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Liver cyst infections often necessitate long-term hospital admission and are associated with considerable morbidity and mortality. We conducted a modified Delphi study to reach expert consensus for a clinical decision framework. The expert panel consisted of 24 medical specialists, including 12 hepatologists, from nine countries across Europe, North America, and Asia. The Delphi had three rounds. The first round (response rate 21/24 [88%]) was an online survey with questions constructed from literature review and expert opinion, in which experts were asked about their management preferences and rated possible management strategies for seven clinical scenarios. Experts also rated 14 clinical decision-making items for relevancy and defined treatment outcomes. During the second round (response rate 13/24 [54%]), items that did not reach consensus and newly suggested themes were discussed in an online panel meeting. In the third round (response rate 16/24 [67%]), experts voted on definitions and management strategies using an online survey based on previous answers. Consensus was predefined as a vote threshold of at least 75%. We identified five subclassifications of liver cyst infection according to cyst phenotypes and patient immune status and consensus on episode definitions (new, persistent, and recurrent) and criteria for treatment success or failure was reached. The experts agreed that fever and elevated C-reactive protein are pivotal decision-making items for initiating and evaluating the management of liver cyst infections. Consensus was reached on 26 management statements for patients with liver cyst infections across multiple clinical scenarios, including two treatment algorithms, which were merged into one after comments. We provide a clinical decision framework for physicians managing patients with liver cyst infections. This framework will facilitate uniformity in the management of liver cyst infections and can constitute the basis for the development of future guidelines., Competing Interests: Declaration of interests JH has received a grant from Deutsche Forschungsgemeinschaft—German Research Foundation. JC has received support from Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement (Agency for Management of University and Research Grants 2021; SGR 01331), Instituto Carlos III (PI22/01234) co-funded by the EU; a research grant by Asociación Española Estudio del Hígado (2022–23); and consulting fees, honoraria, and support for travel or attending meetings from Astellas, Chiesi, and Novartis. MS has received a grant from the Dutch Kidney Foundation (19OK002 and 23OK1044). MCH received a research grant from Camarus Pharmaceuticals. Hôpital Beaujon, Clichy, France, received, on behalf of MR, consulting fees from Quantum Surgical. MR has received honoraria from Guerbet, Angiodynamics, AstraZeneca, General Electric, Terumo, and Servier. VV has received consulting fees from Guerbet; honoraria from Canon Medical, GE Healthcare, Roche, and Sirtex; payment for expert testimony from Bayer, Guerbet, Sirtex, Boston Scientific, and Quantum Surgical; support for attending meetings or travel from Canon Medical, GE Healthcare, Roche, and Sirtex; and is Scientific Director of European School of Radiology without financial compensation. PS has received grants from Arrowhead, Grifols, CSL Behring, Vertex, and Dicerna; consulting fees from Biomarin, Intellia, Dicerna, NovoNordisk, GSK, Ono, and Takeda; honoraria from Advanz, Sanofi, CSL Behring, Grifols, and Sobi; support for attending meetings or travel from CSL Behring, Takeda, and Biogen; participates on data and safety monitoring boards for Albireo, Dicerna, Takeda, Biomarin, Intellia, and Sobi; has a leadership role in Alpha1 Global and Alpha1-Deutschland; and received materials from Takeda. RTa received grants from Chronix Biomedical/Oncocyte; consulting fees from MSD (2022), Tiefenbacher AEG (2022), Chiesi (2023), Pierre Fabre (2023), and Chronix Biomedical/Oncocyte (2023); speaker fees from Orphalan, Biotest, Alexion, and Chiesi; is co-inventor of a patent of Hannover Medical School, Hanover, Germany (autoantibodies tests against HIP1R to diagnose autoimmunhepatitis in adults and children; European patent number 18789434.0); and has received provision of consumables from Innova and Euroimmun. RTo is President-elect of European Renal Association. TJGG received grants from the Dutch Digestive Foundation and Gilead for the development of mylivercoach and received travel support from AbbVie to attend International Liver Congress 2022. VC received honoraria from Ipseon and Albireo. On behalf of JPHD, Radboudumc received a research grant from AbbVie. JPHD acts as a board member of the European Reference Network RARE-Liver and principal investigator of the POSITANO study by Camarus. MAL received grants from the Dutch Digestive Foundation, Vaillant fonds, and NVGE Gastrostart. