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. 2011 Jun;9(6):517-523.e3.
doi: 10.1016/j.cgh.2011.02.019. Epub 2011 Feb 26.

Clinical and histopathologic features of fluoroquinolone-induced liver injury

Eric S Orman  1 , Hari S Conjeevaram, Raj Vuppalanchi, James W Freston, James Rochon, David E Kleiner, Paul H Hayashi; DILIN Research Group
Affiliations

Clinical and histopathologic features of fluoroquinolone-induced liver injury

Eric S Orman et al. Clin Gastroenterol Hepatol. 2011 Jun.

Abstract

Background & aims: Fluoroquinolone-induced liver injury is rare; no prospective studies of well-characterized case series have been published. We studied patients with fluoroquinolone-induced hepatotoxicity from the Drug-Induced Liver Injury Network (DILIN) to characterize injury patterns, outcomes, and associated features.

Methods: We identified subjects with fluoroquinolone hepatotoxicity enrolled in the DILIN from September 2004 to January 2010. Demographic, clinical, and laboratory data were analyzed by descriptive statistical methods.

Results: Of the 679 registrants in the DILIN prospective study, 12 had fluoroquinolone hepatotoxicity (6 ciprofloxacin, 4 moxifloxacin, 1 levofloxacin, and 1 gatifloxacin). Seven were women; median age was 57 years (range, 23-80 years), and median time from fluoroquinolone start to symptoms was only 4 days (range, 1-39 days). Nine patients developed symptoms on medication; 3 did so 2, 8, and 32 days after stopping the medication. Cases were equally distributed among hepatocellular injury (predominantly increased levels of alanine aminotransferase), cholestatic injury (predominantly increased levels of alkaline phosphatase), and both. Seven patients had immunoallergic features. Patients with mixed hepatocellular and cholestatic injury had mild disease without jaundice; all recovered. In contrast, 2 of 4 patients with hepatocellular injury and jaundice died, 1 of acute liver failure. One patient with cholestatic injury developed vanishing bile duct syndrome and required liver transplantation; another had a persistently increased serum level of alkaline phosphatase.

Conclusions: Fluoroquinolone liver injury is rapid in onset and often has immunoallergic features, indicating a hypersensitivity reaction. The pattern of injury can be hepatocellular, cholestatic, or mixed; mixed cases are the least severe. Acute and chronic liver failure can occur.

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Figures

Figure 1
Figure 1
Serum ALT, AST, AP and bilirubin over time after 3 different fluoroquinolone induced liver injuries. Expert opinion causality scores for all three cases were 2, or very likely. (a) Ciprofloxacin induced hepatocellular injury causing acute liver failure and death. (b) Levofloxacin induced mixed hepatocellular-cholestatic injury with recovery. (c) Moxifloxicin induced cholestatic liver injury leading to prolonged cholestasis, ductopenia and liver failure requiring transplant.
Figure 1
Figure 1
Serum ALT, AST, AP and bilirubin over time after 3 different fluoroquinolone induced liver injuries. Expert opinion causality scores for all three cases were 2, or very likely. (a) Ciprofloxacin induced hepatocellular injury causing acute liver failure and death. (b) Levofloxacin induced mixed hepatocellular-cholestatic injury with recovery. (c) Moxifloxicin induced cholestatic liver injury leading to prolonged cholestasis, ductopenia and liver failure requiring transplant.
Figure 1
Figure 1
Serum ALT, AST, AP and bilirubin over time after 3 different fluoroquinolone induced liver injuries. Expert opinion causality scores for all three cases were 2, or very likely. (a) Ciprofloxacin induced hepatocellular injury causing acute liver failure and death. (b) Levofloxacin induced mixed hepatocellular-cholestatic injury with recovery. (c) Moxifloxicin induced cholestatic liver injury leading to prolonged cholestasis, ductopenia and liver failure requiring transplant.
Figure 2
Figure 2
Represent histopathology of three cases of fluoroquinolone induced liver injuries. (a) acute hepatitis with giant cell transformation (arrows) during hepatocellular injury, (b) cholestatic hepatitis showing mild zone 3 cholestasis (arrows), (c) mild portal inflammation with plasma cells (black arrows) and scattered eosinophils (red arrows) during cholestatic injury, and (d) vanishing bile duct syndrome after cholestatic injury (All hematoxylin and eosin stains, 400x, 200x, 600x and 400x magnification respectively).
Figure 2
Figure 2
Represent histopathology of three cases of fluoroquinolone induced liver injuries. (a) acute hepatitis with giant cell transformation (arrows) during hepatocellular injury, (b) cholestatic hepatitis showing mild zone 3 cholestasis (arrows), (c) mild portal inflammation with plasma cells (black arrows) and scattered eosinophils (red arrows) during cholestatic injury, and (d) vanishing bile duct syndrome after cholestatic injury (All hematoxylin and eosin stains, 400x, 200x, 600x and 400x magnification respectively).
Figure 2
Figure 2
Represent histopathology of three cases of fluoroquinolone induced liver injuries. (a) acute hepatitis with giant cell transformation (arrows) during hepatocellular injury, (b) cholestatic hepatitis showing mild zone 3 cholestasis (arrows), (c) mild portal inflammation with plasma cells (black arrows) and scattered eosinophils (red arrows) during cholestatic injury, and (d) vanishing bile duct syndrome after cholestatic injury (All hematoxylin and eosin stains, 400x, 200x, 600x and 400x magnification respectively).
Figure 2
Figure 2
Represent histopathology of three cases of fluoroquinolone induced liver injuries. (a) acute hepatitis with giant cell transformation (arrows) during hepatocellular injury, (b) cholestatic hepatitis showing mild zone 3 cholestasis (arrows), (c) mild portal inflammation with plasma cells (black arrows) and scattered eosinophils (red arrows) during cholestatic injury, and (d) vanishing bile duct syndrome after cholestatic injury (All hematoxylin and eosin stains, 400x, 200x, 600x and 400x magnification respectively).
See this image and copyright information in PMC

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