Upfront multi-bipolar radiofrequency ablation for HCC in transplant-eligible cirrhotic patients with salvage transplantation in case of recurrence.

INTRODUCTION: We aim to assess the long-term outcomes of percutaneous multi-bipolar radiofrequency (mbpRFA) as the first treatment for hepatocellular carcinoma (HCC) in transplant-eligible cirrhotic patients, followed by salvage transplantation for intrahepatic distant tumour recurrence or liver failure. MATERIALS AND METHODS: We included transplant-eligible patients with cirrhosis and a first diagnosis of HCC within Milan criteria treated by upfront mbp RFA. Transplantability was defined by age <70 years, social support, absence of significant comorbidities, no active alcohol use and no recent extrahepatic cancer. Baseline variables were correlated with outcomes using the Kaplan-Meier and Cox models. RESULTS: Among 435 patients with HCC, 172 were considered as transplantable with HCCs >2 cm (53%), uninodular (87%) and AFP >100 ng/mL (13%). Median overall survival was 87 months, with 75% of patients alive at 3 years, 61% at 5 years and 43% at 10 years. Age (p = .003) and MELD>10 (p = .01) were associated with the risk of death. Recurrence occurred in 118 patients within Milan criteria in 81% of cases. Local recurrence was observed in 24.5% of cases at 10 years and distant recurrence rates were observed in 69% at 10 years. After local recurrence, 69% of patients were still alive at 10 years. At the first tumour recurrence, 75 patients (65%) were considered transplantable. Forty-one patients underwent transplantation, mainly for distant intrahepatic tumour recurrence. The overall 5-year survival post-transplantation was 72%, with a tumour recurrence of 2.4%. CONCLUSION: Upfront multi-bipolar RFA for a first diagnosis of early HCC on cirrhosis coupled with salvage liver transplantation had a favourable intention-to-treat long-term prognosis, allowing for spare grafts.

Long-term oncological results of percutaneous radiofrequency ablation for intrahepatic cholangiocarcinoma.

INTRODUCTION: The effectiveness of percutaneous radiofrequency ablation (RFA) in intrahepatic cholangiocarcinomas (iCCA) remains insufficiently studied. METHODS: We conducted a retrospective study including patients with histologically proven iCCA within Milan criteria treated by percutaneous RFA from 2000 to 2022. The primary outcome was overall survival in treatment-naive patients and secondary outcomes included ablation completeness, adverse events, local and distant recurrence. A total of 494 patients with hepatocellular carcinoma (HCC) on cirrhosis treated by RFA were included as a comparison group. Oncological events were analysed using Kaplan-Meier, log-rank and univariate/multivariate Cox models. RESULTS: The main population included 71 patients, mostly cirrhotic (80%) with solitary tumours (66%) of a median size of 24 mm. Local recurrence was 45% at 5 years, lower in multibipolar versus monopolar RFA (22% vs. 55%, p = .007). In treatment-naive patients (n = 45), median overall and recurrence-free survivals were 26 and 11 months, respectively. Tumour size (p = .01) and Child-Pugh B (p = .001) were associated with death. The rate of distant recurrence was 59% at 5 years significantly lower for single tumours of less than 2 (p = .002) or 3 cm (p = .02). In cirrhotic patients naïve of previous treatment (n = 40), overall survival was shorter than in HCC (26 vs 68 months, p < .0001), with more local recurrences (p < .0001). Among distant recurrences, 50% were extrahepatic metastases compared to 12% in HCC (p < .001). CONCLUSION: Multibipolar RFA provides better results in terms of tumour recurrence than monopolar RFA and could be used to treat small iCCA (<3 cm). Adjuvant chemotherapy should be discussed due to the frequent extra-hepatic metastasis at recurrence.

Incidence and clinical impact of bile ducts changes after multibipolar radiofrequency ablation for hepatocellular carcinoma.

