Higher need for polycystic liver disease therapy in female patients: sex-specific association between liver volume and need for therapy

BACKGROUND AND AIMS: Prognostic tools or biomarkers are urgently needed in polycystic liver disease (PLD) to monitor disease progression and evaluate treatment outcomes. Total liver volume (TLV) is currently used to assess cross-sectional disease severity, and female patients typically have larger livers than males. Therefore, this study explores the sex-specific association between TLV and volume-reducing therapy (VRT). APPROACH AND RESULTS: In this prospective cohort study, we included patients with PLD from European treatment centers. We explored sex-specific differences in the association between baseline TLV and initiation of volume-reducing therapy and determined the cumulative incidence rates of volume-reducing therapy in our cohort.We included 358 patients, of whom 157 (43.9%) received treatment. Treated patients had a higher baseline TLV (median TLV 2.16 vs. 4.34 liter, p < 0.001), were more frequently female (69.7% vs. 89.8%, p < 0.001), and had a higher risk of liver events (HR 4.381, p < 0.001). The cumulative volume-reducing therapy rate at 1 year of follow-up was 21.0% for females compared to 9.1% for males. Baseline TLV was associated with volume-reducing therapy, and there was an interaction with sex (HR females 1.202, p < 0.001; HR males 1.790, p < 0.001; at 1.5 l). CONCLUSION: Baseline TLV is strongly associated with volume-reducing therapy initiation at follow-up in patients with PLD, with sex-specific differences in this association. Disease staging systems should use TLV to predict the need for future volume-reducing therapy in PLD separately for males and females.