Background/Objectives: Systemic treatment of advanced hepatocellular carcinoma (HCC) is based on combinations of immunotherapies (ITs) and lacks predictive markers of efficacy. Objectives: To define the prognostic value of the CRAFITY and RECA biological scores for overall survival (OS) before and during IT, and to evaluate the value of these two models for predicting the therapeutic response. Patients and methods: This was a multicenter retrospective analysis of 229 patients. OS was analyzed using Kaplan-Meier curves, log-rank tests, and Cox models, through which second-line therapy was modeled as a time-dependent covariate to avoid immortal time bias. The predictive capacity was assessed using univariate logistic regression. Validation was performed within two external Chinese cohorts. Results: Sixty-six percent of patients had Barcelona Clinic Liver Cancer (BCLC) stage C HCC (vascular invasion: 36.3%, metastases: 32.6%). After a mean follow-up of 14.9 (12.8) months, the median OS was 17.4 (6.9-38.0) months. The CRAFITY score distinguished only two different prognostic subgroups before treatment, but its prognostic value was confirmed with three different prognostic groups after 3 and 5 cycles and 6 months of treatment. The RECA score was strongly associated with OS before treatment and after 3 and 5 cycles and after 6 months of IT. Conversely, neither score had a discriminatory ability to predict early therapeutic response. The prognostic value of both models for OS was confirmed in the external cohorts. Conclusions: The RECA and CRAFITY scores have strong prognostic value for OS during IT. Beyond the models, the dynamic effects of systemic inflammation on IT reveal distinct clinical outcomes. Neither score has the ability to predict early therapeutic response, further supporting their use during treatment.

BACKGROUND:How selective internal radiation therapy (SIRT) with personalized dosimetry fits with intermediate and advanced hepatocellular carcinoma (HCC) treatment remains unclear. The aims of our study were to investigate the efficacy and safety of SIRT in real-life settings within a nonsurgical HCC population and to identify prognostic factors for survival. METHODS:From January 2019 to December 2023, 73 consecutive HCC patients who underwent SIRT with personalized dosimetry at three French centers were retrospectively analyzed. A post-matched comparison with a large single-center cohort of HCC patients (n=1,049) enrolled from January 2007 to December 2023 and treated with other therapeutic modalities was performed. Overall survival (OS) was compared between the two patient groups. RESULTS:Patients treated with SIRT had mostly Child-Pugh (CP) grade A cirrhosis and multifocal and unilobar HCCs, which were classified as Barcelona Clinic Liver Cancer (BCLC) stage B or C with vascular invasion (49%) or metastases (5%). SIRT was a first-line therapy in half of the patients and was used in combination for nearly one-quarter of the patients. In total, 94% of the patients received a tumor dose of 205 Gy or higher. After a median follow-up of 11.9 (6.2-21.1) months, 53% of patients treated with SIRT died. Stage B and C HCC patients had median OS times of 35.2 (6.5-infinite) and 12.8 (6.8-infinite) months, respectively. A comparative analysis of the two cohorts revealed the superiority of SIRT in terms of OS for advanced-stage HCCs with unilateral intrahepatic portal vein tumor thrombosis and the similarity of SIRT for intermediate-stage HCCs compared with other modalities. No significant difference in OS was observed after matching BCLC B/C HCC patients who received SIRT with those who did not after a median follow-up of approximately 12 months. The independent prognostic variables for survival following SIRT therapy were CP grade, largest tumor size and hemoglobin level. No deaths occurred in the SIRT group. CONCLUSIONS:This study revealed that SIRT following personalized dosimetry is used in current practice as a therapeutic solution for advanced and intermediate HCC, typically in combination therapies and beyond first-line treatment. Our results support SIRT as an alternative therapeutic option for intermediate-stage HCC and as an effective therapeutic solution for advanced HCC with intrahepatic vascular invasion, with a good safety profile.

