Guideline sources The following summarized guidelines for the evaluation and management of polycystic liver disease (PLD) are prepared by our editorial team based on guidelines from the European Association for the Study of the Liver (EASL 2022), the American College of Gastroenterology (ACG 2014), and the Spanish Working Group on Inherited Kidney Diseases (SWG-IKD 2014). 1 2 3 Guidelines 1. Screening and diagnosis Indications for screening: Obtain abdominal ultrasound to screen for PLD in all patients diagnosed with autosomal dominant polycystic kidney disease. B Do not obtain genetic testing for the screening of PLD. D https://web.pathway.md/diseases/recX8QWM045sF7TpS 1/7 6/29/23, 11:16 PM Polycystic liver disease Pathway 2. Classification and risk stratification Severity assessment: Consider using disease-specific symptom severity questionnaires upon the emergence of symptoms to assess disease severity in patients with PLD. C Use disease-specific symptom severity questionnaires to assess treatment efficacy in patients with PLD. A 3. Diagnostic investigations Diagnostic imaging: obtain ultrasound as the first-line imaging for the diagnosis of PLD. B Show 3 more Evaluation of sarcopenia: consider obtaining CT to assess sarcopenia in patients with PLD and massive hepatomegaly displacing adjacent organs (such as the stomach and bowels), as these patients are at risk of malnutrition. C Evaluation of cyst infection: As per EASL 2022 guidelines, diagnose definite hepatic cyst infection in the presence of neutrophil debris and/or microorganisms in cyst aspirate. B Show 2 more As per SWG-IKD 2014 guidelines, obtain CT in patients with suspected hepatic cyst infection. B Show 2 more Evaluation of cyst hemorrhage: As per EASL 2022 guidelines, consider obtaining imaging to detect intracystic hemorrhage in patients with sudden and severe abdominal pain. C Show 2 more As per SWG-IKD 2014 guidelines, obtain MRI for the diagnosis of hepatic cyst hemorrhage. B Evaluation of Caroli disease/syndrome: evaluate for congenital hepatic fibrosis to differentiate Caroli disease from Caroli syndrome in patients with multiple segmental cystic or saccular dilatations of bile ducts. B Evaluation of mucinous cystic neoplasms: View a combination of 1 major and 1 minor feature as worrisome features for mucinous cystic neoplasms of the liver: major features: thick septation, nodularity minor features: upstream biliary dilatation, thin septations, internal hemorrhage, perfusional change, < 3 coexistent hepatic cysts. B Show 2 more 4. Medical management General principles: Decide on the choice of treatment based on symptoms and complications related to the presence of cysts in combination with liver phenotypes: https://web.pathway.md/diseases/recX8QWM045sF7TpS 2/7 6/29/23, 11:16 PM Polycystic liver disease Pathway Situation Guidance Abdominal fullness Symptoms Lack of appetite or early satiety Acid reflux Nausea and vomiting Pain in rib cage, sides, abdomen or back Shortness of breath Limited mobility, fatigue Anxiety about the future Concern or dissatisfaction with abdomen size Problems with intercourse Involuntary weight loss Jaundice Complications Hepatic venous outflow obstruction Portal hypertension Recurrent cyst infection Recurrent cyst hemorrhage Numerous small-to-medium-sized cysts throughout the liver Phenotypes Large or strategically located cyst percutaneously accessible Single or multiple large superficial cysts Small-to-medium-sized cysts clustered in a few segments in the presence of some less affected liver segments Massive PLD Severely affecting the quality of life or accompanied by recurrent complications. B Show 2 more mTOR inhibitors: do not use mTOR inhibitors in patients with PLD. D Somatostatin analogs: do not use somatostatin analogs in patients with PLD. D Hormonal therapy: As per EASL 2022 guidelines, discontinue exogenous estrogen in female patients with PLD. B As per SWG-IKD 2014 guidelines: https://web.pathway.md/diseases/recX8QWM045sF7TpS 3/7 6/29/23, 11:16 PM Polycystic liver disease Pathway Advise avoiding estrogens and drugs stimulating cyclic adenosine monophosphate accumulation (such as caffeine) in patients with moderate-to-severe PLD. B Use the lowest effective dose when hormonal RRT is planned in patients with mild cystic liver disease. Prefer the transdermal route since it may exert a different biological effect on liver cysts by avoiding the first-pass effect. B 5. Nonpharmacologic interventions Nutrition and physical activity: provide intensive nutrition and exercise rehabilitation under the supervision of dietitians and physical therapists in patients with PLD and sarcopenia. B 6. Therapeutic procedures Drainage: As per ACG 2014 guidelines, consider performing aspiration or surgical resection/deroofing of dominant cysts based on the patient's clinical presentation and underlying hepatic reserve. C As per SWG-IKD 2014 guidelines, perform volume-reducing procedures (aspiration and sclerotherapy or deroofing/resection) only in highly symptomatic patients with PLD. B 7. Surgical interventions Cyst fenestration and resection: As per ACG 2014 guidelines, consider performing deroofing, surgical resection, or aspiration of dominant cysts based on the patient's clinical presentation and underlying hepatic reserve. C As per SWG-IKD 2014 guidelines, perform deroofing or segmental liver resection, performed only by a surgeon with expertise in PLD owing to the abnormal anatomy of the liver and the high