Caroli Disease: Comprehensive Disease-Characteristics Report

Target: Caroli disease (CD)
Category: rare Mendelian cholangiopathy / developmental ciliopathy
Core distinction: CD denotes non-obstructive segmental or diffuse ectasia of the large intrahepatic bile ducts without congenital hepatic fibrosis. Caroli syndrome (CS) denotes the same duct abnormality plus congenital hepatic fibrosis (CHF), often with portal hypertension and renal manifestations of the autosomal-recessive polycystic kidney disease spectrum. The distinction is clinically important and is sometimes blurred in publications and databases. (tidwell2024heritablechroniccholestatic pages 6-7, tidwell2024heritablechroniccholestatic pages 5-6)

The following table summarizes the principal structured findings; the narrative thereafter addresses all 15 requested domains.

Table: This table provides a compact knowledge-base style summary of Caroli disease, explicitly distinguishing it from Caroli syndrome and organizing the main supported facts across genetics, phenotype, mechanism, diagnosis, treatment, prognosis, and models. It is useful as a structured extraction layer from the gathered evidence.

Evidence scope and limitations

The strongest recent sources retrieved were two peer-reviewed 2024 reviews: Tidwell and Wu, published June 2024 (DOI 10.14218/JCTH.2024.00119), and Mahboobipour et al., published April 2024 (DOI 10.1186/s13023-024-03187-w). Mechanistic model evidence was supplemented by Mariotti et al. (DOI 10.1016/j.bbadis.2017.06.027, published April 2018). Most quantitative clinical estimates come from small retrospective cohorts or systematic reviews assembled from case series; they should not be interpreted as population-level precision estimates. No individual-patient EHR data were used.

1. Disease information

Definition and nomenclature

Caroli disease is a congenital malformation of the large intrahepatic bile ducts characterized by non-obstructive, communicating, saccular or fusiform duct dilatation. It predisposes to bile stasis, hepatolithiasis, recurrent bacterial cholangitis, hepatic abscess, sepsis, and cholangiocarcinoma. Pure CD lacks the portal fibrosis and portal hypertension that define CS. (tidwell2024heritablechroniccholestatic pages 6-7, tidwell2024heritablechroniccholestatic pages 5-6)

Common names: Caroli disease; Caroli’s disease; communicating cavernous ectasia of the intrahepatic ducts; simple-type Caroli disease. “Caroli syndrome” is related but not synonymous.

Identifiers:

• MONDO: MONDO:0010913, as supplied and corroborated by the retrieved Open Targets disease record.
• Orphanet: commonly indexed within the Caroli disease/Caroli syndrome spectrum; an exact ORPHA number was not independently verified in the retrieved full text.
• OMIM: the molecularly overlapping PKHD1/ARPKD–CHF spectrum is generally represented through PKHD1-associated polycystic kidney disease; an isolated-CD OMIM number was not verified here.
• MeSH: Caroli Disease.
• ICD: no uniquely validated ICD-10-CM code was established from retrieved evidence; implementations often place it under congenital malformations of bile ducts. ICD coding should therefore be validated against the target jurisdiction and release rather than inferred.

The knowledge represented here is aggregated disease-level evidence from reviews, cohorts, genetic databases, and model studies—not observations extracted from a particular patient record.

2. Etiology, risk, and protective factors

Causal factors

The established causal framework is developmental and genetic. Pathogenic dysfunction in PKHD1, encoding fibrocystin/polyductin, disrupts cholangiocyte primary-cilium and epithelial-tubule biology. The resulting ductal-plate/tubular-architecture abnormality produces large-duct ectasia. Open Targets gives PKHD1–CD an association score of 0.514, supported by genetic literature, clinical variation resources, and animal models; weaker database associations with CYS1 and DZIP1L should not be treated as equivalent, clinically established causes of isolated human CD. (OpenTargets Search: Caroli disease-PKHD1)

A whole-exome study in a Chinese twin family identified recessive compound-heterozygous PKHD1 variants (PMID 24710345). The same report emphasized that PKHD1 variant detection has historically been lower in patients labeled specifically as CD than in severe ARPKD/CHF, consistent with genetic heterogeneity, incomplete testing, or phenotype-classification problems. (OpenTargets Search: Caroli disease-PKHD1)

