Autosomal dominant polycystic liver disease

Mendelian MONDO:0000447 Pathograph 9 autosomal dominant disease liver disorder

Autosomal dominant polycystic liver disease (ADPLD), also called isolated polycystic liver disease, is an adult-onset inherited disorder in which numerous cholangiocyte-derived cysts spread through the liver. Cyst burden causes hepatomegaly, abdominal distention, early satiety, dyspnea, pain, and reflux while liver synthetic function is usually preserved. Disease-causing germline variants include PRKCSH, SEC63, ALG8, and LRP5; the best-defined mechanism links PRKCSH and SEC63 endoplasmic-reticulum protein biogenesis defects to inefficient polycystin maturation, reduced polycystin-1 dosage, and progressive hepatic cystogenesis.

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1
Mappings
1
Definitions
1
Inheritance
4
Pathophys.
19
Phenotypes
9
Pathograph
4
Genes
3
Treatments
4
Subtypes
10
References
1
Deep Research
🔗

Mappings

MONDO
MONDO:0000447 autosomal dominant polycystic liver disease
skos:exactMatch MONDO Orphanet:2924 xref
MONDO:0000447 carries Orphanet:2924 as a disease cross-reference, and ORPHA:2924 is the Orphanet structured record used by this entry.
📘

Definitions

1
Orphanet isolated PCLD definition
Genetic isolated polycystic liver disease characterized by numerous cysts spread throughout the liver, usually described as ADPLD.
OTHER
Show evidence (1 reference)
ORPHA:2924 SUPPORT Other
"Isolated polycystic liver disease (PCLD) is a genetic disorder characterized by the appearance of numerous cysts spread throughout the liver and that in most cases is described as autosomal dominant polycystic liver disease (ADPCLD)."
Orphanet provides the structured definition for this entry.
👪

Inheritance

1
Autosomal dominant inheritance HP:0000006
ADPLD is inherited in an autosomal dominant pattern.
Autosomal dominant inheritance
Show evidence (1 reference)
ORPHA:2924 SUPPORT Other
"- Autosomal dominant"
Orphanet records autosomal dominant inheritance for isolated polycystic liver disease.
◆

Subtypes

4
PRKCSH-related polycystic liver disease 1 MONDO:0008265
PRKCSH link
PRKCSH-related ADPLD subtype with numerous liver cysts and possible kidney cysts.
Show evidence (1 reference)
ORPHA:2924 SUPPORT Other
"PRKCSH | PRKCSH beta subunit of glucosidase II | hgnc:9411 | Disease-causing germline mutation(s) in"
Orphanet lists PRKCSH as a disease-causing gene for the ADPLD record.
SEC63-related polycystic liver disease 2 MONDO:0014860
SEC63 link
SEC63-related ADPLD subtype with numerous liver cysts and possible kidney cysts.
Show evidence (1 reference)
ORPHA:2924 SUPPORT Other
"SEC63 | SEC63 protein translocation regulator | hgnc:21082 | Disease-causing germline mutation(s) in"
Orphanet lists SEC63 as a disease-causing gene for the ADPLD record.
ALG8-related ADPLD
ALG8 link
ALG8-related ADPLD is included in the Orphanet gene-disease table for isolated polycystic liver disease.
Show evidence (1 reference)
ORPHA:2924 SUPPORT Other
"ALG8 | ALG8 alpha-1,3-glucosyltransferase | hgnc:23161 | Disease-causing germline mutation(s) in"
Orphanet lists ALG8 as a disease-causing gene for the ADPLD record.
LRP5-related ADPLD
LRP5 link
LRP5-related ADPLD is included in the Orphanet gene-disease table for isolated polycystic liver disease.
Show evidence (1 reference)
ORPHA:2924 SUPPORT Other
"LRP5 | LDL receptor related protein 5 | hgnc:6697 | Disease-causing germline mutation(s) in"
Orphanet lists LRP5 as a disease-causing gene for the ADPLD record.
⚙

Pathophysiology

4
PRKCSH and SEC63 ER protein biogenesis defects
PRKCSH and SEC63 encode endoplasmic-reticulum proteins involved in protein biogenesis and quality control. Disease-causing variants impair maturation of integral membrane and secreted proteins that restrain cyst formation.
PRKCSH link SEC63 link
endoplasmic-reticulum protein folding link ↓ DECREASED
endoplasmic reticulum link
Downstream
Inefficient polycystin maturation and reduced PC1 dosage ER biogenesis defects impair maturation of polycystin proteins.
Show evidence (1 reference)
PMID:26877954 SUPPORT Model Organism
"The two genes responsible for isolated polycystic liver disease, PRKCSH and SEC63, are both involved in modulating protein biogenesis and quality control for integral membrane and secreted proteins in the endoplasmic reticulum."
This review summarizes model-derived evidence that PRKCSH and SEC63 affect ER protein biogenesis and quality control.
Inefficient polycystin maturation and reduced PC1 dosage
Inefficient polycystin maturation lowers functional polycystin-1 dosage. Reduced PC1 availability is a rate-limiting cyst-promoting step in polycystic liver and kidney models.
polycystin protein maturation link ↓ DECREASED
endoplasmic reticulum link
Downstream
Cholangiocyte hyperproliferation and hepatic cystogenesis Reduced polycystin dosage promotes epithelial cyst formation through altered cystic epithelial signaling.
Show evidence (1 reference)
PMID:26877954 SUPPORT Model Organism
"Overexpression of Pkd1, but not Pkd2, can overcome the tendency toward cyst formation in Prkcsh and Sec63 mutants, thereby establishing PC1 as the rate-limiting component whose dosage determines both the rate and extent of cyst formation in ADPKD"
Mouse-model evidence supports PC1 dosage as a rate-limiting cystogenesis mechanism downstream of PRKCSH and SEC63 defects.
Cholangiocyte hyperproliferation and hepatic cystogenesis
Hepatic cystogenesis involves cholangiocyte hyperproliferation, abnormal fluid secretion, and altered cell-matrix interaction, generating multiple epithelial cysts throughout the liver.
cholangiocyte link
cholangiocyte hyperproliferation link ↑ INCREASED
liver link
Downstream
Mass-effect hepatomegaly with preserved liver function Progressive hepatic cyst expansion enlarges the liver and compresses adjacent structures.
Show evidence (2 references)
PMID:23296249 SUPPORT Human Clinical
"Processes involved in hepatic cystogenesis include ductal plate malformation with concomitant abnormal fluid secretion, altered cell-matrix interaction and cholangiocyte hyperproliferation."
The clinical review identifies cholangiocyte hyperproliferation and fluid secretion as hepatic cystogenesis processes.
PMID:27016902 SUPPORT Human Clinical
"Polycystic liver disease (PLD) is characterized by the presence of multiple cholangiocyte-derived epithelial cysts that cause progressive liver enlargement."
The surgical cohort describes PLD cysts as cholangiocyte-derived epithelial cysts that enlarge the liver.
Mass-effect hepatomegaly with preserved liver function
Multiple liver cysts enlarge the liver and compress neighboring structures, producing abdominal distention, early satiety, dyspnea, reflux, pain, edema, and occasional cholestatic features. Liver function commonly remains preserved despite substantial cyst burden.
liver link
Show evidence (2 references)
PMID:35487607 SUPPORT Human Clinical
"Though isolated PCLD and PCLD due to ADPKD are genetically distinct, they follow a similar clinical course of hepatomegaly from multiple cysts with preserved liver function."
The review supports the core clinical course of hepatomegaly with preserved liver function.
PMID:24886261 SUPPORT Human Clinical
"Major complaints include abdominal pain, abdominal distension and atypical symptoms because of voluminous cysts resulting in compression of adjacent tissue or failure of the affected organ."
The review supports mass-effect symptoms from voluminous cysts.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Autosomal dominant polycystic liver disease Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

