, Peláez G, Durán JA, et al. Determinants of the clinical expression of amoxicillin–clavulanate hepatotoxicity: a prospective series from Spain. Hepatology. 2006;44:850–856. doi: 10.1002/hep.21324. [DOI] [PubMed] [Google Scholar]
  • 2.Agencia Española del Medicamento Uso de la asociación amoxicilina–clavulánico y riesgo de hepatotoxicidad. Boletín de la Tarjeta Amarilla. 2006;23:4.1. [Google Scholar]
  • 3.Andrade RJ, Lucena MI, Fernández MC, Peláez G, Pachkoria K, García-Ruiz E, et al (on behalf of the Spanish Group for the Study of Drug-Induced Liver Disease) (2005) Drug-induced liver injury: An analysis of 461 incidences submitted to the Spanish registry over a 10-year period. Gastroenterology 129:512–521 [DOI] [PubMed]
  • 4.Gresser U. Amoxicillin–clavulanic acid therapy may be associated with severe side effects—review of the literature. Eur J Med Res. 2001;6:139–149. [PubMed] [Google Scholar]
  • 5.Tajiri K, Shimizu Y. Practical guidelines for diagnosis and early management of drug-induced liver injury. World J Gastroenterol. 2008;14:6774–6785. doi: 10.3748/wjg.14.6774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Ferrando J, Sanz P, Sevilla G, Figueras P, Martín I. Insuficiencia hepática secundaria a hepatitis por amoxicilina-ácido clavulánico. Tratamiento con corticoides. Med Interna. 2002;19:551–552. [PubMed] [Google Scholar]
  • 7.Giannattasio A, D'Ambrosi M, Volpicelli M, Iorio R. Steroid therapy for a case of severe drug-induced cholestasis. Ann Pharmacother. 2006;40:1196–1199. doi: 10.1345/aph.1G345. [DOI] [PubMed] [Google Scholar]
  • 8.Katsinelos P, Vasiliadis T, Xiarchos P, Patakiouta F, Christodoulou K, Pilpilidis I, Eugenidis N. Ursodeoxycholic acid (UDCA) for the treatment of amoxycillin–clavulanate potassium (Augmentin)-induced intra-hepatic cholestasis: report of two cases. Eur J Gastroenterol Hepatol. 2000;12:365–368. doi: 10.1097/00042737-200012030-00017. [DOI] [PubMed] [Google Scholar]
  • 9.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;46:1323–1330. doi: 10.1016/0895-4356(93)90101-6. [DOI] [PubMed] [Google Scholar]
  • 10.Van den Broek JWG, Buennemeyer BLM, Stricker BHCh. Cholestatische hepatitis door de combinatie amoxicilline en clavulaanzuur (Augmentin) Ned Tijdschr Geneeskd. 1988;132:1495–1497. [PubMed] [Google Scholar]
  • 11.Hussaini SH, O'Brien CS, Despott EJ, Dalton HR. Antibiotic therapy: a major cause of drug-induced jaundice in southwest England. Eur J Gastroenterol Hepatol. 2007;19:15–20. doi: 10.1097/01.meg.0000250581.77865.68. [DOI] [PubMed] [Google Scholar]
  • 12.Larrey D, Vial T, Micaleff A, Babany G, Morichau-Beauchant M, Michel M, Benhamou JP. Hepatitis associated with amoxicillin–clavulanic acid combination: report of 15 cases. Gut. 1992;33:368–371. doi: 10.1136/gut.33.3.368. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.O'Donohue J, Oien KA, Donaldson P, Underhill J, Clare M, MacSween RN, Mills PR. Co-amoxiclav jaundice: clinical and histological features and HLA class II association. Gut. 2000;47:717–720. doi: 10.1136/gut.47.5.717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.De Abajo FJ, Montero D, Madruga M, García LA. Acute and clinically relevant drug-induced liver injury: a population based case–control study. Br J Clin Pharmacol. 2004;58:71–80. doi: 10.1111/j.1365-2125.2004.02133.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Thomson JA, Fairley CK, Ugoni AM, Forbes AB, Purcell PM, Desmond PV, et al. Risk factors for the development of amoxcycillin–clavulanic acid associated jaundice. Med J Aust. 1995;162:638–640. doi: 10.5694/j.1326-5377.1995.tb126049.x. [DOI] [PubMed] [Google Scholar]
  • 16.Lee W. Drug-induced hepatotoxicity. N Eng J Med. 2003;349:474–485. doi: 10.1056/NEJMra021844. [DOI] [PubMed] [Google Scholar]
  • 17.Luxon BA. Diagnosis and treatment of autoimmune hepatitis. Gastroenterol Clin North Am. 2008;37:461–478. doi: 10.1016/j.gtc.2008.02.002. [DOI] [PubMed] [Google Scholar]

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