Guideline sources The following summarized guidelines for the evaluation and management of focal liver lesions are prepared by our editorial team based on guidelines from the European Association for the Study of the Liver (EASL 2022; 2016), the American College of Radiology (ACR 2020), the European Federation of Societies for Ultrasound (EFSU 2020), the American College of Gastroenterology (ACG 2014), and the Spanish Working Group on Inherited Kidney Diseases (SWG-IKD 2014). 1 2 3 4 5 6 Guidelines 1. Diagnostic investigations Contrast-enhanced ultrasound: As per ACR 2020 guidelines: Obtain contrast-enhanced abdominal ultrasound of an indeterminate > 1 cm liver lesion on initial ultrasound in patients with a normal liver with no suspicion or evidence of extrahepatic malignancy or underlying liver disease. B Obtain contrast-enhanced abdominal ultrasound of an incidental liver lesion > 1 cm on initial ultrasound, non-contrast or single-phase CT, or non-contrast MRI in patients with known chronic liver disease. B As per EFSU 2020 guidelines, obtain liver ultrasound using B-mode and Doppler mode before obtaining contrast-enhanced ultrasound to characterize focal liver lesions. B Show 14 more Cross-sectional imaging: https://web.pathway.md/diseases/recKkO8VoEkTQ5cHC 1/5 6/29/23, 4:06 AM Focal liver lesions Pathway As per ACR 2020 guidelines, obtain contrast-enhanced multiphase CT, contrast-enhanced MRI, or contrast-enhanced ultrasound of an indeterminate > 1 cm liver lesion on initial ultrasound in patients with a normal liver with no suspicion or evidence of extrahepatic malignancy or underlying liver disease. B Show 7 more As per ACG 2014 guidelines, obtain MRI or triple-phase CT in patients with cirrhosis with a lesion of > 1 cm on ultrasound. B 2. Specific circumstances Patients with simple hepatic cysts, evaluation: As per EASL 2022 guidelines, obtain ultrasound as the first-line imaging for the diagnosis of hepatic cysts. B Show 2 more As per ACG 2014 guidelines, obtain CT or MRI for further evaluation of a hepatic cyst identified on ultrasound with septations, fenestrations, calcifications, irregular walls, or daughter cysts. B Patients with simple hepatic cysts, management: As per EASL 2022 guidelines, offer the best locally available volume-reducing therapy for the treatment of symptomatic simple hepatic cysts without biliary communication. B As per ACG 2014 guidelines, observe asymptomatic patients with simple hepatic cysts with expectant management. B Show 2 more Patients with simple hepatic cysts (surveillance): do not monitor asymptomatic patients with simple hepatic cysts or peribiliary cysts. D Show 2 more Patients with polycystic liver disease (evaluation): obtain abdominal ultrasound to screen for polycystic liver disease in all patients diagnosed with autosomal dominant polycystic kidney disease. B Do not obtain genetic testing for the screening of polycystic liver disease. B Show 4 more Patients with polycystic liver disease, management: As per EASL 2022 guidelines, decide on the choice of treatment based on symptoms and complications related to the presence of cysts in combination with liver phenotypes: 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 https://web.pathway.md/diseases/recKkO8VoEkTQ5cHC 2/5 6/29/23, 4:06 AM Focal liver lesions Pathway 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 polycystic liver disease Severely affecting the quality of life or accompanied by recurrent complications. B Show 3 more As per ACG 2014 guidelines, do not use mTOR inhibitors or somatostatin analogs in patients with polycystic liver disease. D Show 2 more As per SWG-IKD 2014 guidelines, perform volume-reducing procedures (aspiration and sclerotherapy, fenestration, or segmental liver resection), performed only by a surgeon with expertise in polycystic liver disease owing to the abnormal anatomy of the liver and the high morbidity of these surgical procedures, only in highly symptomatic patients with polycystic liver disease. B Patients with hepatic hemangioma: As per EASL 2016 guidelines, suspect hepatic hemangioma in the presence of a hyperechoic lesion in patients with a normal and healthy liver. Obtain ultrasound to confirm the diagnosis with