19
Blood 1
Gastrointestinal hemorrhage OCCASIONAL Gastrointestinal hemorrhage (HP:0002239)
Show evidence (1 reference)
ORPHA:2924 SUPPORT Other
"HP:0002239 | Gastrointestinal hemorrhage | Occasional (29-5%)"
Orphanet lists gastrointestinal hemorrhage as occasional.
Cardiovascular 1
Abnormal heart valve morphology OCCASIONAL Abnormal heart valve morphology (HP:0001654)
Show evidence (1 reference)
ORPHA:2924 SUPPORT Other
"HP:0001654 | Abnormal heart valve morphology | Occasional (29-5%)"
Orphanet lists abnormal heart valve morphology as occasional.
Digestive 5
Hepatomegaly VERY_FREQUENT Hepatomegaly (HP:0002240)
Show evidence (2 references)
ORPHA:2924 SUPPORT Other
"HP:0002240 | Hepatomegaly | Very frequent (99-80%)"
Orphanet lists hepatomegaly as very frequent.
PMID:35487607 SUPPORT Human Clinical
"they follow a similar clinical course of hepatomegaly from multiple cysts with preserved liver function."
The review directly links PCLD to hepatomegaly from multiple cysts.
Abdominal distention VERY_FREQUENT Abdominal distention (HP:0003270)
Show evidence (2 references)
ORPHA:2924 SUPPORT Other
"HP:0003270 | Abdominal distention | Very frequent (99-80%)"
Orphanet lists abdominal distention as very frequent.
PMID:24886261 SUPPORT Human Clinical
"Major complaints include abdominal pain, abdominal distension and atypical symptoms because of voluminous cysts resulting in compression of adjacent tissue or failure of the affected organ."
The review names abdominal distension among major complaints.
Early satiety FREQUENT Early satiety (HP:0033842)
Show evidence (2 references)
ORPHA:2924 SUPPORT Other
"HP:0033842 | Early satiety | Frequent (79-30%)"
Orphanet lists early satiety as frequent.
PMID:27016902 SUPPORT Human Clinical
"Indications for surgery were abdominal distention, abdominal pain, early satiety, supine dyspnea, fatigue, uterine pro-lapse, hepatic venous outflow obstruction with ascites, obstruction of the inferior vena cava and dialysis hypotension, bile duct obstruction, and infected cysts."
The surgical cohort includes early satiety among symptomatic PLD indications for surgery.
Gastroesophageal reflux OCCASIONAL Gastroesophageal reflux (HP:0002020)
Show evidence (2 references)
ORPHA:2924 SUPPORT Other
"HP:0002020 | Gastroesophageal reflux | Occasional (29-5%)"
Orphanet lists gastroesophageal reflux as occasional.
PMID:27016902 SUPPORT Human Clinical
"Cystic enlargement causes liver enlargement, which can be marked and result in dyspnea, early satiety, gastroesophageal reflux, mechanical back pain, hepatic venous outflow obstruction, portal vein and inferior vena cava compression, and, rarely, jaundice from bile duct compression."
The cohort links cystic enlargement to gastroesophageal reflux.
Jaundice OCCASIONAL Jaundice (HP:0000952)
Show evidence (2 references)
ORPHA:2924 SUPPORT Other
"HP:0000952 | Jaundice | Occasional (29-5%)"
Orphanet lists jaundice as occasional.
PMID:27016902 SUPPORT Human Clinical
"Cystic enlargement causes liver enlargement, which can be marked and result in dyspnea, early satiety, gastroesophageal reflux, mechanical back pain, hepatic venous outflow obstruction, portal vein and inferior vena cava compression, and, rarely, jaundice from bile duct compression."
The cohort supports jaundice as a rare compression complication.
Genitourinary 1
Multiple renal cysts FREQUENT Multiple renal cysts (HP:0005562)
Show evidence (2 references)
ORPHA:2924 SUPPORT Other
"HP:0005562 | Multiple renal cysts | Frequent (79-30%)"
Orphanet lists multiple renal cysts as frequent in this ADPLD record.
PMID:29038287 SUPPORT Human Clinical
"autosomal dominant polycystic liver diseases (ADPLD), which result in significant PLD with minimal PKD."
The genetics review supports limited kidney cyst involvement in ADPLD.
Respiratory 2
Dyspnea OCCASIONAL Dyspnea (HP:0002094)
Show evidence (2 references)
ORPHA:2924 SUPPORT Other
"HP:0002094 | Dyspnea | Occasional (29-5%)"
Orphanet lists dyspnea as occasional.
PMID:27016902 SUPPORT Human Clinical
"Cystic enlargement causes liver enlargement, which can be marked and result in dyspnea, early satiety, gastroesophageal reflux, mechanical back pain, hepatic venous outflow obstruction, portal vein and inferior vena cava compression, and, rarely, jaundice from bile duct compression."
The cohort links marked liver enlargement to dyspnea.
Respiratory insufficiency OCCASIONAL Respiratory insufficiency (HP:0002093)
Show evidence (1 reference)
ORPHA:2924 SUPPORT Other
"HP:0002093 | Respiratory insufficiency | Occasional (29-5%)"
Orphanet lists respiratory insufficiency as occasional.
Constitutional 2
Abdominal pain OCCASIONAL Abdominal pain (HP:0002027)
Show evidence (2 references)
ORPHA:2924 SUPPORT Other
"HP:0002027 | Abdominal pain | Occasional (29-5%)"
Orphanet lists abdominal pain as occasional.
PMID:24886261 SUPPORT Human Clinical
"Major complaints include abdominal pain, abdominal distension and atypical symptoms because of voluminous cysts resulting in compression of adjacent tissue or failure of the affected organ."
The review names abdominal pain among major complaints.
Back pain OCCASIONAL Back pain (HP:0003418)
Show evidence (2 references)
ORPHA:2924 SUPPORT Other
"HP:0003418 | Back pain | Occasional (29-5%)"
Orphanet lists back pain as occasional.
PMID:27016902 SUPPORT Human Clinical
"Cystic enlargement causes liver enlargement, which can be marked and result in dyspnea, early satiety, gastroesophageal reflux, mechanical back pain, hepatic venous outflow obstruction, portal vein and inferior vena cava compression, and, rarely, jaundice from bile duct compression."
The cohort links cystic enlargement to mechanical back pain.
Other 7
Polycystic liver disease VERY_FREQUENT Polycystic liver disease (HP:0006557)
Show evidence (2 references)
ORPHA:2924 SUPPORT Other
"HP:0006557 | Polycystic liver disease | Very frequent (99-80%)"
Orphanet lists polycystic liver disease as very frequent.
PMID:36246085 SUPPORT Human Clinical
"Polycystic liver disease (PLD) manifests as numerous fluid-filled cysts scattered throughout the liver parenchyma."
Human cohort framing supports numerous liver cysts as the core phenotype.
Elevated alkaline phosphatase OCCASIONAL Elevated circulating alkaline phosphatase concentration (HP:0003155)
Show evidence (1 reference)
ORPHA:2924 SUPPORT Other
"HP:0003155 | Elevated circulating alkaline phosphatase concentration | Occasional (29-5%)"
Orphanet lists elevated alkaline phosphatase as occasional.
Elevated gamma-glutamyltransferase OCCASIONAL Elevated gamma-glutamyltransferase level (HP:0030948)
Show evidence (1 reference)
ORPHA:2924 SUPPORT Other
"HP:0030948 | Elevated gamma-glutamyltransferase level | Occasional (29-5%)"
Orphanet lists elevated gamma-glutamyltransferase as occasional.
Hyperbilirubinemia OCCASIONAL Increased total bilirubin (HP:0003573)
Show evidence (1 reference)
ORPHA:2924 SUPPORT Other
"HP:0003573 | Increased total bilirubin | Occasional (29-5%)"
Orphanet lists increased total bilirubin as occasional.
Pedal edema OCCASIONAL Pedal edema (HP:0010741)
Show evidence (1 reference)
ORPHA:2924 SUPPORT Other
"HP:0010741 | Pedal edema | Occasional (29-5%)"
Orphanet lists pedal edema as occasional.
Dilatation of the cerebral artery OCCASIONAL Dilatation of the cerebral artery (HP:0004944)
Show evidence (1 reference)
ORPHA:2924 SUPPORT Other
"HP:0004944 | Dilatation of the cerebral artery | Occasional (29-5%)"
Orphanet lists cerebral artery dilatation as occasional.
Abnormality of the pancreas OCCASIONAL Abnormality of the pancreas (HP:0001732)
Show evidence (1 reference)
ORPHA:2924 SUPPORT Other
"HP:0001732 | Abnormality of the pancreas | Occasional (29-5%)"
Orphanet lists pancreatic abnormalities as occasional.
🧬

