Congestive Hepatopathy: Pathophysiology, Workup, and Imaging Findings with Pathologic Correlation.

Liver congestion is increasingly encountered in clinical practice and presents diagnostic pitfalls of which radiologists must be aware. The complex altered hemodynamics associated with liver congestion leads to diffuse parenchymal changes and the development of benign and malignant nodules. Distinguishing commonly encountered benign hypervascular lesions, such as focal nodular hyperplasia (FNH)-like nodules, from hepatocellular carcinoma (HCC) can be challenging due to overlapping imaging features. FNH-like lesions enhance during the hepatic arterial phase and remain isoenhancing relative to the background liver parenchyma but infrequently appear to wash out at delayed phase imaging, similar to what might be seen with HCC. Heterogeneity, presence of an enhancing capsule, washout during the portal venous phase, intermediate signal intensity at T2-weighted imaging, restricted diffusion, and lack of uptake at hepatobiliary phase imaging point toward the diagnosis of HCC, although these features are not sensitive individually. It is important to emphasize that the Liver Imaging Reporting and Data System (LI-RADS) algorithm cannot be applied in congested livers since major LI-RADS features lack specificity in distinguishing HCC from benign hypervascular lesions in this population. Also, the morphologic changes and increased liver stiffness caused by congestion make the imaging diagnosis of cirrhosis difficult. The authors discuss the complex liver macro- and microhemodynamics underlying liver congestion; propose a more inclusive approach to and conceptualization of liver congestion; describe the pathophysiology of liver congestion, hepatocellular injury, and the development of benign and malignant nodules; review the imaging findings and mimics of liver congestion and hypervascular lesions; and present a diagnostic algorithm for approaching hypervascular liver lesions. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Superb Microvascular Imaging in Pediatric Focal Nodular Hyperplasia.

OBJECTIVE: To investigate superb microvascular imaging (SMI), a novel Doppler ultrasound technique that can visualize low-velocity microvascular flow, for assessing pediatric focal nodular hyperplasia (FNH). PATIENTS AND METHODS: Nine FNH lesions in 6 patients were enrolled. On SMI and color Doppler imaging (CDI), intralesional vascularity was assessed visually and categorized as typical spoke-wheel pattern (central vessel radiating from the center to the periphery), multifocal spoke-wheel pattern, and nonspecific pattern. We compared the vascular features of the lesions between SMI and CDI and evaluated vascular patterns according to lesion size. RESULTS: In terms of vascularity pattern, the typical spoke-wheel pattern of FNH was noted more frequently on SMI (67%) than on CDI (11%; P < 0.05). In addition, a multifocal spoke-wheel pattern was noted in all remaining lesions (33%) on SMI. On the contrary, a nonspecific vascular pattern was detected in the majority (78%) of CDI. Regarding the lesion size and vascularity on SMI, the typical spoke-wheel pattern was seen more frequently in the small FNH group than in the large FNH group. The intralesional vascular signal was detected more frequently on SMI (100%) than on CDI (89%). CONCLUSION: SMI is feasible in evaluating FNH in children and has a greater ability to demonstrate the spoke-wheel pattern than CDI.

Association Between Gadoxetic Acid-Enhanced Magnetic Resonance Imaging, Organic Anion Transporters, and Farnesoid X Receptor in Benign Focal Liver Lesions.

