Pathophysiology, epidemiology, classification and treatment options for polycystic liver diseases

Table 1 Comparative epidemiological and genetic mutation characteristics of autosomal dominant polycystic kidney disease associated polycystic liver disease and isolated polycystic liver disease

Characteristics	ADPKD associated PLD	Isolated PLD
Prevalence	0.20%	< 0.01%
Type of inheritance	AD	AD
Gene mutated	PKD1; PKD2	PRKCSH; SEC63
Encoded product	Polycystin-1; Polycystin-2	Hepatocystin; Sec63 protein
Chromosome locus	216p13.3; 4q21	19p13.2; 6q21

AD: Autosomal dominant; ADPKD: Autosomal dominant polycystic kidney disease; PLD: Polycystic liver disease.

Table 2 Risk factors for liver-cyst growth in polycystic liver disease

Risk factors for liver-cyst growth in polycystic liver disease
Advancing patient age
Female gender
Estrogen exposure: multiple pregnancies, OCPs, estrogen replacement therapy
Severity of renal dysfunction and renal cyst volume

OCPs: Oral contraceptive pills.

Table 3 Summary of the most frequent symptoms caused by polycystic liver disease

Symptoms due to mass effect	Symptoms due to complications of the cysts
Abdominal distention	Infection
Early satiety	Torsion
Postprandial fullness	Rupture
Gastro-oesophageal reflux	Haemorrhage
Malnutrition
Dyspnoea
Hepatic venous-outflow obstruction (Budd-Chiari syndrome)
Inferior vena cava syndrome
Portal-vein compression
Bile-duct compression

Table 4 The ravine diagnostic criteria for autosomal dominant polycystic kidney disease

Patient’s age (yr)	Number of cysts
	Positive family history	Negative family history
≤ 30	At least 2 cysts affecting 1 or both kidneys	At least 5 cysts
31-59	At least 2 cysts in each kidney	At least 5 cysts
≥ 60	At least 4 cysts in each kidney	At least 8 cysts

Table 5 Summary of Schnelldorfer’s classification that aims at differentiating patients who could benefit from resection or transplantation

	Type A	Type B	Type C	Type D
Symptoms	Absent or mild	Moderate or severe	Severe (or moderate)	Severe (or moderate)
Cyst characteristics	Any	Limited No. large cysts	Any	Any
Areas of relative normal liver parenchyma	Any	≥ 2 sectors	≥ 1 sector	< 1 sector
Presence of portal vein or hepatic vein occlusion in the preserved hepatic sectors	Any	Absent	Absent	Present
Recommended therapy	Observation or medical therapy	Cyst fenestration	Partial hepatectomy with possible fenestration of remnant cysts	Liver Transplantation

Table 6 Summary of treatment options for polycystic liver disease

Treatment approach	Treatment type
Nonsurgical	Medical
	Somatostatin analogues
	mTOR inhibitors
	Interventional radiology:
	Arterial embolization
	Percutaneous sclerotherapy
Surgical	Fenestration
	Hepatic resection with fenestration
	Liver transplantation

OCP’s: Oral contraceptive pills; mTOR: Mammalian target of rapamycin.

Table 7 Summary of largest series published on the surgical techniques used for cystic fenestration of symptomatic polycystic liver disease

Ref.	No. of patients	Technique	Outcome	Complications	Follow-up (mo)
van Erpecum et al[35]	15	Open fenestration	0% symptom recurrence	One mortality	Mean of 48
Kabbej et al[37]	13	Lap fenestration	72% symptom recurrence	54% morbidity	Mean follow-up 26
Gigot et al[38]	10	Open fenestration	11% symptom recurrence	60% morbidity	73 mean follow-up
van Keimpema et al[82]	12	Lap fenestration	Reduction in liver volume by 12.5%	Bile leak, vena cava occlusion and sepsis	-
Pirenne et al[92]	4	Lap fenestration	100% symptom relief	50% cyst recurrence	-
Liska et al[95]	7	Lap fenestration plus open	-	No mortality	Mean 41
Bai et al[96]	10	Lap fenestration	Symptom and cyst recurrence in 20%	3 patients with minor complications. No mortality	Mean of 57
Palanivelu et al[97]	4	Lap fenestration	100% cyst recurrence	-	-
Garcea et al[98]	6	Lap/Open fenestration	16.7% symptom recurrence, 33.3% cyst recurrence	50% morbidity	5-36
Neri et al[99]	3	Lap fenestration	100% symptom relief	50% morbidity	-
Kornprat et al[100]	8	Lap fenestration	0% symptom recurrence	-	-
Robinson et al[101]	11	Lap fenestration	54.5% symptom recurrence	-	-
Fiamingo et al[102]	6	Lap fenestration	30% symptom recurrence	50% morbidity	1-64
Tocchi et al[103]	18	Lap/open fenestration	-	-	-
Koperna et al[104]	39	Open fenestration (n = 34); Lap (n = 5)	21% symptom recurrence	-	75 mean follow-up
Morino et al[105]	7	Lap fenestration	40% symptom recurrence	44% morbidity rate	-
Farges et al[106]	13	Open fenestration	23% symptom recurrence	69% morbidity	84 follow-up
Ueno et al[118]	13	Open fenestration (n = 6); Lap (n = 13)	71% symptom recurrence	30% morbidity	37 mean follow-up