In France, chronic hepatitis C whatever fibrosis stage or comorbidities can be freely treated by any physician. However, screening is still currently based on risk factors, and universal screening remains controversial. The aims of this prospective DEVICHO study were to assess the value of universal screening in hospitalised patients, to evaluate the prevalence of HCV infection and to compare the short-term cost and benefit of this strategy with routine screening. From November 2019 to November 2021, all hospitalised patients from 22 departments were asked by their physicians to be tested for HCV. 4986/25,663 (19.4%) in the DEVICHO study (Group 1) and 1803 patients (7%) outside the study (Group 2) were screened. HCV screening rate varied widely (0%-75.1%) between departments. One hundred and ninety-nine patients (2.9%) were HCV-Ab positive. 29/199 HCV-Ab positive patients (14.6%) or 29/6789 patients tested (0.4%) were HCV-RNA positive. Among the 29 viremic patients, 9 (31%) were treated, all achieving sustained virological response, but two patients died rapidly after treatment. Seventeen patients died untreated within a year of diagnosis, and three patients were not treated. Universal screening compared to routine practice would be more expensive and more effective, resulting in an additional cost of €11,060 per HCV RNA infection identified and €36,600 per HCV cure, both below the GDP per capita of France (€38,000, Eurostat 2023). Even if the population screened is older, often with significant comorbidities, hospital-based HCV screening is efficient because its prevalence is higher in hospitalised patients than in the general population. Additionally, this screening strategy appears to be cost effective. However, healthcare professionals and insufficient linkage to care are the main barriers to screening. Trial Registration: ClinicalTrials.gov identifier: NTC 04437277.

BACKGROUND AND AIMS:The combination of atezolizumab plus bevacizumab (Atz/Bev) has radically changed the treatment strategy for advanced hepatocellular carcinoma (HCC) but raises questions. Our objectives were to determine survival outcomes and safety in a real-life multicenter French cohort, to investigate the on-treatment prognostic value of the bioinflammatory RECA score, and to perform a matched comparison with patients who previously received tyrosine kinase inhibitors (TKIs). METHODOLOGY:A retrospective analysis of 109 consecutive patients enrolled from September 2020 to January 2023 and a post matched comparison with a TKI cohort ( n  = 79) by the propensity score matching method. RESULTS:The Atz/Bev population was mainly nonviral disease patients (69%) with Child-Pugh grade A (90%), performance status 0/1 (90%), and Barcelona Clinic Liver Cancer stage B (38%) or stage C (62%) classification. After a median follow-up of 6.5 months (3.6-11.7), overall survival (OS) was 13.0 (5.1-28.7) months. OS was independently associated with metastasis, increased alkaline phosphatase, and serum bilirubin levels. Treatment-related adverse events were reported in 78% of patients, mostly grade 1 or 2. The RECA score clearly revealed two different prognosis groups after three cycles. No difference in OS was observed after matching between sequential treatment with TKIs and Atz/Bev. CONCLUSION:This real-life study highlights the importance of liver function when using Atz/Bev combination and the necessity of identifying predictive markers of response to HCC therapies. Our findings suggest a change in practices, with a marked proportion of intermediate stages, and support the on-treatment prognostic value of an inflammatory score.

Background and Aims: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) have common features and differences. This real-life study investigated their characteristics, treatment modalities, and prognoses. Meth-ods: This retrospective comparative study was performed in 1,075 patients seen at one tertiary center between January 2008 and December 2020. Overall survival (OS) was estimat -ed by the Kaplan-Meier method. Subclassification of iCCAs af-ter histological and radiological review, and molecular profil -ing was performed. Results: HCCs patients were more likely to have early-stage disease than iCCA patients. iCCA patients were more likely to be female, especially those patients with-out cirrhosis (43% vs. 17%). Cirrhosis was prominent among HCC patients (89% vs. 34%), but no difference in underlying liver disease among cirrhotic patients was found. OS of HCC patients was 18.4 (95% CI: 6.4, 48.3) months, that of iCCA patients was 7.0 (95% CI: 3.4, 20.1) months. OS of Barce-lona Clinic Liver Cancer C HCC patients was 7.8 (95% CI: 4.3, 14.2) months, that of advanced/metastatic iCCA patients was 8.5 (95% CI: 5.7, 12.3) months. In patients treated with sorafenib, OS was longer in HCC patients who received sub-sequent tyrosine kinase inhibitor therapies. No significant OS difference was found between iCCA patients with and without cirrhosis or according to histological subtype. A targetable molecular alteration was detected in 50% of the iCCA pa-tients. Conclusions: In this French series, cirrhosis was com-mon in iCCA, which showed etiological factors comparable to those of HCC, implying a distinct oncogenic pathway. Both entities had a dismal prognosis at advanced stages. However, systemic therapies sequencing in HCC and molecular profiling in iCCA offer new insights.