OBJECTIVES: This study aimed to evaluate the incidence and clinical implications of bile duct changes following multibipolar radiofrequency ablation (mbpRFA) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Radiological, clinical, and biological data from consecutive cirrhotic patients who underwent first-line mbpRFA between 2007 and 2014 for uninodular HCC ≤ 5 cm were retrospectively collected. Follow-up imaging was reviewed to identify bile duct changes and factors associated with biliary changes were assessed using multivariable analysis. Baseline and 6-month liver function tests were compared in patients with and without bile duct changes. Complications, cirrhosis decompensation, and survival rates were compared in both groups. RESULTS: A total of 231 patients (mean age 68 years [39-85], 187 men) underwent 266 mbpRFA sessions for uninodular HCC (mean size 26 mm). Of these, 76 (33%) developed bile duct changes (upstream bile duct dilatations and/or bilomas) with a mean onset time of 3 months. Identified risk factors for these changes were the infiltrative aspect of the tumor (p = 0.035) and its location in segment VIII (p < 0.01). The average increase in bilirubin at 6 months was higher in the group with biliary changes (+2.9 vs. +0.4 µg/mL; p = 0.03). There were no significant differences in terms of complications, cirrhosis decompensation at 1 year (p = 0.95), local and distant tumor progression (p = 0.91 and 0.14 respectively), and overall survival (p = 0.4) between the two groups. CONCLUSION: Bile duct changes are common after mbpRFA for HCC, especially in tumors with an infiltrative aspect or those located in segment VIII. These changes do not appear to negatively impact the course of cirrhosis at 1 year or overall survival. CLINICAL RELEVANCE STATEMENT: Bile duct changes following mbpRFA for HCC are relatively common. Nevertheless, they do not raise clinical concerns in terms of complications, deterioration in liver function, or survival rates. Consequently, specific monitoring or interventions for these bile duct changes are not warranted. KEY POINTS: • Bile duct changes are frequently observed after multibipolar radiofrequency ablation for hepatocellular carcinoma, occurring in 33% of cases in our study. • Patients with bile duct changes exhibited a higher increase in bilirubin levels at 6 months but no more cirrhosis decompensation or liver abscesses. • Biliary changes following multibipolar radiofrequency ablation for hepatocellular carcinoma are not alarming and do not necessitate any specific monitoring or intervention.

Study protocol for FASTRAK: a randomised controlled trial evaluating the cost impact and effectiveness of FAST-MRI for HCC suRveillance in pAtients with high risK of liver cancer.

INTRODUCTION: The surveillance of hepatocellular carcinoma (HCC) using semi-annual liver ultrasound (US) is justified in patients with cirrhosis. In this context, US has a low sensitivity (<30%) for the detection of HCC at the very early stage (ie, Barcelona clinic liver cancer (BCLC) 0, uninodular tumour <2 cm). The sensitivity of abbreviated liver MRI (AMRI) is reported to exceed 80%, but its use is hampered by costs and availability. Our hypothesis is that AMRI used as a screening examination in patients at high risk of HCC (>3% per year) could increase the rates of patients with a tumour detected at an early stage accessible to curative-intent treatment, and demonstrate its cost-effectiveness in this population. METHODS AND ANALYSIS: The FASTRAK trial is a multicentre, randomised controlled trial with two parallel arms, aiming for superiority and conducted on patients at high risk for HCC (yearly HCC incidence >3%). Randomisation will be conducted on an individual basis with a centralised approach and stratification by centre. After inclusion in the trial, each patient will be randomly assigned to the experimental group (semi-annual US and AMRI) or the control group (semi-annual US alone). The main objective is to assess the cost/quality-adjusted life year and cost/patient detected with a BCLC 0 HCC in both arms. A total of 944 patients will be recruited in 37 tertiary French centres during a 36-month period and will be followed-up during 36 months. ETHICS AND DISSEMINATION: The FASTRAK trial received ethical approval on 4 April 2022. Results will be disseminated via publication in peer-reviewed journals as well as presentation at international conferences. TRIAL REGISTRATION NUMBER: Clinical trial number (ClinicaTrials.gov) NCT05095714.

Impact of radiological response and pattern of progression in patients with HCC treated by atezolizumab-bevacizumab.