The organic anion uptake and efflux transporters [organic anion-transporting polypeptide (OATP)1B1, OATP1B3 and multidrug resistance-associated protein (MRP)2 and MRP3] that mediate the transport of the hepatobiliary-specific contrast agent gadoxetate (Gd-EOB-DTPA) are direct or indirect targets of the farnesoid X receptor (FXR), a key regulator of bile acid and lipid homeostasis. In benign liver tumors, FXR expression and activation is not yet characterized. We investigated the expression and activation of FXR and its targets in hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH) and their correlation with Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI). Gd-EOB-DTPA MRI patterns were assessed by an expert radiologist. The intensity of the lesions on the hepatobiliary phase was correlated to mRNA expression levels of OATP1B1, OATP1B3, MRP2, MRP3, FXR, and small heterodimer partner (SHP) in fresh surgical specimens of patients with FNH or HCA subtypes. Normal and tumor sample pairs of 43 HCA and 14 FNH were included. All FNH (14/14) were hyperintense. Of the 34 HCA with available Gd-EOB-DTPA-enhanced MRI, 6 were hyperintense and 28 HCA were hypointense. OATP1B3 was downregulated in the hypointense tumors compared with normal surrounding liver tissue (2.77±3.59 vs. 12.9±15.6, P < 0.001). A significant positive correlation between FXR expression and activation and OATP1B3 expression level was found in the HCA cohort. SHP showed a trend toward downregulation in hypointense HCA. In conclusion, this study suggests that the MRI relative signal in HCA may reflect expression level and/or activity of SHP and FXR. Moreover, our data confirms the pivotal role of OATP1B3 in Gd-EOB-DTPA uptake in HCA. SIGNIFICANCE STATEMENT: FXR represents a valuable target for the treatment of liver disease and metabolic syndrome. Currently, two molecules, ursodeoxycholate and obeticholate, are approved for the treatment of primary biliary cirrhosis and cholestasis, with several compounds in clinical trials for the treatment of metabolic dysfunction-associated fatty liver disease. Because FXR expression and activation is associated with gadoxetate accumulation in HCA, an atypical gadoxetate-enhanced MRI pattern might arise in patients under FXR-targeted therapy, thereby complicating the differential diagnosis.

Key CT and MRI findings of drug-associated hepatobiliary and pancreatic disorders.

Obtaining an imaging diagnosis of various hepatobiliary and pancreatic disorders caused by certain drugs can often be challenging. Familiarity with these conditions may improve diagnostic accuracy and patient management. This review aimed to describe the imaging findings of drug-associated hepatobiliary and pancreatic disorders and identify suggestions for obtaining a correct diagnosis. We focused on relatively common disorders or those that can present with characteristic imaging findings, such as drug-induced acute hepatitis, sinusoidal obstruction syndrome, focal nodular hyperplasia-like lesions, hepatocellular adenoma, pseudocirrhosis, chemotherapy-associated steatohepatitis, amiodarone deposition in the liver, secondary iron overload, drug-induced pancreatitis, pancreatic enlargement after epoprostenol therapy, ceftriaxone-associated gallbladder pseudolithiasis, immune-related adverse events, and methotrexate-associated lymphoproliferative disorders.

Patient with a novel syndrome with multiple benign hepatic lesions and extrahepatic neoplasms.

Simultaneous occurrence of benign hepatic lesions of different types is a sporadic phenomenon. To the best of our knowledge, we report the first clinical case of a syndrome with simultaneous manifestations of three different entities of benign liver tumors (hepatocellular adenoma, focal nodular hyperplasia and hemangioma) with a novel mutation detected in the liver adenoma and in the presence of a number of further extrahepatic organ neoplasms. Furthermore, we describe for the first time the presence of liver epithelial cells of hepatocytic phenotype expressing cytokeratin 7 (CK7) at the border of the adenoma. These findings may be important for explaining pathogenesis of benign as well as malignant tumors based on genetic and histopathological features.

Focal nodular hyperplasia-like nodules arising in the setting of hepatic vascular disorders with portosystemic shunting show ß-catenin activation.

