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

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 .