BACKGROUND AND AIMS: We aim to assess the role of radiological response to atezolizumab-bevacizumab in patients with HCC to predict overall survival. APPROACH AND RESULTS: We retrospectively included patients with HCC treated by atezolizumab-bevacizumab in 2 tertiary centers. A retrospective blinded analysis was performed by 2 radiologists to assess Response Evaluation Criteria in Solid Tumor (RECIST 1.1) and modified RECIST (mRECIST) criteria at 12 weeks. Imaging response and treatment decisions in the multidisciplinary tumor board at 12 weeks were registered. Among 125 patients, 9.6% and 20.8% had a response, 39.2% and 35.2% had stable disease, and 51.2% and 44% had progression, according to RECIST 1.1 and mRECIST, respectively, with a substantial interobserver agreement (k coefficient=0.79). Metastasis was independently associated with a higher risk of progression. Patients classified as responders did not reach median survival, which was 16.2 and 15.9 months for patients classified as stable and 9.1 and 9.0 months for patients classified as progressors, in RECIST 1.1 and mRECIST criteria, respectively. We observed a wide variability in the identification of progression in the multidisciplinary tumor board in clinical practice compared with the blind evaluation by radiologists mainly due to discrepancy in the evaluation of the increase in size of intrahepatic lesions. The appearance of new extrahepatic lesions or vascular invasion lesions was associated with a worse overall survival ( p =0.032). CONCLUSIONS: RECIST 1.1 and mRECIST criteria predict overall survival with more responders identified by mRECIST and the appearance of new extrahepatic lesion or vascular invasion was associated with a poor prognosis. A noticeable discrepancy was observed between patients classified as progressors at reviewing and the decision reached during the multidisciplinary tumor board.

Fat-containing hepatocellular carcinoma in patients with cirrhosis: proposal of a diagnostic modification regarding enhancement characteristics.

OBJECTIVES: The aim of this study was to develop and validate an algorithm for the non-invasive diagnosis of these fat-containing HCCs. METHODS: Eighty-four cirrhotic patients with 77 fat-containing HCCs and 11 non-HCC fat-containing nodules were retrospectively included. All MRIs were reviewed; nodule characteristics, European Association for the Study of the Liver (EASL) and LI-RADS classifications, and survival were collected. One of the major features of LI-RADS v2018 (non-rim-like arterial phase hyperenhancement [APHE]) was changed to include different enhancing patterns at arterial phase and a new fat-LI-RADS algorithm was created for fat-containing nodules in cirrhosis. Its diagnostic performance was evaluated in both a derivation and external validation cohort (external cohort including 58 fat-containing HCCs and 10 non-HCC fat nodules). Reproducibility of this new algorithm was assessed. RESULTS: In the derivation cohort, 54/77 (70.1%) fat-containing HCCs had APHE, 62/77 (80.5%) had enhancement compared to the nodule itself at arterial phase (APE), 43/77 (55.8%) had washout, and 20/77 (26.0%) had an enhancing capsule. EASL and LI-RADS had a sensitivity of 37.7% (29/77) and 36.4% (28/77), respectively, for the diagnosis of fat-containing HCC and both had a specificity of 100% (11/11). The new fat-LI-RADS algorithm increased sensitivity to 50.6% (39/77) without decreasing the specificity of 100% (11/11). The validation cohort confirmed the increased sensitivity, with a slight decrease in specificity. The concordance for the diagnosis of HCC for fat-LR5 was 85.3% (58/68). CONCLUSION: The new fat-LI-RADS algorithm proposed here significantly improves the performance of the non-invasive diagnosis of fat-containing HCC and thus could reduce the number of biopsies conducted for fat-containing HCCs. CLINICAL RELEVANCE STATEMENT: The European Association for the Study of the Liver and LI-RADS guidelines are poorly sensitive for the diagnosis of fat-containing HCC, mainly because of the low rate of arterial phase hyperenhancement (APHE) displayed by fat-containing HCC. Using all types of enhancement instead of APHE improves sensitivity of LI-RADS. KEY POINTS: • Fat-containing HCCs on MRI account for 7.5% of HCCs and have different imaging characteristics from non-fatty HCCs. • The European Association for the Study of the Liver and LI-RADS algorithms for the non-invasive diagnosis of HCC have low sensitivity for the diagnosis of fat-containing HCC with MRI (37.7% and 36.4%, respectively). • The new fat-LI-RADS, which includes a slight modification of the "arterial enhancement" criterion, improves the sensitivity for the diagnosis of fat-containing HCC using MRI, without degrading the specificity.

Detection of arterial phase hyperenhancement of small hepatocellular carcinoma with MRI: Comparison between single arterial and multi-arterial phases and between extracellular and hepatospecific contrast agents.

