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To maximize utility and prevent premature liver transplantation (LT), a delayed LT strategy (DS) was adopted in France in 2015 in patients listed for any single HCC treated with resection or thermal ablation during the waiting phase. The DS involves postponing LT until recurrence. The purpose of this study was to evaluate the DS to make sure that it did not hamper pre- and post-LT outcomes. Patients listed for HCC in France between 2015 and 2018 were studied. After data extraction from the national LT database, 2,025 patients were identified and classified according to six groups: single tumor entering DS, single tumor not entering DS, multiple tumors, no curative treatment, untreatable HCC or T1 tumors. Kaplan-Meier estimates of the 18-month risk of dropout for death, too sick to be transplanted or tumor progression before LT, 5-year post-LT HCC recurrence and post-LT survival rates were compared. Median waiting-time in the DS group was 910 days. Pre-LT dropout probability was significantly lower in the DS group compared to other groups (13% vs. 19%, p = 0.0043) and significantly higher in the T1 group (25.4%, p = 0.05). Post-LT HCC recurrence rate in the multiple nodules group was significantly higher (19.6%, p = 0.019), while 5-year post-LT survival did not differ among groups and was 74% in the DS group (p = 0.22). The DELTA-HCC study shows that DS does not negatively impact either pre- nor post-LT patient outcomes, and has the potential to allow for redistribution of organs to patients in more urgent need of LT. It can reasonably be proposed and pursued. The unexpectedly high risk of dropout in T1 patients seems related to the MELD-based offering rules underserving this subgroup. To maximize utility and prevent premature liver transplantation (LT), a delayed LT strategy was adopted in France in 2015. It involves postponing LT until recurrence in patients listed for any single HCC curatively treated by surgical resection or thermal ablation. The DELTA-HCC study was conducted to evaluate this nationwide strategy. It shows in a European LT program that delayed strategy does not negatively impact pre- nor post-LT patient outcomes and is relevant to up to 20% of LT candidates; thus, it could potentially enable the redistribution of organs to patients in more urgent need of LT. Such a delayed strategy can reasonably be pursued and extended to other LT programs. Of note, an unexpectedly high risk of dropout in T1 patients, seemingly related to MELD-based offering rules which underserve these patients, calls for further scrutinization and revision of allocation rules in this subgroup. [Display omitted] • Patients with single curatively treated HCC account for 20% of LT candidates. • In these patients, LT can be safely delayed without hampering pre/post-LT outcomes. • This strategy has the potential to redirect spared organs to patients in urgent need. • The DELTA-HCC study supports extension of a delayed strategy to other LT programs. [ABSTRACT FROM AUTHOR]

Background and Aims: To measure the impact of socio-economic environment on the incidence of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). Method: The study used data from the French Network of Cancer Registries (FRANCIM) between 2006 and 2016. Classification of patients into HCC and iCCA was performed according to the topographical and morphological codes of the 3rd edition of the International Classification of Diseases for Oncology. Patient addresses were geolocalized and assigned to an IRIS, the smallest French geographic unit. Socio-economic environment was assessed by the European Deprivation Index (EDI). Sex- and age-standardized incidence rates with 95% confidence intervals (CI) were estimated per 100 000 inhabitants, by national quintiles, for each IRIS, sex and age group. Quintile 1 (Q1) characterized the most affluent areas. A Poisson regression was performed to model the impact of deprivation. Results: We included 22 249 cases (79.64% HCC, 16.97% iCCA). Incidence rates were 11.46 and 2.39 per 100 000 person-years for HCC and iCCA, respectively. There was an over-incidence of HCC in quintiles 2, 3, 4 and 5 compared to quintile 1: Q1 10.28 [9.9--10.66] per 100 000 person-years, Q2 11.43 [10.48--12.47] (p < .0001), Q3 11.81 [10.82--12.89] (p < .0001), Q4 12.26 [11.25--13.37] (p < .001) and Q5 11.53 [10.57-- 12.57] (p < .0001). By contrast, there was no difference for iCCa. Deprivation was significantly associated with HCC in men (p = .0018) and women (p = .0009), but not with iCCA (p = .7407). Conclusion: The incidence of HCC is related to socio-economic environment, unlike iCCA. HCC and iCCA should be studied separately in epidemiological studies. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the impact of the COVID-19 pandemic on the outcome of patients on the liver transplantation (LT) waitlist in 2020 in France, in particular, the incidence of deaths and delisting for worsening condition, depending on the allocation score component. The 2020 cohort of patients on the waiting list was compared with the 2018/2019 cohorts. 2020 saw fewer LTs than in either 2019 or 2018 (1128, 1356, and 1325, respectively), together with fewer actual brain dead donors (1355, 1729, and 1743). In 2020, deaths or delisting for worsening condition increased significantly versus 2018/2019 (subdistribution hazard ratio 1.4, 95% confidence interval [CI] 1.2–1.7), after adjustment for age, place of care, diabetes, blood type, and score component, although COVID-19-related mortality was low. This increased risk mainly concerned patients with hepatocellular carcinoma (1.52, 95% CI 1.22–1.90), with 650 MELD exception points (2.19, 95% CI 1.08–4.43), and especially those without HCC and MELD scores from 25 to 30 (3.36 [95% CI 1.82–6.18]). In conclusion, by significantly decreasing LT activity in 2020, the COVID-19 pandemic increased the number of waitlist deaths and delisting for worsening condition, and significantly more for particular components of the score, including intermediate severity cirrhosis. [ABSTRACT FROM AUTHOR]

Intrahepatic cholangiocarcinoma represents 15% of primary liver tumors, second only to hepatocellular carcinoma (HCC). Its incidence in France is increasing. The standard treatment for the localized form is surgical resection followed by adjuvant chemotherapy. In case of liver-limited disease, the use of percutaneous locoregional treatments (thermoablation or external beam radiation therapy) or intra-arterial (in particular selective internal radiation therapy) has been evaluated with promising results as an alternative to surgery in inoperable patients and/or for unresectable tumors. Their use in routine practice can be proposed but with a low level of evidence and precise strategies remain to be defined. [ABSTRACT FROM AUTHOR]

Background and aims: The IMbrave150 clinical trial assessed the efficacy and safety of atezolizumab in combination with bevacizumab (ATZ+BVA) versus sorafenib in adults with advanced/unresectable hepatocellular carcinoma, who have not received prior systemic treatment. Our aim was to assess the cost-effectiveness of ATZ+BVA versus sorafenib in France based on an updated prices and considering French National real-world data, to confirm the initial recommendations from the Heath Technology Assessment submission published in 2021, and provide additional visibility to decision-makers reflecting current clinical practice. Methods: A partition survival model was developed to project clinical outcomes, quality of life, and costs of patients with HCC treated with ATZ+BVA versus sorafenib over a lifetime horizon. Survival outcomes were extrapolated via parametric functions for both treatment strategies. Quality of life (EQ-5D-5L, French tariffs) were sourced from IMbrave150. The Guyot method was considered as a scenario analysis by integrating retrospective real-world data extracted from the French Health Insurance Database to refine long term survival extrapolations. Results: In the reference case, ATZ+BVA was associated with 0.61 additional Quality Adjusted Life Years (QALYs) compared to sorafenib (1.95 vs 1.35), and an incremental cost of €92,704. The incremental cost-utility ratio (ICUR) was 152,974 €/QALY gained. Adjusting the survival curves with French external evidence led to a 14% ICUR reduction (131,163 €/QALY). Conclusions: ATZ+BVA is a cost-effective strategy based on the range recently published for the value of a QALY in France and offers better chances of survival to patients. [ABSTRACT FROM AUTHOR]