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Portal vein thrombosis (PVT) refers to the development of a non-malignant obstruction of the portal vein, its branches, its radicles, or a combination. This Review first provides a comprehensive overview of all aspects of PVT, namely the specifics of the portal venous system, the risk factors for PVT, the pathophysiology of portal hypertension in PVT, the interest in non-invasive tests, as well as therapeutic approaches including the effect of treating risk factors for PVT or cause of cirrhosis, anticoagulation, portal vein recanalisation by interventional radiology, and prevention and management of variceal bleeding in patients with PVT. Specific issues are also addressed including portal cholangiopathy, mesenteric ischaemia and intestinal necrosis, quality of life, fertility, contraception and pregnancy, and PVT in children. This Review will then present endpoints for future clinical studies in PVT, both in patients with and without cirrhosis, agreed by a large panel of experts through a Delphi consensus process. These endpoints include classification of portal vein thrombus extension, classification of PVT evolution, timing of assessment of PVT, and global endpoints for studies on PVT including clinical outcomes. These endpoints will help homogenise studies on PVT and thus facilitate reporting, comparison between studies, and validation of future studies and trials on PVT., Competing Interests: Declaration of interests VHG has received speaker fees from Gore Medical and Cook Medical. ADG has received consulting fees from Astrazeneca and Swedish Orphan Biovitrum. MR serves as consultant from Quantum Surgical (fees paid to institution) and has received speaker fees from Servier, Guerbet, GE Healthcare, Ipsen, Angiodynamics, and AstraZeneca. FN has received speaker fees from Advanz and Permanyer. VML serves as consultant from AstraZaneca and has received speaker fees and travel support from Albireo Ipsen. AB serves as consultant for Boehringer Ingelheim and has received speaker fees from GE Healthcare and Hologic. AA has served as a lecturer for Boehringer-Ingelheim and Gore Medical. AN has received research funding from MSD-Avenir and consulting fees from Abbvie and Janssen. MM serves as a lecturer for AbbVie, Ipsen, Echosens, Gilead Sciences, and Gore Medical, and has received travel support from AbbVie and Gilead Sciences. DP has served as lecturer for Boehringer-Ingelheim and Gore Medical. DT has received research grants from Boehringer-Ingelheim and Novartis and has served as lecturer for Gore Medical. JCGP has received speaker fees from Gore Medical and research grants from Mallinkrodt and AstraZeneca. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Competing Interests: MR received a consulting fee from Quantum Surgical to their institution; has received a speaker fee from General Electric, Terumo, Guerbet, Servier, Angiodynamics, and AstraZeneca. All other authors declare no competing interests.

Background & Aims: Assessment of computed tomography (CT)/magnetic resonance imaging Liver Imaging Reporting and Data System (LI-RADS) v2018 major features leads to substantial inter-reader variability and potential decrease in hepatocellular carcinoma diagnostic accuracy. We assessed the performance and added-value of a machine learning (ML)-based algorithm in assessing CT LI-RADS major features and categorisation of liver observations compared with qualitative assessment performed by a panel of radiologists., Methods: High-risk patients as per LI-RADS v2018 with pathologically proven liver lesions who underwent multiphase contrast-enhanced CT at diagnosis between January 2015 and March 2019 in seven centres in five countries were retrospectively included and randomly divided into a training set (n = 84 lesions) and a test set (n = 345 lesions). An ML algorithm was trained to classify non-rim arterial phase hyperenhancement, washout, and enhancing capsule as present, absent, or of uncertain presence. LI-RADS major features and categories were compared with qualitative assessment of two independent readers. The performance of a sequential use of the ML algorithm and independent readers were also evaluated in a triage and an add-on scenario in LR-3/4 lesions. The combined evaluation of three other senior readers was used as reference standard., Results: A total of 318 patients bearing 429 lesions were included. Sensitivity and specificity for LR-5 in the test set were 0.67 (95% CI, 0.62-0.72) and 0.91 (95% CI, 0.87-0.96) respectively, with 242 (70.1%) lesions accurately categorised. Using the ML algorithm in a triage scenario improved the overall performance for LR-5. (0.86 and 0.93 sensitivity, 0.82 and 0.76 specificity, 78% and 82.3% accuracy for the two independent readers)., Conclusions: Quantitative assessment of CT LI-RADS v2018 major features is feasible and diagnoses LR-5 observations with high performance especially in combination with the radiologist's visual analysis in patients at high-risk for HCC., Impact and Implications: Assessment of CT/MRI LI-RADS v2018 major features leads to substantial inter-reader variability and potential decrease in hepatocellular carcinoma diagnostic accuracy. Rather than replacing radiologists, our results highlight the potential benefit from the radiologist-artificial intelligence interaction in improving focal liver lesions characterisation by using the developed algorithm as a triage tool to the radiologist's visual analysis. Such an AI-enriched diagnostic pathway may help standardise and improve the quality of analysis of liver lesions in patients at high risk for HCC, especially in non-expert centres in liver imaging. It may also impact the clinical decision-making and guide the clinician in identifying the lesions to be biopsied, for instance in patients with multiple liver focal lesions., Competing Interests: Five authors (VM, RQ, LD, JHL and NC) are GE Healthcare France employees. The remaining authors, who are not employees of or consultants for GE Healthcare, had control of inclusion of all data and information that might present a conflict of interest for authors who are employees for GE Healthcare. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Author(s).)