PURPOSE: The purpose of this study was to compare the detection rate of arterial phase hyperenhancement (APHE) in small hepatocellular carcinoma (HCC) between single arterial phase (single-AP) and triple hepatic arterial (triple-AP) phase MRI and between extracellular (ECA) and hepato-specific (HBA) contrast agents. MATERIALS AND METHODS: A total of 109 cirrhotic patients with 136 HCCs from seven centers were included. There were 93 men and 16 women, with a mean age of 64.0 ± 8.9 (standard deviation) years (range: 42-82 years). Each patient underwent both ECA-MRI and HBA (gadoxetic acid)-MRI examination within one month of each other. Each MRI examination was retrospectively reviewed by two readers blinded to the second MRI examination. The sensitivities of triple- and single-AP for the detection of APHE were compared, and each phase of the triple-AP sequence was compared with the other two. RESULTS: No differences in APHE detection were found between single-AP (97.2%; 69/71) and triple-AP (98.5%; 64/65) (P > 0.99) at ECA-MRI. No differences in APHE detection were found between single-AP (93%; 66/71) and triple-AP (100%; 65/65) at HBA-MRI (P = 0.12). Patient age, size of the nodules, use of automatic triggering, type of contrast agent, and type of sequence were not significantly associated with APHE detection. The reader was the single variable significantly associated with APHE detection. For triple-AP, best APHE detection rate was found for early and middle-AP images compared to late-AP images (P = 0.001 and P = 0.003). All APHEs were detected with the combination of early-AP and middle-AP images, except one that was detected on late-AP images by one reader. CONCLUSION: Our study suggests that both single- and triple-AP can be used in liver MRI for the detection of small HCC especially when using ECA. Early AP and middle-AP are the most efficient phases and should be preferred for detecting APHE, regardless of the contrast agent used.

Left gastric vein embolization during TIPS placement for acute variceal bleeding has no effect on bleeding recurrence: Results of a multicenter study.

PURPOSE: The purpose of this study was to evaluate whether concomitant left gastric vein embolization (LGVE) during transjugular intrahepatic portosystemic shunt (TIPS) for acute variceal hemorrhage could reduce the risk of bleeding recurrence. MATERIAL AND METHOD: A national multicenter observational study was conducted in 14 centers between January 2019 and December 2020. All cirrhotic patients who underwent TIPS placement for acute variceal bleeding were included. During TIPS procedure, size of left gastric vein (LGV), performance of LGVE, material used for LGVE and portosystemic pressure gradient (PPG) before and after TIPS placement were collected. A propensity score for the occurrence of LGVE was calculated to assess effect of LGVE on rebleeding recurrence at six weeks and one year. RESULTS: A total of 356 patients were included (mean age 57.3 ± 10.8 [standard deviation] years; 283/356 [79%] men). Median follow-up was 11.2 months [interquartile range: 1.2, 13.3]. The main indication for TIPS was pre-emptive TIPS (162/356; 46%), rebleeding despite secondary prophylaxis (105/356; 29%), and salvage TIPS (89/356; 25%). Overall, 128/356 (36%) patients underwent LGVE during TIPS procedure. At six weeks and one year, rebleeding-free survival did not differ significantly between patients who underwent LGVE and those who did not (6/128 [5%] vs. 15/228 [7%] at six weeks, and 11/128 [5%] vs. 22/228 [7%] at one year, P = 0.622 and P = 0.889 respectively). A total of 55 pairs of patients were retained after propensity score matching. In patients without LGVE, the rebleeding rate was not different from those with LGVE (3/55 [5%] vs. 4/55 [7%], P > 0.99, and 5/55 [9%] vs. 6/55[11%], P > 0.99, at six weeks and one year respectively). Multivariable analysis identified PPG after TIPS placement as the only predictor of bleeding recurrence (hazard ratio = 1.09; 95% confidence interval: 1.02-1.18; P = 0.012). CONCLUSION: In this multicenter national real-life study, we did not observe any benefit of concomitant LGVE during TIPS placement for acute variceal bleeding on bleeding recurrence rate.

Baseline ALBI score and early variation of serum AFP predicts outcomes in patients with HCC treated by atezolizumab-bevacizumab.

