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

Background and 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 histologic 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 histologic 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=0.002). After adjusting for biochemical injury types, black race and possible aging effects, more severe interface hepatitis was noted in biopsies of women < 50 years compared to those of men and women ≥ 50 years (p=0.009 and p=0.055, 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