Genetic Associations

4
Heterozygous PRKCSH pathogenic variants (Causative)
Autosomal dominant inheritance
Show evidence (2 references)
ORPHA:2924 SUPPORT Other
"PRKCSH | PRKCSH beta subunit of glucosidase II | hgnc:9411 | Disease-causing germline mutation(s) in"
Orphanet lists PRKCSH as a disease-causing gene.
PMID:38097330 SUPPORT Human Clinical
"The two major genes are PRKCSH and SEC63"
The genetics review identifies PRKCSH as a major ADPLD gene.
Heterozygous SEC63 pathogenic variants (Causative)
Autosomal dominant inheritance
Show evidence (2 references)
ORPHA:2924 SUPPORT Other
"SEC63 | SEC63 protein translocation regulator | hgnc:21082 | Disease-causing germline mutation(s) in"
Orphanet lists SEC63 as a disease-causing gene.
PMID:38097330 SUPPORT Human Clinical
"The two major genes are PRKCSH and SEC63"
The genetics review identifies SEC63 as a major ADPLD gene.
Heterozygous ALG8 pathogenic variants (Causative)
Autosomal dominant inheritance
Show evidence (2 references)
ORPHA:2924 SUPPORT Other
"ALG8 | ALG8 alpha-1,3-glucosyltransferase | hgnc:23161 | Disease-causing germline mutation(s) in"
Orphanet lists ALG8 as a disease-causing gene.
PMID:29038287 SUPPORT Human Clinical
"ADPLD (PRKCSH, SEC63, LRP5, ALG8, and SEC61B)"
The genetics review includes ALG8 among reported ADPLD genes.
Heterozygous LRP5 pathogenic variants (Causative)
Autosomal dominant inheritance
Show evidence (2 references)
ORPHA:2924 SUPPORT Other
"LRP5 | LDL receptor related protein 5 | hgnc:6697 | Disease-causing germline mutation(s) in"
Orphanet lists LRP5 as a disease-causing gene.
PMID:29038287 SUPPORT Human Clinical
"ADPLD (PRKCSH, SEC63, LRP5, ALG8, and SEC61B)"
The genetics review includes LRP5 among reported ADPLD genes.
💊

Treatments

3
Somatostatin receptor agonist pharmacotherapy
Action: Pharmacotherapy NCIT:C15986
Agent: somatostatin receptor agonist ↗
Somatostatin analogs such as octreotide or lanreotide can reduce or slow polycystic liver growth, but benefits are modest and may be short-lived.
Mechanism Target:
INHIBITS Cholangiocyte hyperproliferation and hepatic cystogenesis — Somatostatin analog therapy reduces liver volume by decreasing cyst size or slowing cyst growth.
Show evidence (1 reference)
PMID:27016902 SUPPORT Human Clinical
"Recent clinical trials have shown that somatostatin analogues, octreotide and lanreotide, can produce a small but significant reduction in hepatic volume from decreased cyst size."
The surgical review summarizes clinical-trial evidence that somatostatin analogs reduce hepatic volume by reducing cyst size.
Show evidence (2 references)
PMID:35487607 SUPPORT Human Clinical
"Somatostatin analogs can slow the growth of polycystic livers but the effect is short-lived."
The review supports somatostatin analog therapy but notes limited durability.
PMID:23296249 SUPPORT Human Clinical
"Somatostatin analogues are promising; several clinical trials have shown that these drugs can reduce the volume of polycystic livers."
This management review supports somatostatin analogs as volume-reducing medical therapy.
Cyst-directed surgical decompression
Action: surgical procedure MAXO:0000004
In symptomatic PLD, aspiration-sclerotherapy, cyst fenestration, and segmental hepatic resection are used selectively to decompress liver cyst burden and improve mass-effect symptoms.
Mechanism Target:
INHIBITS Mass-effect hepatomegaly with preserved liver function — Surgery reduces liver volume and decompresses symptoms caused by massive cyst burden.
Show evidence (1 reference)
PMID:27016902 SUPPORT Human Clinical
"Overall volumetric comparison of preoperative to follow-up liver imaging showed sustained LV reduction"
The surgical cohort demonstrates durable liver-volume reduction after partial hepatectomy and cyst fenestration.
Show evidence (2 references)
PMID:23296249 SUPPORT Human Clinical
"Current radiological and surgical therapies for symptomatic patients include aspiration-sclerotherapy, fenestration, segmental hepatic resection and liver transplantation."
This review lists cyst-directed procedures and liver transplantation for symptomatic PLD.
PMID:27016902 SUPPORT Human Clinical
"Sustained long-term reductions in LV after PHCF can be achieved in selected patients with severe, highly symptomatic PLD."
This cohort supports partial hepatectomy and cyst fenestration as a durable intervention in selected severe symptomatic PLD.
Liver transplantation
Action: liver transplantation MAXO:0001175
Liver transplantation is reserved for severe PLD when cyst burden is not amenable to other therapy, when no liver parenchyma is spared, or when combined liver-kidney transplantation is needed.
Mechanism Target:
RESTORES Mass-effect hepatomegaly with preserved liver function — Transplantation replaces the massively cystic liver when decompressive or resection approaches are unsuitable.
Show evidence (1 reference)
PMID:22974902 SUPPORT Human Clinical
"When none of the liver parenchyma is spared, or kidney insufficiency is marked, the only potentially curable treatment is liver transplantation (LT)."
This case report and review supports transplantation for massive PLD without spared parenchyma or with marked kidney insufficiency.
Show evidence (2 references)
PMID:35487607 SUPPORT Human Clinical
"The only curative therapy for PCLD is liver transplantation."
The review states that liver transplantation is the curative therapy for PCLD.
PMID:22974902 SUPPORT Human Clinical
"Despite preserved liver function, the patient's clinical condition was poor; she experienced dyspnea, advanced anorexia, abdominal pain, and severe ascites."
The case illustrates severe mass-effect PLD prompting transplantation despite preserved liver function.
{ }