BACKGROUND:Starting a second-line systemic treatment for hepatocellular carcinoma (HCC) is a common situation. The only therapeutic options in France are two broad-spectrum tyrosine kinase inhibitors (TKIs), regorafenib (REG) and cabozantinib (CBZ), but no comparative real-life studies are available.AIM:To evaluate the progression-free survival (PFS) of patients treated with REG or CBZ, we investigated the disease control rate (DCR), overall survival (OS), and safety of both drugs. To identify the variables associated with disease progression over time.METHODS:A retrospective multicenter study was performed on the clinical data of patients attending one of three referral centers (Avignon, Marseille, and Nice) between January 2017 and March 2021 using propensity score matching. PFS and OS were assessed using the Kaplan-Meier method. Multivariate analysis (MA) of progression risk factors over time was performed in matched-pair groups.RESULTS:Fifty-eight patients 68 (62-74) years old with HCC, Barcelona clinic liver cancer (BCLC) B/C (86%), Child-Pugh (CP)-A/B (24%) received REG for 3.4 (1.4-10.5) mo as second-line therapy. Twenty-eight patients 68 (60-73) years, BCLC B/C (75%), CP-A/B (25%) received CBZ for 3.7 (1.8-4.9) mo after first-line treatment with sorafenib [3 (2-4) (CBZ) vs 4 (2.9-11.8) mo (REG), P = 0.0226]. Twenty percent of patients received third-line therapy. After matching, PFS and DCR were not significantly different after a median follow-up of 6.2 (2.7-11.7) mo (REG) vs 5.2 (4-7.2) mo (CBZ), P = 0.6925. There was no difference in grade 3/4 toxicities, dose reductions, or interruptions. The OS of CP-A patients was 8.3 (5.2-24.8) vs 4.9 (1.6-11.7) mo (CP-B), P = 0.0468. The MA of risk factors for progression over time identified C-reactive protein (CRP) > 10 mg/L, neutrophil-to-lymphocyte ratio (NLR) > 3, and aspartate aminotransferase (AST) > 45 IU as predictive factors.CONCLUSION:This multicenter indirect comparative study found no significant difference in PFS between REG and CBZ as second-line therapy for advanced HCC. Elevated levels of inflammatory markers (CRP and NLR) and AST were associated with non-control of TKIs over time. A 2-mo online progression risk calculation is proposed.

In Sensoa's HCV prevalence study, only 1 of 260 test results was positive (0.38%) and this was an HIV co-infected patient.The Ex Aequo's HCV prevalence study yielded no positive test results.The HIV prevalences were 1, 15% (Sensoa) and 1, 3% (Ex Aequo) and the syphilis prevalence was 2, 5% (Ex Aequo).Conclusion: There is a big knowledge gap of HBV and HCV infections in the MSM community in Flanders.More awareness campaigns that focus on transmission, disease process, treatment and vaccination need to be created that also target people with a low educational level.The prevalence of hepatitis C infection and other STD's was low in the MSM population studied of 500 participants.Presumably a young MSM population that voluntarily has themself tested represents a rather low risk profile for HCV infection.HCV prevalence may be higher in an older population and/or in an illegal environment where more risk factors for HCV infection co-exist and that is more difficult to reach.However, given the high workload and low case finding, an on-site screening approach cannot be recommended.