Background & Aims: Hepatocellular carcinoma (HCC) is recognized as an inflammation-related cancer. However, the relation between inflammation deriving from the diet and HCC risk among cirrhotic patients has not yet been investigated. This study aimed to examine the association between the dietary inflammatory index (DII®) and HCC risk among cirrhotic patients., Methods: Clinical and dietary data were collected from the French case-control study CiRCE (Cirrhosis and Risk of hepatocellular Carcinoma in the East), which included 401 cirrhotic patients without HCC (controls) and 181 cirrhotic patients with HCC (cases) recruited between 2008 and 2012 in six French university hospitals. DII scores (36 food items and nutrients) were assessed using a validated self-administered diet history questionnaire. Odds ratios (OR) and 95 % confidence intervals (CI) were estimated with logistic regression models (adjusted for age, gender, time from cirrhosis diagnosis, etiology of cirrhosis, Child-Pugh score, and diabetes)., Results: The DII scores ranged between -4.77 and +7.59 with a mean value of 1.03 ± 2.87 among cases and 0.83 ± 2.87 among controls, indicating that both groups were following a pro-inflammatory diet. After multi-variable adjustment, there was a positive association between HCC risk and the DII score when considered as a continuous variable (OR continuous  = 1.14 [1.02-1.27], p-value = 0.021) or categorized in tertiles (OR T3vsT1  = 2.33 [1.16-4.67], p-trend = 0.021). Similar results were found when alcohol was omitted from the DII calculation but considered as a co-variate: OR continuous  = 1.15 [1.03-1.28], p-value = 0.013, and OR T3vsT1  = 2.35 [1.18-4.68], p-trend = 0.015. A positive correlation was observed between the DII scores and two inflammatory biomarkers (CRP, IL-6) among controls., Conclusion: The present study reported an association between a pro-inflammatory DII score and the risk of HCC in cirrhotic patients. Correlations between the scores and biological parameters support a potential role for inflammation in HCC among cirrhotic. Result should be confirmed in larger prospective studies, and could lead to nutritional prevention in cirrhotic patients., Clinical Trial Registry: This study was registered in www., Clinicaltrials: gov as NCT01798173., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Aim: Less than 25 % of hepatocellular carcinoma (HCC) occurs in women, in whom prognosis could be better. Due to the lack of date in Europe, this study aims to assess survival of patients with HCC according sex in a tertiary French liver center., Patients and Methods: Every patient diagnosed with a first diagnosis of HCC presented at our weekly multidisciplinary tumor board between 2013 and 2017 were included. Baseline characteristics of patients and tumors were compared according sex using the Mann-Whitney test for Continuous variables and the Fisher or Chi-square test for dichotomous variables. Survival analyses according sex were conducted using the Kaplan-Meier method, the log-rank test, Cox models and a propensity score., Results: 694 patients were included, of whom 130 (18.7 %) were women. Among them, 587 (86 %) had cirrhosis, mainly compensated (Child A 62.7 %), and related to alcohol (48.7 %), HCV (27.2 %), and/or metabolic-associated fatty liver disease (25.8 %). HCC was unifocal in 54 % of cases, with a mean main nodule size of 37 mm. Curative treatment was administered in 45.4 % of cases (percutaneous ablation 93 %). Compared to men, women diagnosed with HCC were older (73 vs. 65 years, p < 0.001), were more frequently HCV-infected (40 % vs. 24 %, p = 0.0003) and presented more often with a solitary HCC (63 % vs. 52 %, p = 0.020). After a median follow-up of 57 months, overall survival was significantly longer in women both in multivariate analysis (aHR 1.39 (CI95 %: 1.07-1.81) p=0.014) and using a propensity score (HR 1.51 (1.13-2.02, p=0.005))., Conclusion: Despite being diagnosed at an older age, women with HCC exhibit significant better overall survival., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nathalie Ganne Carrie reports a relationship with Roche SAS that includes: consulting or advisory. Pierre Nahon reports a relationship with Roche SAS that includes: consulting or advisory. Pierre Nahon reports a relationship with Bristol Myers Squibb Co that includes: consulting or advisory. Pierre Nahon reports a relationship with MSD France SAS that includes: consulting or advisory. Pierre Nahon reports a relationship with AstraZeneca R&D that includes: consulting or advisory. Pierre Nahon reports a relationship with Ipsen that includes: consulting or advisory. Pierre Nahon reports a relationship with Eisai Inc that includes: consulting or advisory. Jean-Charles Nault reports a relationship with Ipsen that includes: funding grants. Jean-charles Nault reports a relationship with Bayer that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Résumé: Le carcinome hépatocellulaire (CHC) se développe dans la majorité des cas sur un foie cirrhotique. Le dépistage du CHC permet un diagnostic plus précoce de CHC, un accès plus fréquent à des traitements à visée curative et une amélioration de la survie des patients. En France, le dépistage par échographie abdominale semestrielle est recommandé chez les patients cirrhotiques. Cependant, seulement 20 % des patients ont un diagnostic dans le cadre d'un programme de dépistage. En l'absence de dépistage, il peut s'agir de patients ayant une cirrhose connue mais non correctement suivie, ou de patients n'ayant pas de cirrhose ou de fibrose hépatique connue. Reconnaître les patients à risque de maladie chronique du foie et identifier la fibrose avancée chez ces patients sont des axes d'optimisation du dépistage du CHC. Hepatocellular carcinoma (HCC) develops in most cases in a cirrhotic liver. HCC screening allows for an earlier diagnosis of HCC, more frequent access to treatments with curative intents, and improved patient survival. In France, biannual abdominal ultrasound screening for HCC is recommended for cirrhotic patients. However, only 20% of patients are diagnosed with HCC in a screening program. In case of patients diagnosed outside a screening programm, it may be either because they have known cirrhosis but are not properly followed, or because they have no known cirrhosis or liver fibrosis. Recognizing patients at risk for chronic liver disease and identifying advanced fibrosis in these patients are areas for optimizing HCC screening. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to describe treatment efficacy and safety in patients with hepatocellular carcinoma (HCC) undergoing stereotactic body radiation therapy (SBRT). In one of the largest retrospective studies to date, we analyzed the data of 318 patients. The median follow-up period was 70.2 months. The local control rate at 24 and 60 months was 94% (91–97%) and 94% (91–97%), respectively. Relapse-free survival at 12, 24, and 60 months was 62% (55–67%), 29% (23–36%), and 13% (8–19%), respectively. OS at 12, 24, and 60 months was 72% (95%CI 67–77%), 44% (38–50%), and 11% (7–15%), respectively. The outcome is highly related to the natural evolution of the underlying cirrhosis. Child-Pugh score B-C, high BCLC score, portal thrombosis, GTV volume, and higher PTV volume reported on total hepatic volume ratio were significantly associated with OS. SBRT is efficient for the management of HCC with a favorable toxicity profile. This study aimed to describe patient characteristics, treatment efficacy, and safety in patients with hepatocellular carcinoma (HCC) undergoing stereotactic body radiation therapy (SBRT). We retrospectively analyzed data of 318 patients with 375 HCC treated between June 2007 and December 2018. Efficacy (overall survival [OS], relapse-free survival, and local control) and acute and late toxicities were described. The median follow-up period was 70.2 months. Most patients were treated with 45 Gy in three fractions. The median (range) PTV volume was 90.7 (2.6–1067.6) cc. The local control rate at 24 and 60 months was 94% (91–97%) and 94% (91–97%), respectively. Relapse-free survival at 12, 24, and 60 months was 62% (55–67%), 29% (23–36%), and 13% (8–19%), respectively. OS at 12, 24, and 60 months was 72% (95%CI 67–77%), 44% (38–50%), and 11% (7–15%), respectively. Approximately 51% and 38% experienced acute and late toxicity, respectively. Child-Pugh score B-C, high BCLC score, portal thrombosis, high GTV volume, and higher PTV volume reported on total hepatic volume ratio were significantly associated with OS. SBRT is efficient for the management of HCC with a favorable toxicity profile. The outcome is highly related to the natural evolution of the underlying cirrhosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Transarterial chemoembolization is the treatment of choice for intermediate hepatocellular carcinoma, which constitutes the second cause of cancer-related death worldwide. Even though the world population is aging, we lack evidence regarding the safety and efficacy of anticancer treatments in these patients. This study including 271 patients shows how elderly patients treated by transarterial chemoembolization have comparable safety profiles, tumor responses, and survival outcomes to younger patients. Transarterial chemoembolization should always be considered in elderly patients with good performance status and a compensated liver function presenting intermediate hepatocellular carcinoma. (1) Introduction: Transarterial chemoembolization (TACE) is the most widely used treatment for intermediate hepatocellular carcinoma (HCC), with limited data available in elderly patients. This study compares the safety and efficacy of TACE for HCC in elderly patients (≥70 years) versus younger patients (<70 years). (2) Materials and Methods: Patients treated by a first TACE for HCC at Grenoble-Alpes University Hospital from January 2012 to March 2017 were included. The primary objective was to compare the safety and predictive factors of serious adverse events between groups using univariate and multivariate analyses. Secondary objectives included tumor response and survival analyses. (3) Results: 271 patients were included: 88 elderly and 183 under 70 years. A total of 20.5% of elderly patients experienced serious adverse events versus 21.3% of patients under 70 (p = 0.87). The predictive factors of serious adverse events were Child–Pugh ≥ B7 (p < 0.0001), ECOG ≥ 1 (p = 0.0019), and MELD ≥ 9 (p = 0.0415). The serious adverse event rate was not increased with age (p = 0.87). The objective tumor response rate was 89.5% in elderly versus 78.7% in younger patients (p = 0.03). (4) Conclusion: This study showed similar safety profiles of the first TACE between elderly and younger patients, with comparable efficacy outcomes, suggesting that advanced age should not constitute a limitation in itself in treatment decision-making. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Microvascular invasion (MVI) is one of the main prognostic factors of hepatocellular carcinoma (HCC) after liver transplantation (LT), but its occurrence is unpredictable before surgery. The alpha fetoprotein (AFP) model (composite score including size, number, AFP), currently used in France, defines the selection criteria for LT. This study's aim was to evaluate the preoperative predictive value of AFP SCORE progression on MVI and overall survival during the waiting period for LT. Data regarding LT recipients for HCC from 2007 to 2015 were retrospectively collected from a single institutional database. Among 159 collected cases, 34 patients progressed according to AFP SCORE from diagnosis until LT. MVI was shown to be an independent histopathological prognostic factor according to Cox regression and competing risk analysis in our cohort. AFP SCORE progression was the only preoperative predictive factor of MVI (OR = 10.79 [2.35-49.4]; p 0.002). The 5-year overall survival in the progression and no progression groups was 63.9% vs. 86.3%, respectively (p = 0.001). Cumulative incidence of HCC recurrence was significantly different between the progression and no progression groups (Sub-HR = 4.89 [CI 2-11.98]). In selected patients, the progression of AFP SCORE during the waiting period can be a useful preoperative tool to predict MVI. [ABSTRACT FROM AUTHOR]