Source YAML

click to show 
name: Autosomal dominant polycystic liver disease
creation_date: "2026-05-09T06:38:39Z"
updated_date: "2026-05-09T06:38:39Z"
category: Mendelian
description: >-
  Autosomal dominant polycystic liver disease (ADPLD), also called isolated
  polycystic liver disease, is an adult-onset inherited disorder in which
  numerous cholangiocyte-derived cysts spread through the liver. Cyst burden
  causes hepatomegaly, abdominal distention, early satiety, dyspnea, pain, and
  reflux while liver synthetic function is usually preserved. Disease-causing
  germline variants include PRKCSH, SEC63, ALG8, and LRP5; the best-defined
  mechanism links PRKCSH and SEC63 endoplasmic-reticulum protein biogenesis
  defects to inefficient polycystin maturation, reduced polycystin-1 dosage, and
  progressive hepatic cystogenesis.
synonyms:
- ADPLD
- ADPCLD
- Isolated polycystic liver disease
- PCLD
- Polycystic liver disease
disease_term:
  preferred_term: autosomal dominant polycystic liver disease
  term:
    id: MONDO:0000447
    label: autosomal dominant polycystic liver disease
parents:
- autosomal dominant disease
- liver disorder
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0000447
      label: autosomal dominant polycystic liver disease
    mapping_predicate: skos:exactMatch
    mapping_source: MONDO Orphanet:2924 xref
    mapping_justification: >-
      MONDO:0000447 carries Orphanet:2924 as a disease cross-reference, and
      ORPHA:2924 is the Orphanet structured record used by this entry.
external_assertions:
- name: Orphanet isolated polycystic liver disease record
  source: Orphanet
  assertion_type: structured_disease_record
  external_id: ORPHA:2924
  url: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=2924
  description: >-
    Orphanet's ORPHA:2924 structured record defines isolated polycystic liver
    disease, lists autosomal dominant inheritance and adult onset, provides the
    European point-prevalence class, asserts disease-causing gene associations
    for ALG8, LRP5, PRKCSH, and SEC63, and supplies the HPO
    phenotype-frequency table used in this curation.
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Isolated polycystic liver disease (PCLD) is a genetic disorder characterized by the appearance of numerous cysts spread throughout the liver and that in most cases is described as autosomal dominant polycystic liver disease (ADPCLD)."
    explanation: Orphanet defines the disease scope as genetic isolated PCLD, usually described as ADPCLD.
definitions:
- name: Orphanet isolated PCLD definition
  definition_type: OTHER
  description: >-
    Genetic isolated polycystic liver disease characterized by numerous cysts
    spread throughout the liver, usually described as ADPLD.
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Isolated polycystic liver disease (PCLD) is a genetic disorder characterized by the appearance of numerous cysts spread throughout the liver and that in most cases is described as autosomal dominant polycystic liver disease (ADPCLD)."
    explanation: Orphanet provides the structured definition for this entry.
inheritance:
- name: Autosomal dominant inheritance
  description: ADPLD is inherited in an autosomal dominant pattern.
  inheritance_term:
    preferred_term: Autosomal dominant inheritance
    term:
      id: HP:0000006
      label: Autosomal dominant inheritance
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "- Autosomal dominant"
    explanation: Orphanet records autosomal dominant inheritance for isolated polycystic liver disease.
prevalence:
- population: Europe
  percentage: 1-9 / 100,000
  notes: Orphanet reports a European point-prevalence class of 1-9 per 100,000.
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "| 1-9 / 100 000 | Europe | Point prevalence | EXPERT |"
    explanation: Orphadata provides the European point-prevalence class.
progression:
- phase: Onset
  age_range: Adult
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "- Age of onset: Adult"
    explanation: Orphanet records adult age of onset.
- phase: Clinical course
  notes: >-
    Disease expression is variable, ranging from asymptomatic cyst burden to
    severe symptomatic hepatomegaly requiring hospitalization, surgery, or
    transplant assessment.
  evidence:
  - reference: PMID:36246085
    reference_title: "Modelling polycystic liver disease progression using age-adjusted liver volumes and targeted mutational analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Polycystic liver disease (PLD) is a highly variable condition that can be asymptomatic or severe."
    explanation: This cohort study supports the variable clinical course.
has_subtypes:
- name: PCLD1
  display_name: PRKCSH-related polycystic liver disease 1
  subtype_term:
    preferred_term: polycystic liver disease 1
    term:
      id: MONDO:0008265
      label: polycystic liver disease 1
  description: >-
    PRKCSH-related ADPLD subtype with numerous liver cysts and possible kidney
    cysts.
  genes:
  - preferred_term: PRKCSH
    term:
      id: hgnc:9411
      label: PRKCSH
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "PRKCSH | PRKCSH beta subunit of glucosidase II | hgnc:9411 | Disease-causing germline mutation(s) in"
    explanation: Orphanet lists PRKCSH as a disease-causing gene for the ADPLD record.
- name: PCLD2
  display_name: SEC63-related polycystic liver disease 2
  subtype_term:
    preferred_term: polycystic liver disease 2
    term:
      id: MONDO:0014860
      label: polycystic liver disease 2
  description: >-
    SEC63-related ADPLD subtype with numerous liver cysts and possible kidney
    cysts.
  genes:
  - preferred_term: SEC63
    term:
      id: hgnc:21082
      label: SEC63
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "SEC63 | SEC63 protein translocation regulator | hgnc:21082 | Disease-causing germline mutation(s) in"
    explanation: Orphanet lists SEC63 as a disease-causing gene for the ADPLD record.
- name: ALG8-related ADPLD
  description: >-
    ALG8-related ADPLD is included in the Orphanet gene-disease table for
    isolated polycystic liver disease.
  genes:
  - preferred_term: ALG8
    term:
      id: hgnc:23161
      label: ALG8
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "ALG8 | ALG8 alpha-1,3-glucosyltransferase | hgnc:23161 | Disease-causing germline mutation(s) in"
    explanation: Orphanet lists ALG8 as a disease-causing gene for the ADPLD record.
- name: LRP5-related ADPLD
  description: >-
    LRP5-related ADPLD is included in the Orphanet gene-disease table for
    isolated polycystic liver disease.
  genes:
  - preferred_term: LRP5
    term:
      id: hgnc:6697
      label: LRP5
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "LRP5 | LDL receptor related protein 5 | hgnc:6697 | Disease-causing germline mutation(s) in"
    explanation: Orphanet lists LRP5 as a disease-causing gene for the ADPLD record.
pathophysiology:
- name: PRKCSH and SEC63 ER protein biogenesis defects
  description: >-
    PRKCSH and SEC63 encode endoplasmic-reticulum proteins involved in protein
    biogenesis and quality control. Disease-causing variants impair maturation
    of integral membrane and secreted proteins that restrain cyst formation.
  genes:
  - preferred_term: PRKCSH
    term:
      id: hgnc:9411
      label: PRKCSH
  - preferred_term: SEC63
    term:
      id: hgnc:21082
      label: SEC63
  biological_processes:
  - preferred_term: endoplasmic-reticulum protein folding
    modifier: DECREASED
    term:
      id: GO:0006457
      label: protein folding
  cellular_components:
  - preferred_term: endoplasmic reticulum
    term:
      id: GO:0005783
      label: endoplasmic reticulum
  evidence:
  - reference: PMID:26877954
    reference_title: "Cyst growth, polycystins, and primary cilia in autosomal dominant polycystic kidney disease."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "The two genes responsible for isolated polycystic liver disease, PRKCSH and SEC63, are both involved in modulating protein biogenesis and quality control for integral membrane and secreted proteins in the endoplasmic reticulum."
    explanation: This review summarizes model-derived evidence that PRKCSH and SEC63 affect ER protein biogenesis and quality control.
  downstream:
  - target: Inefficient polycystin maturation and reduced PC1 dosage
    causal_link_type: DIRECT
    description: ER biogenesis defects impair maturation of polycystin proteins.
    evidence:
    - reference: PMID:26877954
      reference_title: "Cyst growth, polycystins, and primary cilia in autosomal dominant polycystic kidney disease."
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: "Inactivation of either of these genes results in inefficient maturation of the PCs and cyst formation in both the liver and kidney in mouse models."
      explanation: The cited model evidence directly links PRKCSH or SEC63 inactivation to inefficient polycystin maturation and cyst formation.
- name: Inefficient polycystin maturation and reduced PC1 dosage
  description: >-
    Inefficient polycystin maturation lowers functional polycystin-1 dosage.
    Reduced PC1 availability is a rate-limiting cyst-promoting step in
    polycystic liver and kidney models.
  biological_processes:
  - preferred_term: polycystin protein maturation
    modifier: DECREASED
    term:
      id: GO:0051604
      label: protein maturation
  cellular_components:
  - preferred_term: endoplasmic reticulum
    term:
      id: GO:0005783
      label: endoplasmic reticulum
  evidence:
  - reference: PMID:26877954
    reference_title: "Cyst growth, polycystins, and primary cilia in autosomal dominant polycystic kidney disease."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Overexpression of Pkd1, but not Pkd2, can overcome the tendency toward cyst formation in Prkcsh and Sec63 mutants, thereby establishing PC1 as the rate-limiting component whose dosage determines both the rate and extent of cyst formation in ADPKD"
    explanation: Mouse-model evidence supports PC1 dosage as a rate-limiting cystogenesis mechanism downstream of PRKCSH and SEC63 defects.
  downstream:
  - target: Cholangiocyte hyperproliferation and hepatic cystogenesis
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - altered polycystin-dependent epithelial signaling
    description: Reduced polycystin dosage promotes epithelial cyst formation through altered cystic epithelial signaling.
    evidence:
    - reference: PMID:26877954
      reference_title: "Cyst growth, polycystins, and primary cilia in autosomal dominant polycystic kidney disease."
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: "Inactivation of either of these genes results in inefficient maturation of the PCs and cyst formation in both the liver and kidney in mouse models."
      explanation: The same model evidence connects inefficient polycystin maturation to hepatic and renal cyst formation.