Background & Aims: The fragility index (FI), i.e., theminimum number of best survivors reassigned to the control group required to revert the statistically significant result of a clinical trial to non-significant, is a metric to evaluate the robustness of randomized controlled trials (RCTs). We aimed to assess the FI in the field of HCC., Methods: This is a retrospective analysis of phase 2 and 3 RCTs for the treatment of HCC published between 2002 and 2022. We included two-arm studies with 1:1 randomization and significant positive results for a primary time-to-event endpoint for the FI calculation, which involves the iterative addition of a best survivor from the experimental group to the control group, until positive significance ( p <0,05, Log-rank test) is lost., Results: We identified 51 phase 2 and 3 positive RCTs, of which 29 (57%) were eligible for fragility index calculation. After reconstruction of the Kaplan-Meier curves, 25/29 studies remained significant, among which the analysis was performed. The median (interquartile range (IQR)) FI was 5 (2-10) and Fragility Quotient (FQ) was 3% (1%-6%). Ten trials (40%) had a FI of 2 or less. FI was positively correlated to the blind assessment of the primary endpoint (median FI 9 with blind assessment versus 2 without, p = 0.01), the number of reported events in the control arm (RS = 0.45, p = 0.02) and to impact factor (RS = 0.58, p = 0.003)., Conclusions: Several phases 2 and 3 RCTs in HCC have a low fragility index, underlying the limited robustness on the conclusion of their superiority over control treatments. The fragility index might provide an additional tool to assess the robustness of clinical trial data in HCC., Impact and Implications: The fragility index is a method to assess robustness of a clinical trial and is defined the minimum number of best survivors reassigned to the control group required to revert the statistically significant result of a clinical trial to non-significant. Among 25 randomised controlled trials in HCC, the median fragility index was 5, and 10 trials among 25 (40%) had a fragility index of 2 or less, indicating an important fragility., Competing Interests: JCN has received research funding from Bayer and Ipsen. SS, NS, CC, JG, and FD have no conflicts of interest. NG-C has received honoraria from Abbie, Bayer, Gilead, Ipsen, Roche, and Shionogi. MR has received educational fees from Canon Medical System, GE Healthcare, Ipsen, Guerbet, and Sirtex. VL has no conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Author(s).)

The expression splanchnic vein thrombosis encompasses Budd-Chiari syndrome and portal vein thrombosis. These disorders have common characteristics: they are both rare diseases which can cause portal hypertension and its complications. Budd-Chiari syndrome and portal vein thrombosis in the absence of underlying liver disease share many risk factors, among which myeloproliferative neoplasms represent the most common; a rapid comprehensive work-up for risk factors of thrombosis is needed in these patients. Long-term anticoagulation is indicated in most patients. Portal vein thrombosis can also develop in patients with cirrhosis and in those with porto-sinusoidal vascular liver disease. The presence and nature of underlying liver disease impacts the management of portal vein thrombosis. Indications for anticoagulation in patients with cirrhosis are growing, while transjugular intrahepatic portosystemic shunt is now a second-line option. Due to the rarity of these diseases, studies yielding high-grade evidence are scarce. However, collaborative studies have provided new insight into the management of these patients. This article focuses on the causes, diagnosis, and management of patients with Budd-Chiari syndrome, portal vein thrombosis without underlying liver disease, or cirrhosis with non-malignant portal vein thrombosis., Competing Interests: The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2022 The Author(s).)