Primary Objective: Recently, selective internal radiation therapy using yttrium-90 (Y90) glass microspheres (TheraSphere™) was approved for reimbursement by health authorities in France. The PROACTIF study aims to gather data on effectiveness, patient quality of life, and safety with use of Y90 glass microspheres in real-world clinical settings in France. Inclusion Criteria: Patient with a diagnosis of hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCC), and/or metastatic colorectal cancer (mCRC) who was treated with a dose of Y90 glass microspheres that has been reimbursed in France and who do not oppose use of their personal medical data. Exclusion Criteria: If data collection is opposed, treatment is reimbursed but not administered, or treatment is administered but not reimbursed. Outcome Measures: Primary outcome measures include overall survival from time of Y90 glass microsphere treatment and quality of life, as assessed using the Functional Assessment of Cancer Therapy- Hepatobiliary questionnaire. Estimated Number of Patients to Be Included: This is an open study and there is no set number of patients; 115 have already been enrolled. Planned Subgroup Analyses: Analyses will be stratified by disease state (HCC, iCC, or mCRC). Subgroups to be analyzed include age group, unilobar/bilobar disease at baseline, Eastern Cooperative Oncology Group (ECOG) status at baseline, liver tumor burden at baseline, target lesion size, and standard versus multi-compartment personalized dosimetry treatment. Planned Recruitment and Observation Period: Recruitment includes patients who are prescribed and treated with a commercial vial of Y90 glass microspheres between 01 January 2019 and 31 December 2024. Trial registration: ClinicalTrials.gov Identifier: NCT04069468. [ABSTRACT FROM AUTHOR]

Summary: In France, the listing for liver transplantation (LT) for hepatocellular carcinoma (HCC) requires an AFP score ≤2. This study evaluates whether the number of nodules assessed immediately before LT has a prognostic value among patients already listed within AFP score. Among 143 recipients transplanted with an AFP score ≤2 between 2013 and 2017 in our center, the number of nodules was considered at listing on the waiting list and at last imaging before LT. We compared the overall survival (OS) and disease‐free survival (DFS) post‐LT of patients with ≤3 and >3 nodules (current classification), and aimed to propose a new criteria to exclude patients on list at high risk of recurrence. The 3‐year OS of patients with ≤3 HCC vs. >3 HCC at listing was of 90.3% vs. 67.3%, respectively (P = 0.04). At last imaging, eight listed patients presented ≥5 HCC nodules and had a significantly lower OS than <5 nodules patients (5‐year OS: 24.4% vs. 78.1%; P = 0.01). Although the current AFP score offers satisfactory outcomes, we highlight the poorer outcomes when ≥5 nodules persist or appear after listing. A modification of the AFP score is mandatory to consider exclusion of high‐risk patients already listed for LT program. [ABSTRACT FROM AUTHOR]

Summary: Prognostic models of liver transplantation (LT) for hepatocellular carcinoma (HCC) mainly derive from LT cohorts with numerous hepatitis C virus (HCV) patients. The AFP model, which is currently used in France to select LT candidates, was derived from a cohort of LT performed between 1988 and 2001, including a majority of HCV‐positive recipients. The emergence of new direct‐acting antiviral therapies and subsequent decrease of HCV incidence may change the generalizability of such models. We performed an external validation of the AFP model in a cohort of recipients transplanted between 2005 and 2018. Although multivariable analysis identified all three model's factors (AFP level, largest tumor size, number of nodules) as predictors of tumor recurrence, the AFP model showed poor discrimination and calibration in the present cohort. This poor performance could be related to significant differences between the derivation and the present cohort in terms of etiology, severity of underlying liver disease, tumor burden and differentiation, and use of neoadjuvant treatments. The present findings suggest that the decline of HCV‐induced HCC among LT candidates may compromise the generalizability of the AFP model in more recent LT cohorts. Further studies are required for updating or building more robust prognostic models. [ABSTRACT FROM AUTHOR]

Viral hepatitis B is a global public health problem affecting nearly two billion subjects; 3.3% of whom are from the WHO (World Health Organization) Eastern Mediterranean Region (EMRO). It induces both acute and chronic hepatic disorders with subsequent liver cirrhosis and hepatocellular carcinoma (HCC) in a considerable percentage of patients based on the age of exposure. In this review, hepatitis B virus (HBV) and HCC prevalence, distribution and prevalence of different genotypes, and male/female infection frequencies in relation to the vaccination status in the Mediterranean countries were reported. Study Design. This systematic review describes the prevalence of hepatitis B infection, genotype distribution of hepatitis B virus, and prevalence and incidence of hepatocellular carcinoma in Mediterranean countries belonging to three different continents: Southern Europe (Spain, France, Italy, Croatia, and Greece), North Africa (Morocco, Algeria, Tunisia, Libya, and Egypt), and the Near East region (Syria, Lebanon, Turkey, Israel, and Palestine). We tried to collect new data from electronic databases: PubMed, ScienceDirect, ResearchGate, Google Scholar, and public health reports between 1980 and 2019. For each publication, we recorded reference, publication year, study characteristics (date, locations, sample size, and study population), and participant characteristics (population group, year, age, and sex). No language limitation was imposed, and articles or reports from non-peer-reviewed sources were not considered for this analysis. The main keywords were HBV prevalence, hepatitis B infection, HBV genotype, and HCC. Inclusion and Exclusion Criteria. Healthy population-based studies included the following sample populations: (i) voluntary blood donors, (ii) pregnant women, (iii) community studies, (iv) hemodialysis patients, (v) hospitalized patients, (vi) healthcare workers, (vii) sex workers, (viii) drug abusers, and (ix) prisoners. We excluded studies from the following special groups who were assumed to be at a special high risk: patients from sexually transmitted disease clinics and thalassemia clinics and professional or paid blood donors. [ABSTRACT FROM AUTHOR]

Background: Data on alcohol-related HCC are limited.Aims: Our aim was to describe the incidence, management, and prognosis of alcohol compared to Hepatitis C (HCV)-related HCC at a national level.Methods: Incident cases of HCC were identified in French healthcare databases between 2009 and 2012 and analyzed retrospectively. Demographic data, type, location, and annual HCC-caseload of the hospitals where patients were first managed were retrieved. Survival of incident cases was computed from the time of diagnosis and adjusted for potential confounding variables.Results: The study population included 14,060 incident cases of alcohol and 2581 HCV-related HCC. Alcohol-related HCC was more frequent than HCV-related HCC (29.37 and 5.39/100,000 adults/year, respectively) with an heterogeneous distribution on the French territory. The optimal treatment was less frequently curative (20.5% vs 35.9%; p < 0.001), and survival was significantly shorter (9.5 [9.0-10.0] versus 16.8 [15.5-18.7] months p < 0.001) in alcohol compared to HCV-related HCC, with marked variations between regions for a given risk factor. In multivariable analysis in the whole study population, curative treatment was a strong predictor of survival (adjusted HR 0.28 [0.27-0.30] months p < 0.001). Being managed at least once in a teaching hospital during follow-up was independently associated with receiving a curative treatment and survival.Conclusion: In France, incidence of alcohol-related HCC is high and prognosis is poor compared to HCV-related HCC, with marked variations between regions. These results should guide future health policy initiatives pertaining to HCC care. Importantly, increasing patient' referral in expert centers could increase chances to receive curative treatment and improve outcomes. [ABSTRACT FROM AUTHOR]