- name: Cholangiocyte hyperproliferation and hepatic cystogenesis
  description: >-
    Hepatic cystogenesis involves cholangiocyte hyperproliferation, abnormal
    fluid secretion, and altered cell-matrix interaction, generating multiple
    epithelial cysts throughout the liver.
  cell_types:
  - preferred_term: cholangiocyte
    term:
      id: CL:1000488
      label: cholangiocyte
  biological_processes:
  - preferred_term: cholangiocyte hyperproliferation
    modifier: INCREASED
    term:
      id: GO:0050673
      label: epithelial cell proliferation
  locations:
  - preferred_term: liver
    term:
      id: UBERON:0002107
      label: liver
  evidence:
  - reference: PMID:23296249
    reference_title: "Diagnosis and management of polycystic liver disease."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Processes involved in hepatic cystogenesis include ductal plate malformation with concomitant abnormal fluid secretion, altered cell-matrix interaction and cholangiocyte hyperproliferation."
    explanation: The clinical review identifies cholangiocyte hyperproliferation and fluid secretion as hepatic cystogenesis processes.
  - reference: PMID:27016902
    reference_title: "Outcomes and Durability of Hepatic Reduction after Combined Partial Hepatectomy and Cyst Fenestration for Massive Polycystic Liver Disease."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Polycystic liver disease (PLD) is characterized by the presence of multiple cholangiocyte-derived epithelial cysts that cause progressive liver enlargement."
    explanation: The surgical cohort describes PLD cysts as cholangiocyte-derived epithelial cysts that enlarge the liver.
  downstream:
  - target: Mass-effect hepatomegaly with preserved liver function
    causal_link_type: DIRECT
    description: Progressive hepatic cyst expansion enlarges the liver and compresses adjacent structures.
    evidence:
    - reference: PMID:27016902
      reference_title: "Outcomes and Durability of Hepatic Reduction after Combined Partial Hepatectomy and Cyst Fenestration for Massive Polycystic Liver Disease."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Cystic enlargement causes liver enlargement, which can be marked and result in dyspnea, early satiety, gastroesophageal reflux, mechanical back pain, hepatic venous outflow obstruction, portal vein and inferior vena cava compression, and, rarely, jaundice from bile duct compression."
      explanation: The cohort directly links cystic enlargement to hepatomegaly and mass-effect symptoms.
- name: Mass-effect hepatomegaly with preserved liver function
  description: >-
    Multiple liver cysts enlarge the liver and compress neighboring structures,
    producing abdominal distention, early satiety, dyspnea, reflux, pain, edema,
    and occasional cholestatic features. Liver function commonly remains
    preserved despite substantial cyst burden.
  locations:
  - preferred_term: liver
    term:
      id: UBERON:0002107
      label: liver
  evidence:
  - reference: PMID:35487607
    reference_title: "Polycystic Kidney/Liver Disease."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Though isolated PCLD and PCLD due to ADPKD are genetically distinct, they follow a similar clinical course of hepatomegaly from multiple cysts with preserved liver function."
    explanation: The review supports the core clinical course of hepatomegaly with preserved liver function.
  - reference: PMID:24886261
    reference_title: "Polycystic liver disease: an overview of pathogenesis, clinical manifestations and management."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Major complaints include abdominal pain, abdominal distension and atypical symptoms because of voluminous cysts resulting in compression of adjacent tissue or failure of the affected organ."
    explanation: The review supports mass-effect symptoms from voluminous cysts.
genetic:
- name: Heterozygous PRKCSH pathogenic variants
  gene_term:
    preferred_term: PRKCSH
    term:
      id: hgnc:9411
      label: PRKCSH
  association: Causative
  relationship_type: CAUSATIVE
  features: >-
    PRKCSH is an Orphanet-listed disease-causing gene and one of the two major
    genes reported for ADPLD.
  inheritance:
  - name: Autosomal dominant inheritance
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "PRKCSH | PRKCSH beta subunit of glucosidase II | hgnc:9411 | Disease-causing germline mutation(s) in"
    explanation: Orphanet lists PRKCSH as a disease-causing gene.
  - reference: PMID:38097330
    reference_title: "Genetic Spectrum of Polycystic Kidney and Liver Diseases and the Resulting Phenotypes."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The two major genes are PRKCSH and SEC63"
    explanation: The genetics review identifies PRKCSH as a major ADPLD gene.
- name: Heterozygous SEC63 pathogenic variants
  gene_term:
    preferred_term: SEC63
    term:
      id: hgnc:21082
      label: SEC63
  association: Causative
  relationship_type: CAUSATIVE
  features: >-
    SEC63 is an Orphanet-listed disease-causing gene and one of the two major
    genes reported for ADPLD.
  inheritance:
  - name: Autosomal dominant inheritance
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "SEC63 | SEC63 protein translocation regulator | hgnc:21082 | Disease-causing germline mutation(s) in"
    explanation: Orphanet lists SEC63 as a disease-causing gene.
  - reference: PMID:38097330
    reference_title: "Genetic Spectrum of Polycystic Kidney and Liver Diseases and the Resulting Phenotypes."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The two major genes are PRKCSH and SEC63"
    explanation: The genetics review identifies SEC63 as a major ADPLD gene.
- name: Heterozygous ALG8 pathogenic variants
  gene_term:
    preferred_term: ALG8
    term:
      id: hgnc:23161
      label: ALG8
  association: Causative
  relationship_type: CAUSATIVE
  features: ALG8 is an Orphanet-listed ADPLD disease-causing gene.
  inheritance:
  - name: Autosomal dominant inheritance
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "ALG8 | ALG8 alpha-1,3-glucosyltransferase | hgnc:23161 | Disease-causing germline mutation(s) in"
    explanation: Orphanet lists ALG8 as a disease-causing gene.
  - reference: PMID:29038287
    reference_title: "Genetic Complexity of Autosomal Dominant Polycystic Kidney and Liver Diseases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "ADPLD (PRKCSH, SEC63, LRP5, ALG8, and SEC61B)"
    explanation: The genetics review includes ALG8 among reported ADPLD genes.
- name: Heterozygous LRP5 pathogenic variants
  gene_term:
    preferred_term: LRP5
    term:
      id: hgnc:6697
      label: LRP5
  association: Causative
  relationship_type: CAUSATIVE
  features: LRP5 is an Orphanet-listed ADPLD disease-causing gene.
  inheritance:
  - name: Autosomal dominant inheritance
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "LRP5 | LDL receptor related protein 5 | hgnc:6697 | Disease-causing germline mutation(s) in"
    explanation: Orphanet lists LRP5 as a disease-causing gene.
  - reference: PMID:29038287
    reference_title: "Genetic Complexity of Autosomal Dominant Polycystic Kidney and Liver Diseases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "ADPLD (PRKCSH, SEC63, LRP5, ALG8, and SEC61B)"
    explanation: The genetics review includes LRP5 among reported ADPLD genes.
phenotypes:
- category: Hepatic
  name: Polycystic liver disease
  frequency: VERY_FREQUENT
  description: Numerous liver cysts are the defining manifestation.
  phenotype_term:
    preferred_term: Polycystic liver disease
    term:
      id: HP:0006557
      label: Polycystic liver disease
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0006557 | Polycystic liver disease | Very frequent (99-80%)"
    explanation: Orphanet lists polycystic liver disease as very frequent.
  - reference: PMID:36246085
    reference_title: "Modelling polycystic liver disease progression using age-adjusted liver volumes and targeted mutational analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Polycystic liver disease (PLD) manifests as numerous fluid-filled cysts scattered throughout the liver parenchyma."
    explanation: Human cohort framing supports numerous liver cysts as the core phenotype.
- category: Hepatic
  name: Hepatomegaly
  frequency: VERY_FREQUENT
  description: Multiple cysts enlarge the liver.
  phenotype_term:
    preferred_term: Hepatomegaly
    term:
      id: HP:0002240
      label: Hepatomegaly
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002240 | Hepatomegaly | Very frequent (99-80%)"
    explanation: Orphanet lists hepatomegaly as very frequent.
  - reference: PMID:35487607
    reference_title: "Polycystic Kidney/Liver Disease."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "they follow a similar clinical course of hepatomegaly from multiple cysts with preserved liver function."
    explanation: The review directly links PCLD to hepatomegaly from multiple cysts.
- category: Gastrointestinal
  name: Abdominal distention
  frequency: VERY_FREQUENT
  description: Enlarged polycystic liver volume causes abdominal distention.
  phenotype_term:
    preferred_term: Abdominal distention
    term:
      id: HP:0003270
      label: Abdominal distention
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0003270 | Abdominal distention | Very frequent (99-80%)"
    explanation: Orphanet lists abdominal distention as very frequent.
  - reference: PMID:24886261
    reference_title: "Polycystic liver disease: an overview of pathogenesis, clinical manifestations and management."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Major complaints include abdominal pain, abdominal distension and atypical symptoms because of voluminous cysts resulting in compression of adjacent tissue or failure of the affected organ."
    explanation: The review names abdominal distension among major complaints.
- category: Renal
  name: Multiple renal cysts
  frequency: FREQUENT
  description: >-
    Kidney cysts can occur in ADPLD, though kidney involvement is limited
    compared with ADPKD.
  phenotype_term:
    preferred_term: Multiple renal cysts
    term:
      id: HP:0005562
      label: Multiple renal cysts
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0005562 | Multiple renal cysts | Frequent (79-30%)"
    explanation: Orphanet lists multiple renal cysts as frequent in this ADPLD record.
  - reference: PMID:29038287
    reference_title: "Genetic Complexity of Autosomal Dominant Polycystic Kidney and Liver Diseases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "autosomal dominant polycystic liver diseases (ADPLD), which result in significant PLD with minimal PKD."
    explanation: The genetics review supports limited kidney cyst involvement in ADPLD.
- category: Gastrointestinal
  name: Early satiety
  frequency: FREQUENT
