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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 STATEMENTFXR 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.

AbstractObjectiveThe impact of the coronavirus disease 2019 (COVID-19) on hepatocellular carcinoma (HCC) care is unclear. This study reports on HCC patterns during the COVID-19 pandemic in the Netherlands.MethodsPatients diagnosed with HCC between 2017 and 2020 were identified from the Netherlands Cancer Registration. Monthly incidence rates were compared between 2020 and 2017–2019. Patient, tumor, process, and treatment characteristics and survival were compared between 2020 and 2017–2019, and between COVID-high (April and May 2020) and COVID-low (June and July 2020) months.ResultsThe incidence of HCC was lower in May 2020 (IRR 0.56, P= 0.001) and higher in June 2020 (IRR 1.32, P= 0.05) compared to the same months in 2017–2019. In 2017–2019, 2134 patients presented with HCC, compared to 660 in 2020. Time-to-treatment was shorter in 2020 (median 60 vs. 70 days, P< 0.001). The percentage of patients undergoing any treatment did not differ, yet if treatment was not performed this was more commonly due to comorbidity in 2020 (52 vs. 39%, P< 0.001). No other differences were found in patient, tumor, process and treatment characteristics and survival between COVID-high and COVID-low months.ConclusionsThis study demonstrated no impact of the COVID-19 pandemic on HCC patients, despite a decrease in HCC diagnoses.

Early recognition and management of postoperative complications, before they become clinically relevant, can improve postoperative outcomes for patients, especially for high-risk procedures such as pancreatic resection.

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Background:Previous studies have suggested body composition as a predictor of sorafenib toxicity and outcome in patients with advanced hepatocellular carcinoma (HCC). Large studies on the impact of body composition parameters in European HCC patients are lacking. Our aim was to validate the prognostic value of body composition parameters in Dutch patients with HCC treated with sorafenib. Patients and Methods:A retrospective analysis was performed in a cohort of HCC patients treated with sorafenib at two Dutch tertiary referral centers between 2007 and 2016. Body composition (adipose and skeletal muscle tissue) was measured at baseline by computed tomography (CT). Low skeletal muscle mass (SMM) and density were defined using published cut-offs. Body composition parameters were correlated with overall survival (OS), time to progression, response rate, and toxicity. Results:A total of 278 patients were included, mostly Child-Pugh class A (85%) and Barcelona Clinic Liver Cancer (BCLC) stage C (73%), with a median OS of 9.5 months (95% CI 8.1–11.0). Patients with combined low SMM and low total adipose tissue index (TATI) (n= 68, 25%) had a poor median OS (5.8, 95% CI 4.8–6.8) compared with other patients (11.7, 95% CI 9.4–14.0). Combined low SMM and low TATI remained an independent predictor of OS (HR 1.56, 95% CI 1.15–2.11, p= 0.004) after adjusting for known prognostic factors. There was no association between body composition and sorafenib toxicity. Conclusions:In Dutch HCC patients treated with sorafenib, the combined presence of low SMM and low TATI was associated with impaired survival, independent of known prognostic factors. CT assessment of body composition may provide additional prognostic information prior to sorafenib treatment.

In patients with resectable perihilar cholangiocarcinoma, biliary drainage is recommended to treat obstructive jaundice and optimise the clinical condition before liver resection. Little evidence exists on the preferred initial method of biliary drainage. We therefore investigated the incidence of severe drainage-related complications of endoscopic biliary drainage or percutaneous transhepatic biliary drainage in patients with potentially resectable perihilar cholangiocarcinoma.

Background Discrepancies are often noted between management of perihilar cholangiocarcinoma (PHC) in regional hospitals and the eventual treatment plan in specialized centers.Objective The objective of this article is to evaluate whether regional centers adhere to guideline recommendations following implementation in 2013.Methods Data were analyzed from all consecutive patients with suspected PHC referred to our academic center between June 2013 and December 2015. Frequency and quality of biliary drainage and imaging at referring centers were assessed as well as the impact of inadequate initial drainage.Results Biliary drainage was attempted at regional centers in 83 of 158 patients (52.5%), with a technical and therapeutic success rate of 79.5% and 50%, respectively, and a complication rate of 45.8%. The computed tomography protocol was not in accordance with guidelines in 52.8% of referrals. In 45 patients (54.2%) who underwent drainage in regional centers, additional drainage procedures were required after referral. Initial inadequate biliary drainage at a regional center was significantly associated with more procedures and a prolonged waiting time until surgery. A trend toward more drainage-related complications was observed among patients with inadequate initial drainage (54.7% vs. 39.0%, p= 0.061).Conclusion Despite available guidelines, suboptimal management of PHC persists in many regional centers and affects eventual treatment strategies.

Portal vein embolization not only induces hypertrophy of the non-embolized liver, but also enhances tumor growth. The latter could be prevented by embolizing the hepatic arteries supplying the tumor-bearing liver segments. This study aimed to determine the effects of transcatheter arterial embolization (TAE) on tumor volume and liver regeneration in a rabbit VX2 tumor model.