Risk factors

• Genetic: biallelic pathogenic PKHD1 variants, an affected sibling, parental carrier status, and consanguinity increase risk under an autosomal-recessive model.
• Clinical modifiers: duct distribution and bile stasis determine vulnerability to stones and infection. Chronic inflammation is a downstream risk factor for cholangiocarcinoma rather than a primary cause.
• Environmental/lifestyle: no reproducible toxin, dietary, occupational, smoking, alcohol, sex, or pollution exposure has been shown to cause the congenital malformation. Infection is a complication facilitated by stasis, not the initiating etiology.

Protective factors and gene–environment interaction

No validated protective allele, diet, lifestyle exposure, or pharmacologic primary-prevention factor was identified. A practical gene–environment interaction is that genetically abnormal duct anatomy creates bile stasis, after which bacterial exposure and obstruction precipitate cholangitis and inflammatory injury. This is mechanistically plausible and clinically observed, but formal G×E effect estimates are unavailable.

3. Phenotypes

The course is highly variable and may remain clinically silent for years. In one 14-patient series summarized in the 2024 review, acute cholangitis occurred in 64%, intrahepatic stones/choledocholithiasis in 33%, right-upper-quadrant pain in 50%, jaundice in 35.7%, fever in 28.6%, and asymptomatic disease in 14.3%. Reported laboratory abnormalities included elevated GGT in 64.3%, alkaline phosphatase in 35.7%, and bilirubin in 28.6%. These percentages are series-specific, not universal frequencies. (tidwell2024heritablechroniccholestatic pages 6-7, tidwell2024heritablechroniccholestatic pages 5-6)

In a 16-patient CS cohort, abdominal pain occurred in eight, fever in six, variceal bleeding in one, and fatigue in one; ten had thrombocytopenia and five prolonged prothrombin time. These findings should not be transferred uncritically to simple CD. (tidwell2024heritablechroniccholestatic pages 6-7)

Quality of life: no validated CD-specific EQ-5D, SF-36, or PROMIS dataset was retrieved. Nevertheless, recurrent painful cholangitis, hospitalization, antibiotic exposure, procedures, and fear of sepsis or cancer impose substantial burden; the 2024 review explicitly associates recurrent cholangitis with early quality-of-life loss. (tidwell2024heritablechroniccholestatic pages 6-7)

4. Genetic and molecular information

Causal gene and protein

• PKHD1: human gene ENSG00000170927; encodes fibrocystin/polyductin, a large ciliary/plasma-membrane protein involved in epithelial tubulogenesis and duct-lumen architecture.
• Origin: disease-causing variants are constitutional/germline, generally biallelic under an autosomal-recessive model—not somatic drivers.
• Functional direction: loss or severe reduction of fibrocystin function.
• Protein interaction: fibrocystin’s C-terminal region interacts with the N-terminal region of polycystin-2 (PC2); fibrocystin loss reduces PC2 expression and perturbs calcium signaling. (mariotti2018animalmodelsof pages 13-17, mahboobipour2024clinicalmanifestationepidemiology pages 5-7)

Variant classes and interpretation

PKHD1 disease alleles across the ARPKD/CHF/CD spectrum include missense, nonsense, frameshift, and splice-altering variants. However, no comprehensive CD-specific ClinVar extraction, ACMG classification table, HGVS list, or gnomAD frequency analysis was available in the retrieved evidence. Knowledge-base curation should therefore import variant-level assertions directly from current ClinVar records and retain submitter/date/review-status fields. Pathogenic recessive alleles are expected to be individually rare; a VUS should not be considered diagnostic without segregation, phenotype, population, and functional evidence.

No established recurrent chromosomal abnormality, repeat expansion, mitochondrial variant, somatic mutation mechanism, genetic anticipation, or germline mosaicism pattern was identified. No validated modifier gene or protective allele is known. DZIP1L is biologically relevant to ciliary transition-zone trafficking of PC1/PC2, but its weaker disease association should be labeled emerging/indirect rather than a routine isolated-CD gene. (OpenTargets Search: Caroli disease-PKHD1, mahboobipour2024clinicalmanifestationepidemiology pages 5-7)

Epigenetics

No disease-specific, replicated DNA-methylation, histone-mark, or chromatin-remodeling signature suitable for clinical annotation was retrieved. Epigenomic testing is not standard diagnosis.