BACKGROUND: The combination of atezolizumab and bevacizumab (AtezoBev) is the current first-line treatment for patients with hepatocellular carcinoma (HCC). Our aim was to evaluate the prognostic role of alpha-foetoprotein (AFP) early response and its combination with albumin-bilirubin (ALBI) in these patients. METHODS: Patients with HCC under AtezoBev with AFP > 20 ng/ml were included in three centres. The optimal threshold of AFP variation after 3 weeks of treatment was identified for overall survival (OS) and radiological response (RR) using RECIST 1.1 and mRECIST and its ability to predict progression-free survival (PFS) and OS was tested using univariate and multivariate analysis in derivation and validation cohorts. RESULTS: Seventy-five patients with AFP values >20 ng/ml were included. Fifty-eight patients were male with a median age of 63.5 years; 73% had cirrhosis and HCC stage was classified as BCLC B (18.7%) or C (81.3%). In the derivation cohort (n = 38), a decline in AFP ≥ 20% at 3 weeks (AFP early response) was associated with RR using mRECIST criteria (OR: 13.09 95% CI: 1.44-19.34 p = .02), PFS (HR: 0.42; 95% CI: 0.19-0.93, p = .03) and OS (HR: 0.35; 95% CI: 0.15-0.83, p = .01). AFP early response was confirmed as predictor of RR (p = .02 for mRECIST) and OS (p = .03) in the validation cohort (n= 37). In the whole cohort, the combination of ALBI and AFP early response was significantly associated with OS (p = .046) and PFS (p = .012) with a poor prognosis in patients belonging to the ALBI2-AFP non-responders class. CONCLUSION: AFP early response at 3 weeks predicts oncological outcomes in HCC patients treated with AtezoBev and combination with ALBI grade refines prognostic discrimination.

Body weight changes and duration of estrogen exposure modulate the evolution of hepatocellular adenomas after contraception discontinuation.

BACKGROUND AND AIMS: The natural history of hepatocellular adenomas (HCAs) remains to be better described, especially in nonresected patients. We aim to identify the predictive factors of HCA evolution after estrogen-based contraception discontinuation. APPROACH AND RESULTS: We retrospectively included patients with a histological diagnosis of HCA from three centers. Clinical, radiological, and pathological data were collected to identify predictive factors of radiological evolution per Response Evaluation Criteria in Solid Tumors, version 1.1, and occurrence of complications (bleeding, malignant transformation). We built a score using variables that modulate estrogen levels: body mass index and duration of estrogen-based contraception. An external cohort was used to validate this score. 183 patients were included in the cohort, including 161 women (89%) using estrogen-based contraception for a median of 12 years. Thirty percent of patients had at least one HNF1A -inactivated HCA, 45.5% at least one inflammatory HCA, and 11% at least one HCA with activation of ß-catenin (bHCA). Twenty-one symptomatic bleedings (11%) and eleven malignant transformations (6%) occurred. Ages < 37 years old ( p = 0.004) and HCA > 5 cm at imaging were independently associated with symptomatic bleeding ( p = 0.003), whereas a bHCA was associated with malignant transformation ( p < 0.001). After a median follow-up of 5 years, radiological regression was observed in 31%, stabilization in 47%, and progression in 22% of patients. Weight loss was associated with regression ( p < 0.0001) and weight gain with progression ( p = 0.02). The estrogen exposure score predicted radiological regression (odds ratio, 2.33; confidence interval 95%, 1.29-4.19; p = 0.005) with a linear relationship between the rate of estrogen exposure and the probability of regression. This result was confirmed in an external cohort of 72 female patients ( p = 0.003). CONCLUSION: Weight variation is strongly associated with radiological evolution after oral contraception discontinuation. A score of estrogen exposure, easily assessable in clinical practice at diagnosis, predicts regression of HCA.

Imaging and histological features of tumor biopsy sample predict aggressive intrasegmental recurrence of hepatocellular carcinoma after radiofrequency ablation.

Aggressive intrasegmental recurrence (AIR) is a form of local recurrence associated with a dismal prognosis and defined by multiple nodules or by an infiltrative mass with a tumor thrombus, occurring in the treated segment, after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). We aimed to identify radiological and/or histological characteristics of tumor biopsy predictive of AIR. We retrospectively analyzed patients treated by No-Touch multi-bipolar RFA (mbpRFA) for a first HCC with a systematic per-procedural tumor biopsy positive for diagnosis of HCC. The first recurrence was classified as non-aggressive local recurrence, AIR or intrahepatic distant recurrence. 212 patients were included (168 men; mean age 67.1 years; mean tumor size 28.6 mm, 181 cirrhosis). AIR occurred in 21/212 patients (10%) and was associated with a higher risk of death (57% in patients with AIR vs 30% without AIR, p = 0.0001). Non-smooth tumor margins, observed in 21% of the patients and macro-trabecular massive histological subtype, observed in 12% of the patients were independently related to a higher risk of AIR (HR: 3.7[1.57;9.06], p = 0.002 and HR:3.8[2.47;10], p = 0.005 respectively). Non smooth margins at imaging and macro-trabecular massive histological subtype are associated with AIR and could be considered as aggressive features useful to stratify therapeutic strategy.

