MO015: The Interaction of Gender and Genotype in the Development of Polycystic Liver Disease in ADPKD

Abstract

Abstract BACKGROUND AND AIMS Liver cysts are the most common extra-renal manifestation in autosomal dominant polycystic kidney disease (ADPKD) and polycystic liver disease (PLD) may result in significant morbidity in a proportion of patients. The major objective of this study was to investigate the relationship between the incidence of liver cysts and PLD with age, gender and genotype in a longitudinal ADPKD patient cohort (n = 625) followed up between 2010 and 2021. METHOD A retrospective analysis of PLD was performed on all patients with available abdominal US (US, n = 565) or abdominal MRI/CT (n = 321) imaging. Liver cyst counts were obtained from routine clinical reports (US) or quantified by a single-blinded observer (MR/CT). Patients were divided into subgroups of different severity based on cyst numbers detected on US (QIAN 0–4) or MRI/CT (CHEN 0–3): QIAN 0 (0), 1 (<10), 2 (10–20), 3/4 (>20); CHEN 0 (0), 1 (<20), 2 (21–40), 3 (>40). Patients who were genotyped (n = 390) were classified into those with PKD1 (T, truncating or NT, non-truncating), PKD2, other genes (non-PKD1 or PKD2) or NMD (no mutation detected). The potential influence of genotype and gender on the incidence of liver cysts and the time to the development of PLD (defined as QIAN 3/4 or CHEN 3) was investigated by survival analysis (Kaplan–Meier plots). Hazard ratios (HR) were calculated and statistical significance was determined via Log-rank (Mantel-Cox) or Chi-square tests. RESULTS Liver cysts were detected in 61% of patients by US and 72% by MRI/CT, increasing with age. Kaplan–Meier plots showed a significant effect of gender for the presence of liver cysts (M: F HR of 0.74 US, 0.69 MR/CT). Genotype had a major effect on the prevalence of liver cysts (US, n = 344) with a median age of 46, 53, 59, 75 and 77 years for PKD1-T, PKD1-NT, PKD2, other genes or NMD, respectively. A similar trend was noted for patients with MR/CT imaging. The percentage of patients with PLD (QIAN 3/4 or CHEN 3) ranged between 26% (US) and 36% (MR/CT) with a median age for developing PLD of 51 (US; min-max range 23–80 years) and 50 years (MR/CT; min-max range 27–81 years), respectively. The incidence of PLD was more strongly influenced by gender (M: F HR 0.53 US, 0.56 MR/CT) and was highly enriched in patients with PKD1 or PKD2 mutations. CONCLUSION Female patients with a PKD1-T genotype appear to be at the highest risk of developing PLD. Genotypes other than PKD1 or PKD2 are unlikely to develop PLD. Further work is needed to improve risk stratification and treatments for PLD by identifying additional pathogenic factors.