5. Environmental information

There is no evidence that toxins, radiation, pollution, occupational exposure, smoking, alcohol, diet, or inactivity cause CD. Ascending bacteria are clinically important in cholangitis, but no single pathogen defines the disease. Common biliary organisms may act opportunistically after stasis or instrumentation. Environmental and lifestyle information should therefore be annotated as not established, rather than “absent by proof.”

6. Mechanism and pathophysiology

Causal chain

1. Upstream germline defect: biallelic PKHD1 dysfunction reduces or alters fibrocystin.
2. Ciliary/tubular defect: abnormal fibrocystin at the cholangiocyte primary cilium/plasma membrane disrupts PC2-associated calcium sensing, planar-cell-polarity/tubulogenesis, and maintenance of duct-lumen architecture.
3. Developmental lesion: malformed large intrahepatic ducts become segmentally or diffusely ectatic and remain connected to the biliary tree.
4. Biophysical consequence: ectatic ducts cause sluggish flow and bile stasis, promoting pigment stones, sludge, obstruction, and bacterial colonization.
5. Clinical consequence: recurrent cholangitis produces pain, fever, jaundice, abscess, and sepsis.
6. Inflammatory/fibrotic amplification: cAMP/β-catenin and NF-κB signaling increases IL-1β, CXCL1, CXCL10, and CXCL12; JAK/STAT and NLRP3/caspase-1 signaling amplify inflammation. Recruited macrophages provide TNF-α and TGF-β; cholangiocyte αvβ6 integrin activates latent TGF-β1, recruiting portal myofibroblasts and extracellular-matrix deposition. This axis is especially important in CS/CHF. (mariotti2018animalmodelsof pages 13-17, tidwell2024heritablechroniccholestatic pages 1-2)
7. Long-term malignant risk: prolonged stasis, epithelial turnover, and inflammation create a field favoring cholangiocarcinoma. (tidwell2024heritablechroniccholestatic pages 6-7)

Human biliary epithelium in CD has shown strong NOTCH1–4 expression relative to weak/negative expression in CHF, but whether this is initiating, compensatory, or downstream remains unresolved. (tidwell2024heritablechroniccholestatic pages 5-6)

Cells, processes, and ontology suggestions

• Primary cell: cholangiocyte / biliary epithelial cell — CL:0000068 may be used after ontology-version validation.
• Secondary cells: macrophages, portal fibroblasts/myofibroblasts, hepatic stellate cells, and vascular cells within portal tracts.
• GO biological processes: cilium organization; epithelial tube morphogenesis; calcium-ion transmembrane transport/signaling; canonical Wnt/β-catenin signaling; NF-κB signaling; chemokine production; macrophage chemotaxis; TGF-β receptor signaling; extracellular-matrix organization; inflammatory response.
• GO cellular components: primary cilium, ciliary membrane, plasma membrane, basal-body/centrosomal region.

Molecular profiling and advanced technologies

No validated CD-specific transcriptomic, proteomic, metabolomic, lipidomic, single-cell, spatial-transcriptomic, or multi-omic clinical signature was retrieved. Contemporary ciliopathy organoids can model patient-specific genotype–phenotype relationships and permit drug screening, but this remains a research application rather than a validated CD diagnostic or therapy.