Background & Aims: Transarterial radioembolization (TARE) with Yttrium-90 resin microspheres is an established treatment option for patients with hepatocellular carcinoma (HCC). However, optimising treatment application and patient selection remains challenging. We report here on the effectiveness, safety and prognostic factors, including dosing methods, associated with TARE for HCC in the prospective observational CIRT study., Methods: We analysed 422 patients with HCC enrolled between Jan 2015 and Dec 2017, with follow-up visits every 3 months for up to 24 months after first TARE. Patient characteristics and treatment-related data were collected at baseline; adverse events and time-to-event data (overall survival [OS], progression-free survival [PFS] and hepatic PFS) were collected at every 3-month follow-up visit. We used the multivariable Cox proportional hazard model and propensity score matching to identify independent prognostic factors for effectiveness outcomes., Results: The median OS was 16.5 months, the median PFS was 6.1 months, and the median hepatic PFS was 6.7 months. Partition model dosimetry resulted in improved OS compared to body surface area calculations on multivariable analysis (hazard ratio 0.65; 95% CI 0.46-0.92; p  = 0.0144), which was confirmed in the exact matching propensity score analysis (hazard ratio 0.56; 95% CI 0.35-0.89; p = 0.0136). Other independent prognostic factors for OS were ECOG-performance status >0 ( p = 0.0018), presence of ascites ( p = 0.0152), right-sided tumours ( p = 0.0002), the presence of portal vein thrombosis ( p = 0.0378) and main portal vein thrombosis ( p = 0.0028), ALBI grade 2 ( p = 0.0043) and 3 ( p = 0.0014). Adverse events were recorded in 36.7% of patients, with 9.7% of patients experiencing grade 3 or higher adverse events., Conclusions: This large prospective observational dataset shows that TARE is an effective and safe treatment in patients with HCC. Using partition model dosimetry was associated with a significant improvement in survival outcomes., Impact and Implications: Transarterial radioembolization (TARE) is a form of localised radiation therapy and is a potential treatment option for primary liver cancer. We observed how TARE was used in real-life clinical practice in various European countries and if any factors predict how well the treatment performs. We found that when a more complex but personalised method to calculate the applied radiation activity was used, the patient responded better than when a more generic method was used. Furthermore, we identified that general patient health, ascites and liver function can predict outcomes after TARE., Clinical Trial Number: NCT02305459., Competing Interests: Frank Kolligs participated on a data safety monitoring or advisory board of Bayer, MSD, and Roche. Dirk Arnold received consulting fees and honoraria for presentations and lectures and travel support from Boston Scientific and Terumo, is on the guidelines committee of the European Society for Medical Oncology, and supported oncopolicy manuscripts for the European Cancer Organisation. Rita Golfieri participated on a Data Safety Monitoring Board or Advisory Board and received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Roche, Guerbet and Sirtex. Maciej Pech received grants or contracts and honoraria from lectures from Sirtex and Bayer. Maxime Ronot received honoraria for lectures from GE Healthcare, Ipsen, Canon-Toshiba, Alexion Pharmaceuticals, Guerbet, and Sirtex. Bruno Sangro received grants or contracts from Sirtex and BMS, consulting fees from Adaptimmune, Astra Zeneca, Bayer, BMS, Boston Scientific, Eisai, Eli Lilly, Incyte, Ipsen, Roche, Sirtex Medical, Terumo; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astra Zeneca, Bayer, BMS, Eisai, Incyte, Ipsen, Roche, Sirtex Medical; Participation on a data safety monitoring board or advisory board from Adaptimmune, Astra Zeneca, Bayer, BMS, Boston Scientific, Eisai, Eli Lilly, Incyte, Ipsen, Roche, Sirtex Medical, Terumo, and has a leadership or fiduciary role in the International Liver Cancer Association. Geert Maleux received honoraria for speaker’s bureau from Sirtex Medical and operated as proctor for Sirtex. Bora Peynircioglu, Thomas Pfammatter, Niklaus Schaefer, Graham Munneke, Helena Pereira, Bleranda Zeka, Niels de Jong and Thomas Helmberger had nothing to declare. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2022 The Author(s).)

Portal hypertension is defined by an increase in the portosystemic venous gradient. In most cases, increased resistance to portal blood flow is the initial cause of elevated portal pressure. More than 90% of cases of portal hypertension are estimated to be due to advanced chronic liver disease or cirrhosis. Transjugular intrahepatic portosystemic shunts, a non-pharmacological treatment for portal hypertension, involve the placement of a stent between the portal vein and the hepatic vein or inferior vena cava which helps bypass hepatic resistance. Portal hypertension may also be a result of extrahepatic portal vein thrombosis or compression. In these cases, percutaneous portal vein recanalisation restores portal trunk patency, thus preventing portal hypertension-related complications. Any portal blood flow impairment leads to progressive parenchymal atrophy and triggers hepatic regeneration in preserved areas. This provides the rationale for using portal vein embolisation to modulate hepatic volume in preparation for extended hepatic resection. The aim of this paper is to provide a comprehensive evidence-based review of the rationale for, and outcomes associated with, the main imaging-guided interventions targeting the portal vein, as well as to discuss the main controversies around such approaches., Competing Interests: The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2022 The Authors.)

