Hepatocellular carcinoma with macrovascular invasion: multimodality imaging features for the diagnosis

Hepatocellular carcinoma (HCC) is frequently associated with macrovascular invasion of the portal vein or hepatic veins in advanced stages. The accurate diagnosis of macrovascular invasion and the differentiation from bland non-tumoral thrombus has significant clinical and management implications, since it narrows the therapeutic options and it represents a mandatory contraindication for liver resection or transplantation. The imaging diagnosis remains particularly challenging since the imaging features of HCC with macrovascular invasion may be subtle, especially in lesions showing infiltrative appearance. However, each radiologic imaging modality may provide findings suggesting the presence of tumor thrombus rather than bland thrombus. The purpose of this paper is to review the current guidelines and imaging appearance of HCC with macrovascular invasion. Knowledge of the most common imaging features of HCC with macrovascular invasion may improve the diagnostic confidence of tumor thrombus in clinical practice and help to guide patients’ management

Differentiation of hepatocellular adenoma by subtype and hepatocellular carcinoma in non-cirrhotic liver by fractal analysis of perfusion MRI

Background: To investigate whether fractal analysis of perfusion differentiates hepatocellular adenoma (HCA) subtypes and hepatocellular carcinoma (HCC) in non-cirrhotic liver by quantifying perfusion chaos using four-dimensional dynamic contrast-enhanced magnetic resonance imaging (4D-DCE-MRI). Results: A retrospective population of 63 patients (47 female) with histopathologically characterized HCA and HCC in non-cirrhotic livers was investigated. Our population consisted of 13 hepatocyte nuclear factor (HNF)-1 alpha-inactivated (H-HCAs), 7 beta-catenin-exon-3-mutated (b(ex3)-HCAs), 27 inflammatory HCAs (I-HCAs), and 16 HCCs. Four-dimensional fractal analysis was applied to arterial, portal venous, and delayed phases of 4D-DCE-MRI and was performed in lesions as well as remote liver tissue. Diagnostic accuracy of fractal analysis was compared to qualitative MRI features alone and their combination using multi-class diagnostic accuracy testing including kappa-statistics and area under the receiver operating characteristic curve (AUC). Fractal analysis allowed quantification of perfusion chaos, which was significantly different between lesion subtypes (multi-class AUC = 0.90, p < 0.001), except between I-HCA and HCC. Qualitative MRI features alone did not allow reliable differentiation between HCA subtypes and HCC (kappa = 0.35). However, combining qualitative MRI features and fractal analysis reliably predicted the histopathological diagnosis (kappa = 0.89) and improved differentiation of high-risk lesions (i.e., HCCs, b(ex3)-HCAs) and low-risk lesions (H-HCAs, I-HCAs) from sensitivity and specificity of 43% (95% confidence interval [CI] 23-66%) and 47% (CI 32-64%) for qualitative MRI features to 96% (CI 78-100%) and 68% (CI 51-81%), respectively, when adding fractal analysis. Conclusions: Combining qualitative MRI features with fractal analysis allows identification of HCA subtypes and HCCs in patients with non-cirrhotic livers and improves differentiation of lesions with high and low risk for malignant transformation

New insights in the management of Hepatocellular Adenoma

Hepatocellular adenoma (HCA) are benign liver tumours that may be complicated by haemorrhage or malignant transformation to hepatocellular carcinoma. Epidemiological data are fairly outdated, but it is likely to assume that the incidence has increased over the past decades as HCA are more often incidentally found due to the more widespread use of imaging techniques and the increased incidence of obesity. Various molecular subgroups have been described. Each of these molecular subgroups are defined by specific gene mutations and pathway activations. Additionally, they are all related to specific risk factors and show a various biological behaviour. These molecular subgroups may be identified using immunohistochemistry and molecular characterization. Contrast-enhanced MRI is the recommended imaging modality to analyse patients with suspected hepatocellular adenoma allowing to determine the subtype in up to 80%. Surgical resection remains to be the golden standard in treating HCA, although resection is deemed unnecessary in a large number of cases, as studies have shown that the majority of HCA will regress over time without complications such as haemorrhage or malignant transformation occurring. It is preferable to treat patients with suspected HCA in high volume centres with combined expertise of liver surgeons, hepatologists, radiologists and (molecular) pathologists