BACKGROUND:Careful selection of hepatocellular carcinoma (HCC) patients prior to chemoembolization treatment is a daily reality, and is even more necessary with new available therapeutic options in HCC.AIM:To propose two new models to better stratify patients and maximize clinical benefit: "6 and 12" and "pre/post-TACE-predict" (TACE, transarterial chemoembolization).METHODS:We evaluated and compared their performance in predicting overall survival with other systems {Barcelona Clinic Liver Cancer (BCLC), Albumin-Bilirubin (ALBI) and NIACE [Number of tumor(s), Infiltrative HCC, alpha-fetoprotein, Child-Pugh (CP), and performance status]} in two HCC French cohorts of different stages enrolled between 2010 and 2018.RESULTS:The cohorts included 324 patients classified as BCLC stages A/B (cohort 1) and 137 patients classified as BCLC stages B/C (cohort 2). The majority of the patients had cirrhosis with preserved liver function. "Pre-TACE-predict" and "6 and 12" models identified three distinct categories of patients exhibiting different prognosis in cohort 1. However, their prognostic value was no better than the BCLC system or NIACE score. Liver function based on CP and ALBI grades significantly impacted patient survival. Conversely, the "post-TACE-predict" model had a higher predictive value than other models. The stratification ability as well as predictive performance of these new models in an intermediate/advanced stage population was less efficient (cohort 2).CONCLUSION:The newly proposed "Pre-TACE-predict" and "6 and 12" models offer an interesting stratification into three categories in a recommended TACE population, as they identify poor candidates, those with partial control and durable response. The models' contribution was reduced in a population with advanced stage HCCs.

Background: Sorafenib is the first-line treatment for advanced hepatocellular carcinoma (HCC). The management of its side effects is improving. This study aimed to assess, in real life, if this translates into a better prognosis. Methods: This was a retrospective study of advanced HCC patients treated with sorafenib between 2007 and 2017. Results: 188 advanced HCC patients received > 4 weeks of sorafenib. Median treatment duration was 5.4 months and median overall survival (mOS) 10 months (95% confidence interval 15-27). Sorafenib was initiated in 65 patients in 2007-2012 and 123 in 2013-2017. Both groups were comparable except for Barcelona Clinic liver cancer class. Tumor progression, disease control (DC) rate, and incidence of toxicity were similar in the 2 periods, but the duration of treatment (4.3 vs. 5.9 months; p < 0.01) and mOS (8 vs. 12 months; p < 0.002) differed. Among progressive disease patients, mOS was similar (7 months) but for those who had DC at 8 weeks, mOS was longer in the recent period (13 vs. 27 months; p < 0.0001). In the univariate analysis of OS, the period of treatment had a prognostic value. Conclusion: When comparing 2 periods of treatment in advanced HCC patients under sorafenib, duration of treatment and mOS were higher in the recent period. While mOS did not differ for patients who progressed, it was 2-fold higher in the recent period for those who had tumor control. Improvements in the use of sorafenib seem to be associated with better outcomes limited to patients with DC.

BACKGROUNDConventional transarterial chemoembolization (cTACE) with lipiodol is widely performed in patients with hepatocellular carcinoma (HCC) unsuitable for curative treatment. Additional tumor parameters such as HCC macroscopic appearance based on imaging might be helpful for transarterial chemoembolization prognostication and management.PATIENTS AND METHODSA total of 405 patients with HCC who underwent cTACE between 2008 and 2016 from a real-life multicenter French cohort were retrospectively reviewed. Tumors were classified into two macroscopic types according to HCC gross appearance on imaging: nodular versus non-nodular. The study population was stratified into two groups: derivation and validation cohorts. Independent prognostic factors of survival based on multivariate cox regression models were determined and then assessed in the validation set. Thereafter, time to progression (TTP) and radiological response rate were investigated for each prognostic factors of survival.RESULTSMedian overall survival (OS) was 35 months for Barcelona Clinic Liver Cancer (BCLC) stage A, 22 months for BCLC stage B and 12 months for BCLC stage C patients (P<0.0001). The corresponding TTP for these patients was 12 (7-17) months, 5 (3-6) months and 1.2 (1.2-3) months (P<0.0001). Multivariate analysis revealed that tumors size and number, non-nodular type, alpha-fetoprotein, aspartate aminotransferase serum levels and impairment of performance status-1 were independent predictors of survival among the study groups. Non-nodular type was the most powerful factor that influences OS, TTP and radiological response rate for the recommended transarterial chemoembolization candidates. TTP was consistent with OS within each stage.CONCLUSIONHCC macroscopic appearance on imaging is a determinant predictor of outcome after cTACE in a real-life multicenter cohort.