typical imaging features (homogeneous hyperechoic, sharp margin, posterior enhancement, and absence of halo sign) in a lesion < 3 cm. obtain contrast-enhanced imaging (such as contrast-enhanced ultrasound, contrast- enhanced CT, or MRI) in patients with an oncological condition or an underlying liver disease. (evidence level II-2, grade of recommendation 1). B Show 5 more As per ACG 2014 guidelines, obtain MRI or CT for the diagnosis of hepatic hemangioma. B https://web.pathway.md/diseases/recKkO8VoEkTQ5cHC 3/5 6/29/23, 4:06 AM Focal liver lesions Pathway Show 4 more Patients with focal nodular hyperplasia: As per EASL 2016 guidelines, obtain contrast-enhanced ultrasound, CT, or MRI for the diagnosis of focal nodular hyperplasia (~ 100% specificity with typical imaging features observed in combination). Recognize that MRI has the highest diagnostic performance overall, and the highest diagnostic accuracy by contrast-enhanced ultrasound is achieved in focal nodular hyperplasia < 3 cm. B Show 3 more As per ACG 2014 guidelines, obtain MRI or CT for the diagnosis of focal nodular hyperplasia. Do not perform a routine liver biopsy to confirm the diagnosis. B Show 4 more Patients with nodular regenerative hyperplasia: perform liver biopsy for the diagnosis of nodular regenerative hyperplasia. B Show 3 more Patients with hepatic 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 4 more Patients with biliary mucinous cystic neoplasms: Do not perform routine fluid aspiration in patients with suspected biliary cystadenoma because of the limited sensitivity and the risk of malignant dissemination. D Perform complete surgical excision, by an experienced team, in patients with imaging characteristics suggestive of biliary cystadenoma or biliary cystadenocarcinoma, such as internal septations, fenestrations, calcifications, or irregular walls. B Patients with hepatocellular adenoma: As per EASL 2016 guidelines, prefer MRI as it is superior to all other imaging modalities and due to its intrinsic properties to detect fat and vascular spaces it offers an opportunity to subtype hepatocellular adenoma up to 80%. B Show 11 more As per ACG 2014 guidelines, avoid the use of oral contraceptives, hormone-containing intrauterine devices, and anabolic steroids in patients with hepatocellular adenoma. D Show 4 more Patients with hepatocellular carcinoma: suspect HCC, until otherwise proven, in patients with chronic liver disease, especially with cirrhosis, presenting with a solid focal liver lesion, as they are at very high risk for having HCC. B Show 2 more Patients with cholangiocarcinoma: Obtain MRI or CT in patients with clinically or sonographically suspected cholangiocarcinoma. B Perform liver biopsy to establish the diagnosis of cholangiocarcinoma if the patient is non- operable. B https://web.pathway.md/diseases/recKkO8VoEkTQ5cHC 4/5 6/29/23, 4:06 AM Focal liver lesions Pathway Patients with hydatid cysts: prefer MRI over CT for concomitant evaluation of the biliary tree and cystic contents in patients with suspected hydatid cysts. B Show 4 more References 1. Expert Panel on Gastrointestinal Imaging, Victoria Chernyak, Jeanne M Horowitz et al. ACR Appropriateness Criteria Liver Lesion-Initial Characterization. J Am Coll Radiol. 2020 Nov;17 11S S429 S446. Open 2. 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 3. European Association for the Study of the Live. EASL Clinical Practice Guidelines on the management of cystic liver diseases. EASL. 2022 Jun. Open 4. European Association for the Study of the Liver EASL . EASL Clinical Practice Guidelines on the management of benign liver tumours. J Hepatol. 2016 Aug;65 2 386 98. Open 5. 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 6. Christoph F Dietrich, Christian P llson Nols e, Richard G Barr et al. Guidelines and Good Clinical Practice Recommendations for Contrast-Enhanced Ultrasound CEUS in the Liver-Update 2020 WFUMB in Cooperation with EFSUMB, AFSUMB, AIUM, and FLAUS. Ultrasound Med Biol. 2020 Oct;46 10 2579 2604. Open 7. Tram T Tran, Joseph Ahn, Nancy S Reau. ACG Clinical Guideline: Liver Disease and Pregnancy. Am J Gastroenterol. 2016 Feb;111 2 176 94; quiz 196. Open https://web.pathway.md/diseases/recKkO8VoEkTQ5cHC 5/5