Quantification échographique de la stéatose hépatique et évaluation multiparamétrique par IRM de la stéatose hépatique non alcoolique

Ce travail de thèse explore deux thèmes : 1) la quantification non invasive par ultrasons (US) de la stéatose hépatique en utilisant deux nouvelles méthodes : l'estimation de la vitesse du son (SSE) et l'imagerie d'atténuation (ATI). 2) l'évaluation multiparamétrique par IRM de la stéatohépatite non alcoolique (NASH), avec une étude clinique rétrospective et une étude prospective murine. Pour évaluer la performance de la SSE pour le diagnostic et quantification de stéatose hépatique la proton density fat fraction (PDFF) a été utilisé en référence. 50 patients dans une cohorte d'étude et 50 dans une de validation ont étés inclus. La stéatose a été classifiée en fonction des valeurs de PDFF (S0= 22%). Basé sur le fit optimal des données dérivé de notre étude nous avons proposé une correspondance entre la PDFF et un index graisseux US. Le coefficient de détermination R2 a été utilisé pour évaluer la qualité du fit (robuste si R2>0.6). La SSE a montré une sensibilité de 80% et une spécificité de 86% pour le diagnostic de stéatose (S1-S3). Une correspondance robuste entre l'index graisseux en US et la PDFF a été démontrée pour les deux cohortes (R2= 0.73 et R2= 0.76). Pour évaluer les performances de l'ATI échographique pour le diagnostic et la quantification de la stéatose hépatique 101 patients ont eu une biopsie et une échographie avec mesure du coefficient d'atténuation (AC) le même jour. La stéatose a été classée absente (S0 66%). La valeur du AC était corrélée avec le degré de stéatose (r=0.58; p0.69 dB/cm/MHz avait une sensibilité de 76% et une spécificité de 86% pour le diagnostic de stéatose (S1-S3) (AUC=0.80). Une valeur >0.72 dB/cm/MHz avait une sensibilité de 96% et une spécificité de 74% pour le diagnostic de stéatose modérée-sévère (S2-S3) (AUC=0.89). Pour l'évaluation des patients avec stéatose hépatique non alcoolique nous avons testé la capacité des multiples paramètres IRM (composition des acides gras, PDFF, T2*, susceptibilité magnétique), dérivés d'une seule séquence multi-écho à différencier la stéatose de la NASH. Nous avons inclus rétrospectivement 76 patients avec stéatose, avec référence histologique. Selon l'algorithme FLIP, 39 patients avaient de la NASH. En analyse univariée, la PDFF était plus élevée (15± 8.3% vs 9.9± 5.7%; p= 22%. Based on the optimal data fit derived from our study, we proposed a correspondence between MR-PDFF and US fat index. Coefficient of determination R2 was used to evaluate fit quality, and was considered as robust when R2>0.6. SSE showed 80% sensitivity and 86% specificity for steatosis diagnosis (S1-S3) in the training cohort. Robust correspondence between MR-PDFF and the US fat index was found both for the training (R2=0.73) and the validation cohorts (R2=0.76). To evaluate the performance of US Attenuation Coefficient (AC) using ATI for the diagnosis and quantification of hepatic steatosis, liver biopsy was used as reference standard. 101 patients underwent biopsy and US-AC measurement on the same day. Liver steatosis was graded as absent (S0 66%). AC was positively correlated with steatosis(%) (r=0.58, p0.69 dB/cm/MHz had a sensitivity and specificity of 76% and 86%, respectively for diagnosing any grade of steatosis (S1-3) (AUROC=0.80), and AC> 0.72 dB/cm/MHz had a sensitivity and specificity of 96% and 74%, respectively for diagnosing S2-S3 (AUROC=0.89). In patients with non-alcoholic fatty liver disease, we investigated the value of several MR parameters (fatty acid composition, PDFF, T2*, magnetic susceptibility) derived from a single multi-echo sequence for distinguishing between NASH and steatosis. We retrospectively included a cohort of 76 patients with non-alcoholic fatty liver disease using histology as reference standard. According to the FLIP algorithm 39/76 patients had NASH. Univariate analysis showed that liver PDFF was higher patients with NASH than in patients with simple steatosis (15± 8.3% vs 9.9± 5.7% p<0.01). Liver T2* was shorter in patients with NASH than in patients with simple steatosis (18.5±5.6ms vs. 21.1±3.4ms; p=0.02). Logistic regression showed that solely PDFF was a determinant of NASH (O.R. 1.14). Finally we performed a study in a murine cohort divided in three groups, receiving respectively a normal diet, a high fat diet and a high fat diet, deficient in choline and supplemented with methionine. The liver was imaged with a 7T small animal MR scanner. PDFF, R2*, magnetic susceptibility and mechanical properties at 400, 600 and 800Hz including storage modulus (G'), loss modulus (G''), damping ratio, complex shear modulus (G*) and wave dispersion coefficient were obtained with dedicated sequences. Explanted livers were evaluated and according to the FLIP algorithm, 16 mice had normal liver, 22 mice had simple steatosis (with inflammation in 15 and ballooning in 1) and 19 mice had NASH (with fibrosis < grade 2 in 15). G'' at 400Hz had the highest AUC for diagnosing NASH (0.82- 95%C.I. 0.69-0.94). G'' and damping ratio at 400 Hz differed significantly between mice with NASH and simple steatosis. At multivariate analysis, wave dispersion coefficient was highly related to liver inflammation. In conclusion SSE and ATI showed good performance in US quantification of hepatic steatosis, while viscosity related MR elastography parameters are helpful for NASH diagnosis