Background Direct-acting antivirals (DAAs) therapy against hepatitis C viral (HCV) infection has markedly improved the sustained viral response. However, recent studies have suggested an unsuspected high rate of hepatocellular carcinoma (HCC) recurrence. Patients and methods A retrospective case–control study was carried out to investigate the impact of DAAs on tumor recurrence in patients with complete response to HCC treatment within our HCV-related cirrhosis cohort. Patients who received [group 1 (G1), n=22] or not [group 2 (G2), n=49] a DAAs therapy were matched 1 : 2 for age, sex, liver function, HCC stage, and treatment. Results Initial HCC were mostly Barcelona Clinic Liver Cancer stage A (95% G1, 94% G2). Sustained viral response with DAAs was achieved in 86% of patients. After a similar median overall follow-up time with similar radiologic surveillance after HCC treatment, 41% of patients developed radiologic tumor recurrence in G1 versus 35% of patients in G2 (P=0.7904). There was no significant difference in time to progression between the two groups [12 (9–16) months G1 vs. 14 (8–21) months G2, P=0.7688], or Barcelona Clinic Liver Cancer stage at recurrence. However, the interval between HCC treatment and antiviral therapy was significantly different among DAAs patients with recurrence and those without recurrence [7.0 (2.5–9.0) months vs. 36.0 (9.0–58.0) months, P=0.0235, respectively]. Conclusion In our case–control study, HCV therapy with DAAs does not accelerate or prevent early HCC recurrence compared with untreated patients. The rate of recurrence, time to progression, and HCC pattern are similar. Early DAAs treatment (<12 months) after HCC cure should be discouraged considering the HCC recurrence rate during this period.

The advent of oral direct-acting antiviral agents (DAAs) has dramatically improved the hepatitis C virus (HCV) treatment landscape in the last 4 years, providing cure rates over 95% with a shorter duration of treatment and a very good safety profile. This has enabled access to treatment in nearly all HCV infected patients. The launch of two pangenotypic fixed dose combinations (FDCs) in 2017 made a new step forward in HCV treatment by slightly increasing efficacy and more importantly allowing the treatment of patients without HCV genotyping, and in some cases without fibrosis assessment. However, retreatment of the few DAA failure patients was still an issue for some HCV genotypes. The launch of the triple regimen FDC, sofosbuvir/velpatasvir/voxilaprevir, solves this issue by providing a cure rate over 96% regardless of HCV genotype. In this review, we describe the current HCV treatment landscape and focus on the development of this triple FDC either in treatment-naïve or treatment-experienced patients with previous failure on a DAA regimen.

Liver cancer stands now as the second leading cause of cancer-related death in men and the fifth in women. In 2015 there were 854,000 incident cases of liver cancer, primarily hepatocellular carcinoma (HCC) making it the 6 th leading cause of cancer worldwide (1). Most HCC occur in chronic hepatitis or cirrhosis, and the major risk factors include hepatitis B virus and hepatitis C virus (HCV) infections. HCV is responsible for nearly 366,000 deaths annually and one-quarter of all cases of HCC and cirrhosis worldwide (2). The cumulative incidence of HCC in untreated cirrhotic patients with HCV infection has been estimated in 3–5% per year. Viral eradication is associated with a reduction in fibrosis progression and an improvement in clinical outcomes. It is well known that sustained virological response (SVR) following interferon (INF) therapy was associated with a significant reduction in de novo HCC occurrence.

AIMTo compare the performances of the Barcelona clinic liver cancer (BCLC) nomogram and others systems (BCLC, HKLC, CLIP, NIACE) for survival prediction in a large hepatocellular carcinoma (HCC) French cohort. METHODSData were collected retrospectively from 01/2007 to 12/2013 in five French centers.Newly diagnosed HCC patients were analyzed.The discriminatory ability, homogeneity ability, prognostic stratification ability Akaike information criterion (AIC) and C-index were compared among scoring systems. RESULTSThe cohort included 1102 patients, mostly men, median age 68 [60-74] years with cirrhosis (81%), child-Pugh A (73%), alcohol-related (41%), HCV-related (27%).HCC were multinodular (59%) and vascular invasion was present in 41% of cases.At time of HCC diagnosis BCLC stages were A (17%), B (16%), C (60%) and D (7%).First line HCC treatment was curative in 23.5%, palliative in 59.5%, BSC in 17% of our population.Median OS was 10.8 mo [4.9-28.0].Each system distinguished different survival prognosis groups (P < 0.0001).The nomogram had the highest discriminatory ability, the highest C-index value.NIACE score had the lowest AIC value.The nomogram distinguished sixteen different prognosis groups.By classifying unifocal large HCC into tumor burden 1, the nomogram was less powerful. CONCLUSIONIn this French cohort, the BCLC nomogram and the NIACE score provided the best prognostic information, but the NIACE could even help treatment strategies.