  description: Liver mass effect can cause early fullness with meals.
  phenotype_term:
    preferred_term: Early satiety
    term:
      id: HP:0033842
      label: Early satiety
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0033842 | Early satiety | Frequent (79-30%)"
    explanation: Orphanet lists early satiety as frequent.
  - reference: PMID:27016902
    reference_title: "Outcomes and Durability of Hepatic Reduction after Combined Partial Hepatectomy and Cyst Fenestration for Massive Polycystic Liver Disease."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Indications for surgery were abdominal distention, abdominal pain, early satiety, supine dyspnea, fatigue, uterine pro-lapse, hepatic venous outflow obstruction with ascites, obstruction of the inferior vena cava and dialysis hypotension, bile duct obstruction, and infected cysts."
    explanation: The surgical cohort includes early satiety among symptomatic PLD indications for surgery.
- category: Gastrointestinal
  name: Abdominal pain
  frequency: OCCASIONAL
  description: Cystic liver enlargement and compression can cause abdominal pain.
  phenotype_term:
    preferred_term: Abdominal pain
    term:
      id: HP:0002027
      label: Abdominal pain
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002027 | Abdominal pain | Occasional (29-5%)"
    explanation: Orphanet lists abdominal pain as occasional.
  - reference: PMID:24886261
    reference_title: "Polycystic liver disease: an overview of pathogenesis, clinical manifestations and management."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Major complaints include abdominal pain, abdominal distension and atypical symptoms because of voluminous cysts resulting in compression of adjacent tissue or failure of the affected organ."
    explanation: The review names abdominal pain among major complaints.
- category: Respiratory
  name: Dyspnea
  frequency: OCCASIONAL
  description: Massive hepatomegaly can mechanically impair breathing, especially supine.
  phenotype_term:
    preferred_term: Dyspnea
    term:
      id: HP:0002094
      label: Dyspnea
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002094 | Dyspnea | Occasional (29-5%)"
    explanation: Orphanet lists dyspnea as occasional.
  - reference: PMID:27016902
    reference_title: "Outcomes and Durability of Hepatic Reduction after Combined Partial Hepatectomy and Cyst Fenestration for Massive Polycystic Liver Disease."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Cystic enlargement causes liver enlargement, which can be marked and result in dyspnea, early satiety, gastroesophageal reflux, mechanical back pain, hepatic venous outflow obstruction, portal vein and inferior vena cava compression, and, rarely, jaundice from bile duct compression."
    explanation: The cohort links marked liver enlargement to dyspnea.
- category: Respiratory
  name: Respiratory insufficiency
  frequency: OCCASIONAL
  description: Severe liver enlargement can compromise respiratory mechanics.
  phenotype_term:
    preferred_term: Respiratory insufficiency
    term:
      id: HP:0002093
      label: Respiratory insufficiency
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002093 | Respiratory insufficiency | Occasional (29-5%)"
    explanation: Orphanet lists respiratory insufficiency as occasional.
- category: Gastrointestinal
  name: Gastroesophageal reflux
  frequency: OCCASIONAL
  description: Liver enlargement can compress adjacent upper gastrointestinal structures.
  phenotype_term:
    preferred_term: Gastroesophageal reflux
    term:
      id: HP:0002020
      label: Gastroesophageal reflux
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002020 | Gastroesophageal reflux | Occasional (29-5%)"
    explanation: Orphanet lists gastroesophageal reflux as occasional.
  - reference: PMID:27016902
    reference_title: "Outcomes and Durability of Hepatic Reduction after Combined Partial Hepatectomy and Cyst Fenestration for Massive Polycystic Liver Disease."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Cystic enlargement causes liver enlargement, which can be marked and result in dyspnea, early satiety, gastroesophageal reflux, mechanical back pain, hepatic venous outflow obstruction, portal vein and inferior vena cava compression, and, rarely, jaundice from bile duct compression."
    explanation: The cohort links cystic enlargement to gastroesophageal reflux.
- category: Musculoskeletal
  name: Back pain
  frequency: OCCASIONAL
  description: Mechanical back pain can result from massive liver enlargement.
  phenotype_term:
    preferred_term: Back pain
    term:
      id: HP:0003418
      label: Back pain
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0003418 | Back pain | Occasional (29-5%)"
    explanation: Orphanet lists back pain as occasional.
  - reference: PMID:27016902
    reference_title: "Outcomes and Durability of Hepatic Reduction after Combined Partial Hepatectomy and Cyst Fenestration for Massive Polycystic Liver Disease."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Cystic enlargement causes liver enlargement, which can be marked and result in dyspnea, early satiety, gastroesophageal reflux, mechanical back pain, hepatic venous outflow obstruction, portal vein and inferior vena cava compression, and, rarely, jaundice from bile duct compression."
    explanation: The cohort links cystic enlargement to mechanical back pain.
- category: Hepatic
  name: Jaundice
  frequency: OCCASIONAL
  description: Bile duct compression can rarely cause jaundice.
  phenotype_term:
    preferred_term: Jaundice
    term:
      id: HP:0000952
      label: Jaundice
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000952 | Jaundice | Occasional (29-5%)"
    explanation: Orphanet lists jaundice as occasional.
  - reference: PMID:27016902
    reference_title: "Outcomes and Durability of Hepatic Reduction after Combined Partial Hepatectomy and Cyst Fenestration for Massive Polycystic Liver Disease."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Cystic enlargement causes liver enlargement, which can be marked and result in dyspnea, early satiety, gastroesophageal reflux, mechanical back pain, hepatic venous outflow obstruction, portal vein and inferior vena cava compression, and, rarely, jaundice from bile duct compression."
    explanation: The cohort supports jaundice as a rare compression complication.
- category: Hepatic
  name: Elevated alkaline phosphatase
  frequency: OCCASIONAL
  description: Cholestatic enzyme elevation can occur in a subset of patients.
  phenotype_term:
    preferred_term: Elevated alkaline phosphatase
    term:
      id: HP:0003155
      label: Elevated circulating alkaline phosphatase concentration
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0003155 | Elevated circulating alkaline phosphatase concentration | Occasional (29-5%)"
    explanation: Orphanet lists elevated alkaline phosphatase as occasional.
- category: Hepatic
  name: Elevated gamma-glutamyltransferase
  frequency: OCCASIONAL
  description: GGT elevation can occur in a subset of patients.
  phenotype_term:
    preferred_term: Elevated gamma-glutamyltransferase
    term:
      id: HP:0030948
      label: Elevated gamma-glutamyltransferase level
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0030948 | Elevated gamma-glutamyltransferase level | Occasional (29-5%)"
    explanation: Orphanet lists elevated gamma-glutamyltransferase as occasional.
- category: Hepatic
  name: Hyperbilirubinemia
  frequency: OCCASIONAL
  description: Increased total bilirubin can occur in a subset of patients.
  phenotype_term:
    preferred_term: Increased total bilirubin
    term:
      id: HP:0003573
      label: Increased total bilirubin
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0003573 | Increased total bilirubin | Occasional (29-5%)"
    explanation: Orphanet lists increased total bilirubin as occasional.
- category: Gastrointestinal
  name: Gastrointestinal hemorrhage
  frequency: OCCASIONAL
  description: Gastrointestinal bleeding is reported as an occasional complication.
  phenotype_term:
    preferred_term: Gastrointestinal hemorrhage
    term:
      id: HP:0002239
      label: Gastrointestinal hemorrhage
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002239 | Gastrointestinal hemorrhage | Occasional (29-5%)"
    explanation: Orphanet lists gastrointestinal hemorrhage as occasional.
- category: Cardiovascular
  name: Pedal edema
  frequency: OCCASIONAL
  description: Venous compression and advanced mass effect can cause lower-extremity edema.
  phenotype_term:
    preferred_term: Pedal edema
    term:
      id: HP:0010741
      label: Pedal edema
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0010741 | Pedal edema | Occasional (29-5%)"
    explanation: Orphanet lists pedal edema as occasional.
- category: Vascular
  name: Dilatation of the cerebral artery
  frequency: OCCASIONAL
  description: Cerebral artery dilatation is reported in a subset of patients.
  phenotype_term:
    preferred_term: Dilatation of the cerebral artery
    term:
      id: HP:0004944
      label: Dilatation of the cerebral artery
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0004944 | Dilatation of the cerebral artery | Occasional (29-5%)"
    explanation: Orphanet lists cerebral artery dilatation as occasional.
- category: Cardiovascular
  name: Abnormal heart valve morphology
  frequency: OCCASIONAL
  description: Cardiac valve morphology abnormalities are reported occasionally.
  phenotype_term:
    preferred_term: Abnormal heart valve morphology
    term:
      id: HP:0001654
      label: Abnormal heart valve morphology
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001654 | Abnormal heart valve morphology | Occasional (29-5%)"
    explanation: Orphanet lists abnormal heart valve morphology as occasional.
- category: Gastrointestinal
  name: Abnormality of the pancreas
  frequency: OCCASIONAL
  description: Pancreatic abnormalities are reported occasionally.
  phenotype_term:
    preferred_term: Abnormality of the pancreas
    term:
      id: HP:0001732
      label: Abnormality of the pancreas
  evidence:
  - reference: ORPHA:2924
    reference_title: "Isolated polycystic liver disease"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001732 | Abnormality of the pancreas | Occasional (29-5%)"
    explanation: Orphanet lists pancreatic abnormalities as occasional.
diagnosis:
- name: Abdominal ultrasonography
  description: >-
    Ultrasonography is a first-line imaging approach for identifying a
    polycystic liver phenotype and distinguishing isolated PCLD from ADPKD by
    hepatorenal cyst distribution.
  diagnosis_term:
    preferred_term: ultrasonography procedure
    term:
      id: MAXO:0000072
      label: ultrasonography procedure
  evidence:
  - reference: PMID:23296249