Background: Although direct-acting antivirals have been used extensively to treat patients with chronic hepatitis C virus (HCV) infection, their clinical effectiveness has not been well reported. We compared the incidence of death, hepatocellular carcinoma, and decompensated cirrhosis between patients treated with direct-acting antivirals and those untreated, in the French ANRS CO22 Hepather cohort.Methods: We did a prospective study in adult patients with chronic HCV infection enrolled from 32 expert hepatology centres in France. We excluded patients with chronic hepatitis B, those with a history of decompensated cirrhosis, hepatocellular carcinoma, or liver transplantation, and patients who were treated with interferon-ribavirin with or without first-generation protease inhibitors. Co-primary study outcomes were incidence of all-cause mortality, hepatocellular carcinoma, and decompensated cirrhosis. The association between direct-acting antivirals and these outcomes was quantified using time-dependent Cox proportional hazards models. This study is registered with ClinicalTrials.gov, number NCT01953458.Findings: Between Aug 6, 2012, and Dec 31, 2015, 10 166 patients were eligible for the study. 9895 (97%) patients had available follow-up information and were included in analyses. Median follow-up was 33·4 months (IQR 24·0-40·7). Treatment with direct-acting antivirals was initiated during follow-up in 7344 patients, and 2551 patients remained untreated at the final follow-up visit. During follow-up, 218 patients died (129 treated, 89 untreated), 258 reported hepatocellular carcinoma (187 treated, 71 untreated), and 106 had decompensated cirrhosis (74 treated, 32 untreated). Exposure to direct-acting antivirals was associated with increased risk for hepatocellular carcinoma (unadjusted hazard ratio [HR] 2·77, 95% CI 2·07-3·71) and decompensated cirrhosis (3·83, 2·29-6·42). After adjustment for variables (age, sex, body-mass index, geographical origin, infection route, fibrosis score, HCV treatment-naive, HCV genotype, alcohol consumption, diabetes, arterial hypertension, biological variables, and model for end-stage liver disease score in patients with cirrhosis), exposure to direct-acting antivirals was associated with a decrease in all-cause mortality (adjusted HR 0·48, 95% CI 0·33-0·70) and hepatocellular carcinoma (0·66, 0·46-0·93), and was not associated with decompensated cirrhosis (1·14, 0·57-2·27).Interpretation: Treatment with direct-acting antivirals is associated with reduced risk for mortality and hepatocellular carcinoma and should be considered in all patients with chronic HCV infection.Funding: INSERM-ANRS (France Recherche Nord & Sud Sida-HIV Hépatites), ANR (Agence Nationale de la Recherche), DGS (Direction Générale de la Santé), MSD, Janssen, Gilead, AbbVie, Bristol-Myers Squibb, and Roche. [ABSTRACT FROM AUTHOR]

Background: Hepatocholangiocarcinoma (cHCC-ICC) is a rare liver tumour for which no data on chemosensitivity exist. The aims of this multicentre study were to evaluate overall survival (OS), progression-free survival (PFS), and prognostic factors in cHCC-ICC treated by gemcitabine plus platinum as first-line.Methods: Unresectable cHCC-ICC treated by gemcitabine plus platinum-based chemotherapy between 2008 and 2017 were retrospectively analysed. Diagnosis was based on histology or, in case of ICC or HCC histology, on discordant computerised tomography scan enhancement patterns associated with discordant serum tumour marker elevation suggesting the alternative tumour. OS and PFS were evaluated by Kaplan-Meier method and prognostic factors by Log-rank test and Cox model.Results: Among 30 patients included, cHCC-ICC was histologically proven in 22 (73.3%). 18 (60%) received gemcitabine plus oxaliplatin (GEMOX), 9 (30%) GEMOX plus bevacizumab, and 3 (10%) gemcitabine plus cisplatin. RECIST criteria were reported in 28 patients: 8 (28.6%) showed partial response, 14 (50%) stable disease, and 6 (21.4%) tumour progression at first evaluation. Median PFS and OS were 9.0 and 16.2 months, respectively. Serum bilirubin ⩾30 μmol l-1 (P=0.001) and positive serology for HBV and/or HCV (P=0.014) were independent poor prognostic factors for OS.Conclusions: Gemcitabine plus platinum-based chemotherapy is effective as first-line for advanced cHCC-ICC. [ABSTRACT FROM AUTHOR]

Background No prognostic classification is currently used for patients treated with systemic therapies for Hepatocellular Carcinoma (HCC). Methods We retrospectively analysed data from patients treated with sorafenib for HCC from five centres in France and in the United Kingdom (UK). The training set comprised data from two centres and the validation set from three. Variables independently associated with Overall Survival (OS) in the training set were used to build the SAP (Sorafenib Advanced HCC Prognosis) score. The score was tested in the validation set, then compared with other prognostication systems. Results The training set and validation set included 370 and 468 patients respectively. In the training set, variables independently associated with OS in multivariable analysis were: performance status (PS) >0, alpha-fetoprotein (AFP) >400 ng/ml, tumour size >7 cm, bilirubin >17 μmol/l and albumin <36 g/l. The SAP score was built giving one point to each abnormal variable, and three classes were constructed. The SAP score was significantly associated with OS in the training set, with median OS of 14.9 months for SAP A, 7.2 months for SAP B and 2.5 months for SAP C ( P < 0.001). In the validation set, the SAP score was significantly associated with OS, and showed greater discriminative abilities than Barcelona Clinic Liver Cancer (BCLC) and albumin-bilirubin (ALBI) scores. However, the hepatoma arterial embolisation prognostic (HAP) score showed greater discriminative abilities than the SAP score. Conclusion In European patients treated with sorafenib, the HAP was the most discriminant prognostic score and may facilitate stratification in trials and inform clinical decision making. [ABSTRACT FROM AUTHOR]

Introduction: The benefit of by laparoscopic resection for lesions located in postero-superior segments is unclear. The present series aimed at comparing intraoperative and post-operative results in patients undergoing either laparoscopic RPS or laparoscopic RH for colorectal liver metastases located in the right postero-superior segments.Methods: From 2000 to 2015, patients who underwent laparoscopic resection of segment 6 and/or 7 (RPS group) were compared with those with right hepatectomy (RH group) in terms of tumour characteristics, surgical treatment, and short-term outcomes.Results: Among the 177 selected patients, 78 (44.1 %) had laparoscopic RPS and 99 (55.9 %) a laparoscopic RH. Among RPS patients, 26 (33.3 %) underwent anatomical resection of either segment 7, 8 or both. Three (3 %) patients undergoing RH died in the post-operative course and none in the RPS group. Sixty-three (35.5 %) patients experienced post-operative complications, including major complications in 24 (13.5 %) patients. Liver failure (17.1 vs. 0 %, p = 000.1), biliary leakage (6.0 vs. 1.2 %, p = 00.1), intra-abdominal collection (19.1 vs. 2.5 %, p = 000.1), and pulmonary complication (16.1 vs. 1.2 %, p = 000.1) were significantly increased in the RH group.Conclusion: The present series suggests that patients who underwent laparoscopic resection of CRLM located in the postero-superior segments developed significantly less complications than patients undergoing formal RH. [ABSTRACT FROM AUTHOR]