Les traitements antiviraux par analogues nucléosidiques ou nucléotidiques du VHB ou par interféron ou par antiviraux directs (AVD) du VHC diminuent le risque de carcinome hépatocellulaire (CHC), avec un risque résiduel qui dépend de la gravité de l’hépatopathie sous-jacente et de facteurs de comorbidités (alcool, syndrome métabolique). Le traitement par analogues nucléosidiques ou nucléotidiques du VHB permet de réduire le risque de récidive du CHC et d’améliorer la fonction hépatique. Dans le traitement de l’hépatite C, la réponse virologique soutenue, obtenue par une bithérapie pégylée ou plus fréquemment par AVD, notamment dans les hépatopathies les plus sévères, diminue le risque de survenue ou de récidive du CHC. Le bénéfice du traitement par AVD sur la prévention de la survenue ou de la récidive à moyen et long termes du CHC doit être évalué sur les cohortes prospectives.

Background and Aim Endoscopic access to the common bile duct ( CBD ) remains difficult in 10% of cases, requiring alternative techniques .CBD access was difficult after either five unsuccessful attempts, five unintentional insertions into the pancreatic duct or >10‐min‐long unsuccessful attempts. This retrospective study with historical controls aimed to evaluate the benefit of the double guidewire ( DGW ) technique after failure of standard CBD cannulation. Methods From January 2012 to December 2014, all patients requiring therapeutic endoscopic retrograde cholangiopancreatography ( ERCP ) with difficult access to CBD were included in a Studied group. This group was compared to a historical ERCP control group from January 2009 to December 2011. In the Studied group, a sequential strategy including DGW technique was done when the guidewire was unintentionally passed into the pancreatic duct. In the control group, only pre‐cut technique was used. Results Among the 538 patients with naive papilla eligible for ERCP , 73 had difficult CBD access. Successful CBD access rate was higher in the Studied group: 91% (50/55) versus 67% (12/18) P = 0.0215. Complication rates were similar in both groups: 28% versus 20%, P = 0.5207. LOS was shorter in the Studied group (9.2 ± 8.5 vs 14.4 ± 7.4 days, P = 0.0028). Post‐ ERCP cholangitis were lower in the Studied group: 2% (1/55) versus 22% (4/18), P = 0.0118. Conclusion After standard cannulation failure, DGW technique increased successful CBD access rate and decreased LOS without increasing complications.

Background and aims Hepatocellular carcinoma (HCC) prognostic scores could be useful in addition to the Barcelona Clinic Liver Cancer (BCLC) system to clarify patient prognosis and guide treatment decision. The NIACE (tumor Nodularity, Infiltrative nature of the tumor, serum Alpha-fetoprotein level, Child–Pugh stage, ECOG performance status) score distinguishes different prognosis groups among BCLC A, B, and C HCC patients. Our aims are to evaluate the NIACE score and its additive value in two HCC cohorts treated either by surgery or by chemoembolization, and then according to the BCLC recommendations. Patients and methods This was a retrospective multicenter study with two BCLC A, B, and C HCC cohorts treated either by surgery ( n =207) or by chemoembolization ( n =168) carried out between 2008 and 2013. We studied survival time according to the baseline NIACE score and compared it with the Cancer of the Liver Italian Program score and the BCLC system. Results The NIACE score differentiates between subgroups of patients with different prognosis within each BCLC class. Among BCLC A patients treated by surgery and BCLC B patients treated by chemoembolization, the NIACE score differentiates between two subgroups with a significant difference in survival time: 68 (55–81) months versus 35 (21–56) months ( P =0.0004) and 20 (17–24) months versus 13 (7–17) months ( P =0.0008), respectively. Among those subgroups, the NIACE score has a significantly better prognostic value than the BCLC system or the Cancer of the Liver Italian Program score. Conclusion In this study, among HCC patients treated according to the BCLC recommendations, the NIACE score predicts more accurately than any other system the survival time.