morbidity of these surgical procedures, only in highly symptomatic patients with PLD. B Liver transplantation: As per EASL 2022 guidelines, consider referring patients meeting the following criteria for liver transplantation or combined liver-kidney transplantation, taking into consideration the local allocation systems, local waitlist criteria, anticipated waiting times, and risk of deterioration while waiting for a liver graft: liver transplantation: clinically apparent liver disease due to massive polycystic liver severely affecting the quality of life, massive PLD, and complications (severe malnutrition, hepatic venous outflow obstruction, ascites, portal hypertension, variceal hemorrhage, recurrent hepatic cyst infections) that can exclusively be treated by liver transplantation, failure of non-transplant-related interventions and contraindications for non-transplant- related interventions combined liver-kidney transplantation: CrCl < 30 mL/min. C As per ACG 2014 guidelines, consider performing liver transplantation with or without kidney transplantation in patients with polycystic kidney disease and PLD with refractory symptoms https://web.pathway.md/diseases/recX8QWM045sF7TpS 4/7 6/29/23, 11:16 PM Polycystic liver disease Pathway and significant cyst burden. C 8. Specific circumstances Patients with cyst infection, antibiotic therapy: As per EASL 2022 guidelines, administer fluoroquinolones and third-generation cephalosporins for 4-6 weeks B as empirical first-line antibiotics in patients with hepatic cyst infection. B As per SWG-IKD 2014 guidelines, administer quinolones for at least 6 weeks in patients with infected hepatic cysts. Add a third-generation cephalosporin if fever persists after 72 hours. B Patients with cyst infection, drainage: As per EASL 2022 guidelines, perform drainage of infected hepatic cysts in the presence of any of the following features: persistence of temperature > 38.5 C after 48 hours on empirical antibiotic therapy isolation of pathogens unresponsive to antibiotic therapy from a cyst aspirate severe immunocompromise CT or MRI detecting gas in a cyst large infected hepatic cysts. B As per SWG-IKD 2014 guidelines, consider performing percutaneous drainage if the infection persists after 3-5 days on antibiotics and the causative cyst is identified and accessible. C Patients with cyst infection (secondary prophylaxis): Do not administer secondary prophylaxis for hepatic cyst infection. D Insufficient evidence to recommend selective decontamination of the digestive tract to prevent hepatic cyst infection. I Patients with cyst hemorrhage: As per EASL 2022 guidelines, interrupt anticoagulants temporarily in patients with hepatic cyst hemorrhage B , and consider resuming 7-15 days after the onset of hepatic cyst hemorrhage. B As per SWG-IKD 2014 guidelines, administer non-opioid and opioid analgesics and advise rest for the management of patients with hepatic cyst hemorrhage. B Patients with Caroli disease/syndrome: Consider obtaining surveillance for cholangiocarcinoma with MRCP every 12 months after diagnosis in patients with Caroli disease and syndrome. C Consider referring patients with Caroli disease or syndrome with recurrent cholangitis for liver transplantation in the presence of bilobar involvement or monolobar involvement in combination with liver fibrosis or portal hypertension when the possibility of liver resection has been excluded. B https://web.pathway.md/diseases/recX8QWM045sF7TpS 5/7 6/29/23, 11:16 PM Polycystic liver disease Pathway Patients with mucinous cystic neoplasms: perform surgical resection, aiming for complete resection, as the gold standard for management of patients with suspected mucinous cystic neoplasms. B 9. Patient education Preconception counseling: Provide preconception counseling concerning the risk of passing on PLD to the newborn in patients with PLD. B Do not counsel patients with PLD against pregnancy. D 10. Follow-up and surveillance Indications for referral: refer patients with symptomatic PLD to centers of expertise. B Serial imaging assessment: do not obtain routine follow-up imaging after aspiration sclerotherapy or surgical procedures for hepatic cysts. D Clinical findings Symptoms Past medical history Back pain Acute cholangitis Bloating GERD Early satiety Gastroesophageal varices Fever Gastrointestinal bleeding Loss of appetite Hepatic encephalopathy Nausea Polycystic kidney disease Orthopnea Portal hypertension Postprandial fullness Abdominal exam RUQ pain Shortness of breath Abdominal distension Vomiting Abdominal hernia Weight loss Ascites Hepatomegaly Anthropomorphic exam Palpable liver Malnutrition RUQ tenderness Musculoskeletal exam Integument exam Sarcopenia Jaundice Lab findings Hematological findings ESR WBC count serum ALP serum CRP https://web.pathway.md/diseases/recX8QWM045sF7TpS 6/7 6/29/23, 11:16 PM Polycystic liver disease Pathway References 1. Marrero JA, Ahn J, Rajender Reddy K et al. ACG clinical guideline: the diagnosis and management of focal liver lesions. Am J Gastroenterol. 2014 Sep;109 9 1328 47. Open 2. European Association for the Study of the Live. EASL Clinical Practice Guidelines on the management of cystic liver diseases. EASL. 2022 Jun. Open 3. Elisabet Ars, Carmen Bernis, Gloria Fraga et al. Spanish guidelines for the management of autosomal dominant polycystic kidney disease. Nephrol Dial Transplant. 2014 Sep;29 Suppl 4:iv95 105. Open https://web.pathway.md/diseases/recX8QWM045sF7TpS 7/7