Download PDF
Semin Liver Dis 2014; 34(02): 246-251
DOI: 10.1055/s-0034-1375964
Diagnostic Problems in Hepatology
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Severe Ductopenia and Cholestasis from Levofloxacin Drug-Induced Liver Injury: A Case Report and Review

Calley Levine
1   Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
,
Anshu Trivedi
2   The Lillian and Henry M. Stratton-Hans Popper Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York
,
Swan N. Thung
2   The Lillian and Henry M. Stratton-Hans Popper Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York
,
Ponni V. Perumalswami
1   Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
› Author Affiliations
Further Information

Publication History

Publication Date:
31 May 2014 (online)

    Permissions and Reprints

Abstract

A 67-year-old woman with hypertension, hypothyroidism, and glaucoma was referred for jaundice and elevated liver function tests. She was treated for streptococcal endophthalmitis with 2 weeks of intravenous (IV) levofloxacin followed by 2 months of oral levofloxacin. The patient had no prior history of liver disease and denied alcohol intake. Her physical exam was remarkable for jaundice and scleral icterus without any stigmata of liver disease. Viral hepatitis serologies and antibodies, including myeloperoxidase, proteinase 3, and antinuclear, antimitochondrial, antiliver kidney microsome, antismooth muscle antibodies, were all within normal limits. The liver biopsy revealed severe cholestasis, extensive bile duct loss, and fibrosis. The patient had no known exposure to any other systemic medications or inciting factors other than levofloxacin. Although there are a few reported cases of drug-induced liver disease (DILI) related to levofloxacin, this case is believed to be the first reported case of ductopenia or vanishing bile duct syndrome (VBDS) associated with levofloxacin. Although fluoroquinolones, such as levofloxacin, are generally considered safe antibiotics, health practitioners must be aware of their association with DILI, as the diagnosis of DILI is one of exclusion and requires a high index of suspicion.

Keywords

antibiotics - drug-induced liver injury - hepatotoxicity - levofloxacin - vanishing bile duct syndrome
 

