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Liver Int. 2017 Nov;37(11):1723-1730. doi: 10.1111/liv.13380. Epub 2017 Mar 2.

Associations of gender and a proxy of female menopausal status with histological features of drug-induced liver injury.

Author information

1
Gastroenterology, Duke University, Durham, NC, USA.
2
Duke Clinical Research Institute, Durham, NC, USA.
3
Section on Gastroenterology & Hepatology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
4
University of North Carolina, Chapel Hill, NC, USA.
5
Gastroenterology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
6
Gastroenterology, University of Michigan Medical Center, Ann Arbor, MI, USA.
7
Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.

Abstract

BACKGROUND & AIM:

Gender and menopause may contribute to type and severity of drug-induced liver injury (DILI) by influencing host responses to injury. The aim of this study was to assess the associations of gender and female age 50 [a proxy of menopause] with histological features of liver injury in 212 adults enrolled in the Drug-Induced Liver Injury Network (DILIN) registry.

METHODS:

All participants had a causality score of at least 'probable', a liver biopsy within 30 days of DILI onset, and no prior chronic liver disease. Biochemical and histological injury types were classified as hepatocellular or cholestatic/mixed injury. The cohort was divided into three gender/age categories: men (41.0%), women <50 years (27.4%) and women ≥50 years of age (31.6%). Interaction of gender and age category (≥50 or not) was assessed.

RESULTS:

Hepatocellular injury was more prevalent in women <50 years vs. others (P=.002). After adjusting for biochemical injury types, black race and possible ageing effects, more severe interface hepatitis was noted in biopsies of women <50 years compared to those of men and women ≥50 years (P=.009 and P=.055 respectively). Compared to those of men, biopsies of women showed greater plasma cell infiltration, hepatocyte apoptosis, hepatocyte rosettes and lobular disarray but less iron-positive hepatocytes and histological cholestasis (P<.05). These associations persisted after excluding cases of amoxicillin/clavulanic acid, anabolic steroids or nitrofurantoin DILI which showed gender-specific distributions.

CONCLUSION:

Gender and a proxy of menopause were associated with various features of inflammation and injury in DILI.

KEYWORDS:

drug-induced liver injury; gender difference; hepatotoxicity; liver histology; menopause

PMID:
28161910
PMCID:
PMC5545077
DOI:
10.1111/liv.13380
[Indexed for MEDLINE]
Free PMC Article

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