Lap: Laparoscopic.

Table 8 Summary of largest series published on the surgical techniques used for cystic fenestration and resection of symptomatic polycystic liver disease

Ref.	No.	Technique	Outcome	Complications	Follow-up (mo)
Que et al[36]	31	Fenestration and resection	3% symptom recurrence	3% mortality, 58% morbidity	Mean of 28
Schnelldorfer et al[64]	124	Fenestration and resection	93% symptom relief, 72.6% recurrent cyst formation	72.6% morbidity, 3.2% mortality	Mean of 48
Kornprat et al[100]	9	Fenestration and resection	100% symptom relief, 11% recurrence	33.35% morbidity	24-98
Koperna et al[104]	5	Fenestration and resection	0% symptom recurrence	-	-
Li et al[107]	21	Fenestration and resection	14.3% cyst recurrence	76.2% cyst morbidity, 0% mortality	10-155
Gamblin et al[108]	51	Fenestration and resection	3.9% symptom recurrence	17.6% morbidity, no mortality	1-49
Yang et al[109]	7	Fenestration and resection	100% symptom recurrence	100% morbidity, no mortality	Mean of 20
Vons et al[110]	12	Resection	17% symptom recurrence	8% mortality, 83% morbidity	Mean of 34
Soravia et al[111]	10	Fenestration and resection	33% symptom recurrence	10% mortality, 20% morbidity	Mean of 69
Henne-Bruns et al[112]	8	Fenestration and resection	50% symptom recurrence	No mortality, 38% morbidity	Mean of 15
Vauthey et al[113]	5	Fenestration and resection	0% symptom recurrence	0% mortality, 100% morbidity	Mean of 14
Sanchez et al[114]	9	Resection	100% symptom relief, 100% recurrence	0% mortality	Mean of 35
Newman et al[115]	9	Fenestration and resection	88.9% symptom relief, 0% recurrence	11.1% mortality, 55.6% morbidity	2-44
Iwatsuki et al[116]	9	Resection	44.4% symptom relief, 44.4% recurrence	0% mortality, 33.3% morbidity	12-180

Table 9 Summary of largest series published on the outcomes of patients undergoing liver transplantation for symptomatic polycystic liver disease

Ref.	No. of patients	Previous surgery	Combined liver and kidney transplantation	Morbidity	Mortality	Follow-up (mo)	Re-transplantation
Pirenne et al[92]	16	25%	6%	38%	13%	Range 18-120	0%
Taner et al[117]	13	-	54%	85%	31%	-	0%
Ueno et al[118]	14	-	36%	64%	21%	-	0%
Ueda et al[119]	3	-	0	33%	0%	Mean of 32	0%
Gustafsson et al[120]	7	57%	43%	57%	43%	Mean of 4	0%
Swenson et al[121]	9	44%	33%	44%	11%	Mean of 26	11%
Lang et al[122]	17	35%	47%	47%	29%	Mean of 12	12%
Washburn et al[123]	5	90%	20%	0%	20%	Mean of 38	0%
Starzl et al[124]	4	0%	25%	0%	50%	Mean of 38	0%

Table 10 Suggested management strategies based on Gigot’s classification

Gigot’s I	Gigot’s II - III
Percutaneous sclerotherapy	Hepatic resection with fenestration if feasible
Fenestration	Liver transplantation