Hepatocellular nodules can develop in the setting of chronic hepatic vascular disorders including those characterized by portosystemic shunts such as Abernethy malformation and post-Fontan procedure. The nodules can range from benign lesions such as regenerative nodules, focal nodular hyperplasia (FNH), and hepatocellular adenoma (HCA) to malignant neoplasms such as hepatocellular carcinoma (HCC). In many instances, these nodules are difficult to place into well-defined categories based on radiologic or histologic features. Nodular lesions that resemble FNH are common in this context and have been described as FNH-like nodules, the nature of which is not well-established. This study examines 6 liver resections from patients with vascular disease characterized by portosystemic shunts. A wide range of nodules were present in these cases, including regenerative nodules (n = 2), FNH and FNH-like (n = 30), HCA (n = 10), HCA-like (n = 13), and HCC (n = 2). Six nodules from 3 patients were categorized as FNH-like due to one or more features such as nodular architecture, fibrous septa, and ductular reaction, but lack of typical map-like glutamine synthetase (GS) staining. Further characterization of these 6 FNH-like nodules showed diffuse GS staining in all nodules (3 diffuse homogeneous, 3 diffuse heterogeneous). Targeted next-generation sequencing identified CTNNB1 alterations in all tested FNH-like nodules (n = 4). These results indicate that FNH-like nodules in the setting of chronic hepatic vascular disorders can be neoplastic. Since the presence of ß-catenin activation portends a potential risk for malignant progression, GS and ß-catenin immunohistochemistry should be obtained in all cases showing FNH-like morphology, with molecular analysis performed in cases with indeterminate staining pattern.

Lack of endothelial autophagy does not impair liver regeneration after partial hepatectomy in mice.

Liver sinusoidal endothelial cells (LSEC) are key elements in regulating the liver response to injury and regeneration. While endothelial autophagy is essential to protect endothelial cells from injury-induced oxidative stress and fibrosis, its role in liver regeneration has not been elucidated. This study was intended to investigate the role of endothelial autophagy in liver regeneration in the context of partial hepatectomy (PHx). Analysis of autophagy levels in rat LSEC after PHx indicated a tendency to decrease activity the first 2 days after surgery. PHx performed in mice with impaired endothelial autophagy (Atg7flox/flox ;VE-Cadherin-Cre+ ) and their littermate controls showed no differences neither in liver-to-body weight ratio, histological analysis, hepatocyte proliferation nor vascular integrity during the first 7 days after PH and liver regeneration was completely achieved. Our results indicate that endothelial autophagy does not play an essential role in the coordination of the liver regeneration process after PHx.

Large focal nodular hyperplasia of the liver treated with transcatheter arterial embolization and laparoscopic resection: A case report.

Focal nodular hyperplasia (FNH) is a rare benign hepatic tumor which is frequently observed in women of reproductive age, and therapeutic intervention needs to be considered in cases wherein the tumor has a risk of rupture. The laparoscopic approach is beneficial, especially for young women, but is often challenging because the tumor is large and hemorrhagic. Herein, we report a case of large FNH in a 22-year-old woman. The patient was asymptomatic; however, the tumor was approximately 15 cm in diameter and protruded from the liver. Given the risk of rupture, we decided to perform surgical resection. Preoperative transcatheter arterial embolization led to rapid shrinkage of the tumor and control of intraoperative bleeding, which enabled us to safely perform laparoscopic liver resection. The combination of surgical resection with intravascular embolization may be a promising therapeutic option for hypervascular tumors such as FNH.

Inflammatory Hepatocellular Adenoma Mimicking Focal Nodular Hyperplasia That Grew during Pregnancy and Changed Its Appearance on Magnetic Resonance Imaging after Delivery.

We reported a notable case of inflammatory hepatocellular adenoma that grew during pregnancy, consequently changing its appearance on magnetic resonance imaging remarkably. A 5-months-pregnant 35-year-old woman presented with a 37-mm liver nodule that had been diagnosed as focal nodular hyperplasia 3 years earlier. She had never used oral contraceptives. After 2 months, the nodule grew to 57 mm. The patient delivered a full-term infant without complications. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging performed after delivery revealed markedly different findings compared with the first images. A liver biopsy was performed, and the tumor was diagnosed as inflammatory hepatocellular adenoma.

Suspected focal nodular hyperplasia in male adults: 10-year experience from a large liver centre.