  • References

  • 1 Bénichou C. Criteria of drug-induced liver disorders. Report of an international consensus meeting. J Hepatol 1990; 11 (2) 272-276
    CrossrefPubMedGoogle Scholar
  • 2 Suk KT, Kim DJ. Drug-induced liver injury: present and future. Clin Mol Hepatol 2012; 18 (3) 249-257
    CrossrefPubMedGoogle Scholar
  • 3 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 (3) 558-562 , quiz 693
    CrossrefPubMedGoogle Scholar
  • 4 Reuben A, Koch DG, Lee WM ; Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology 2010; 52 (6) 2065-2076
    CrossrefPubMedGoogle Scholar
  • 5 Reuben A. Hy's law. Hepatology 2004; 39 (2) 574-578
    CrossrefPubMedGoogle Scholar
  • 6 Zimmerman H. Hepatotoxicity - The Adverse Effects of Drugs and Other Chemicals on the Liver. Philadelphia: Lippincott, Williams & Wilkins; 1999. :606, 616–618
    Google Scholar
  • 7 Larrey D. Epidemiology and individual susceptibility to adverse drug reactions affecting the liver. Semin Liver Dis 2002; 22 (2) 145-155
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Stine JG, Lewis JH. Drug-induced liver injury: a summary of recent advances. Expert Opin Drug Metab Toxicol 2011; 7 (7) 875-890
    CrossrefPubMedGoogle Scholar
  • 9 Bleibel W, Kim S, D'Silva K, Lemmer ER. Drug-induced liver injury: review article. Dig Dis Sci 2007; 52 (10) 2463-2471
    CrossrefPubMedGoogle Scholar
  • 10 Rockey DC, Seeff LB, Rochon J , et al; US Drug-Induced Liver Injury Network. Causality assessment in drug-induced liver injury using a structured expert opinion process: comparison to the Roussel-Uclaf causality assessment method. Hepatology 2010; 51 (6) 2117-2126
    CrossrefPubMedGoogle Scholar
  • 11 Andrade RJ, Lucena MI, Fernández MC , et al; Spanish Group for the Study of Drug-Induced Liver Disease. Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period. Gastroenterology 2005; 129 (2) 512-521
    CrossrefPubMedGoogle Scholar
  • 12 Aithal PG, Day CP. The natural history of histologically proved drug induced liver disease. Gut 1999; 44 (5) 731-735
    CrossrefPubMedGoogle Scholar
  • 13 Fontana RJ, Seeff LB, Andrade RJ , et al. Standardization of nomenclature and causality assessment in drug-induced liver injury: summary of a clinical research workshop. Hepatology 2010; 52 (2) 730-742
    CrossrefPubMedGoogle Scholar
  • 14 Ostapowicz G, Fontana RJ, Schiødt FV , et al; U.S. Acute Liver Failure Study Group. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med 2002; 137 (12) 947-954
    CrossrefPubMedGoogle Scholar
  • 15 Orman ES, Conjeevaram HS, Vuppalanchi R , et al; DILIN Research Group. Clinical and histopathologic features of fluoroquinolone-induced liver injury. Clin Gastroenterol Hepatol 2011; 9 (6) 517-523 , e3
    CrossrefPubMedGoogle Scholar
  • 16 Linder JA, Huang ES, Steinman MA, Gonzales R, Stafford RS. Fluoroquinolone prescribing in the United States: 1995 to 2002. Am J Med 2005; 118 (3) 259-268
    CrossrefPubMedGoogle Scholar
  • 17 Licata A, Randazzo C, Morreale I, Butera G, D'Alessandro N, Craxì A. Fluoroquinolone-induced liver injury: three new cases and a review of the literature. Eur J Clin Pharmacol 2012; 68 (5) 525-532
    CrossrefPubMedGoogle Scholar
  • 18 Questions and Answers on Trovafloxacin Public Health Advisory U.S. Food and Drug administration website. Available at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/PublicHealthAdvisories/ucm053104.htm . Accessed September 28, 2013
    PubMed
  • 19 Karim A, Ahmed S, Rossoff LJ, Siddiqui RK, Steinberg HN. Possible levofloxacin-induced acute hepatocellular injury in a patient with chronic obstructive lung disease. Clin Infect Dis 2001; 33 (12) 2088-2090
    CrossrefPubMedGoogle Scholar
  • 20 Spahr L, Rubbia-Brandt L, Marinescu O, Armenian B, Hadengue A. Acute fatal hepatitis related to levofloxacin. [letter] J Hepatol 2001; 35 (2) 308-309
    CrossrefPubMedGoogle Scholar
  • 21 Robinson W, Habr F, Manlolo J, Bhattacharya B. Moxifloxacin associated vanishing bile duct syndrome. [letter] J Clin Gastroenterol 2010; 44 (1) 72-73
    CrossrefPubMedGoogle Scholar
  • 22 Desmet VJ. Vanishing bile duct syndrome in drug-induced liver disease. J Hepatol 1997; 26 (Suppl. 01) 31-35
    CrossrefPubMedGoogle Scholar
  • 23 Levy C, Lindor KD. Drug-induced cholestasis. Clin Liver Dis 2003; 7 (2) 311-330
    CrossrefPubMedGoogle Scholar
  • 24 Reau NS, Jensen DM. Vanishing bile duct syndrome. Clin Liver Dis 2008; 12 (1) 203-217 , x
    CrossrefPubMedGoogle Scholar
  • 25 Bataille L, Rahier J, Geubel A. Delayed and prolonged cholestatic hepatitis with ductopenia after long-term ciprofloxacin therapy for Crohn's disease. J Hepatol 2002; 37 (5) 696-699
    CrossrefPubMedGoogle Scholar