Clinical features and long-term outcomes of patients with ZFYVE19 variants

ZFYVE19-associated progressive familial intrahepatic cholestasis is a rare ciliopathy, with limited information on its natural history.

Investigate long-term outcomes, especially after liver transplantation (LT), in ZFYVE19-deficient patients.

Medical data of 13 Chinese individuals genetically diagnosed with ZFYVE19 deficiency, including 4 unreported patients, were reviewed.

All patients harbored biallelic null variants in ZFYVE19 and were alive at a median age of 13.2 years (range 1.1-39) with a median follow-up of 6.4 years (range 1-19.7). The first manifestation was neonatal cholestasis in 4 patients, isolated abnormal hepatobiliary-injury biomarkers in 3, and portal hypertension in 6. Eleven patients were administered ursodeoxycholic acid, with temporary normalization of hepatobiliary-injury biomarkers in 7. Six patients underwent LT (4 with living-related donors) at a median age of 3.5 years (range 0.6-7). After a median follow-up of 5.3 years (range 0.5-19) after LT, all 6 patients survived and were asymptomatic. Chronic renal disease or malignancy has not supervened.

ZFYVE19 deficiency caused by biallelic null variants primarily affects the liver without clinically significant involvement of other organs. ZFYVE19-related neonatal cholestasis can progress to liver failure necessitating LT in infancy. Ursodeoxycholic acid may improve hepatobiliary indices but may not avoid cirrhosis / LT. LT outcomes are generally good, even with parental grafts.