Impact of sarcopenia on tumor response and survival outcomes in patients with hepatocellular carcinoma treated by trans-arterial (chemo)-embolization.

BACKGROUND: At the diagnosis of hepatocellular carcinoma (HCC), more than 90% of HCC patients present cirrhosis, a clinical condition often associated to malnutrition. Sarcopenia is an indirect marker of malnutrition assessable on computed tomography (CT). AIM: To evaluate the prognostic value of sarcopenia in patients with HCC treated by trans-arterial (chemo)-embolization. METHODS: Patients with HCC treated by a first session of trans-arterial (chemo)embolization and an available CT scan before treatment were included. Sarcopenia was assessed using skeletal muscle index at baseline and at the first radiological assessment. Radiological response was recorded after the first session of treatment using mRECIST. RESULTS: Of 225 patients treated by trans-arterial bland embolization (n = 71) or trans-arterial chemoembolization (n = 154) for HCC between 2007 and 2013, Barcelona Clinic of Liver Cancer stage was A, B, and C in 27.5%, 55%, and 16.8% of cases, respectively. Sarcopenia was present in 57.7% of the patients. Patients with sarcopenia presented a higher rate of progressive disease (19% vs 8%, P = 0.0236), a shorter progression-free survival (8.3 vs 13.2 mo, P = 0.0035), and a shorter median overall survival (19.4 mo vs 35.5 mo, P = 0.0149) compared with non-sarcopenic patients. Finally, patients whose sarcopenia appeared after first transarterial treatment had the worst prognosis (P = 0.0004). CONCLUSION: Sarcopenia is associated with tumor progression and poor survival outcomes after trans-arterial (chemo)-embolization for HCC.

New concepts in the treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death and occurs mainly in the context of chronic liver disease at cirrhosis stage. The Barcelona Clinic Liver Cancer classification, first established in 1999, is the most commonly used staging system for HCC in Western countries that link tumor burden, liver function and performance status with prognosis and therapeutic management. Since the first publication of this classification, it has been implemented in several clinical guidelines and recent major therapeutic advances in the management of HCC have modified the therapeutic landscape of HCC. Accordingly, an updated version was recently published in 2022, incorporating an expert clinical decision-making component and the concept of treatment stage migration. This update also introduces the positive results of recent randomized clinical trials, and introduces atezolizumab/bevacizumab (A/B) as a first-line combination regimen for patients with advanced HCC. Finally, the complexity of the management of patients with HCC highlights the need for a multidisciplinary approach including input from hepatology, surgery, radiology, medical oncology, and radiation oncology.

Non-invasive diagnosis and follow-up of primary malignant liver tumours.

Among a wide range of malignant liver tumours, hepatocellular carcinoma (HCC) developed on a background of cirrhosis represents the most frequent clinical situation. In this setting, HCC is one of the rare solid tumours for which histological confirmation is not mandatory. The convergence of multiple arguments obtained by non-invasive parameters using radiological findings allows to avoid liver biopsy in a large proportion of patients when a diagnosis of underlying cirrhosis is ascertained. Conversely, in case of atypical presentation or in order to exclude other rare malignant tumours mostly developed in the absence of cirrhosis, liver biopsy will then be essential. Based on typical radiological patterns described by contrast-enhanced imaging, numerous clinical guidelines have endorsed non-invasive diagnosis, staging and monitoring of HCC patients under treatment since 20 years. These algorithms have evolved over the years, taking into account progress in radiological technology and advances in curative or palliative procedures. Large cohort studies have also helped to refine diagnostic criteria and prognostication in the setting of complex therapeutic strategy. Unsupervised multi-analysis approaches both at the biological and radiological levels will in the future enrich the panel of non-invasive markers useful in clinical practice to manage HCC and other malignant tumours.

