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



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.



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.



Gender and a proxy of menopause were associated with various features of inflammation and injury in DILI.
Gastroenterology, Duke University, Durham, NC, USA.
Ayako
0000-0003-1824-1067
A
Suzuki
Duke Clinical Research Institute, Durham, NC, USA.
Huiman
H
Barnhart
Duke Clinical Research Institute, Durham, NC, USA.
Jiezhun
J
Gu
Section on Gastroenterology & Hepatology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.|University of North Carolina, Chapel Hill, NC, USA.
Herbert L
HL
Bonkovsky
Gastroenterology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
Hans L
HL
Tillmann
Gastroenterology, University of Michigan Medical Center, Ann Arbor, MI, USA.
Robert J
RJ
Fontana
Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
David E
DE
Kleiner
D000328:Adult; D000368:Aged; D056486:Chemical and Drug Induced Liver Injury / Q000145:classification* / Q000473:pathology*; D002779:Cholestasis / Q000139:chemically induced / Q000473:pathology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008593:Menopause; D008875:Middle Aged; D012737:Sex Factors
drug-induced liver injury; gender difference; hepatotoxicity; liver histology; menopause