Background & Aims: Reinforced hepatocellular carcinoma (HCC) surveillance using magnetic resonance imaging (MRI) could increase early tumour detection but faces cost-effectiveness issues. In this study, we aimed to evaluate the cost-effectiveness of MRI for the detection of very early HCC (Barcelona Clinic Liver Cancer [BCLC] 0) in patients with an annual HCC risk >3%., Methods: French patients with compensated cirrhosis included in 4 multicentre prospective cohorts were considered. A scoring system was constructed to identify patients with an annual risk >3%. Using a Markov model, the economic evaluation estimated the costs and life years (LYs) gained with MRI vs . ultrasound (US) monitoring over a 20-year period. The incremental cost-effectiveness ratio (ICER) was calculated by dividing the incremental costs by the incremental LYs., Results: Among 2,513 patients with non-viral causes of cirrhosis (n = 840) and/or cured HCV (n = 1,489)/controlled HBV infection (n = 184), 206 cases of HCC were detected after a 37-month follow-up. When applied to training (n = 1,658) and validation (n = 855) sets, the construction of a scoring system identified 33.4% and 37.5% of patients with an annual HCC risk >3% (3-year C-Indexes 75 and 76, respectively). In patients with a 3% annual risk, the incremental LY gained with MRI was 0.4 for an additional cost of €6,134, resulting in an ICER of €15,447 per LY. Compared to US monitoring, MRI detected 5x more BCLC 0 HCC. The deterministic sensitivity analysis confirmed the impact of HCC incidence. At a willingness to pay of €50,000/LY, MRI screening had a 100% probability of being cost-effective., Conclusions: In the era of HCV eradication/HBV control, patients with annual HCC risk >3% represent one-third of French patients with cirrhosis. MRI is cost-effective in this population and could favour early HCC detection., Lay Summary: The early identification of hepatocellular carcinoma in patients with cirrhosis is important to improve patient outcomes. Magnetic resonance imaging could increase early tumour detection but is more expensive and less accessible than ultrasound (the standard modality for surveillance). Herein, using a simple score, we identified a subgroup of patients with cirrhosis (accounting for >one-third), who were at increased risk of hepatocellular carcinoma and for whom the increased expense of magnetic resonance imaging would be justified by the potential improvement in outcomes., Competing Interests: Pr Nahon has received honoraria from and/or consults for AstraZeneca, Abbvie, Bayer, Bristol-Myers Squibb, Eisai, Gilead, Ipsen, MSD and Roche. He received research grants from AstraZeneca, AbbVie, Bristol-Myers Squibb and Eisai. Pr Ganne-Carrié consults for and/or received personal fees from Abbvie, Bayer, Gilead, Ipsen, and Shionogi, outside the submitted work. Pr Pol has received grants from Gilead, Roche, Abbvie. He consults for BMS, Janssen Cilag, Gilead, Roche, Merck/Schering-Plough, Abbvie, Vivv, Shinogui, Biotest, LFB. Pr Durand-Zaleski consults for AbbVie, Bristol-Myers Squibb, Janssen and MSD. All other authors report no conflict of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2021 The Author(s).)