Percutaneous radiofrequency ablation for hepatocellular carcinoma developed on non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Long-term outcomes after percutaneous radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD) have been poorly studied. We aim to determine the outcomes after multibipolar RFA in these patients compared to other aetiologies as well as the prognostic impact of metabolic syndrome (MS). METHODS: Patients who underwent multibipolar RFA as the first treatment for HCC within Milan criteria (2008-2018) were enrolled in this multicentre retrospective cohort from four tertiary centres in France. The association of MS and NAFLD with adverse events and outcomes after percutaneous RFA were assessed using Kaplan Meier method, log-rank test and uni/multivariate analysis with the Cox models. RESULTS: Among 520 patients, 390 patients (75%) had at least one component of MS including obesity (30%) and 95% had cirrhosis. Sixty-two patients (12.6%) had NAFLD-HCC, 225 (45.5%) had alcohol-related-HCC, 36 (7.3%) had HBV-HCC and 171 (34.6%) had HCV-HCC. Patients with NAFLD-HCC were significantly older (median age 72.6 years, P < .001), more obese (median BMI 30.3 kg/m2 , P < .001) and had more components of MS. Patients with NAFLD-HCC achieved a median overall survival (OS) of 79 months (1-year, 3-year and 5-year OS of 90%, 71% and 59%). There were no differences in morbidity, tumour recurrence and OS among patients with NAFLD-HCC vs other aetiologies as well as no prognostic impact of metabolic components. CONCLUSIONS: Percutaneous multibipolar RFA is an efficient treatment in HCC patients with NAFLD or metabolic syndrome and achieved similar long-term oncological outcomes compared to other aetiologies.

Use of Virtual Target Fluoroscopic Display of Three-Dimensional CO2 Wedged Hepatic Vein Portography for TIPS Placement.

PURPOSE: To describe and evaluate an image fusion technique for the portal vein puncture guidance during TIPS procedure: a three-dimensional (3D) virtual target fluoroscopic display obtained with an automated 3D carbon dioxide wedged hepatic vein portography (3D CO2-WHVP). MATERIALS AND METHODS: All the 37 TIPS creations performed in our institution between 3/2017 and 12/2018 were retrospectively reviewed. Seventeen procedures were guided using the 3D CO2-WHVP technique (group 1) and were compared with the other 20 procedures performed under conventional 2D fluoroscopic guidance (group 2). Image acquisition for the 3D CO2-WHVP consisted of combining a CBCT acquisition and an automatic CO2 injection. Once located on the multiplanar reformatted images of the CBCT acquisition, the portal bifurcation was manually segmented to create a virtual target that was overlaid onto live fluoroscopy allowing a real-time 3D guidance during portal vein puncture. RESULTS: Primary success was 100% in group1 and 95% in group2. Median intervention length, fluoroscopy time and dose area product (DAP) were, respectively, 124 min [IQR 94-137], 40 min [IQR 26-52] and 12140 cGy.cm2 [IQR 10147-18495] in group 1 and 146 min [IQR 118-199], 40 min [IQR 36-60] and 13290 cGy.cm2 [IQR 10138-19538] in group 2. No technical parameter was significantly different between the two groups. Intraprocedural complication rate was 0% in group 1 and 20% in group 2 (p = 0.05). CONCLUSION: Three-dimensional virtual target fluoroscopic display using a CBCT-acquired CO2 wedged portography is an effective and safe technique to ease intrahepatic puncture of the portal vein during TIPS procedures.

Percutaneous ablation for locally advanced hepatocellular carcinoma with tumor portal invasion.

INTRODUCTION: We aim to assess the outcomes of percutaneous ablation of locally advanced HCC in a tertiary center, which is usually not indicated. We compared to sorafenib or trans-arterial radioembolization (TARE). METHODS: We included 272 patients with HCC and tumor portal invasion treated by percutaneous ablation (n = 44) assessed retrospectively from one center compared to a control group from the SARAH trial including patients treated with sorafenib (n = 123) or TARE (n = 105). A propensity-score matching was performed in a subgroup of patients with similar baselines characteristics. RESULTS: 84% of patients treated by ablation were male with a unique nodule (median size 50 mm) in 72.7% of the case. Complete tumor ablation was achieved in 75% of the patients with 20% Dindo-Clavien III-V adverse events including 6.8% of 90-days mortality. Sum of tumor size ≥70 mm was associated with incomplete ablation (p = 0.0239) and a higher risk of death (p = 0.0375). Patients in control group had a higher tumor burden, and more Vp3/4 compared to ablation group. Median overall survival was similar in the ablation and in the control group (16.4 and 14.0 months respectively, p = 0.48). The median progression-free survival was 6.6 months in ablation group compared to 4.2 months in the control group (p = 0.12). CONCLUSION: Percutaneous ablation for locally advanced HCC was feasible and associated with similar long-term outcomes to sorafenib or TARE.