Background & Aims How risk factors associated with chronic hepatitis B (CHB) modify liver disease progression and mortality has been scarcely reported outside of Asia. We aimed to evaluate these risk factors in a French population between 2008 and 2013. Methods All individuals discharged with CHB from acute and post-acute care hospitals in Metropolitan France between January 2008 and December 2013 were selected. Associations between liver- and non-liver-related risk factors and both liver disease progression (end-stage liver disease or hepatocellular carcinoma) and mortality were assessed by multivariate Cox proportional hazard models. Results Overall, liver disease progression, liver transplantation and death were recorded in 7479 (15.5%), 433 (8.2%) and 5299 (11.0%) patients, respectively. An additional liver-related risk factor was recorded in 5426 (72.6%) patients with liver disease progression and 2699 (75.5%) patients with liver transplantation or liver death. Adjusted hazard ratios (95% confidence interval) for liver disease progression of hepatitis D virus co-infection, hepatitis C virus co-infection, alcohol use disorders, diabetes mellitus, and other rare causes of chronic liver disease were 1.44 (1.35–1.53), 1.77 (1.68–1.87), 3.37 (3.20–3.55), 1.40 (1.32–1.48), and 2.19 (1.98–2.42), respectively. All liver-related risk factors increased the risk of all-cause mortality, especially after liver disease progression. Adjusted hazard ratios for liver disease progression and in-hospital mortality of HIV co-infection without acquired immune deficiency syndrome (AIDS) were 0.60 (0.52–0.70) and 0.63 (0.51–0.78), respectively. Conclusions In France, 2008–2013, liver disease progression among patients with CHB was closely related to other risk factors. HIV co-infected patients without AIDS had better outcomes, suggesting better care in this group of patients. Lay summary In France, 2008–2013, about three-quarters of patients with chronic hepatitis B who progressed to a liver-related complication, including liver transplantation and liver-related death, had an additional liver-related risk factor. Despite a higher prevalence of liver-related risk factors, HIV co-infected patients without AIDS had better outcomes. Prognosis of patients with chronic hepatitis B is closely related to other risk factors. Treatment of patients with chronic hepatitis B, including control of chronic hepatitis B-associated risk factors, is more efficient in HIV co-infected patients. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to describe the proportion of liver-related diseases ( LRDs) as a cause of death in HIV-infected patients in France and to compare the results with data from our five previous surveys. Methods In 2010, 24 clinical wards prospectively recorded all deaths occurring in around 26 000 HIV-infected patients who were regularly followed up. Results were compared with those of previous cross-sectional surveys conducted since 1995 using the same design. Results Among 230 reported deaths, 46 (20%) were related to AIDS and 30 (13%) to chronic liver diseases. Eighty per cent of patients who died from LRDs had chronic hepatitis C, 16.7% of them being coinfected with hepatitis B virus ( HBV). Among patients who died from an LRD, excessive alcohol consumption was reported in 41%. At death, 80% of patients had undetectable HIV viral load and the median CD4 cell count was 349 cells/μL. The proportion of deaths and the mortality rate attributable to LRDs significantly increased between 1995 and 2005 from 1.5% to 16.7% and from 1.2‰ to 2.0‰, respectively, whereas they tended to decrease in 2010 to 13% and 1.1‰, respectively. Among liver-related causes of death, the proportion represented by hepatocellular carcinoma ( HCC) dramatically increased from 5% in 1995 to 40% in 2010 (p = 0.019). Conclusions The proportion of LRDs among causes of death in HIV-infected patients seems recently to have reached a plateau after a rapid increase during the decade 1995−2005. LRDs remain a leading cause of death in this population, mainly as a result of hepatitis C virus ( HCV) coinfection, HCC representing almost half of liver-related causes of death. [ABSTRACT FROM AUTHOR]

Background. Health-related quality of life (QoL) has been validated as a prognostic factor for cancer patients; however, to be used in routine practice, QoL scores must be dichotomized. Cutoff points are usually based on arbitrary percentile values. We aimed to identify optimal cutoff points for six QoL scales and to quantify their added utility in the performance of four prognostic classifications in patients with hepatocellular carcinoma (HCC). Methods.We reanalyzed data of 271 patients with advanced HCC recruited between July 2002 and October 2003 from 79 institutions in France in the CHOC trial, designed to assess the efficacy of long-acting octreotide. QoL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30). The scores ranged from 0 to 100. Identification of optimal cutoff points was based on the method of Faraggi and Simon [Stat Med 1996;15:2203-2213]. Improvement in the performance of prognostic classifications was studied with Harrell's C-index, the net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results.Wefound that optimal cutoff points were50 for global health, 58.33 for physical functioning, 66.67 for role functioning, 66.67 for fatigue, 0 for dyspnea, and 33.33 for diarrhea.The addition of QoL and clinical factors improved the performance of all four prognostic classifications, with improvement in the range of 0.02-0.09 for the C-index, 0.24-0.78 for 3-month NRI, and 0.02-0.10 for IDI. Conclusion. These cutoff values for QoL scales can be useful to identify HCC patients with very poor prognosis and thus improve design of clinical trials and treatment adjustment for these patients. [ABSTRACT FROM AUTHOR]

Background Sorafenib is the only systemic treatment that has shown a significant benefit in overall survival (OS) and in progression-free survival (PFS) in advanced hepatocellular carcinoma (HCC) patients. No standard of care currently exists for second-line treatment. The association of Gemcitabine-Oxaliplatine (GEMOX) has shown efficacy in the first-line setting. The aim of this study was to evaluate the efficacy of GEMOX after failure of at least one line of anti-angiogenic (AA) therapy. Patient and methods We performed a multicenter retrospective analysis of advanced HCC patients that received GEMOX chemotherapy after progression on at least one line of AA therapy. Results We analyzed a total of 40 patients that received a median of 7 cycles of GEMOX over a 6-year period. Grade 3/4 toxicity was observed in 25 % of patients, mainly neurotoxicity, thrombocytopenia and neutropenia in 12.5 %, 5 % and 5 % of patients respectively. Grade <3 toxicity was mainly hematological and neurotoxicity. In the sub-cohort of 35 patients evaluable for response, partial response was observed in 20 % of patients, while 46 % had stable disease. Median OS was 8.3 months, with a 6-month OS rate of 59 %. Median PFS was 3.1 months. Prognostic factors for OS in univariable analysis were the performance status and AFP levels at GEMOX start, and the BCLC score at diagnosis. None of these factors were prognostic for PFS or tumor response. Conclusion The GEMOX schedule seems to show clinical activity and an acceptable toxicity profile in advanced HCC patients who progressed after anti-angiogenic treatment. The observed median OS of over 8 months is encouraging in this population of heavily pretreated patients. These results would merit confirmation in a prospective randomized study. [ABSTRACT FROM AUTHOR]

Objective. While marked changes in the frequency of hepatobiliary malignancies, most notably hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), have been observed in different populations, no such data have been reported for Germany. We aimed to provide epidemiological data on recent trends in liver-related mortality, specifically mortality from hepatobiliary malignancies, in Germany. Material and methods. We used incidence and mortality data to determine changes in the frequency of malignant and non-malignant liver disease in Germany over the past 30 years. Results. While overall liver disease mortality has slightly declined in Germany, deaths from hepatobiliary malignancies have declined in women, but remained constant in men. Among hepatobiliary malignancies, ICC stands out, because mortality has more than tripled both in men and women between 1998 and 2008. This is mirrored by a marked increase in new cases reported to local cancer registries, that is, incidence. Over the same time period, HCC and extrahepatic cholangiocarcinoma (ECC) have remained largely constant while gall bladder cancers (GBC) have declined twofold. The rapid rise in ICC is in line with finding from different regions worldwide, but in contrast to recent data from Denmark and France, two of Germany's direct neighbors. Conclusions. The incidence of and mortality from ICC are rising markedly in Germany. The risk factors underlying this trend are as yet unclear. [ABSTRACT FROM AUTHOR]

The article presents abstracts of papers presented at the 39th European Society of Clinical Pharmacy (ESCP) European Symposium on Clinical Pharmacy and the 3th Société Française de Pharmacie Clinique (SFPC) Congress: Clinical Pharmacy at the Front Line of Innovations in Lyon, France, including "Hallucinations Due to Therapeutic Doses of Ertapenem," "Carboplatin Dosage in Overweight Patient: Case Report" and "Severe Hypokalemia Associated With Flucloxacillin."

