Potential impact of hormone replacement therapy on the risk of hepatocellular carcinoma in women of the PLCO cohort

Abstract Objectives Studies on the impact of hormone replacement therapy (HRT) on hepatocellular carcinoma (HCC) have been investigated in the past. This study aims to further address this topic using a large population dataset of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial (NIH, USA). Methods Multivariable logistic regression was used for the analysis of women in the entire PLCO cohort. Results A non-significant reduction in the risk of developing HCC was observed in women using HRT compared to never users (OR=0.61, 95 % CI: 0.21–1.79, p=0.367). Oral contraceptive use was significantly associated with reduced risk of HCC in the HRT group, (OR=0.17, 95 % CI: 0.00–0.82, p=0.028), and there was a nearly-significant interaction between HRT use and oral contraceptive use (p=0.054). Regardless of HRT use, those with pre-existing liver comorbidities of hepatitis or cirrhosis were at the highest risk of developing HCC (OR=5.09, 95 % CI: 1.13–22.81, p=0.034). However, liver comorbidities of hepatitis or cirrhosis and exposure to HRT showed a significant interaction (p=0.0001). Conclusions In those taking HRT, oral contraceptive use was significantly protective against HCC, suggesting that a longer period of hormone use (oral contraceptive plus HRT) provides additional protection against HCC than HRT alone. Overall, the low numbers of HCC diagnoses, which reflect the wider healthy female population, limited our ability to establish statistical significance regarding the impact of HRT on HCC incidence, which requires further prospective studies of larger populations.