Lesions hyper- to isointense to surrounding liver in the hepatobiliary phase of gadoxetic acid-enhanced MRI.

OBJECTIVES: Hyper- or isointensity in the hepatobiliary phase (HBP) of gadoxetic acid-enhanced MRI has high specificity for focal nodular hyperplasia (FNH) but may be present in hepatocellular adenoma and carcinoma (HCA/HCC). This study aimed to identify imaging characteristics differentiating FNH and HCA/HCC. MATERIALS AND METHODS: This multicenter retrospective cohort study included patients with pathology-proven FNH or HCA/HCC, hyper-/isointense in the HBP of gadoxetic acid-enhanced MRI between 2010 and 2020. Diagnostic performance of imaging characteristics for the differentiation between FNH and HCA/HCC were reported. Univariable analyses, multivariable logistic regression analyses, and classification and regression tree (CART) analyses were conducted. Sensitivity analyses evaluated imaging characteristics of B-catenin-activated HCA. RESULTS: In total, 124 patients (mean age 40 years, standard deviation 10 years, 108 female) with 128 hyper-/isointense lesions were included. Pathology diagnoses were FNH and HCA/HCC in 64 lesions (50%) and HCA/HCC in 64 lesions (50%). Imaging characteristics observed exclusively in HCA/HCC were raster and atoll fingerprint patterns in the HBP, sinusoidal dilatation on T2-w, hemosiderin, T1-w in-phase hyperintensity, venous washout, and nodule-in-nodule partification in the HBP and T2-w. Multivariable logistic regression and CART additionally found a T2-w scar indicating FNH, less than 50% fat, and a spherical contour indicating HCA/HCC. In our selected cohort, 14/48 (29%) of HCA were B-catenin activated, most (13/14) showed extensive hyper-/isointensity, and some had a T2-w scar (4/14, 29%). CONCLUSION: If the aforementioned characteristics typical for HCA/HCC are encountered in lesions extensively hyper- to isointense, further investigation may be warranted to exclude B-catenin-activated HCA. CLINICAL RELEVANCE: Hyper- or isointensity in the HBP of gadoxetic acid-enhanced MRI is specific for FNH, but HCA/HCC can also exhibit this feature. Therefore, we described imaging patterns to differentiate these entities. KEY POINTS: FNH and HCA/HCC have similar HBP intensities but have different malignant potentials. Six imaging patterns exclusive to HCA/HCC were identified in this lesion population. These features in liver lesions hyper- to isointense in the HBP warrant further evaluation.

Engaging stimulatory immune checkpoint interactions in the tumour immune microenvironment of primary liver cancers - how to push the gas after having released the brake.

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are the first and second most common primary liver cancer (PLC). For decades, systemic therapies consisting of tyrosine kinase inhibitors (TKIs) or chemotherapy have formed the cornerstone of treating advanced-stage HCC and CCA, respectively. More recently, immunotherapy using immune checkpoint inhibition (ICI) has shown anti-tumour reactivity in some patients. The combination regimen of anti-PD-L1 and anti-VEGF antibodies has been approved as new first-line treatment of advanced-stage HCC. Furthermore, gemcibatine plus cisplatin (GEMCIS) with an anti-PD-L1 antibody is awaiting global approval for the treatment of advanced-stage CCA. As effective anti-tumour reactivity using ICI is achieved in a minor subset of both HCC and CCA patients only, alternative immune strategies to sensitise the tumour microenvironment of PLC are waited for. Here we discuss immune checkpoint stimulation (ICS) as additional tool to enhance anti-tumour reactivity. Up-to-date information on the clinical application of ICS in onco-immunology is provided. This review provides a rationale of the application of next-generation ICS either alone or in combination regimen to potentially enhance anti-tumour reactivity in PLC patients.

Cryptogenic non-cirrhotic HCC: Clinical, prognostic and immunologic aspects of an emerging HCC etiology.

The incidence of hepatocellular carcinoma (HCC) in non-cirrhotic livers is rising significantly, but clear risk factors for screening remain elusive. This study sought to characterize non-cirrhotic HCC etiologies. HCC cases from 2009 to 2020 in a Dutch referral center were examined, revealing 371 out of 1654 cases (22%) as non-cirrhotic. Notably, the incidence of non-cirrhotic HCC increased by 61% in the time frame between 2009 and 2020. Interestingly 39% of non-cirrhotic HCC cases had cryptogenic origins. Cryptogenic non-cirrhotic HCC exhibited similarities with non-cirrhotic NAFLD HCC, but displayed advanced tumor stages, lower surgical rates, and a more frequent presence of symptoms, which substantiated in poor survival rates. Advanced cryptogenic non-cirrhotic HCC stages exhibited elevated serum interleukin-6 levels compared to non-cirrhotic HCC with defined etiologies. Comparative analysis encompassing cryptogenic and NAFLD non-cirrhotic HCC cohorts and controls unveiled comparable circulating immune biomarker profiles and PNPLA3 polymorphisms. To conclude, the primary etiology of non-cirrhotic HCC in our cohort has not defined risk factors. This cryptogenic variant exhibits distinct traits, such as advanced tumors and increased symptoms, and most resemble burned-out NAFLD. Understanding this HCC variant is crucial for improving screening and management strategies.