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Abstract: Eight liver centres in France have joined their effort to collect, preserve and distribute tissue samples from hepatocellular carcinomas, according to the recommendations for Biological Resources Centres (BRC) released by the Organisation for Economic Cooperation and Development (OECD), which were recently implemented in France. This led to the creation of a Liver cancer biobanks network which is recognized by the Ministry of research and the Ministry of health and sponsored by the main research agencies, namely Inserm and INCa. Samples are collected and stored locally, whereas related annotations are remotely collected within a central database. The management of the network includes a Scientific Committee, an Executive Board and an Epidemiology and Management Coordinating Centre. Samples are made available to research groups following acceptance of research projects submitted to the scientific committee. Samples from the Liver cancer biobanks network were used in recent works aiming at identifying key genomic alterations occurring in the development of hepatocellular carcinomas, as well as new set of biomarkers, including transcriptomic and proteomic signatures, and candidate targets for anti-cancer drugs. [Copyright &y& Elsevier]

Background/Aims: Longer exposure to hepatitis C (HCV) or B virus (HBV) and the increased use of hepatitis treatment might have an impact on liver-related deaths in patients co-infected with the Human Immunodeficiency Virus (HIV). We describe the proportion of liver-related deaths among HIV-infected patients in 2005 compared with 2000. Methods: In a nationwide survey (341 hospital departments involved in HIV management), all deaths of HIV-infected patients were prospectively reported. Deaths from either cirrhosis, hepatocellular carcinoma or fulminant hepatitis were defined as liver-related deaths. Results: Of the 898 deaths reported in 2005, liver-related causes accounted for 15.4%; this is compared to 13.4% in 2000. Among liver-related deaths, hepatocellular carcinoma increased from 15% to 25% (p =0.04). Among hepatocellular carcinoma-related deaths: in 2000, 10% were HCV-infected; in 2005, 25% were HCV-infected (p =0.03). Half of the HCV-related deaths had been treated for HCV but 98% remained HCV-RNA positive at time of death. The proportion of HBV-related deaths remained stable between 2000 and 2005. Conclusions: Liver-related deaths, mainly liver cancers, have increased in HIV-infected patients in France despite wide access to HCV treatment. The stability of HBV-related deaths might be explained by the use of dually active antiretroviral drugs in co-infected patients. [Copyright &y& Elsevier]

Background/Aims: In France, two recent studies enabled modeling of the impact of viral eradication on HCV mortality. Methods: The French HCV population was simulated from infection to death using a computer-based model. We took into account the impact of alcohol, present screening and antiviral therapy to predict 2006–2025 HCV mortality and to assess the impact of viral eradication. Results: In 2006, the model estimated that among HCV-RNA+, 55% were F0–F1, 18% F2, 22% F3–F4 and 6% had liver complications. The mortality ratio was 11-fold higher in alcoholic patients 40–65 years old. Current therapy will save 14,400 (95% CI, 13,900–15,000) lives compared to absence of therapy. Sensitivity analyses did not change the main results. Contrary to guidelines, if patients F <2 were treated in the same proportions as those with F ⩾2, 700 (95% CI, 700–750) lives would be saved. If screening were to reach 75% in 2010, 4 years earlier than model expectation, 950 (95% CI, 900–1000) lives would be saved. If a new molecule improving eradication for genotype 1/4 by 40% were to become available in 2010, 1500 (95% CI, 1400–1600) lives would be saved. Conclusions: Current therapy is reducing HCV mortality. Therapeutic guidelines must take into account their impact on HCV mortality. [Copyright &y& Elsevier]

Tumor thrombus in major vasculature is a frequent finding with a poor long-term prognosis in patients with hepatocellular carcinoma (HCC). The utility of surgical resection is still controversial. This study compared morbidity and survival after resection for HCC with and without tumor thrombus. Data of 108 patients who underwent major hepatic resection for HCC were prospectively recorded. Patients were divided into two groups. The venous thrombectomy (VT) group included 26 patients who had HCC with tumor thrombus in the portal or hepatic veins. The matched control group included 82 patients who had HCC without tumor thrombus. Surgical technique, early outcome, and late survival were analyzed in each group. Multivariate analysis was performed to assess the prognostic value of this feature. Surgical technique was comparable in the VT and control group with regard to extent of hepatectomy, procedure duration, and transfusion requirements. Early postoperative outcome was also comparable. Actuarial survival at 1, 3, and 5 years was 38%, 20%, and 13%, respectively, in the VT group (median: 9 months) versus 74%, 56%, and 33%, respectively, in the control group (median: 41 months). In the subgroup of patients with tumor thrombus limited to the portal vein, actuarial survival at 1, 3, and 5 years was 50%, 26%, and 17%, respectively, (median: 12 months) and two patients lived longer than 5 years. Multivariate analysis showed that incomplete resection, alphafetoprotein level greater than 100 N, more than two tumor nodules, and tumor thrombus in major vasculature were independent factors of poor prognosis. Survival after resection for HCC with tumor thrombus in the major vasculature is poorer than after resection for HCC without tumor thrombus. However, an aggressive surgical strategy can provide significant survival with comparable morbidity in selected cases, that is, tumor thrombus located in the portal vein only and expected complete resection of the lesions. [Copyright &y& Elsevier]

Background/Aims: In France, the prevalence of hepatitis C virus (HCV) exceeds that of HIV, but in the absence of treatment, HIV infection progresses more rapidly than HCV. More HIV-infected patients, however, have received treatment. Using reported public health data in France and natural history models, we applied the back-calculation method to project future mortality from HCV and HIV incorporating current therapies.Methods: The HCV model was based on literature data for the natural history of HCV and reports of hepatocellular carcinoma mortality. The HIV model used estimates from the French Hospital Database on HIV and reported AIDS cases and deaths.Results: Peak annual mortality from HIV at 5000 occurred in 1994 and was 1000 in 1998, but HCV mortality likely increased through the 1990s and reached 3000 in 1998. Considering only HCV infections occurring until 1998 and currently available therapy, our model suggested that annual HCV-related mortality would continue to rise and would reach 4500 deaths in 2022. In contrast, AIDS-related deaths began to decrease in 1997.Conclusions: The public health burden of HCV is likely on the rise, while the burden of HIV, given the fairly widespread use of effective medications, may be on the decline. These results may help health policymakers in planning their responses to these epidemics. [Copyright &y& Elsevier]

Background & Aims: Microvascular invasion (MVI), a major risk factor for tumor recurrence after surgery in hepatocellular carcinoma (HCC), is only detectable by microscopic examination of the surgical specimen. We aimed to define a transcriptomic signature associated with MVI in HCC than can be applied to formalin-fixed paraffin-embedded (FFPE) biopsies for use in clinical practice., Methods: To identify a gene expression signature related to MVI by using NanoString technology, we selected a set of 200 genes according to the literature and RNA-sequencing data obtained from a cohort of 150 frozen HCC samples previously published. We used 178 FFPE-archived HCC samples, including 109 surgical samples for the training set and 69 paired pre-operative biopsies for the validation set. In 14 cases of the training set, a paired biopsy was available and was also analyzed., Results: We identified a 6-gene signature (ROS1, UGT2B7, FAS, ANGPTL7, GMNN, MKI67) strongly associated with MVI in the training set of FFPE surgical HCC samples, with 82% accuracy (sensitivity 82%, specificity 81%, AUC 0.82). The NanoString gene expression was highly correlated in 14 paired surgical/biopsy HCC samples (mean R: 0.97). In the validation set of 69 FFPE HCC biopsies, the 6-gene NanoString signature predicted MVI with 74% accuracy (sensitivity 73%, specificity 76%, AUC 0.74). Moreover, on multivariate analysis, the MVI signature was associated with overall survival in both sets (hazard ratio 2.29; 95% CI 1.03-5.07; p = 0.041)., Conclusion: We defined a 6-gene signature that can accurately predict MVI in FFPE HCC biopsy samples, which is also associated with overall survival, although its survival impact must be confirmed by extensive study with further clinical data., Lay Summary: Microvascular invasion, a major risk factor for tumor recurrence after surgery in hepatocellular carcinoma, is only detectable by microscopic examination of a surgical specimen. In this study, we defined a relevant surrogate signature of microvascular invasion in hepatocellular carcinoma that may be applied in clinical practice with routine tumor biopsy and integrated into the therapeutic strategy., Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021. Published by Elsevier B.V.)