7. Anatomical structures affected

• Primary organ/system: liver and biliary system; large intrahepatic bile ducts.
• Distribution: diffuse in 50%, right-lobe localized in 28.6%, and left-lobe localized in 21.4% in one small cohort. CD is not intrinsically lateralized; it can be segmental, lobar, or bilobar. (tidwell2024heritablechroniccholestatic pages 5-6)
• Tissue: biliary epithelium and peribiliary/portal connective tissue.
• Cell: cholangiocyte; macrophages and portal myofibroblasts become involved downstream.
• Subcellular: primary cilium/ciliary membrane and plasma-membrane fibrocystin–PC2 complex.
• Secondary structures: portal venous system and spleen in CS; kidneys and occasionally pancreatic cysts in the broader PKHD1 spectrum. (tidwell2024heritablechroniccholestatic pages 6-7)

Suggested anatomical annotations are UBERON liver, intrahepatic bile duct, biliary tree, portal tract, kidney collecting duct, and spleen; exact numeric UBERON identifiers should be ontology-release validated before ingestion.

8. Temporal development

The anatomical defect is congenital, but recognition is often delayed. Most patients reportedly remain asymptomatic until approximately age 20, while more than 80% become symptomatic before age 30. A small adult CD series had a mean diagnostic age of 42 years (range 15–68), illustrating ascertainment variability. (tidwell2024heritablechroniccholestatic pages 6-7, tidwell2024heritablechroniccholestatic pages 5-6)

The course is lifelong and commonly episodic: asymptomatic structural disease may progress to recurrent cholangitis and stones, followed by abscess/sepsis, repeated interventions, or malignancy. Pure CD need not progress to cirrhosis; portal-hypertension progression suggests CS/CHF or secondary advanced injury. Spontaneous anatomical remission is not expected. A critical intervention window occurs when disease remains localized enough for curative-intent resection, before diffuse infection or malignant transformation.

9. Inheritance and population

• Incidence/prevalence: approximately 1 per 1,000,000 is frequently cited, but the retrieved review labels this as incidence and does not establish a rigorous population denominator or annual incidence. Robust registry-based prevalence is lacking. (tidwell2024heritablechroniccholestatic pages 6-7)
• Inheritance: autosomal recessive in the PKHD1-associated spectrum. (tidwell2024heritablechroniccholestatic pages 5-6)
• Penetrance/expressivity: exact penetrance is unknown; expressivity is clearly variable, spanning isolated duct ectasia, CS/CHF, and renal-predominant ARPKD.
• Sex: no sex predominance in the cited 14-patient series. (tidwell2024heritablechroniccholestatic pages 5-6)
• Ethnicity/geography: worldwide case reports exist, but no validated high-risk ancestry or geographic endemicity was identified.
• Founder effects/carrier frequency: no CD-specific founder allele or carrier-frequency estimate was retrieved.
• Anticipation: not expected for a recessive loss-of-function ciliopathy and not reported.
• Consanguinity: increases the probability of biallelic recessive disease, but a CD-specific attributable fraction is unknown.

For confirmed biallelic disease, recurrence risk is conventionally 25% for each pregnancy when both parents are heterozygous carriers, subject to confirmation of phase and parentage.

10. Diagnostics

Imaging and clinical evaluation

MRCP is the preferred non-invasive diagnostic modality. It maps the morphology and communication of intrahepatic duct ectasia while avoiding diagnostic ERCP risks. Contrast CT or MRI may reveal the central dot sign: a portal-vein branch or hepatic-artery branch surrounded by an ectatic duct. Ultrasound can identify duct dilatation and stones; hepatobiliary scintigraphy may show beading. The central dot sign is highly characteristic but its absence does not exclude disease. (tidwell2024heritablechroniccholestatic pages 6-7)

NCT04007575 (IMACA), completed in 2020, retrospectively studied 61 patients to develop MRCP criteria based on duct shape and distribution, the dot sign, calculi, liver abnormalities, and portal-hypertension signs, with the aim of distinguishing CD from benign or malignant obstructive dilatation. This was an observational diagnostic study, not a therapeutic trial. ClinicalTrials.gov: NCT04007575. (NCT04007575 chunk 1)

Laboratory and pathology

During cholangitis, expected findings include neutrophilic leukocytosis, direct hyperbilirubinemia, and elevated alkaline phosphatase/GGT; blood cultures should be obtained before antibiotics when feasible. Renal function, blood counts, coagulation, and portal-hypertension indices help distinguish broader CS/ARPKD involvement. Histology can show dilated non-obstructed ducts with intraluminal wall protrusions and patent portal vascular channels. CK7, MUC1, and β-catenin expression supports fetal/congenital duct phenotype, although biopsy is not routinely necessary when imaging is diagnostic. (tidwell2024heritablechroniccholestatic pages 6-7)