Successful adult domino living donor liver transplantation in methylmalonic acidemia: case report.

Background: Liver transplantation (LT) is a therapeutic option in multiple inherited metabolic diseases (IMDs), including methylmalonic acidemia (MMA), as LT reduces the risk of acute metabolic decompensations and long-term complications associated with these diseases. In certain IMDs, such as maple syrup urine disease (MSUD), domino liver transplant (DLT) is an accepted and safe method which expands the donor pool. However, only one adult case of DLT using an MMA donor liver has been reported; outcome and safety are still unknown and questioned. Case Description: In this case report, we describe our experience with DLT using MMA livers. Two adult MMA patients underwent living donor liver transplant (LDLT); their MMA livers were consecutively transplanted into two patients on the liver transplant waiting list who had limited chance of receiving a liver transplant in the short term due to their low model for end-stage liver disease (MELD) scores. No severe peri- or postoperative complications occurred, however the recipients of the MMA livers biochemically now have mild MMA. Conclusions: DLT using MMA grafts is a feasible strategy to treat end-stage liver disease and expand the donor organ pool. However, the recipient of the MMA domino liver may develop mild MMA which could affect quality of life, and long-term safety remains unclear. Further long-term of outcomes for domino recipients of MMA livers, focusing on quality of life and any metabolic complications of transplantation are needed to better define the risks and benefits.

Evaluation of Hepatocellular Carcinoma Surveillance with Contrast-enhanced MRI in a High-Risk Western European Cohort.

AIM: To investigate the utilization of MRI using a MRI liver protocol with extracellular contrast-enhanced series for hepatocellular carcinoma (HCC) surveillance in high-risk patients. METHODS: Consecutive high-risk patients of a western European cohort who underwent repeated liver MRI for HCC screening were included. Lesions were registered according to the Liver Reporting & Data System (LIRADS) 2018. HCC was staged as very early stage HCC (BCLC stage 0) and more advanced stages of HCC (BCLC stage A-D). Differences in time interval between MRI's for BCLC stage 0 and stage A-D were calculated with the Mann-Whitney U test. The HCC cumulative incidence at one-, three- and five years was calculated with the Kaplan Meier estimator. RESULTS: From 2010 to 2019 a total of 240 patients were included (71% male; median age: 57 years; IQR: 50-64 years) with 1350 MRI's. Most patients (83 %) had cirrhosis with hepatitis C as the most common underlying cause. Patients underwent on average four MRI's (IQR: 3-7). Forty-two patients (17.5%) developed HCC (52 HCC lesions: 43 LIRADS-5, eight LIRADS-4, and one LIRADS-TIV). Eighteen patients (43%) had BCLC stage 0 HCC with a significant shorter screening time interval (10 months; IQR: 6-21) compared to patients with BCLC stage A-D (21 months; IQR: 10-32) (p = 0.03). Thirty seven percent of patients with a LIRADS-3 lesion (n=43) showed HCC development within twelve months (median: 7.4 months). One, three- and five-year HCC cumulative incidence in cirrhotic patients was 1%, 10% and 17%, respectively. CONCLUSION: High-risk patients who underwent surveillance with contrast-enhanced MRI developed HCC in 17.5 % during a follow up period of over 4 years median. Very early stage HCC was seen in compensated cirrhosis after a median time interval of 10 months. Later stages of HCC were related to prolonged screening time interval (median 21 months).

Do treats facilitate the interpretation of findings on caloric restriction?

Introduction: Food can build social bonds and enhance interpersonal relationships. An area of research perhaps at odds with food abundance, is caloric restriction (CR), intermittent fasting (IF) or short-term fasting (STF). We aimed to study the impact of offering treats on the audience during presentations on IF and STF and whether this impacted the audience's reception of the subject. The contradiction of the tempting nature of sharing brownies juxtaposed with the potential health benefits presented is a light-hearted subject in a world where nutritional intake and health outcomes are the object of intense academic discussion. Objective: Investigate how treats influence hospital personnel interpretation of information presented on the potential benefits of CR, IF and STF. Methods: This trial consists of a cross-sectional study (CSS) and a randomised controlled trial (RCT) conducted at three study centres. The CSS involved a survey administered to healthcare professionals to assess their knowledge, experience and willingness regarding IF and/or STF. In the RCT, brownies were randomly provided to healthcare staff attending a scientific meeting on restricting calories. Results: 135 participants were included in the CSS and 64 participants joined the randomised experiment. We found that the randomisation had no statistically significant effect. Only 2 out of 64 were aware of the irony of the provided treatment. In the CSS, participants most often cited the expected beneficial effects on their short-term and long-term health as important reasons for adhering to IF and/or STF. Perceiving fasting as beneficial was mostly influenced by knowledge on the topic and previously adhering to a fasting diet. Discussion: In this light-hearted, holiday-inspired exploratory study, we found that providing your audience with treats does not influence participants' opinion of you or your research, even when it focuses on the benefits of reducing calorie intake. The recipients of the treat will remain critical of presented findings, and due to prior experiences will be receptive to the counterintuitive topic of fasting.