Combination of Model for End-Stage Liver Disease and Lactate Predicts Death in Patients Treated With Salvage Transjugular Intrahepatic Portosystemic Shunt for Refractory Variceal Bleeding.

BACKGROUND AND AIMS: Data about the prognosis of salvage transjugular intrahepatic portosystemic shunt (TIPS) using covered stents for refractory variceal bleeding caused by portal hypertension are scarce. We aimed to assess survival and to identify predictors of mortality in these patients. APPROACH AND RESULTS: One hundred sixty-four patients with cirrhosis from five centers treated with salvage TIPS between 2007 and 2017 were retrospectively divided into a derivation cohort (83 patients) and a validation cohort (81 patients). Comparisons were performed using the Mann-Whitney and Fischer's exact test. Six-week overall survival (OS) was correlated with variables on the day of the TIPS using Kaplan-Meier curves with log-rank test and univariate/multivariate analyses using the Cox model. Eighty-three patients were included in the derivation cohort (male, 78%; age, 55 years, alcohol-associated cirrhosis, 88%; Model for End-Stage Liver Disease [MELD], 19 [15-27]; arterial lactate, 3.7 mmol/L [2.0-8.3]). Six-week OS rate was 58%. At multivariate analysis, the MELD score (OR, 1.064; 95% CI, 1.005-1.126; P = 0.028) and arterial lactate (OR, 1.063; 95% CI, 1.013-1.114; P = 0.032) were associated with 6-week OS. Six-week OS rates were 100% in patients with arterial lactate ≤2.5 mmol/L and MELD score ≤ 15 and 5% in patients with lactate ≥12 mmol/L and/or MELD score ≥ 30. The 81 patients of the validation cohort had similar MELD and arterial lactate level but lower creatinine level (94 vs 106 µmol/L, P = 0.008); 6-week OS was 67%. Six-week OS rates were 86% in patients with arterial lactate ≤2.5 mmol/L and MELD score ≤ 15 and 10% for patients with lactate ≥12 mmol/L and/or MELD score ≥ 30. In the overall cohort, rebleeding rate was 15.8% at 6 weeks, and the acute-on-chronic liver failure grade (OR, 1.699; 95% CI, 1.056-1.663; P = 0.040) was independently associated with rebleeding. CONCLUSIONS: After salvage TIPS, 6-week mortality remains high and can be predicted by MELD score and lactate. Survival rate at 6 weeks was >85% in patients with arterial lactate ≤2.5 mmol/L and MELD score ≤ 15, while mortality was >90% for lactate ≥12 mmol/L and/or MELD score ≥ 30.

Comparison of Trans-Arterial Chemoembolization and Bland Embolization for the Treatment of Hepatocellular Carcinoma: A Propensity Score Analysis.

No definitive conclusion could be reached about the role of chemotherapy in adjunction of embolization in the treatment of hepatocellular carcinoma (HCC). We aim to compare radiological response, toxicity and long-term outcomes of patients with hepatocellular carcinoma (HCC) treated by trans-arterial bland embolization (TAE) versus trans-arterial chemoembolization (TACE). We retrospectively included 265 patients with HCC treated by a first session of TACE or TAE in two centers. Clinical and biological features were recorded before the treatment and radiological response was assessed after the first treatment using modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Correlation between the treatment and overall, progression-free and transplantation-free survival was performed after adjustment using a propensity score matching: 86 patients were treated by bland embolization and 179 patients by TACE, including 44 patients with drug-eluting beads and 135 with lipiodol TACE, 89.8% of patients were male with a median age of 65 years old. Cirrhosis was present in 90.9% of patients with a Child Pugh score A in 84% of cases. After adjustment, no difference in the rate of AE, including liver failure, was observed between the two treatments. TACE was associated with a significant increase in complete radiological response (odds ratio (OR) = 8.5 (95% confidence interval (CI): 2.8-25.4)) but not in the overall response rate (OR = 2.2 (95% CI = 0.8-5.8)). No difference in terms of overall survival (p = 0.3905), progression-free survival (p = 0.4478) and transplantation-free survival (p = 0.9020) was observed between TACE and TAE. TACE was associated with a higher rate of complete radiological response but without any impact on overall radiological response, progression-free survival and overall survival compared to TAE.