Background & Aims: The histopathological subtypes of hepatocellular carcinoma (HCC) are associated with distinct clinical features and prognoses. This study aims to report Liver Imaging Reporting and Data System (LI-RADS)-defined imaging features of different HCC subtypes in a cohort of resected tumours and to assess the influence of HCC subtypes on computed tomography (CT)/magnetic resonance imaging (MRI) LI-RADS categorisation in the subgroup of high-risk patients., Methods: This retrospective institutional review board-approved study included patients with resected HCCs and available histopathological classification. Three radiologists independently reviewed preoperative CT and MRI exams. The readers evaluated the presence of imaging features according to LI-RADS v2018 definitions and provided a LI-RADS category in patients at high risk of HCC. Differences in LI-RADS features and categorisations were assessed for not otherwise specified (NOS-HCC), steatohepatitic (SH-HCC), and macrotrabecular-massive (MTM-HCC) types of HCCs., Results: Two hundred and seventy-seven patients (median age 64.0 years, 215 [77.6%] men) were analysed, which involved 295 HCCs. There were 197 (66.7%) NOS-HCCs, 62 (21.0%) SH-HCCs, 23 (7.8%) MTM-HCCs, and 13 (4.5%) other rare subtypes. The following features were more frequent in MTM-HCC: elevated α-foetoprotein serum levels ( p <0.001), tumour-in-vein ( p <0.001 on CT, p ≤0.052 on MRI), presence of at least 1 LR-M feature ( p ≤0.010 on CT), infiltrative appearance ( p ≤0.032 on CT), necrosis or severe ischaemia ( p ≤0.038 on CT), and larger size ( p ≤0.006 on CT, p ≤0.011 on MRI). SH-HCC was associated with fat in mass ( p <0.001 on CT, p ≤0.002 on MRI). The distribution of the LI-RADS major features and categories in high-risk patients did not significantly differ among the 3 main HCC subtypes., Conclusions: The distribution of LI-RADS major features and categories is not different among the HCC subtypes. Nevertheless, careful analysis of tumour-in-vein, LR-M, and ancillary features as well as clinico-biological data can provide information for the non-invasive diagnosis of HCC subtypes., Lay Summary: In high-risk patients, the overall distribution of LI-RADS major features and categories is not different among the histological subtypes of hepatocellular carcinoma, but tumour-in-vein, presence of LR-M features, and ancillary features can provide information for the non-invasive diagnosis of hepatocellular carcinoma subtypes., Competing Interests: The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2021 The Authors.)

Background & Aims: Malignant transformation of hepatocellular adenoma (MT-HCA) may occur in up to 5% of tumours. However, the prognostic value of this event remains poorly described. In this study, we aimed to analyse the long-term outcomes of patients undergoing liver resection (LR) for MT-HCA compared to those of patients resected for hepatocellular carcinoma (HCC) occurring on normal liver parenchyma (NP-HCC)., Methods: This single-centre retrospective study included all patients who underwent LR for MT-HCA at Beaujon Hospital between 2001 and 2019. MT-HCAs were classified as small foci of malignant transformation HCA (SF-HCA) and as malignant HCA (M-HCA) in cases of predominant HCC foci. Recurrence-free survival (RFS) of MT-HCA was compared with that of NP-HCC after propensity score matching., Results: Forty patients (24 men, 16 women) underwent LR for MT-HCA, including 23 with SF-HCA and 17 with M-HCA. Of these cases, 16/40 (40%) had β-catenin mutations, 19/40 (47.5%) were inflammatory, 1 was HNF1α-mutated HCA and 4 (10%) were unclassified HCA. Microvascular invasion (12% vs. 0%, p = 0.091) and satellite nodules (25% vs. 4%, p = 0.028) were more frequently observed in M-HCA than in SF-HCA. After a median follow-up of 67 months, 10 (25%) patients with MT-HCA had tumour recurrence, including 9 with M-HCA and 1 with SF-HCA ( p = 0.007). M-HCA was linked to significantly poorer 1-, 3-, 5- and 10-year RFS rates than SF-HCA (76%, 63%, 39%, 37% vs. 100%, 100%, 100%, 91%, p = 0.003). Multivariate analysis showed that SF-HCA was independently associated with improved RFS (hazard ratio 0.064; 95% CI 0.008-0.519; p = 0.01). After propensity score matching, NP-HCC was associated with significantly poorer 1-, 3-, 5- and 10-year RFS rates than MT-HCA ( p = 0.01)., Conclusions: HCA with malignant transformation yields a better long-term prognosis than NP-HCC. Among MT-HCA, SF-HCA is associated with a better prognosis than M-HCA., Lay Summary: The prognostic relevance of malignant transformation of hepatocellular adenoma (HCA) remains unknown. Thus, the aim of our study was to compare the outcomes of patients undergoing liver resection for malignant transformation to those of patients undergoing liver resection for hepatocellular carcinoma (HCC). The main long-term risk after resection for carcinoma is recurrence. In this study, 10/40 patients with malignant transformation of HCA relapsed after resection and we identified age >55 years, presence of satellite nodes, and microvascular invasion as risk factors for long-term recurrence. Compared to patients with HCC, patients who underwent liver resection for HCA with malignant transformation had better long-term survival., Competing Interests: The authors declare no conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2021 The Authors.)