PURPOSE: Focal nodular hyperplasia (FNH) is commonly found in females of reproductive age. In males, the diagnosis is made more cautiously due to its lower incidence and higher incidence of hepatocellular carcinoma, which can have overlapping imaging features. Follow-up or biopsy is sometimes required. This retrospective study aims to assess management of suspected FNH in male adult patients at our institution over a 10-year period. METHODS: Male adults (≥ 18 years) suspected of having FNH from January 2010-June 2020 were identified using a departmental radiology information system search. Data was collected from radiology reports and patient pathway manager. RESULTS: Of 342 patients with suspected FNH, 62 were male (18.1%; F:M of 4.5:1). We only included patients investigated and followed up by MRI, total of 57 patients. Median age was 40 years (range 18-74 years). Background liver disease present in 21/57 (36.8%), majority with hepatic steatosis. Average number of lesions per patient 1.7. 22/57 (38.6%) had at least one MRI follow-up using liver-specific contrast with 7 lesions demonstrating variation in size (range growth: -3.27 mm/year to + 4 mm/year). In 7 cases, MRI was not definitive; 6 required biopsy and 1 resection. Only 2/7 demonstrated malignancy. Of the total 57 patients, 6 have deceased and none due to a misdiagnosed or mismanaged hepatic lesion. CONCLUSION: FNH is relatively uncommon in males, however, our data suggests that lesions with typical MRI characteristics do not require follow-up and diagnosis can be made confidently, similar to females. Any atypical features should prompt a biopsy.

A systematic review and meta-analysis of spectral CT to differentiate focal liver lesions.

AIM: To determine the feasibility of spectral computed tomography (CT) in the differentiation of focal liver lesions from hepatocellular carcinoma (HCC) using a network meta-analysis (NMA). MATERIALS AND METHODS: The review was completed in accordance with PRISMA guidelines. Searches of three medical databases were performed. A total of nine articles were found for the qualitative synthesis. The meta-analysis was performed on five studies for the normalised iodine concentration (NIC; which is the iodine concentration in the lesion divided by the iodine concentration in the aorta) and the lesion-normal parenchyma iodine ratio (LNR; which is the iodine concentration in the lesion divided by the iodine concentration in the non-tumour hepatic parenchyma) on portal venous and arterial phase images due to sufficient data. RESULTS: Spectral CT can be used to differentiate HCC from hepatic haemangioma (HH), focal nodular hyperplasia (FNH), regenerative nodules, neuroendocrine tumours (NETs), abscesses, and angiomyolipoma (AML). Hepatic metastases versus abscess and FNH versus HH could also be differentiated. The NMA demonstrated that HCC, NETs, and regenerative nodules could be differentiated due to lower quantitative iodine values. FNH, AML, and HH all had higher values. CONCLUSION: Spectral CT shows promise in differentiating focal liver lesions. Studies with larger sample sizes are warranted. Future studies should be performed comparing benign lesions using quantitative markers.

The Early-Enhancing Hepatic Vein: Differentiating Focal Nodular Hyperplasia and Hepatic Adenoma With Pathologic Validation in MRI.

BACKGROUND: Focal nodular hyperplasia (FNH) and hepatic adenoma (HA) are two common benign liver lesions with different management options. In particular, resection is considered for large HA lesions to avoid possible bleeding complications or rarely malignant degeneration. PURPOSE: To determine whether early enhancement of a draining hepatic vein (EDHV) and absence of perilesional enhancement (PLE) on arterial phase MR images are useful for distinguishing FNH from HA. STUDY TYPE: Retrospective. POPULATION: A total of 34 patients: 16 with FNH and 18 with HA lesions. FIELD STRENGTH/SEQUENCE: A1.5 T, axial T1 fat-suppressed arterial postcontrast. ASSESMENT: Four abdominal radiologists blinded to pathologic diagnosis assessed for the presence or absence of EDHV in association with the lesion, definitively characterized by pathology. This was considered present if contrast could be identified in a hepatic vein contiguous with the lesion in question. Secondarily, PLE was evaluated. STATISTICAL TESTS: Fleiss's multirater kappa statistic, Chi-squared statistic, Phi-coefficient. Significance level P < 0.05. RESULTS: Considering all observations obtained from the four readers, an EDHV was identified with FNH 48.5% of the time. EDHV was seen with HA in 8.8% of cases. PLE was seen with significantly greater frequency in HA. The presence of an EDHV was associated with the absence of PLE. DATA CONCLUSION: In a lesion that may be either an FNH or HA, confident identification on arterial phase images of an EDHV should lead the reader to favor FNH, while the presence PLE should dissuade the reader from FNH. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.

