Clinical and histologic features of azithromycin-induced liver injury

Melissa A. Martinez, Raj Vuppalanchi, Robert J. Fontana, Andrew Stolz, David E. Kleiner, Paul H. Hayashi, Jiezhun Gu, Jay H. Hoofnagle, Naga Chalasani

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Background and Aims: Rare cases of azithromycin-induced hepatotoxicity have been reported, with variable clinical and histologic features. We characterized clinical features and outcomes of azithromycin-induced liver injury. Methods: We identified patients with azithromycin-induced liver injury from the Drug-Induced Liver Injury Network Prospective Study who had causality scores of definite, highly likely, or probable. Demographic, clinical, and laboratory data and 6-month outcomes were examined. Results: Eighteen patients (72% female, mean age, 37 y) had causality scores of definite (n= 1), highly likely (n= 9), or probable (n= 8). Common presenting symptoms were jaundice, abdominal pain, nausea, and/or pruritus. For 16 patients, abnormal results from liver tests were first detected 14 days after azithromycin cessation (range, 9-20 d). The median duration of azithromycin treatment was 4 days (range, 2-7 d). The pattern of injury was hepatocellular in 10 patients, cholestatic in 6 patients, and mixed in 2 patients. The mean peak level of alanine aminotransferase was 2127 IU/L, of alkaline phosphatase was 481 IU/L, and of total bilirubin was 9.2 mg/dL. Liver histology showed ductopenia and veno-occlusive changes in a few patients. Two individuals had severe hypersensitivity cutaneous reactions. After 6 months, 8 patients had recovered, 4 patients had chronic injury, 1 patient died, and 1 patient underwent liver transplantation (outcomes were unavailable for 4 patients). Two of the patients who died or underwent liver transplantation had underlying chronic liver disease. Conclusions: Azithromycin-induced liver injury occurs within 1 to 3 weeks after azithromycin initiation and predominantly is hepatocellular in nature. Although most patients recover fully, severe cutaneous reactions, chronic injury, and serious complications leading to death or liver transplantation can occur (. ClinicalTrials.gov identifier, NCT00345930).

Original languageEnglish
Pages (from-to)369-376
Number of pages8
JournalClinical Gastroenterology and Hepatology
Volume13
Issue number2
DOIs
StatePublished - 2015

Fingerprint

Azithromycin
Liver
Wounds and Injuries
Liver Transplantation
Causality
Chemical and Drug Induced Liver Injury
Skin
Pruritus
Jaundice
Alanine Transaminase
Bilirubin
Nausea
Abdominal Pain
Alkaline Phosphatase
Liver Diseases

Keywords

  • Antibiotic
  • DILI
  • Liver toxicity
  • Macrolide

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Clinical and histologic features of azithromycin-induced liver injury. / Martinez, Melissa A.; Vuppalanchi, Raj; Fontana, Robert J.; Stolz, Andrew; Kleiner, David E.; Hayashi, Paul H.; Gu, Jiezhun; Hoofnagle, Jay H.; Chalasani, Naga.

In: Clinical Gastroenterology and Hepatology, Vol. 13, No. 2, 2015, p. 369-376.

Research output: Contribution to journalArticle

Martinez, MA, Vuppalanchi, R, Fontana, RJ, Stolz, A, Kleiner, DE, Hayashi, PH, Gu, J, Hoofnagle, JH & Chalasani, N 2015, 'Clinical and histologic features of azithromycin-induced liver injury', Clinical Gastroenterology and Hepatology, vol. 13, no. 2, pp. 369-376. https://doi.org/10.1016/j.cgh.2014.07.054
Martinez, Melissa A. ; Vuppalanchi, Raj ; Fontana, Robert J. ; Stolz, Andrew ; Kleiner, David E. ; Hayashi, Paul H. ; Gu, Jiezhun ; Hoofnagle, Jay H. ; Chalasani, Naga. / Clinical and histologic features of azithromycin-induced liver injury. In: Clinical Gastroenterology and Hepatology. 2015 ; Vol. 13, No. 2. pp. 369-376.
@article{d4a3b72329734524b7522f9951c4b1d2,
title = "Clinical and histologic features of azithromycin-induced liver injury",
abstract = "Background and Aims: Rare cases of azithromycin-induced hepatotoxicity have been reported, with variable clinical and histologic features. We characterized clinical features and outcomes of azithromycin-induced liver injury. Methods: We identified patients with azithromycin-induced liver injury from the Drug-Induced Liver Injury Network Prospective Study who had causality scores of definite, highly likely, or probable. Demographic, clinical, and laboratory data and 6-month outcomes were examined. Results: Eighteen patients (72{\%} female, mean age, 37 y) had causality scores of definite (n= 1), highly likely (n= 9), or probable (n= 8). Common presenting symptoms were jaundice, abdominal pain, nausea, and/or pruritus. For 16 patients, abnormal results from liver tests were first detected 14 days after azithromycin cessation (range, 9-20 d). The median duration of azithromycin treatment was 4 days (range, 2-7 d). The pattern of injury was hepatocellular in 10 patients, cholestatic in 6 patients, and mixed in 2 patients. The mean peak level of alanine aminotransferase was 2127 IU/L, of alkaline phosphatase was 481 IU/L, and of total bilirubin was 9.2 mg/dL. Liver histology showed ductopenia and veno-occlusive changes in a few patients. Two individuals had severe hypersensitivity cutaneous reactions. After 6 months, 8 patients had recovered, 4 patients had chronic injury, 1 patient died, and 1 patient underwent liver transplantation (outcomes were unavailable for 4 patients). Two of the patients who died or underwent liver transplantation had underlying chronic liver disease. Conclusions: Azithromycin-induced liver injury occurs within 1 to 3 weeks after azithromycin initiation and predominantly is hepatocellular in nature. Although most patients recover fully, severe cutaneous reactions, chronic injury, and serious complications leading to death or liver transplantation can occur (. ClinicalTrials.gov identifier, NCT00345930).",
keywords = "Antibiotic, DILI, Liver toxicity, Macrolide",
author = "Martinez, {Melissa A.} and Raj Vuppalanchi and Fontana, {Robert J.} and Andrew Stolz and Kleiner, {David E.} and Hayashi, {Paul H.} and Jiezhun Gu and Hoofnagle, {Jay H.} and Naga Chalasani",
year = "2015",
doi = "10.1016/j.cgh.2014.07.054",
language = "English",
volume = "13",
pages = "369--376",
journal = "Clinical Gastroenterology and Hepatology",
issn = "1542-3565",
publisher = "W.B. Saunders Ltd",
number = "2",