Background & Aims: In 2005, the registration of all randomised controlled trials (RCTs) before enrolment of participants became a condition for publication by the International Committee of Medical Journal Editors to increase transparency in trial reporting. Among RCTs on transarterial chemoembolisation (TACE) for the treatment of hepatocellular carcinoma (HCC) published after 2007, we assess the proportion that were registered and compare registered primary outcomes (PO) with those reported in publications to determine whether primary outcome reporting bias favoured significant outcomes., Methods: We searched MEDLINE and EMBASE for reports of RCTs evaluating TACE for HCC treatment between 1 September 2007 and 31 March 2018. Registration and publication information for each included RCT was compared using a standardised data extraction form., Results: Thirteen out of 53 (25%) included RCTs were correctly registered ( i.e. before the starting date of the RCT), 14 (26%) were registered after the RCT starting date, and 26 (49%) were not registered. Six out of 14 of the retrospectively registered RCTs (43%) were registered after their completion date. The PO was clearly reported in the published article of all registered RCTs, whereas the report was not clear in 8/26 (31%) of the non-registered RCTs ( p  = 0.01). Among registered RCTs, 8/27 (30%) had major discrepancies between registered and published PO. The influence of these discrepancies could be assessed in 6 of them and was shown to statistically favour significant results in 2., Conclusions: Registration and outcome reporting in RCTs on TACE for HCC are often inadequate. Registration should be reinforced because it is a key to transparency., Lay Summary: Trial registration is fundamental to our understanding and interpretation of results, as it provides information on all relevant clinical trials (to place the results in a broader context), and on the details of their associated protocols (to ensure that the scientific plan is followed). Once a randomised controlled trial (RCT) is completed, the trial results are usually publicly shared via scientific articles that are expected to thoroughly and objectively report them. This study shows that half of the RCTs evaluating transarterial chemoembolisation for hepatocellular carcinoma were not registered, and identified major discrepancies between registered and published primary outcome favouring significant results., Competing Interests: The authors declare no conflict of interest than pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2020 The Author(s).)

Hepatocholangiocarcinoma, fibrolamellar carcinoma, hepatic haemangioendothelioma and hepatic angiosarcoma represent less than 5% of primary liver cancers. Fibrolamellar carcinoma and hepatic haemangioendothelioma are driven by unique somatic genetic alterations ( DNAJB1-PRKCA and CAMTA1-WWTR1 fusions, respectively), while the pathogenesis of hepatocholangiocarcinoma remains more complex, as suggested by its histological diversity. Histology is the gold standard for diagnosis, which remains challenging even in an expert centre because of the low incidences of these liver cancers. Resection, when feasible, is the cornerstone of treatment, together with liver transplantation for hepatic haemangioendothelioma. The role of locoregional therapies and systemic treatments remains poorly studied. In this review, we aim to describe the recent advances in terms of diagnosis and clinical management of these rare primary liver cancers., Competing Interests: Jean-Charles Nault received research grant from 10.13039/100004326Bayer for 10.13039/501100001677Inserm UMR1148, Nathalie Ganne-Carrié received personal fees from Bayer, Gilead, Ipsen and Shionogi. Elia Gigante, François Cauchy, Maxime Ronot, Valérie Paradis, Olivier soubrane: none to declare. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2020 The Author(s).)

Background & Aims: We compare the performance of liver surface nodularity (LSN) and liver stiffness measurements (LSM) using transient elastography (TE) for the detection of clinically significant portal hypertension (CSPH) in patients with cirrhosis and hepatocellular carcinoma (HCC)., Methods: All patients with cirrhosis and HCC who underwent computed tomography, LSM and hepatic venous pressure gradient (HVPG) measurements within 30 days between 2015 and 2018 were included. The estimation of CSPH by LSN and LSM, and the LSM-spleen-size-to-platelet ratio score (LSPS) were evaluated and compared., Results: In total, 140 patients were included (109 men [78%], mean age 63 ± 9 years old), including 39 (28%) with CSPH. LSN measurements were valid in 130 patients (93%) and significantly correlated with HVPG (r = 0.68; p <0.001). Patients with CSPH had higher LSN measurements compared with those without [3.1 ± 0.4 vs . 2.5 ± 0.3, p <0.001; area under the receiver operating characteristic (AUROC): 0.87 ± 0.31]. LSM and LSPS were valid in 132 patients (94%) and significantly correlated with HVPG (r = 0.75, p <0.001; AUROC 0.87 ± 0.04 and r = 0.68, p <0.001; AUROC 0.851 ± 0.04, respectively). There was no significant difference in the diagnostic performance between LSN and LSM-LSPS (DeLong, p  = 0.28, 0.37, and 0.65, respectively) in patients with both valid tests (n = 122). LSN <2.50 had a 100% negative predictive value for CSPH. A 2-step algorithm combining LSN and LSPS for the diagnosis of CSPH classified 108/140 patients (77%) with an 8% error., Conclusions: The diagnostic performance and feasibility of LSN measurements were similar to those of LSM for the detection of CSPH in patients with compensated cirrhosis and HCC. Combining LSN and LSPS accurately detected CSPH in >75% of patients. Such a combination could be useful in centres where the HVPG measurement is unavailable., Lay Summary: The diagnostic performance and feasibility of liver surface nodularity was similar to that of liver stiffness measurement (LSM) for the detection of clinically significant portal hypertension in patients with compensated cirrhosis. Thus, liver surface nodularity could be an option for the preoperative detection of clinically significant portal hypertension in patients with hepatocellular carcinoma. Combining liver surface nodularity with LSM-spleen-size-to-platelet ratio score resulted in the accurate detection of clinically significant portal hypertension in >75% of patients, thus limiting the need for HVPG measurements., Competing Interests: The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2020 The Author(s).)