Liver imaging and pregnancy: what to expect when your patient is expecting

Abstract Liver diseases in pregnancy can be specific to gestation or only coincidental. In the latter case, the diagnosis can be difficult. Rapid diagnosis of maternal-fetal emergencies and situations requiring specialized interventions are crucial to preserve the maternal liver and guarantee materno-fetal survival. While detailed questioning of the patient and a clinical examination are highly important, imaging is often essential to reach a diagnosis of these liver diseases and lesions. Three groups of liver diseases may be observed during pregnancy: (1) diseases related to pregnancy: intrahepatic cholestasis of pregnancy, pre-eclampsia, eclampsia, hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, and acute fatty liver of pregnancy; (2) liver diseases that are more frequent during or exacerbated by pregnancy: acute herpes simplex hepatitis, Budd-Chiari syndrome, hemorrhagic hereditary telangiectasia, hepatocellular adenoma, portal vein thrombosis, and cholelithiasis; (3) coincidental conditions, including acute hepatitis, incidental focal liver lesions, metabolic dysfunction–associated steatotic liver disease, cirrhosis, hepatocellular carcinoma, liver abscesses and parasitosis, and liver transplantation. Specific knowledge of the main imaging findings is required to reach an early diagnosis, for adequate follow-up, and to avoid adverse consequences in both the mother and the fetus. Critical relevance statement Pregnancy-related liver diseases are the most important cause of liver dysfunction in pregnant patients and, in pregnancy, even common liver conditions can have an unexpected turn. Fear of radiations should never delay necessary imaging studies in pregnancy. Key points • Pregnancy-related liver diseases are the most frequent cause of liver dysfunction during gestation. • Fear of radiation should never delay necessary imaging studies. • Liver imaging is important to assess liver emergencies and for the diagnosis and follow-up of any other liver diseases. • Common liver conditions and lesions may take an unexpected turn during pregnancy. • Pregnancy-specific diseases such as pre-eclampsia and HELLP syndrome must be rapidly identified. However, imaging should never delay delivery when it is considered to be urgent for maternal-fetal survival. Graphical Abstrac

CT and MR imaging of chemotherapy-induced hepatopathy

Chemotherapy-induced hepatopathy includes a wide variety of parenchymal and vascular hepatic changes on imaging, including diffuse or focal hepatopathies (i.e. hepatitis, steatosis, fibrosis, pseudocirrhosis, or sinusoidal obstruction). These changes can profoundly alter the hepatic parenchyma on imaging and result in both false negative and false-positive diagnoses of hepatic metastases and lead to errors in patient management strategies. It is therefore important for radiologists to have a comprehensive knowledge of the imaging patterns that may develop following chemotherapy. The purpose of this review is to explore the broad spectrum of hepatic parenchymal and vascular chemotherapy-induced changes on CT and MR imaging