We present the update of the recommendations of the French society of oncological radiotherapy on hepatic tumours. Recent technological progress led to develop the concept of focused liver radiation therapy. We must distinguish primary and secondary tumours, as the indications are restricted and must be discussed as an alternative to surgical or medical treatments. The tumour volume, its liver location close to the organs at risk determine the irradiation technique (repositioning method, total dose delivered, dose fractionation regimens). Tumour (and liver) breathing related motions should be taken into account. Strict dosimetric criteria must be observed with particular attention to the dose-volume histograms of non-tumoral liver as well as of the hollow organs, particularly in case of hypofractionated high dose radiotherapy "under stereotaxic conditions". Stereotactic body radiotherapy is being evaluated and is often preferred to radiofrequency for primary or secondary tumours (usually less than 5cm). An adaptation can be proposed, with a conformal fractionated irradiation protocol with or without intensity modulation, for hepatocellular carcinomas larger than 5cm., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Simple Summary: The α-fetoprotein (AFP) model officially replaced the Milan criteria in France for liver transplantation (LT) for hepatocellular carcinoma (HCC) in January 2013. The aim of our retrospective study was to analyze the agreement of the criteria and the results of LT with an intention-to-treat design since the adoption of the AFP model and to compare them to the practice and results of LT before the adoption of the AFP model. We did not observe significant changes in practices in 523 consecutively listed patients, with a good agreement (88%) to AFP criteria on the explants before and after the adoption of the AFP model. However, the prognosis of patients listed in the most recent period was worse, maybe because of a significant increase in bridging treatments and in the waiting time. This observational study provides an insight into the real-life course of LT for HCC. Purpose: To compare the agreement for the criteria on the explant and the results of liver transplantation (LT) before and after adoption of the AFP (α-fetoprotein) model. Methods: 523 patients consecutively listed in five French centers were reviewed to compare results of the Milan criteria period (MilanCP, n = 199) (before 2013) and the AFP score period (AFPscP, n = 324) (after 2013). (NCT03156582). Results: During AFPscP, there was a significantly longer waiting time on the list (12.3 vs. 7.7 months, p < 0.001) and higher rate of bridging therapies (84 vs. 75%, p = 0.012) compared to the MilanCP. Dropout rate was slightly higher in the AFPscP (31 vs. 24%, p = 0.073). No difference was found in the histological AFP score between groups (p = 0.838) with a global agreement in 88% of patients. Post-LT recurrence was 9.2% in MilanCP vs. 13.2% in AFPscP (p = 0.239) and predictive factors were AFP > 2 on the last imaging, downstaging policy and salvage transplantation. Post-LT survival was similar (83 vs. 87% after 2 years, p = 0.100), but after propensity score analysis, the post-listing overall survival (OS) was worse in the AFPscP (HR 1.45, p = 0.045). Conclusions: Agreement for the AFP model on explant analysis (≤2) did not significantly change. AFP score > 2 was the major prognostic factor for recurrence. Graft allocation policy has a major impact on prognosis, with a post-listing OS significantly decreased, probably due to the increase in waiting time, increase in bridging therapies, downstaging policy and salvage transplantation. [ABSTRACT FROM AUTHOR]

Background & Aims: Liver adenomatosis (LA) is characterized by the presence of at least 10 hepatocellular adenomas (HCAs), but the natural history of this rare liver disorder remains unclear. Thus, we aimed to reappraise the natural history and the risk of complications in a cohort of patients with at least 10 HCAs., Methods: We analyzed the natural history of 40 patients with LA, excluding glycogen storage disorders, in a monocentric cohort. Pathological examination was performed, with immunostaining and molecular biology carried out on surgical specimens or liver biopsies., Results: Forty patients (36 female) were included with a median follow-up of 10.6 (1.9-26.1) years. Six (15%) patients had familial LA, all with germline HNF1A mutations. Median age at diagnosis was 39 (9-55) years. Thirty-three (94%) women had a history of oral contraception, and 29 (81%) women had a pregnancy before LA diagnosis. Overall, thirty-seven (93%) patients underwent surgery at diagnosis. Classification of HCAs showed 46% of patients with HNF1A-mutated HCA, 31% with inflammatory HCA, 3% with sonic hedgehog HCA, 8% with unclassified HCA. Only 15% of the patients demonstrated a "mixed LA" with different HCA subtypes. Hepatic complications were identified in 7 patients: 1 patient (3%) died from recurrent hepatocellular carcinoma after liver transplantation; 6 (15%) had hemorrhages, of which 5 occurred at diagnosis, with 1 fatal case during pregnancy, and 2 occurred in male patients with familial LA. Four patients (10%) had repeated liver resections. Finally, 4 (10%) patients developed extrahepatic malignancies during follow-up., Conclusions: The diversity in HCA subtypes, as well as the occurrence of bleeding and malignant transformation during long-term follow-up, underline the heterogeneous nature of LA, justifying close and specific management. In patients with germline HNF1A mutation, familial LA occurred equally frequently in males and females, with a higher rate of bleeding in male patients., Lay Summary: Liver adenomatosis is a rare disease characterized by the presence of 10 or more hepatocellular adenomas that may rarely be of genetic origin. Patients with liver adenomatosis have multiple adenomas of different subtypes, with a risk of bleeding and malignant transformation that justify a specific management and follow-up., (Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