Genetic testing

A practical algorithm is:

1. Confirm compatible communicating intrahepatic duct ectasia by MRCP.
2. Assess kidneys, portal hypertension, fibrosis, and family history.
3. Use a cystic-kidney/cholangiopathy multigene panel including PKHD1 when phenotype is atypical or syndromic.
4. If suspicion remains high, perform deletion/duplication analysis and WES/WGS with phenotype-driven reanalysis.
5. Confirm candidate recessive variants by segregation and ACMG/AMP classification.

PKHD1 next-generation sequencing is available. CMA, karyotyping, FISH, mitochondrial sequencing, and repeat-expansion testing are not first-line unless an independent indication exists. (tidwell2024heritablechroniccholestatic pages 6-7)

Differential diagnosis

Principal alternatives include primary sclerosing cholangitis, recurrent pyogenic cholangitis, obstructive stones or strictures, cholangiocarcinoma, choledochal cyst/type V duct disease terminology, polycystic liver disease, primary biliary disorders, and secondary sclerosing cholangitis. PSC tends to show multifocal stricturing and beading rather than congenital saccular ectasia with central vascular dots; recurrent pyogenic cholangitis is usually accompanied by obstructing pigment stones and acquired strictures. (tidwell2024heritablechroniccholestatic pages 6-7, NCT04007575 chunk 1)

There is no population or newborn screening program. Cascade testing is appropriate after a molecular diagnosis.

11. Outcome and prognosis

Major morbidity arises from recurrent cholangitis, hepatolithiasis, abscesses, sepsis, hospitalization, and repeated biliary procedures. In CS, portal hypertension, variceal bleeding, hypersplenism, and kidney failure add substantial morbidity. Sepsis and hepatic abscess are reported major causes of death. (tidwell2024heritablechroniccholestatic pages 6-7)

Cancer risk

A multicenter dataset found cholangiocarcinoma in 6.3% of CD and 7.6% of CS patients. A systematic review of 561 CD patients reported a 6.6% incidence; among affected cancer cases, one-year survival was 36% and recurrence 75%. Heterogeneous referral and surgical ascertainment likely inflate or destabilize these estimates, but the direction of risk is clear. (tidwell2024heritablechroniccholestatic pages 6-7)

Treatment-associated prognosis

After transplantation, reported patient survival was 99%, 96.2%, and 94.6% at one, three, and five years; corresponding graft survival was 94.9%, 91.1%, and 89.6%. These excellent selected-cohort outcomes should not be interpreted as untreated natural-history survival. (tidwell2024heritablechroniccholestatic pages 5-6)

No validated CD-specific prognostic biomarker or risk calculator exists. Clinically adverse indicators include diffuse/bilobar disease, recurrent uncontrolled infection, abscess, portal hypertension, renal failure, and suspected malignancy.

12. Treatment and current implementation

No approved drug corrects the congenital duct lesion or PKHD1 defect. Management is anatomy- and complication-directed.

Medical and interventional care

• Acute cholangitis: prompt broad-spectrum antibiotics, cultures, supportive care, and biliary decompression when obstruction or failure of medical therapy is present. Suggested NCIt concept: antibiotic therapy.
• Hepatolithiasis: ursodeoxycholic acid may be used for intrahepatic stones, although robust CD-specific response trials are lacking. Suggested chemical annotation: ursodeoxycholic acid; NCIt intervention: pharmacologic treatment.
• Bridging: chronic suppressive antibiotics may be used in selected patients with recurrent infection awaiting transplantation. (tidwell2024heritablechroniccholestatic pages 6-7, tidwell2024heritablechroniccholestatic pages 5-6)
• Endoscopic/percutaneous drainage: useful for accessible stones, strictures, abscesses, or acute decompression; repeated instrumentation can itself introduce infection.