The goal of assessing tumour response on imaging is to identify patients who are likely to benefit - or not - from anticancer treatment, especially in relation to survival. The World Health Organization was the first to develop assessment criteria. This early score, which assessed tumour burden by standardising lesion size measurements, laid the groundwork for many of the criteria that followed. This was then improved by the Response Evaluation Criteria in Solid Tumours (RECIST) which was quickly adopted by the oncology community. At the same time, many interventional oncology treatments were developed to target specific features of liver tumours that result in significant changes in tumours but have little effect on tumour size. New criteria focusing on the viable part of tumours were therefore designed to provide more appropriate feedback to guide patient management. Targeted therapy has resulted in a breakthrough that challenges conventional response criteria due to the non-linear relationship between response and tumour size, requiring the development of methods that emphasize the appearance of tumours. More recently, research into functional and quantitative imaging has created new opportunities in liver imaging. These results have suggested that certain parameters could serve as early predictors of response or could predict later tumour response at baseline. These approaches have now been extended by machine learning and deep learning. This clinical review focuses on the progress made in the evaluation of liver tumours on imaging, discussing the rationale for this approach, addressing challenges and controversies in the field, and suggesting possible future developments., Competing Interests: The authors declare that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2020 The Author(s).)

Background & Aims: Hepatobiliary phase (HBP) images can discriminate between benign and malignant liver lesions, but it is unclear if this approach can be used in patients with Budd-Chiari syndrome (BCS). Thus, we aimed to assess the diagnostic utility of HBP images in patients with BCS., Methods: This retrospective study included all patients admitted to our institution with a diagnosis of BCS and focal liver lesions on hepatobiliary contrast agent-enhanced MR imaging (HBCA-MRI) from 2000 to 2019. MR images were reviewed by 2 radiologists blinded to the diagnosis of the lesions. Patient and lesion characteristics were recorded, focusing on HBP imaging features., Results: Twenty-six patients (mean 35 ± 11 years old [13-65]; 21 women [81%] 35 ± 12 years old [13-65]; 5 men [19%] 36 ± 10 years old [19-44]) with 99 benign liver lesions and 12 hepatocellular carcinomas (HCCs) were analyzed. Patients with HCC were significantly older than those with benign lesions (mean 50 ± 10 vs. 33 ± 9 years old, p  = 0.003), with higher alpha-fetoprotein (AFP) levels (3/4 [75%] vs. 1/22 [5%] with AFP >15 ng/ml, p <0.001). Homogeneous hypointense signals were identified on HBP in 14 lesions, including 12/12 (100%) HCCs, and 2/99 (2%) benign lesions ( p <0.001). Most benign liver lesions showed either peripheral (n = 52/99 [53%]) or homogeneous hyperintensity (n = 23/99 [23%]) on HBP. Lesions with signal hypointensity on HBP in patients with AFP serum levels >15 ng/ml were all HCCs., Conclusion: Most benign lesions showed homogeneous or peripheral hyperintensity on HBP images while all HCCs were homogeneously hypointense. HBP images are helpful to differentiate between benign lesions and HCCs and outperform other sequences. They should be systematically acquired for the characterization of focal lesions in patients with BCS., Lay Summary: Hepatobiliary phase imaging is an approach that has recently been shown to discriminate between benign and malignant lesions in the liver. However, it was not known whether this imaging approach could be used effectively in patients with Budd-Chiari syndrome. Herein, we have shown that hepatobiliary phase imaging appears to be useful for differentiating between benign and malignant liver lesions in patients with Budd-Chiari syndrome., Competing Interests: The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2020 The Author(s).)