The French "cancer plan" has created a framework for good practice in the course of care for cancer patients. Decisions must be made in a multidisciplinary team meeting (MDM) and an individualized care plan (ICP) is to be established for each patient. Hepatocellular carcinoma (HCC) is a common cancer with complex treatments that warrant a dedicated meeting. Cancer coordination centers (3C) ensure the organization and the functioning of MDMs. Multidisciplinary, standardized and systematic assessment of HCC patients allows for personalized management and orients them toward treatment that is either curative (transplantation, surgical resection, ablathermy) or palliative (chemoembolization, radiotherapy, systemic treatment, supportive care). MDMs bring together all the professionals treating the disease, and who are tasked with producing an enforceable document effective that justifies decisions and is often an essential step towardinclusion of patients in a clinical trial. It must be carried out according to a systematic schema in an approach applied from initial diagnosis to treatment outset and throughout the treatment. Numerous advances in HCC treatments have rendered their management complex, with the possibility of liver transplantation, twhose access is regulated by the Biomedicine Agency requiring the submission of MDM reports. MDMs must meet specific quality criteria to ensure effective management based on general guidelines and yet specifically tailored to each patient., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Purpose: The purpose of this paper was to describe local control, overall survival, progression-free survival and toxicity of CyberKnife ® -based stereotactic body radiation therapy of hepatocellular carcinoma., Material and Methods: Records of all the patients treated for hepatocellular carcinoma at the Eugene-Marquis cancer centre, Rennes and the Bretonneau hospital, Tours (France), between November 2010 and December 2016, were reviewed. Radiation therapy was performed as a salvage treatment, while awaiting liver transplantation or if no other treatment was possible., Results: One hundred and thirty-six patients were consecutively included in the study. The median follow-up was 13months. Median total dose prescribed, fractionation and overall treatment time were respectively 45Gy, three fractions and 5 days. Overall survival, progression-free survival and local control rates at 1year and 2years were 79.8 % and 63.5 %, 61.3 % and 39.4 %; 94.5 % and 91 %. Two grade 3 acute toxicity events and two grade 4 late toxicity events corresponding to a duodenal ulcer have been reported. Seven patients underwent classic radiation-induced hepatitis and 13 patients showed non-classical radiation-induced hepatitis. Barcelona Clinic Liver Cancer stage, World Health Organisation grade and planning target volume were correlated with overall survival in univariate Cox analysis., Conclusion: Stereotactic body radiation therapy is effective and well-tolerated for inoperable hepatocellular carcinoma or as a bridge to liver transplantation. Toxicity is mainly related to cirrhotic background and requires a selection of patients and strict dose constraints., (Copyright © 2019 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Background & Aims: HIV/HCV co-infected patients with hepatocellular carcinoma (HCC) have poorer survival than HCV mono-infected patients. We aimed to evaluate the prognostic factors for survival., Methods: From 2006 to 2013, 55 incident HCCs among HIV+/HCV+ patients, from three ANRS cohorts, were compared with 181 HCCs in HIV-/HCV+ patients from the ANRS Cirvir cohort., Results: HIV+/HCV+ patients were younger (50 years [IQR: 47-53] vs 62 [54-70], P < 0.001), male (89% vs 63%, P < 0.001) than HIV-/HCV+ patients. At HCC diagnosis, both groups had a majority of non-responders to anti-HCV-therapy, and HIV+/HCV+ patients had more frequently known a previous cirrhosis decompensation (31% vs 14%, P = 0.005). At diagnostic imaging, there were more infiltrative forms of HCC in HIV+/HCV+ group (24% vs 14%, P < 0.001), associated with tumour portal thrombosis in 29%. During a median follow-up period of 11.96 [5.51-27] months since HCC diagnosis, a majority of palliative treatments were decided in HIV+/HCV+ patients (51% vs 19%, P < 0.001). The 1 and 2-year crude survival rates were 61% versus 78% and 47% versus 63%, P = 0.003 respectively. In a Cox model multivariate analysis adjusted for the cohort, age and sex, the most important prognostic factor for survival was the infiltrative form of the tumour (aRR: 8.10 [4.17-15.75], P < 0.001)., Conclusions: The radiological aggressiveness of the tumour is the best prognostic factor associated with poorer survival of HCC in HIV+/HCV+ patients. High α-foetoprotein level and decompensated cirrhosis are other ones. This justifies a particular attention to the detection and the management of small nodules in this high-risk population., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Eighty percent of hepatocellular carcinoma (HCC) cases occur after cirrhosis from various etiologies. The association between diet and cancer is well accepted, but the links with cirrhosis progression and HCC risk have been poorly investigated. However, we hypothesized that diet could be a modifiable preventive factor for HCC. Thus, the aim of our study was to explore the relationships between dietary factors and the risk of HCC in a population of cirrhotic patients. A total of 582 cirrhotic patients were studied: 401 without HCC (controls) and 181 with HCC (cases). These patients were recruited between 2008 and 2012 for the "CiRCE" case-control study conducted in six French university hospitals. Information about the consumption of 208 food items and 23 nutrients were collected through a diet history questionnaire. Unconditional multivariate logistic regressions were performed for each residual food group and nutrients in tertiles. HCC patients were more often men, diabetic and older than controls. After adjustment, a significant positive association was found between HCC risk and carbonated beverages (OR Tertile3vsTertile1  = 2.44 [1.17-5.09] p-trend = 0.021), total cereals (OR T3vsT1  = 1.87 [1.09-3.22] p-trend = 0.035), processed meat (OR T3vsT1  = 1.97 [1.14-3.41] p-trend = 0.028) and sodium (OR T3vsT1  = 2.00 [1.14-3.53] p-trend = 0.043). Conversely, the consumption of fiber (OR T3vsT1  = 0.49 [0.28-0.86] p-trend = 0.012), vitamin E (OR T3vsT1  = 0.52 [0.30-0.89] p-trend = 0.017), vitamin B9 (folate and folic acid) (OR T3vsT1  = 0.56 [0.33-0.95] p-trend = 0.036), manganese (OR T3vsT1  = 0.56 [0.32-0.97] p-trend = 0.038) and potassium (OR T3vsT1  = 0.44 [0.25-0.76] p-trend = 0.004) were significantly lower in HCC patients compared with cirrhotic controls. Although these findings must be confirmed in prospective studies, using dietary patterns or biological parameters, they suggest that certain dietary components may modulate HCC risk in cirrhotic patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background & Aims: No-touch multibipolar radiofrequency ablation (NTM-RFA) represents a novel therapy that surpasses standard RFA for hepatocellular carcinoma (HCC), but it has not been compared to surgical resection (SR). We aimed to compare the outcomes of NTM-RFA and SR for intermediate-sized HCC., Methods: Between 2012 and 2016, 141 patients with solitary HCC ranging from 2 to 5 cm were treated by NTM-RFA or SR at a single-center. The outcomes of 128 patients were compared after using inverse probability of treatment weighting (IPTW)., Results: Seventy-nine patients had NTM-RFA and 62 had SR. After IPTW, the two groups were well-balanced for most baseline characteristics including tumor size, location, etiology, severity of underlying liver disease and alpha-fetoprotein level. Morbidity was higher (67.9% vs. 50.0%, p = 0.042) and hospital stay was longer (12 [IQR 8-13] vs. 7 [IQR 5-9] days, p <0.001) after SR. Local recurrence rates at one and three years were 5.5% and 10.0% after NTM-RFA and 1.9% and 1.9% after SR, respectively (p = 0.065). The rates of systematized recurrence (within the treated segment or in an adjacent segment within a 2 cm distance from treatment site) were higher after NTM-RFA (7.4% vs. 1.9% at one year, 27.8% vs. 3.3% at three years, p = 0.008). Most patients with recurrence were eligible for rescue treatment, resulting in similar overall survival (86.7% after NTM-RFA, 91.4% after SR at three years, p = 0.954) and disease-free survival (40.8% after NTM-RFA, 56.4% after SR at three years, p = 0.119)., Conclusion: Compared to SR, NTM-RFA for solitary intermediate-sized HCC was associated with less morbidity and more systematized recurrence, while the rate of local recurrence was not significantly different. Most patients with intrahepatic recurrence remained eligible for rescue therapies, resulting in equivalent long-term oncological results after both treatments., Lay Summary: Outcomes of patients treated for intermediate-sized hepatocellular carcinoma by surgical resection or no-touch multibipolar radiofrequency ablation were compared. No-touch multibipolar radiofrequency ablation was associated with a lower overall morbidity and a higher rate of systematized recurrence within the treated segment or in an adjacent segment within a 2 cm distance from the initial tumor site. Most patients with intrahepatic recurrence remained eligible for rescue curative therapy, enabling them to achieve similar long-term oncological results after both treatments., (Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Recent data suggest that alcohol-related hepatocellular carcinoma (HCC) is diagnosed at a later stage. The aim of this study was to compare HCC characteristics and outcomes in an alcohol-related group (group A) and a non-alcohol-related group (group NA)., Methods: A total of 1207 patients with newly diagnosed HCC were prospectively included between May 2008 and October 2009. Patients with multiple causes (alcohol plus another cause) were excluded. Patients were followed every year for 5 years. Recorded variables, including etiologies were tested as prognostic factors of survival in a multivariate Cox model after adjustments for a lead-time bias., Results: In all, 894 patients were analyzed: 582 (65.1%) were in group A, and 312 (34.9%) were in group NA. Alcohol-related HCC was more likely to be diffuse and detected in patients with a worse performance status and worse liver function. After adjustments for a lead-time bias, the median overall survival (OS) was 9.7 and 5.7 months in groups NA and A, respectively (P = .0002), and 5.8 and 5.0 months in alcohol-abstinent and alcohol non-abstinent groups, respectively (P = .09). The prognostic role of alcohol disappeared when survival was assessed at each Barcelona Clinic Liver Cancer (BCLC) stage. Patients with HCC detected during a cirrhosis follow-up program (n = 199 [22.3% of the whole cohort]) had increased lead time-adjusted median OS in comparison with patients with HCC diagnosed incidentally (11.7 vs 5.4 months; P < .0001)., Conclusions: In comparison with patients with non-alcohol-related HCC, patients with alcohol-related HCC have reduced OS, mainly because of worse liver function and tumor characteristics at diagnosis, as attested by similar survival within each BCLC stage. Cancer 2018;124:1964-72. © 2018 American Cancer Society., (© 2018 American Cancer Society.)

Background & Aims: Microvascular invasion (mVI) is a major prognostic factor in hepatocellular carcinoma (HCC) that cannot be detected before surgery. Predictive biomarkers of mVI are thus urgently needed. We have developed an original approach of virtual biopsy to assess the performance of an immunohistochemical panel comprising three biomarkers of mVI (H4K16ac, H4K20me2, PIVKA-II) for the prediction of mVI in HCC core needle biopsies (CNB)., Methods: A test set of HCC surgical specimens (n = 64) and an independent validation set of HCC CNB (n = 42) were retrospectively constituted. Immunostainings were first quantified in the test set on the whole tissue section, to determine optimal cut-off values for each marker. From the digitised image of the whole section, three virtual biopsies were provided. Immunostainings and accuracy of the panel for the prediction of mVI were further assessed in virtual biopsies and in the validation set of CNB., Results: In virtual biopsies, PIVKA-II/H4K16ac had the best performance for prediction of mVI, with sensitivity, specificity, predictive positive value (PPV), and predictive negative value (PNV) of 30%, 97%, 91%, 56%, respectively. In CNB, PIVKA-II/H4K20me2 showed the best accuracy for prediction of mVI, with sensitivity, specificity, PPV, and NPV of 43%, 95%, 90%, and 62%, respectively. The two panels were independent predictive factors of mVI (PIVKA-II/H4K16ac, P = .037; PIVKA-II/H4K20me2, P = .026)., Conclusion: This study shows that a panel of two markers is able to predict mVI in HCC CNB, and pave the way for the future development of prognostic biomarkers in HCC that could guide the therapeutic strategy., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The increasing incidence of hepatocellular carcinoma (HCC) in Western countries requests reliable tumour markers for preclinical diagnosis. We evaluated the diagnostic accuracy of des-gamma-carboxy prothrombin (DCP), in comparison with alpha-fetoprotein (AFP) in a French cohort using a new analyser. One hundred and sixty-two patients with virus-related cirrhosis (46 HCC patients and 116 controls) were recruited in this retrospective proof-of-concept study. DCP was measured on new Lumipulse ® G600 analyzer and AFP on usual Cobas e602 analyzer in serum samples that were collected at the time of HCC diagnosis for HCC patients or during follow-up for controls. DCP and AFP levels were higher in HCC patients. The area under receiver operating characteristic curve was larger for DCP than for AFP (0.89 vs 0.77, P=.03). At the cut-off value of 128 mAU/mL, sensitivity and specificity for DCP were 74% and 92%. At the cut-off value of 20 μg/L, sensitivity and specificity for AFP were 63% and 82%. NRI >0 for the association of "AFP+DCP" were 101%, P<.0001, and 23%, P=.03, compared to "AFP" or "DCP" alone, respectively. We conclude that DCP outperformed AFP for the detection of HCC., (© 2016 John Wiley & Sons Ltd.)