Surgery

• Localized unilobar/segmental CD: anatomical hepatectomy can remove the diseased reservoir and may be definitive.
• Diffuse/bilobar disease, recurrent life-threatening cholangitis, portal-hypertensive CS, or unresectable disease: liver transplantation.
• Clinically important renal failure/ARPKD: simultaneous liver–kidney transplantation may be appropriate. (tidwell2024heritablechroniccholestatic pages 5-6)

Reported surgical complications include bile leak 26%, revision 16%, pleural effusion 5.5%, and urinary infection 5.5%. A reviewed surgical cohort of 21 patients had no deaths over five years, but the sample was small and selected. (tidwell2024heritablechroniccholestatic pages 6-7)

Suggested NCIt intervention concepts: hepatectomy, partial hepatectomy, liver transplantation, combined liver–kidney transplantation, endoscopic biliary drainage, percutaneous drainage, antibiotic therapy, and ursodeoxycholic acid treatment.

Advanced and experimental treatment

No established gene therapy, CRISPR therapy, ASO/siRNA therapy, cell therapy, or targeted anti-ciliary drug is approved for CD. cAMP, β-catenin, inflammatory, and TGF-β pathways are preclinical targets, but systemic inhibition may be toxic and evidence has not reached disease-specific clinical efficacy. The trial search identified observational natural-history/imaging studies rather than active interventional CD drug trials. NCT01401998 is an observational ARPKD database study, relevant to the broader PKHD1 spectrum but not a CD treatment trial.

No CD-specific pharmacogenomic guideline from CPIC/PharmGKB was identified.

13. Prevention

Primary prevention: the congenital genetic lesion cannot currently be prevented by lifestyle modification or vaccination. Genetic counseling, carrier testing after familial variants are known, prenatal diagnosis, and preimplantation genetic testing are reproductive-risk options—not treatments of an affected person.

Secondary prevention: no population screening is recommended. Family cascade testing and imaging/genetic evaluation of at-risk siblings can enable earlier detection. Periodic clinical, biochemical, and imaging review is reasonable, although an evidence-based surveillance interval was not established.

Tertiary prevention: rapid treatment of cholangitis, removal or drainage of obstructing stones, avoidance of unnecessary biliary instrumentation, management of portal hypertension and renal disease, and timely referral for resection/transplantation can reduce complications. Given the increased cholangiocarcinoma risk, expert hepatobiliary follow-up is appropriate, but no screening method or interval has proven mortality benefit. Vaccination according to chronic-liver-disease/transplant schedules may reduce unrelated infectious morbidity; it does not prevent CD.

14. Other species and natural disease

No well-established, common naturally occurring veterinary counterpart with validated breed-specific inheritance was retrieved. Caroli-like hepatobiliary lesions can occur in animal disease descriptions, but the principal comparative evidence comes from engineered or spontaneous laboratory models rather than a recognized zoonosis.

There is no zoonotic potential and no cross-species transmission: CD is an inherited developmental disorder. PKHD1/fibrocystin function is evolutionarily conserved across vertebrates, enabling rodent modeling.

15. Model organisms

PCK rat

The PCK rat carries an orthologous Pkhd1 splicing defect and develops progressive intrahepatic bile-duct dilatation and hepatic cystic lesions, together with renal outer-medullary collecting-duct cysts. With age, some cystic structures disconnect from the biliary system. The model develops mild portal fibrosis but generally lacks the full fibrous septa and portal hypertension of severe human CS. It is useful for studying cholangiocyte cilia, cyst growth, bile-duct remodeling, and candidate antifibrotic/cyst-directed treatments. (mariotti2018animalmodelsof pages 13-17)

Pkhd1del4/del4 mouse

This mouse develops intrahepatic duct dysgenesis followed by cyst-like configuration and peribiliary fibrosis after approximately three months; more than 50% show splenomegaly by six months, consistent with clinically relevant portal hypertension. It is especially useful for dissecting macrophage–cholangiocyte–myofibroblast signaling. (mariotti2018animalmodelsof pages 13-17)