    reference_title: "Diagnosis and management of polycystic liver disease."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Ultrasonography is very useful for achieving a correct diagnosis of a polycystic liver and to differentiate between ADPKD and PCLD."
    explanation: This review directly supports ultrasonography for diagnosis and differential separation.
  - reference: PMID:24886261
    reference_title: "Polycystic liver disease: an overview of pathogenesis, clinical manifestations and management."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Ultrasonography is the first instrument to assess liver phenotype."
    explanation: This review identifies ultrasonography as the first imaging instrument for liver phenotype assessment.
- name: CT or MRI liver volume assessment
  description: >-
    CT or MRI measurement of total liver volume supports severity assessment,
    prognosis, and individualized management.
  diagnosis_term:
    preferred_term: magnetic resonance imaging procedure
    term:
      id: MAXO:0000424
      label: magnetic resonance imaging procedure
  results: Total liver and kidney volumes can be measured and correlated with clinical endpoints.
  evidence:
  - reference: PMID:36246085
    reference_title: "Modelling polycystic liver disease progression using age-adjusted liver volumes and targeted mutational analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Identified genotypes were correlated with total liver and kidney volume (assessed by CT or MRI), organ function, co-morbidities, and clinical endpoints."
    explanation: The cohort used CT or MRI liver-volume assessment for genotype-phenotype and outcome correlation.
- name: Molecular genetic testing
  description: >-
    Genetic testing confirms ADPLD gene variants and is especially useful when
    imaging or family screening is ambiguous.
  diagnosis_term:
    preferred_term: genetic testing
    term:
      id: MAXO:0000127
      label: genetic testing
  evidence:
  - reference: PMID:24886261
    reference_title: "Polycystic liver disease: an overview of pathogenesis, clinical manifestations and management."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Ambiguous imaging or screening may be assisted by genetic counseling and molecular diagnostics."
    explanation: The review supports molecular diagnostics when imaging or screening is ambiguous.
  - reference: PMID:38097330
    reference_title: "Genetic Spectrum of Polycystic Kidney and Liver Diseases and the Resulting Phenotypes."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "employing a next-generation sequencing panel containing all known PKD and ciliopathy genes is recommended for clinical testing."
    explanation: The genetics review supports broad NGS-panel clinical testing because of gene and phenotype overlap.
treatments:
- name: Somatostatin receptor agonist pharmacotherapy
  description: >-
    Somatostatin analogs such as octreotide or lanreotide can reduce or slow
    polycystic liver growth, but benefits are modest and may be short-lived.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: somatostatin receptor agonist
      term:
        id: NCIT:C62799
        label: Somatostatin Receptor Agonist
  target_mechanisms:
  - target: Cholangiocyte hyperproliferation and hepatic cystogenesis
    treatment_effect: INHIBITS
    description: Somatostatin analog therapy reduces liver volume by decreasing cyst size or slowing cyst growth.
    evidence:
    - reference: PMID:27016902
      reference_title: "Outcomes and Durability of Hepatic Reduction after Combined Partial Hepatectomy and Cyst Fenestration for Massive Polycystic Liver Disease."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Recent clinical trials have shown that somatostatin analogues, octreotide and lanreotide, can produce a small but significant reduction in hepatic volume from decreased cyst size."
      explanation: The surgical review summarizes clinical-trial evidence that somatostatin analogs reduce hepatic volume by reducing cyst size.
  evidence:
  - reference: PMID:35487607
    reference_title: "Polycystic Kidney/Liver Disease."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Somatostatin analogs can slow the growth of polycystic livers but the effect is short-lived."
    explanation: The review supports somatostatin analog therapy but notes limited durability.
  - reference: PMID:23296249
    reference_title: "Diagnosis and management of polycystic liver disease."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Somatostatin analogues are promising; several clinical trials have shown that these drugs can reduce the volume of polycystic livers."
    explanation: This management review supports somatostatin analogs as volume-reducing medical therapy.
- name: Cyst-directed surgical decompression
  description: >-
    In symptomatic PLD, aspiration-sclerotherapy, cyst fenestration, and
    segmental hepatic resection are used selectively to decompress liver cyst
    burden and improve mass-effect symptoms.
  treatment_term:
    preferred_term: surgical procedure
    term:
      id: MAXO:0000004
      label: surgical procedure
  target_mechanisms:
  - target: Mass-effect hepatomegaly with preserved liver function
    treatment_effect: INHIBITS
    description: Surgery reduces liver volume and decompresses symptoms caused by massive cyst burden.
    evidence:
    - reference: PMID:27016902
      reference_title: "Outcomes and Durability of Hepatic Reduction after Combined Partial Hepatectomy and Cyst Fenestration for Massive Polycystic Liver Disease."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Overall volumetric comparison of preoperative to follow-up liver imaging showed sustained LV reduction"
      explanation: The surgical cohort demonstrates durable liver-volume reduction after partial hepatectomy and cyst fenestration.
  evidence:
  - reference: PMID:23296249
    reference_title: "Diagnosis and management of polycystic liver disease."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Current radiological and surgical therapies for symptomatic patients include aspiration-sclerotherapy, fenestration, segmental hepatic resection and liver transplantation."
    explanation: This review lists cyst-directed procedures and liver transplantation for symptomatic PLD.
  - reference: PMID:27016902
    reference_title: "Outcomes and Durability of Hepatic Reduction after Combined Partial Hepatectomy and Cyst Fenestration for Massive Polycystic Liver Disease."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Sustained long-term reductions in LV after PHCF can be achieved in selected patients with severe, highly symptomatic PLD."
    explanation: This cohort supports partial hepatectomy and cyst fenestration as a durable intervention in selected severe symptomatic PLD.
- name: Liver transplantation
  description: >-
    Liver transplantation is reserved for severe PLD when cyst burden is not
    amenable to other therapy, when no liver parenchyma is spared, or when
    combined liver-kidney transplantation is needed.
  treatment_term:
    preferred_term: liver transplantation
    term:
      id: MAXO:0001175
      label: liver transplantation
  target_mechanisms:
  - target: Mass-effect hepatomegaly with preserved liver function
    treatment_effect: RESTORES
    description: Transplantation replaces the massively cystic liver when decompressive or resection approaches are unsuitable.
    evidence:
    - reference: PMID:22974902
      reference_title: "Liver transplantation for massive hepatomegaly due to polycystic liver disease: an extreme case."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "When none of the liver parenchyma is spared, or kidney insufficiency is marked, the only potentially curable treatment is liver transplantation (LT)."
      explanation: This case report and review supports transplantation for massive PLD without spared parenchyma or with marked kidney insufficiency.
  evidence:
  - reference: PMID:35487607
    reference_title: "Polycystic Kidney/Liver Disease."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The only curative therapy for PCLD is liver transplantation."
    explanation: The review states that liver transplantation is the curative therapy for PCLD.
  - reference: PMID:22974902
    reference_title: "Liver transplantation for massive hepatomegaly due to polycystic liver disease: an extreme case."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Despite preserved liver function, the patient's clinical condition was poor; she experienced dyspnea, advanced anorexia, abdominal pain, and severe ascites."
    explanation: The case illustrates severe mass-effect PLD prompting transplantation despite preserved liver function.
references:
- reference: ORPHA:2924
  title: "Isolated polycystic liver disease"
  found_in:
  - Autosomal_Dominant_Polycystic_Liver_Disease-deep-research-fallback.md
  findings: []
- reference: PMID:23296249
  title: Diagnosis and management of polycystic liver disease.
  found_in:
  - Autosomal_Dominant_Polycystic_Liver_Disease-deep-research-fallback.md
  findings: []
- reference: PMID:24886261
  title: "Polycystic liver disease: an overview of pathogenesis, clinical manifestations and management."
  found_in:
  - Autosomal_Dominant_Polycystic_Liver_Disease-deep-research-fallback.md
  findings: []
- reference: PMID:26877954
  title: "Cyst growth, polycystins, and primary cilia in autosomal dominant polycystic kidney disease."
  found_in:
  - Autosomal_Dominant_Polycystic_Liver_Disease-deep-research-fallback.md
  findings: []
- reference: PMID:27016902
  title: Outcomes and Durability of Hepatic Reduction after Combined Partial Hepatectomy and Cyst Fenestration for Massive Polycystic Liver Disease.
  found_in:
  - Autosomal_Dominant_Polycystic_Liver_Disease-deep-research-fallback.md
  findings: []
- reference: PMID:22974902
  title: "Liver transplantation for massive hepatomegaly due to polycystic liver disease: an extreme case."
  found_in:
  - Autosomal_Dominant_Polycystic_Liver_Disease-deep-research-fallback.md
  findings: []
- reference: PMID:29038287
  title: Genetic Complexity of Autosomal Dominant Polycystic Kidney and Liver Diseases.
  found_in:
  - Autosomal_Dominant_Polycystic_Liver_Disease-deep-research-fallback.md
  findings: []
- reference: PMID:35487607
  title: Polycystic Kidney/Liver Disease.
  found_in:
  - Autosomal_Dominant_Polycystic_Liver_Disease-deep-research-fallback.md
  findings: []
- reference: PMID:36246085
  title: Modelling polycystic liver disease progression using age-adjusted liver volumes and targeted mutational analysis.
  found_in:
  - Autosomal_Dominant_Polycystic_Liver_Disease-deep-research-fallback.md
  findings: []
- reference: PMID:38097330
  title: Genetic Spectrum of Polycystic Kidney and Liver Diseases and the Resulting Phenotypes.
  found_in:
  - Autosomal_Dominant_Polycystic_Liver_Disease-deep-research-fallback.md
  findings: []
📚