Variation in the management of benign liver tumors: A European survey and case vignette study.

BACKGROUND: Management of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA), is multidisciplinary and subject to practice variation. We aimed to evaluate variation in clinical management of FNH and HCA in Europe. METHODS: We distributed an online survey (November 2021-March 2022) among 294 European experts. The survey included questions on local practice and included eight clinical vignettes. The clinical vignettes focused on FNH or HCA management in the setting of sex, lifestyle modification, and pregnancy. RESULTS: The response rate was 32% and respondents included surgeons (38%), gastroenterologists/hepatologists (25%), radiologists (32%), and pathologists (1.6%) from ten European countries. We observed practice variation with regard to lifestyle modification and imaging follow-up in patients with FNH, and with regard to the management of HCA >5 cm before and during pregnancy. Finally, the management of HCA >5 cm after lifestyle modification deviated from EASL guideline recommendations. CONCLUSION: Our survey illustrates variability in FNH and HCA management in Europe. Several areas were identified for future research and guideline recommendations, including FNH follow-up and the management of HCA >5 cm. We propose the organization of Delphi consensus meetings to prioritize areas of research and update current guidelines to optimize management for all patients with benign liver tumors.

Outcomes of transarterial embolization for large symptomatic focal nodular hyperplasia in 17 pediatric patients.

BACKGROUND: To evaluate the safety and the long-term outcomes of transarterial embolization (TAE) with lipiodol-bleomycin emulsion (LBE) plus N-Butyl cyanoacrylate (NBCA) in the treatment of children with large symptomatic focal nodular hyperplasia (FNH). METHODS: This is a retrospective case serial study. Children (aged <18 years) with FNH were treated. Indications for TAE were patients who were presenting with FNH related abdominal pain and the maximum diameter of FNH is more than 7 cm, and who were not candidates for surgical treatment. Technical success, adverse events, symptoms relief rate, and changes in the lesion size after TAE were evaluated. RESULTS: Between January 2003 and February 2018, 17 pediatric patients were included. Technical success was achieved in all patients. Mean follow-up was 67.5 months. All patients had complete resolution of abdominal symptom. The mean largest diameter of the lesions decreased from 10.5 cm to 1.9 cm (P < 0.01). The mean volume reduction rate was 96.9%. The complete resolution of the FNH was observed in 16 patients. No further therapy was needed for all patients. CONCLUSIONS: TAE with LBE plus NBCA appears to be a safe and effective treatment in pediatric patients with large symptomatic FNH. It could be considered as the first-line treatment for symptomatic large FNH.

Differentiation of focal nodular hyperplasia and hepatocellular adenoma using qualitative and quantitative imaging features and classification and regression tree analysis.