Mechanistic findings and limitations

Fibrocystin-deficient cholangiocytes produce CXCL1, CXCL10, and CXCL12 through overactive β-catenin signaling. Macrophage-derived TNF-α/TGF-β promotes αvβ6-integrin-mediated local activation of TGF-β1 and portal fibrosis; macrophage depletion with clodronate reduces fibrosis in model systems. Pkhd1 knockout also increases cholangiocyte CTGF production. (mariotti2018animalmodelsof pages 13-17, mahboobipour2024clinicalmanifestationepidemiology pages 5-7)

These models recapitulate major features of the ARPKD–CHF–CS spectrum better than they reproduce isolated adult simple CD. Species differences, variable renal involvement, and incomplete human phenotypic heterogeneity limit direct translation. Liver/cholangiocyte organoids and patient-derived iPSC systems offer a complementary human platform, but no validated organoid-guided treatment is currently implemented clinically.

Overall assessment

Caroli disease is best understood as a rare developmental cholangiociliopathy centered on abnormal large intrahepatic ducts. PKHD1/fibrocystin dysfunction is the strongest established genetic mechanism, but variant detection and genotype–phenotype mapping are less complete for isolated CD than for classic ARPKD/CHF. The major real-world priorities are accurate MRCP-based diagnosis, strict separation of CD from CS, rapid management of cholangitis and stones, anatomical resection for localized disease, transplantation for diffuse or life-threatening disease, and long-term expert monitoring for infection and cholangiocarcinoma. Recent 2024 literature primarily refines genetic-cholestasis classification and ciliary mechanisms; it has not yet delivered a disease-modifying molecular therapy. (tidwell2024heritablechroniccholestatic pages 6-7, OpenTargets Search: Caroli disease-PKHD1, tidwell2024heritablechroniccholestatic pages 1-2, tidwell2024heritablechroniccholestatic pages 5-6)

References

1. (tidwell2024heritablechroniccholestatic pages 6-7): Jasmine Tidwell and George Y. Wu. Heritable chronic cholestatic liver diseases: a review. Journal of Clinical and Translational Hepatology, 12:726-738, Jun 2024. URL: https://doi.org/10.14218/jcth.2024.00119, doi:10.14218/jcth.2024.00119. This article has 14 citations.

2. (tidwell2024heritablechroniccholestatic pages 5-6): Jasmine Tidwell and George Y. Wu. Heritable chronic cholestatic liver diseases: a review. Journal of Clinical and Translational Hepatology, 12:726-738, Jun 2024. URL: https://doi.org/10.14218/jcth.2024.00119, doi:10.14218/jcth.2024.00119. This article has 14 citations.

3. (OpenTargets Search: Caroli disease-PKHD1): Open Targets Query (Caroli disease-PKHD1, 4 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.

4. (mariotti2018animalmodelsof pages 13-17): Valeria Mariotti, Mario Strazzabosco, Luca Fabris, and Diego F. Calvisi. Animal models of biliary injury and altered bile acid metabolism. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1864:1254-1261, Apr 2018. URL: https://doi.org/10.1016/j.bbadis.2017.06.027, doi:10.1016/j.bbadis.2017.06.027. This article has 237 citations and is from a peer-reviewed journal.

5. (tidwell2024heritablechroniccholestatic pages 1-2): Jasmine Tidwell and George Y. Wu. Heritable chronic cholestatic liver diseases: a review. Journal of Clinical and Translational Hepatology, 12:726-738, Jun 2024. URL: https://doi.org/10.14218/jcth.2024.00119, doi:10.14218/jcth.2024.00119. This article has 14 citations.

6. (mahboobipour2024clinicalmanifestationepidemiology pages 5-7): Amir Ali Mahboobipour, Moein Ala, Javad Safdari Lord, and Arash Yaghoobi. Clinical manifestation, epidemiology, genetic basis, potential molecular targets, and current treatment of polycystic liver disease. Orphanet Journal of Rare Diseases, Apr 2024. URL: https://doi.org/10.1186/s13023-024-03187-w, doi:10.1186/s13023-024-03187-w. This article has 23 citations and is from a peer-reviewed journal.

7. (NCT04007575 chunk 1): Study of New Imaging Criteria for the Diagnosis of Caroli's Disease. Assistance Publique - Hôpitaux de Paris. 2020. ClinicalTrials.gov Identifier: NCT04007575

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