References & Deep Research

References

10
ORPHA:2924
Isolated polycystic liver disease
No top-level findings curated for this source.
PMID:23296249
Diagnosis and management of polycystic liver disease.
No top-level findings curated for this source.
PMID:24886261
Polycystic liver disease: an overview of pathogenesis, clinical manifestations and management.
No top-level findings curated for this source.
PMID:26877954
Cyst growth, polycystins, and primary cilia in autosomal dominant polycystic kidney disease.
No top-level findings curated for this source.
PMID:27016902
Outcomes and Durability of Hepatic Reduction after Combined Partial Hepatectomy and Cyst Fenestration for Massive Polycystic Liver Disease.
No top-level findings curated for this source.
PMID:22974902
Liver transplantation for massive hepatomegaly due to polycystic liver disease: an extreme case.
No top-level findings curated for this source.
PMID:29038287
Genetic Complexity of Autosomal Dominant Polycystic Kidney and Liver Diseases.
No top-level findings curated for this source.
PMID:35487607
Polycystic Kidney/Liver Disease.
No top-level findings curated for this source.
PMID:36246085
Modelling polycystic liver disease progression using age-adjusted liver volumes and targeted mutational analysis.
No top-level findings curated for this source.
PMID:38097330
Genetic Spectrum of Polycystic Kidney and Liver Diseases and the Resulting Phenotypes.
No top-level findings curated for this source.

Deep Research

1
Autosomal Dominant Polycystic Liver Disease Deep Research Fallback ▸

Autosomal Dominant Polycystic Liver Disease Deep Research Fallback

Provider Attempts

  • falcon: timeout --foreground 120s just research-disorder falcon Autosomal_Dominant_Polycystic_Liver_Disease produced no usable content and was terminated with signal 15.
  • openai: timeout --foreground 120s just research-disorder openai Autosomal_Dominant_Polycystic_Liver_Disease produced no usable content and was terminated with signal 15.

Because the preferred deep-research providers did not return usable content in bounded attempts, this fallback records the literature scope used for curation. All YAML evidence was taken from generated Orphanet and PubMed reference caches, not from hand-created reference text.

Literature Scope

Autosomal dominant polycystic liver disease corresponds to MONDO:0000447 and Orphanet ORPHA:2924. The Orphanet record for isolated polycystic liver disease defines the condition as genetic PCLD with numerous cysts throughout the liver, usually described as ADPCLD. It records adult onset, autosomal dominant inheritance, a European point-prevalence band of 1-9 per 100,000, HPO phenotype-frequency rows, and disease-causing gene assertions for ALG8, LRP5, PRKCSH, and SEC63.

Human clinical reviews and cohorts were used to anchor the phenotype, diagnosis, and management sections. PLD reviews define PCLD as distinct from ADPKD-associated PLD but clinically similar in producing hepatomegaly from multiple cysts with preserved liver function. They support ultrasonography as the first imaging instrument, CT or MRI liver-volume assessment for severity and risk stratification, molecular diagnostics when imaging or screening is ambiguous, and management that ranges from conservative care to somatostatin analogs, cyst-directed procedures, and liver transplantation.

The mechanistic pathophysiology is centered on the best-supported PRKCSH and SEC63 branch. The principal mechanism review links PRKCSH and SEC63 to endoplasmic-reticulum protein biogenesis and quality control, inefficient polycystin maturation, and PC1 dosage as a rate-limiting component of cystic disease in model systems. Human clinical and surgical sources then support the downstream cholangiocyte-derived epithelial cysts, hepatic enlargement, and mass-effect symptom burden.

Curation Decisions

  • Used MONDO:0000447 as the disease term because it carries the Orphanet:2924 cross-reference and matches the ADPLD/PCLD scope.
  • Included all ORPHA very frequent and frequent HPO phenotypes: polycystic liver disease, hepatomegaly, abdominal distention, multiple renal cysts, and early satiety.
  • Added selected ORPHA occasional phenotypes with coherent clinical relevance to mass-effect, hepatobiliary, vascular, cardiac, or pancreatic involvement. Feeding difficulties in infancy and the broad respiratory-system parent row were not included because this entry is adult-onset and already includes the more specific dyspnea and respiratory insufficiency rows.
  • Modeled subtypes for PRKCSH/PCLD1 and SEC63/PCLD2 with MONDO term bindings, and included ALG8-related and LRP5-related ADPLD as Orphanet-supported gene-defined subtypes without forcing unavailable local MONDO subtype terms.
  • Represented somatostatin analog therapy with generic pharmacotherapy plus an NCIT somatostatin receptor agonist therapeutic-agent binding, and kept cyst-directed surgery and liver transplantation as separate treatment entries.