PURPOSE: To assess qualitative and quantitative analysis of gadoxetate disodium-enhanced hepatobiliary phase MR imaging (MRI) and assess the performance of classification and regression tree analysis for the differentiation of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA). MATERIALS AND METHODS: This retrospective study was approved by our local ethics committee. One hundred seventy patients suspected of having FNH or HCA underwent gadoxetate disodium-enhanced MRI. The reference standard was either pathology or follow-up imaging. Two readers reviewed images to identify qualitative imaging features and measure signal intensity on unenhanced, dynamic, and hepatobiliary phase images. For quantitative analysis, contrast enhancement ratio (CER), lesion-to-liver contrast (LLC), signal intensity ratio (SIR), and relative signal enhancement ratio (RSER) were calculated. A classification and regression tree (CART) analysis was developed. RESULTS: Eighty-five patients met the inclusion criteria, with a total of 97 FNHs and 43 HCAs. For qualitative analysis, the T1 signal intensity on the hepatobiliary phase provided the highest overall classification performance (91.9% sensitivity, 90.1% specificity, and 90.9% accuracy). For quantitative analysis, RSER in the hepatobiliary phase with a threshold of 0.723 provided the highest classification performance (92.6% sensitivity and 89.4% specificity) to differentiate FNHs from HCAs. A CART model based on five qualitative imaging features provided an accuracy of 94.4% (95% confidence interval 90.0-98.9%). CONCLUSION: Gadoxetate disodium-enhanced hepatobiliary phase provides high diagnostic performance as demonstrated in quantitative and qualitative analysis in differentiation of FNH and HCA, supported by a CART decision model.

Focal Nodular Hyperplasia-Like Lesions With Glypican-3 Positivity in Infancy.

PURPOSE AND CONTEXT: Glypican-3 is often used to discriminate between neoplastic and nonneoplastic liver. In focal lesions, positivity may be considered suggestive of a malignancy such as hepatoblastoma. However, glypican-3 is also normally expressed in the immature liver. We present a series of 5 cases of focal nodular hyperplasia (FNH)-like lesions arising in very young patients with glypican-3 expression and highlight the challenges these lesions present in the differential diagnosis of hepatoblastoma. METHODS: Cases were obtained from the files of 3 tertiary pediatric hospitals. Clinical data were obtained from the electronic medical record and histopathologic material including immunohistochemical stains were reviewed. KEY RESULTS: Patients were aged 2 weeks to 6 months with peak AFP levels ranging from 88.6 to 204,696 ng/mL. Microscopically, all were variably demarcated hepatocellular lesions with cords of hepatocytes, marked sinusoidal dilatation, and occasional fibrous bands and areas reminiscent of central scar with bile ducts. No significant cytologic atypia or increased mitotic activity were present. All showed glypican-3 expression and were negative for nuclear beta-catenin with intact reticulin framework. CONCLUSIONS: Our study highlights the pitfalls of evaluating focal liver lesions in infants when high AFP levels and glypican-3 expression may reflect immaturity rather than neoplasia.

Hepatocellular carcinoma and focal nodular hyperplasia in patients with Fontan-associated liver disease: characterisation using dynamic gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced MRI.

AIM: To identify the characteristic diagnostic features of hepatocellular carcinoma (HCC) and focal nodular hyperplasia (FNH) in Fontan-associated liver disease (FALD) patients using dynamic gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI). MATERIALS AND METHODS: Thirty-one FALD patients (mean age, 28.3 ± 7.2 years) with liver nodules who underwent dynamic Gd-EOB-DTPA-enhanced MRI were enrolled prospectively. Twenty-five patients (mean age, 72.8 ± 11.4 years) with hepatitis C virus (HCV)-related HCC constituted the control group. The tumour-to-liver signal intensity (SI) ratio was measured at 30, 60, 100, 180 seconds and 15 minutes, and the SI ratio was compared among FALD-HCC, FALD-FNH, and HCV-HCC. RESULTS: FALD-HCC exhibited weak early enhancement with mild washout in late phases. FALD-FNH exhibited marked early enhancement that continued until the late phases. The SI ratio was significantly lower for FALD-HCC than for FALD-FNH in all phases. The SI ratio was significantly lower for FALD-HCC than for HCV-HCC only at 30 seconds (p<0.05), whereas poorer washout was seen in FALD-HCC than HCV-HCC in other phases. In 15 minutes, FALD-HCC had a significantly lower SI ratio compared to FALD-FNH (p<0.001). CONCLUSIONS: The time course of Gd-EOB-DTPA-enhanced MRI signal intensity in FALD-HCC was different from that in FALD-FNH or HCV-HCC. This imaging finding may be useful adjunctive information to distinguish FALD-HCC from FALD-FNH.