Caroli disease (CD) is a rare congenital hepatobiliary disorder characterized by multifocal segmental dilatation of the intrahepatic bile ducts, which may involve the entire liver or only a specific region. This rare pathology is seen in a very small proportion of the global population. Clinical manifestations vary between individuals and may overlap with other hepatobiliary disorders, making diagnosis and management challenging. Due to limited understanding and experience, early diagnosis and intervention are crucial for improving survival. In our case, Caroli disease is associated with autosomal recessive polycystic kidney disease (ARPKD), both of which are autosomal recessive disorders most commonly found in infants and children, with survival into adulthood being rare.

To evaluate the clinical outcomes of liver transplantation (LT) in patients with Caroli syndrome. We retrospectively analyzed clinical data from 20 patients diagnosed with Caroli syndrome who underwent LT at Beijing Friendship Hospital, Capital Medical University, between April 2014 and May 2024. Data included baseline characteristics, surgical parameters, complications, and survival. Follow-up concluded in February 2025. These 20 cases accounted for 1.23% (20/1623) of all LTs during the study period. Thirteen patients received living donor liver transplants (LDLT), and seven received deceased donor liver transplants (DDLT). The cohort included 15 males and 5 females, aged 3–56 years (median 23.3). Common preoperative conditions included cirrhosis (n = 18), portal hypertension (n = 17), polycystic kidney disease (n = 16), and splenomegaly (n = 17). The median APACHE II score was 14; the predicted mortality averaged 26.0%. The median interval from the first major complication (e.g., recurrent cholangitis or decompensation) to LT was 12 months (IQR 4.5–21). No patients underwent cross-match or auxiliary LT; three had concurrent partial splenectomy. Postoperative complications included abdominal hemorrhage (n = 3) and seizures (n = 1). Chronic renal failure occurred in six patients during follow-up, and four experienced acute rejection (three recurrent). Compared with adults, pediatric patients had a higher proportion of females (p = 0.001), while chronic renal failure was more common in adults preoperatively (p = 0.010). Four patients (20%) died: one from heart failure (day 8), one from sudden death (6 months), one from pulmonary infection (1 year), and one from unknown causes (5.2 years). Median follow-up was 74.6 months (range 7-125). One-, three-, and five-year survival rates were 90%, 85%, and 78.5%, respectively. Liver transplantation significantly improves the survival prognosis for patients with Caroli syndrome, but attention to kidney function preservation and individualized immunosuppressive management is critical for optimal outcomes.

Caroli disease (CD) and Caroli syndrome (CS) are rare inherited disorders characterized by dilatation of intrahepatic bile ducts, caused by PKHD1 pathogenic variants. Prenatal diagnosis of CD or CS is extremely rare, with only two cases having genetic analysis worldwide. In this study, we describe the prenatal imaging and genetic findings in two Chinese fetuses with CD/CS. Prenatal ultrasound and magnetic resonance imaging (MRI) findings were collected for both fetuses. Whole exome sequencing was performed in family 1 and fetus 2, using fetal umbilical cord and parental peripheral blood. The candidate variants were validated using Sanger sequencing. The effect of the splice site variant was evaluated by in vitro minigene assays with the pcMINI-C and pcMINI vectors. Both fetuses presented with multiple dilated intrahepatic bile ducts and features consistent with autosomal recessive polycystic kidney disease (ARPKD) on ultrasound and MRI at 33 weeks (Fetus 1) and 39 weeks (Fetus 2) gestation; Fetus 2 also exhibited oligohydramnios. Trio WES analysis revealed two compound heterozygous variants of PKHD1, a missense variant c.7912T>A (p.Tyr2638Asn) and an intronic splice-site variant c.3364 + 3A>T, in Fetus 1, with the father carrying c.7912T>A and the mother c.3364 + 3A>T. WES analysis in Fetus 2 identified two PKHD1 candidate variants, c.9901G>T (p.Glu3301Ter) and c.2507T>C (p.Val836Ala). These variants were confirmed by Sanger sequencing, and in silico prediction and conservation analysis suggested their potential pathogenicity. The c.3364 + 3A>T variant has been previously reported postnatally but functionally uncharacterized. In vitro minigene assays demonstrated that it caused exon 29 skipping, leading to a frameshift and a premature stop codon (c.3229_3364del p.Gly1077Alafs*12). We reported the first prenatally diagnosed CD/CS cases with genetic analysis in the Chinese population, and experimentally validated the pathogenicity of the recurrent splice site variant c.3364 + 3A>T by a minigene assay. Our findings broaden the PKHD1 variation spectrum in these rare cases and recommend including prenatal cases to refine the reported genotype-phenotype correlations. We also emphasize the need of WES in probands with CD or CS for early molecular diagnosis in subsequent pregnancies.

Caroli syndrome is a rare but serious congenital disorder associated with portal hypertension and polycystic kidney disease. Early diagnosis via imaging, particularly MRCP, is crucial to prevent life-threatening complications such as cholangitis and biliary cirrhosis. Timely intervention and close monitoring can significantly improve patient outcomes.