}

TY - JOUR

T1 - Clinical and histologic features of azithromycin-induced liver injury

AU - Martinez, Melissa A.

AU - Vuppalanchi, Raj

AU - Fontana, Robert J.

AU - Stolz, Andrew

AU - Kleiner, David E.

AU - Hayashi, Paul H.

AU - Gu, Jiezhun

AU - Hoofnagle, Jay H.

AU - Chalasani, Naga

PY - 2015

Y1 - 2015

N2 - Background and Aims: Rare cases of azithromycin-induced hepatotoxicity have been reported, with variable clinical and histologic features. We characterized clinical features and outcomes of azithromycin-induced liver injury. Methods: We identified patients with azithromycin-induced liver injury from the Drug-Induced Liver Injury Network Prospective Study who had causality scores of definite, highly likely, or probable. Demographic, clinical, and laboratory data and 6-month outcomes were examined. Results: Eighteen patients (72% female, mean age, 37 y) had causality scores of definite (n= 1), highly likely (n= 9), or probable (n= 8). Common presenting symptoms were jaundice, abdominal pain, nausea, and/or pruritus. For 16 patients, abnormal results from liver tests were first detected 14 days after azithromycin cessation (range, 9-20 d). The median duration of azithromycin treatment was 4 days (range, 2-7 d). The pattern of injury was hepatocellular in 10 patients, cholestatic in 6 patients, and mixed in 2 patients. The mean peak level of alanine aminotransferase was 2127 IU/L, of alkaline phosphatase was 481 IU/L, and of total bilirubin was 9.2 mg/dL. Liver histology showed ductopenia and veno-occlusive changes in a few patients. Two individuals had severe hypersensitivity cutaneous reactions. After 6 months, 8 patients had recovered, 4 patients had chronic injury, 1 patient died, and 1 patient underwent liver transplantation (outcomes were unavailable for 4 patients). Two of the patients who died or underwent liver transplantation had underlying chronic liver disease. Conclusions: Azithromycin-induced liver injury occurs within 1 to 3 weeks after azithromycin initiation and predominantly is hepatocellular in nature. Although most patients recover fully, severe cutaneous reactions, chronic injury, and serious complications leading to death or liver transplantation can occur (. ClinicalTrials.gov identifier, NCT00345930).

AB - Background and Aims: Rare cases of azithromycin-induced hepatotoxicity have been reported, with variable clinical and histologic features. We characterized clinical features and outcomes of azithromycin-induced liver injury. Methods: We identified patients with azithromycin-induced liver injury from the Drug-Induced Liver Injury Network Prospective Study who had causality scores of definite, highly likely, or probable. Demographic, clinical, and laboratory data and 6-month outcomes were examined. Results: Eighteen patients (72% female, mean age, 37 y) had causality scores of definite (n= 1), highly likely (n= 9), or probable (n= 8). Common presenting symptoms were jaundice, abdominal pain, nausea, and/or pruritus. For 16 patients, abnormal results from liver tests were first detected 14 days after azithromycin cessation (range, 9-20 d). The median duration of azithromycin treatment was 4 days (range, 2-7 d). The pattern of injury was hepatocellular in 10 patients, cholestatic in 6 patients, and mixed in 2 patients. The mean peak level of alanine aminotransferase was 2127 IU/L, of alkaline phosphatase was 481 IU/L, and of total bilirubin was 9.2 mg/dL. Liver histology showed ductopenia and veno-occlusive changes in a few patients. Two individuals had severe hypersensitivity cutaneous reactions. After 6 months, 8 patients had recovered, 4 patients had chronic injury, 1 patient died, and 1 patient underwent liver transplantation (outcomes were unavailable for 4 patients). Two of the patients who died or underwent liver transplantation had underlying chronic liver disease. Conclusions: Azithromycin-induced liver injury occurs within 1 to 3 weeks after azithromycin initiation and predominantly is hepatocellular in nature. Although most patients recover fully, severe cutaneous reactions, chronic injury, and serious complications leading to death or liver transplantation can occur (. ClinicalTrials.gov identifier, NCT00345930).

KW - Antibiotic

KW - DILI

KW - Liver toxicity

KW - Macrolide

UR - http://www.scopus.com/inward/record.url?scp=84927691893&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84927691893&partnerID=8YFLogxK

U2 - 10.1016/j.cgh.2014.07.054

DO - 10.1016/j.cgh.2014.07.054

M3 - Article

C2 - 25111234

AN - SCOPUS:84927691893

VL - 13

SP - 369

EP - 376

JO - Clinical Gastroenterology and Hepatology

JF - Clinical Gastroenterology and Hepatology

SN - 1542-3565

IS - 2

ER -